VOL 3 - Layout 1

LEON DĂNĂILĂ
Fu n c t i o n a l
Neuroanatomy
of the Brain
Third Part
To Alexandra
CONTENTS
Foreword ........................................................................................................................................XXXI
FIRST PART
Chapter 1
HISTORY OF THE BRAIN AND MIND
Introduction .................................................................................................................................1
Egyptian physician Imhotep ........................................................................................................9
The Ebers Papyrus ....................................................................................................................11
Three faces of Greece and Hippocrates ...................................................................................12
1. Early Greece .........................................................................................................................12
2. The Golden Age of Greece ...................................................................................................13
ALCMAEON OF CROTON .......................................................................................................14
HIPPOCRATES .........................................................................................................................17
3. The Hellenistic Era ................................................................................................................20
PLATO .......................................................................................................................................22
ARISTOTLE ..............................................................................................................................22
GALEN ......................................................................................................................................23
The Middle Ages .......................................................................................................................26
RHAZES ....................................................................................................................................26
ESMAIL JORJANI .....................................................................................................................26
AVICENNA ................................................................................................................................28
MONDINO DE’ LIUZZI ..............................................................................................................31
The Renaissance .......................................................................................................................31
LEONARDO DA VINCI...............................................................................................................32
JACOPO BERENGARIO DA CARPI..........................................................................................32
VESALIUS..................................................................................................................................32
GABRIELE FALLOPIO...............................................................................................................35
GIULIO CASSERIO ..................................................................................................................35
JOHANN VESLING ...................................................................................................................36
JOHANN JAKOB WEPFER ......................................................................................................36
RENÉ DESCARTES .................................................................................................................36
PACCHIONI ..............................................................................................................................38
LANCISI ....................................................................................................................................39
WILLIS ......................................................................................................................................41
SWEDENBORG ........................................................................................................................44
THE 4 GENERATIONS OF THE MECKEL FAMILY ..................................................................45
GALVANI ...................................................................................................................................54
VOLTA .......................................................................................................................................55
GALL (PHRENOLOGY) ............................................................................................................56
FLOURENS ...............................................................................................................................60
DARWIN ....................................................................................................................................61
JEAN-BAPTISTE BOUILLAUD .................................................................................................62
V
LEON DăNăILă – Functional neuroanatomy of the brain
GABRIEL ANDRAL ...................................................................................................................63

MARC DAX ...............................................................................................................................64
PIERRE PAUL BROCA .............................................................................................................66
CARL WERNICKE ....................................................................................................................71
HUGHLINGS JACKSON ...........................................................................................................75
FRITSCH AND HITZIG .............................................................................................................78
FRIEDRICH L. GOLTZ ..............................................................................................................80
DAVID FERRIER .......................................................................................................................82
HERMANN MUNK ....................................................................................................................86
KORBINIAN BRODMANN ........................................................................................................90
SHERRINGTON ........................................................................................................................93
The discovery of neurotransmitters ...........................................................................................98
HENRY DALE .........................................................................................................................100
OTTO LOEWI ..........................................................................................................................103
Ways by which neurons communicate ....................................................................................106
RITA LEVI-MONTALCINI .........................................................................................................107
SPERRY .................................................................................................................................109
Chapter 2
INTRODUCTION IN THE NERVOUS SYSTEM
Basic division of the brain stem ...............................................................................................142
Medulla oblongata ...................................................................................................................142
Pons ........................................................................................................................................143
Cerebellum ..............................................................................................................................143
Midbrain ..................................................................................................................................143
Forebrain .................................................................................................................................144
Diencephalon ..........................................................................................................................144
The basal nuclei or basal ganglia ............................................................................................146
Cerebral hemispheres .............................................................................................................150
Cerebral cortex ........................................................................................................................151
White matter of the cerebral hemispheres ..............................................................................153
Chapter 3
MEDULLA OBLONGATA (OR BULB)
External structure ....................................................................................................................156
Internal structure .....................................................................................................................158
I. Level of motor (pyramidal) decussation ...............................................................................160
Dorsal column nuclei ...............................................................................................................160
Spinal trigeminal nucleus and its tracts ...................................................................................166
Other tracts .............................................................................................................................168
II. Level of sensory (lemniscal) decussation ...........................................................................169
Medial lemniscus .....................................................................................................................169
Medial longitudinal fasciculus (MLF) .......................................................................................170
Accessory cuneate nucleus ....................................................................................................171
Arcuate nuclei .........................................................................................................................171
Area postrema .........................................................................................................................172
VI
CONTENTS
Cranial nerve nuclei ................................................................................................................172

III. Level of olive ......................................................................................................................172
Medullary reticular formation ...................................................................................................175
Cranial nerve nuclei of the medulla .........................................................................................178
Clinical considerations ............................................................................................................181
The medulla and respiratory functions ....................................................................................201
The medulla and cardiovascular control .................................................................................202
The medulla and swallowing ...................................................................................................202
The medulla and sneezing ......................................................................................................203
Neuroanatomy of yawning ......................................................................................................203
Neuroanatomy of vomiting ......................................................................................................204
Chapter 4
PONS
The ventral surface of the pons ...............................................................................................210
The dorsal surface of the pons ................................................................................................211
Internal structure of the pons ..................................................................................................212
Ventral (basilar) pons ..............................................................................................................212
Dorsal pons (pontine tegmentum) ...........................................................................................214
Vestibular system ....................................................................................................................223
Vestibular apparatus ...............................................................................................................224
Bony labyrinth .........................................................................................................................224
Membranous labyrinth .............................................................................................................225
Microstructure of the vestibular system ...................................................................................226
Utricle ......................................................................................................................................229
Saccule ...................................................................................................................................230
Vestibulocochlear nuclei and nerve .........................................................................................231
The vestibular nerve and nuclei ..............................................................................................231
Central pathways ....................................................................................................................232
Vestibular nuclear complex .....................................................................................................233
Afferent projections (input) to the vestibular nuclei .................................................................234
Efferent projections (output) from the vestibular nuclei ...........................................................238
The cochlear nerve and nuclei ................................................................................................252
Anatomy of hearing .................................................................................................................255
Central transmission ................................................................................................................258
The cochlear nuclei .................................................................................................................259
Auditory pathways ...................................................................................................................261
Superior olivary nuclei .............................................................................................................264
Lateral lemniscus ....................................................................................................................264
Inferior colliculus .....................................................................................................................265
Medial geniculate nucleus .......................................................................................................266
Auditory cortex ........................................................................................................................268
The auditory pathway through the reticular formation .............................................................270
Descending auditory projections .............................................................................................270
Sound reflex ............................................................................................................................272
Sections of the pons ................................................................................................................272
VII
Caudal pons ............................................................................................................................272

Abducent nucleus and nerve ...................................................................................................272
Unilateral MLF lesion: internuclear ophthalmoplegia ..............................................................276
The one-and-a-half syndrome .................................................................................................276
The medial tegmental syndrome .............................................................................................277
Facial nucleus and nerve (CN VII) ..........................................................................................277
Middle pons .............................................................................................................................283
Trigeminal nerve (CN V) ..........................................................................................................283
Trigeminal tracts ......................................................................................................................297
Trigeminal reflexes ..................................................................................................................311
Trigeminal neuralgia ................................................................................................................315
Rostral pons ............................................................................................................................316
The ventral portion of the pons ...............................................................................................317
The medial longitudinal fasciculus (MLF) ................................................................................317
Superior cerebellar peduncle ..................................................................................................318
Chapter 5
MIDBRAIN
Pretectal area ..........................................................................................................................336
Tectum .....................................................................................................................................337
The superior colliculi ............................................................................................................337
Efferent connections ...............................................................................................................338
Afferent connections ...............................................................................................................340
The inferior colliculi ..............................................................................................................342
Afferent connections ...............................................................................................................342
Efferent connections ...............................................................................................................343
Tegmentum .............................................................................................................................344
Nuclear groups ........................................................................................................................345
The red nucleus ......................................................................................................................351
The posterior commissure .......................................................................................................355
Basal portion of the midbrain ..................................................................................................357
Cerebral peduncle ...................................................................................................................357
Substantia nigra ......................................................................................................................358
Mesencephalic dopaminergic cell groups ...............................................................................362
Pupillary reflexes .....................................................................................................................364
Supranuclear pathways for accommodation ...........................................................................367
Pupillodilation ..........................................................................................................................368
Vertical gaze ............................................................................................................................369
Midbrain clinical correlates ......................................................................................................370
Syndrome of Weber ................................................................................................................371
Syndrome of Benedikt .............................................................................................................372
Claude’s syndrome .................................................................................................................372
Nothnagel’s syndrome ............................................................................................................373
Plus-minus lid syndrome .........................................................................................................373
Top of the basilar syndrome ....................................................................................................373
Walleyed syndrome .................................................................................................................374
VIII
CONTENTS
Vertical one-and-a-half syndrome ...........................................................................................374

Locked-in syndrome ................................................................................................................374
Peduncular hallucinosis syndrome ..........................................................................................375
Akinetic mutism .......................................................................................................................376
Decerebrate rigidity .................................................................................................................376
Periaqueductal grey matter .....................................................................................................377
Mesencephalic reticular formation ..........................................................................................378
Chapter 6
RETICULAR FORMATION
Introduction .............................................................................................................................385
Organization of the RF ............................................................................................................386
Neurons of the RF ...................................................................................................................386
Reticulospinal tracts ................................................................................................................388
Medullary reticular formation ...................................................................................................389
Afferent fibres to the medullary RF .........................................................................................391
Efferent fibres from the medullary RF .....................................................................................392
The pontine reticular formation ...............................................................................................394
Mesencephalic reticular formation ..........................................................................................398
Chemical specified systems ....................................................................................................400
Monoaminergic system ...........................................................................................................401
Zones of the RF ......................................................................................................................402
Afferents to the RF ..................................................................................................................404
Efferents from the RF ..............................................................................................................404
Nuclei associated with the RF .................................................................................................404
Functions of the RF .................................................................................................................405
Somatic motor function ...........................................................................................................405
The descending influences .....................................................................................................405
Pontine (medial) reticulospinal tract ........................................................................................407
Medullary (lateral) reticulospinal tract .....................................................................................408
Corticoreticular fibres ..............................................................................................................409
Control of eye movements and other cranial nerve function ...................................................410
Somatic sensory function ........................................................................................................412
Control of visceral functions ....................................................................................................413
Respiration ..............................................................................................................................414
Cardiovascular activity ............................................................................................................415
Influence on the endocrine system .........................................................................................417
Ascending reticular activating system .....................................................................................417
Projections from the mesopontine tegmentum to the forebrain ..............................................419
Ascending reticular inhibitory system ......................................................................................426
Chapter 7
CEREBELLUM
Organization of the cerebellum ...............................................................................................439
Morphological approach of the cerebellum .............................................................................440
Functional approach of the cerebellum ...................................................................................444
IX
Gray and white matter .............................................................................................................449

Cerebellar peduncles ..............................................................................................................450
Internal structure .....................................................................................................................452
The intracerebellar nuclei ........................................................................................................452
Afferents to the cerebellum .....................................................................................................456
Spinocerebellar and trigeminocerebellar fibres .......................................................................457
Olivocerebellar fibres ..............................................................................................................461
Vestibulocerebellar fibres ........................................................................................................463
Pontocerebellar fibres .............................................................................................................464
Reticulocerebellar fibres ..........................................................................................................464
Corticoreticulocerebellar pathway ...........................................................................................465
Mossy fibres ............................................................................................................................466
Climbing fibres ........................................................................................................................468
Efferents from the cerebellum .................................................................................................471
Cerebellar circuitry ..................................................................................................................479
Details of cerebellar circuitry ...................................................................................................481
The cerebro-cerebellar circuit .................................................................................................482
Cerebellar cortex .....................................................................................................................484
1. The molecular layer .............................................................................................................486
2. The Purkinje cell layer .........................................................................................................488
3. The granular layer ...............................................................................................................493
Cerebellar cortex – pharmacologic considerations .................................................................495
Cerebellar cortex – physiology ................................................................................................496
Theories of cerebellar function ................................................................................................500
Cerebellum and cognition .......................................................................................................504
Implicit learning .......................................................................................................................504
Procedural learning .................................................................................................................505
Cerebellum and language .......................................................................................................506
Cerebellum and writing ...........................................................................................................508
Cerebellum, working memory, creativity and giftedness .........................................................508
Clinical aspects .......................................................................................................................511
Cognitive affective syndrome ..................................................................................................520
Cerebellum and psychiatric disorders .....................................................................................522
Cerebellum and behavioral syndrome ....................................................................................523
Agenesis of the cerebellum .....................................................................................................525
Very pre-term infants ...............................................................................................................525
Chapter 8
DIENCEPHALON
EPITHALAMUS .......................................................................................................................542
Stria medullaris thalami ...........................................................................................................542
Habenular nuclei .....................................................................................................................542
The Pineal gland .....................................................................................................................542
Functions .................................................................................................................................544
Posterior commissure .............................................................................................................546
THALAMUS .............................................................................................................................546
X
CONTENTS
Anatomy ..................................................................................................................................547
Borders ....................................................................................................................................549
Lateral and external medullary laminae ..................................................................................550
Nuclear groups of the thalamus ..............................................................................................551
Anterior nuclei .........................................................................................................................554
Intralaminar nuclei ...................................................................................................................556
Medial nuclei ...........................................................................................................................559
Median nuclei ..........................................................................................................................561
Metathalamic nuclei ................................................................................................................562
Posterior nuclear complex .......................................................................................................566
Pulvinar nuclei and lateral posterior nucleus ...........................................................................566
Reticular nucleus .....................................................................................................................568
Ventral nuclei ...........................................................................................................................570
Neuronal circuitry ....................................................................................................................582
Functions of the thalamus .......................................................................................................582
Clinical considerations ............................................................................................................584
SUBTHALAMUS .....................................................................................................................586
Subthalamic nucleus ...............................................................................................................587
Forel’s field H (prerubral field) .................................................................................................589
The zona incerta .....................................................................................................................590
HYPOTHALAMUS ..................................................................................................................591
Hypothalamic regions ..............................................................................................................593
Nuclei of the hypothalamic regions .........................................................................................594
Preoptic region ........................................................................................................................597
Suprachiasmatic (supraoptic) region .......................................................................................599
The anterior hypothalamic nucleus .........................................................................................600
Interstitial nuclei of the anterior hypothalamus ........................................................................600
The paraventricular and supraoptic nuclei ..............................................................................601
Tuberal region .........................................................................................................................604
The dorsomedial nucleus ........................................................................................................605
The ventromedial nucleus .......................................................................................................605
The lateral hypothalamic nucleus ............................................................................................605
The arcuate (infundibular) nucleus ..........................................................................................606
Mammillary region ...................................................................................................................607
Hypothalamic zones ................................................................................................................608
Periventricular zone ................................................................................................................609
Medial zone .............................................................................................................................610
Lateral zone ............................................................................................................................610
Ventrolateral preoptic nucleus .................................................................................................613
Connections of the hypothalamus ...........................................................................................613
Local connections ...................................................................................................................613
Extrinsic connections ..............................................................................................................614
Afferent pathways to the hypothalamus ..................................................................................614
Fornix ......................................................................................................................................614
Amygdalohypothalamic tract ...................................................................................................616
Stria terminalis ........................................................................................................................616
XI
Retinosuprachiasmatic tract ....................................................................................................616

Thalamohypothalamic tract .....................................................................................................616
Inferior mammillary peduncle ..................................................................................................617
Dorsal longitudinal fasciculus of Schütz ..................................................................................617
Pallidohypothalamic fibres ......................................................................................................617
Cerebellohypothalamic fibres ..................................................................................................617
Fibres from the reticular formation ..........................................................................................617
Spinohypothalamic fibres ........................................................................................................618
Corticohypothalamic fibres ......................................................................................................618
Medial forebrain bundle ...........................................................................................................618
Stria medullaris thalami ...........................................................................................................619
EFFERENT CONNECTIONS OF THE DIENCEPHALON ......................................................620
Fasciculus mammillary princeps .............................................................................................620
Mammillothalamic tract (tract of Vicq d’Azyr) ..........................................................................620
Mammillotegmental tract .........................................................................................................621
Fornix ......................................................................................................................................621
Mammillointerpeduncular tract ................................................................................................621
Diencephalic periventricular system ........................................................................................621
Dorsal longitudinal fasciculus ..................................................................................................622
The medial forebrain bundle ...................................................................................................622
Hypothalamospinal tract ..........................................................................................................623
Periventricular bundle .............................................................................................................624
Hypothalamocerebellar fibres .................................................................................................624
Hypothalamothalamic fibres ....................................................................................................624
Hypothalamoprefrontal fibres ..................................................................................................624
Hypothalamocortical fibres ......................................................................................................624
The supraopticohypophysial tract ...........................................................................................625
The tuberohypophysial tract ....................................................................................................625
Pituitary gland .........................................................................................................................626
Neurohypophysis ....................................................................................................................628
Adenohypophysis ....................................................................................................................631
Hypophysial portal system ......................................................................................................634
HYPOTHALAMIC FUNCTIONS ..............................................................................................638
The regulation of the neuroendocrine system .........................................................................639
The parvocellular neurosecretory system .............................................................................643
The hypothalamic neurons participate in four reflex classes ................................................645
The reproduction function has a complex integration .............................................................648
Regulation of the autonomic nervous system and of vegetative functions .............................650
The hypothalamus and motivation ..........................................................................................656
Regulation of body temperature ...........................................................................................657
Regulation of hunger and the amount of food intake ..............................................................664
The hypothalamus and the obesity .........................................................................................668
Hypothalamus, anorexia and emaciation ................................................................................671
Drinking and thirst ................................................................................................................673
Disorder of water balance .......................................................................................................676
Diabetes insipidus ...................................................................................................................677
XII
CONTENTS
Essential hypernatremia syndrome ......................................................................................678

The syndrome of increased release of ADH and normal thirst .............................................680
Other hypothalamic functions ..................................................................................................681
Affective-emotional behavior control .......................................................................................683
Regulation of memory .............................................................................................................688
Regulating the circadian rhythm ..............................................................................................689
Circadian regulation on metabolism ........................................................................................697
Circadian regulation on sleep ..................................................................................................698
Hypothalamic regulation of sleep ............................................................................................701
SECOND PART
Chapter 9
THE BASAL GANGLIA
Basal ganglia anatomical organization ....................................................................................732
The striatum ............................................................................................................................735
Caudate nucleus .....................................................................................................................736
Nucleus accumbens ................................................................................................................739
Putamen ..................................................................................................................................740
Globus pallidus ........................................................................................................................743
Subthalamic nucleus (nucleus of Luys) ...................................................................................747
Nuclei associated with the basal ganglia ................................................................................751
The claustrum .........................................................................................................................751
Amygdaloid nucleus (amygdala) .............................................................................................751
Thalamic nuclei .......................................................................................................................751
Connections of the basal ganglia ............................................................................................752
Striatum ...................................................................................................................................753
Afferent fibres (input) ...........................................................................................................753
Corticostriate fibres .................................................................................................................753
Thalamostriate fibres ...............................................................................................................755
Nigrostriate fibres ....................................................................................................................755
Fibres from the ventral tegmental area ...................................................................................756
Fibres from the brainstem pedunculopontine tegmental nucleus ............................................756
Efferent fibres (output) .........................................................................................................756
The ansa system .....................................................................................................................757
The lenticular fasciculus ..........................................................................................................757
The thalamic fasciculus ...........................................................................................................759
Striatopallidal fibres .................................................................................................................760
Striatonigral fibres ...................................................................................................................761
Ventral (limbic) striatum ...........................................................................................................762
Globus pallidus pathway .........................................................................................................763
Afferent fibres (input) ...........................................................................................................763
Striatopallidal fibres .................................................................................................................764
Subthalamopallidal fibres ........................................................................................................764
XIII
Efferent fibres (output) .........................................................................................................764

Pallidosubthalamic fibres ........................................................................................................764
Pallidonigral fibres ...................................................................................................................766
Pallidothalamic fibres ..............................................................................................................766
Pallidotegmental fibres ............................................................................................................767
Pallidohabenular fibres ............................................................................................................767
The subthalamic pathway .......................................................................................................767
Neurotransmitters of the basal ganglia ...................................................................................768
Glutamate-releasing neurons ..................................................................................................768
GABA-releasing neurons ........................................................................................................769
Dopamine-releasing neurons ..................................................................................................769
Acetylcholine-releasing neurons .............................................................................................771
Noradrenergic and serotoninergic system ..............................................................................771
Neuropeptide-releasing neurons .............................................................................................772
Opiod peptide precursor mRNA and opiod receptor levels
in Parkinson’s disease (PD) and levodopa-induced dyskinesia (LID) .....................................772
Basal ganglia circuitry .............................................................................................................773
Cortical-striatal-pallidal-thalamo-cortical circuits .....................................................................774
Sensory-motor loop .................................................................................................................776
Oculomotor loop ......................................................................................................................780
Association (cognitive) loop ....................................................................................................780
Limbic loop pathway ................................................................................................................780
Other circuits of the basal ganglia............................................................................................781
Afferent fibres ..........................................................................................................................781
Efferent fibres ..........................................................................................................................781
Subthalamic nucleus ...............................................................................................................782
Afferent fibres ..........................................................................................................................782
Efferent fibres ..........................................................................................................................782
Pedunculopontine nucleus ......................................................................................................782
Basal ganglia – subcortical loop ..............................................................................................782
Direct and indirect pathways (loops) .......................................................................................783
Circuits that modulate activity of the basal ganglia .................................................................786
Basal ganglia functions ...........................................................................................................788
Motor function .........................................................................................................................789
Cognitive function ....................................................................................................................790
Gating function ........................................................................................................................791
The basal ganglia and learning ...............................................................................................792
Emotion and motivation function of the basal ganglia..............................................................793
High-order cognition and working memory .............................................................................794
The basal ganglia and automatic processing ..........................................................................798
The prefrontal cortex ...............................................................................................................800
Basal ganglia and cerebellum in motor function .....................................................................801
Pathophysiology of basal ganglia disorders (Clinical considerations)......................................802
Hypertonicity and dyskinesias .................................................................................................803
Hyperkinetic disorders .............................................................................................................804
XIV
CONTENTS
Tremor .....................................................................................................................................804
Chorea ....................................................................................................................................804
Athetosis .................................................................................................................................805
Ballisme ...................................................................................................................................805
Huntington’s disease ...............................................................................................................806
Dystonia ..................................................................................................................................807
Tic disorder .............................................................................................................................808
Tourette’s syndrome ................................................................................................................809
Hypokinetic disorders ..............................................................................................................810
Parkinson’s disease ................................................................................................................811
Wilson’s disease .....................................................................................................................821
Chapter 10
LIMBIC LOBE AND LIMBIC SYSTEM
Limbic lobe ..............................................................................................................................843
Limbic system .........................................................................................................................847
Parts of the limbic system .......................................................................................................849
Olfactory system .....................................................................................................................849
Septum ....................................................................................................................................852
Cingulate gyrus and cingulum .................................................................................................855
Alveus, fimbria, and fornix .......................................................................................................858
Thalamus ................................................................................................................................861
Hypothalamus .........................................................................................................................862
Locus ceruleus and dorsal raphe nucleus................................................................................862
Habenular nuclei .....................................................................................................................863
Ventral tegmental area ............................................................................................................863
Dorsal longitudinal fasciculus ..................................................................................................863
Indusium griseum ....................................................................................................................863
Fasciola cinerea ......................................................................................................................865
Limbic functions ......................................................................................................................865
Limbic system and emotion .....................................................................................................866
Negative and positive reinforcement .......................................................................................870
Limbic system and memory ....................................................................................................870
Limbic system disorder ...........................................................................................................873
Chapter 11
HIPPOCAMPAL FORMATION
Introduction .............................................................................................................................883
Anatomy ..................................................................................................................................883
Structure ..................................................................................................................................886
Cornu Ammonis (hippocampus proper) ..................................................................................886
Regional variations ..................................................................................................................891
The cytoarchitectonic organization of the hippocampus .........................................................893
The pyramidal layer .................................................................................................................893
Molecular layer ........................................................................................................................895
Polymorphic layer ....................................................................................................................896
XV
Interneurons ............................................................................................................................896
Hippocampal connections .......................................................................................................899
Afferent fibres ..........................................................................................................................899
Efferent fibres ..........................................................................................................................901
Intrinsic circuitry of the hippocampal formation .......................................................................902
Commissural connections of the hippocampus .......................................................................903
Dentate gyrus ..........................................................................................................................904
Afferents to the dentate gyrus .................................................................................................908
Efferents from the dentate gyrus .............................................................................................910
Subiculum ................................................................................................................................911
Intrinsic connections ................................................................................................................912
Subicular efferents and afferents ............................................................................................912
Presubiculum and parasubiculum ...........................................................................................912
Intrinsic connections ................................................................................................................914
Commissural connections .......................................................................................................914
Presubiculum projections to layer III of the entorhinal cortex ..................................................914
Intrahippocampal connections ................................................................................................915
Entorhinal cortex .....................................................................................................................915
Cytoarchitectonic organization ................................................................................................915
Associational connections .......................................................................................................917
Commissural connections .......................................................................................................917
Perforant and alvear pathway projections ...............................................................................917
Transmitters and receptors of the hippocampal formation ......................................................920
Functional role of the human hippocampus ............................................................................921
Learning and memory .............................................................................................................921
Motor control ...........................................................................................................................934
Emotional behavior .................................................................................................................934
Regulation of the hypothalamo-hypophysial axis ....................................................................935
There is an inverted U-shape function between the level of stress and memory.....................936
Neurogenesis ..........................................................................................................................937
Fast synaptic subcortical control of hippocampal circuits .......................................................939
The hippocampus and human diseases .................................................................................940
Encephalitis and the hippocampus .........................................................................................941
Ischaemic damage to the hippocampus ..................................................................................942
Schizophrenia and the hippocampus ......................................................................................942
Hippocampal sclerosis ............................................................................................................942
Neurotransmitter systems .......................................................................................................948
GABAergic mechanisms .........................................................................................................948
Adenosine ...............................................................................................................................949
Opiod .......................................................................................................................................949
NPY (neuropeptide Y) .............................................................................................................949
Galanin ....................................................................................................................................950
Alzheimer’s disease .................................................................................................................951
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CONTENTS
Chapter 12
AMYGDALA
Introduction .............................................................................................................................989
Anatomical organization of the amygdala ...............................................................................990
Connections ............................................................................................................................993
Major pathways .......................................................................................................................994
Subcortical connectivity ...........................................................................................................995
Afferent connections ............................................................................................................995
Efferent connections ............................................................................................................997
Connections with the olfactory system ..................................................................................1000
Connections with the hippocampal formation .......................................................................1000
Connections with neocortex ..................................................................................................1000
Neurochemical modulation ....................................................................................................1005
Functions of the amygdala ....................................................................................................1006
The fear system and the seeking system ..............................................................................1012
Erasing fear memories ..........................................................................................................1016
The seeking system ..............................................................................................................1018
The amygdala in normal aging ..............................................................................................1019
The human amygdala and fear .............................................................................................1020
The amygdala and learning ...................................................................................................1024
The human amygdala and memory ......................................................................................1024
The role of the human amygdala in perception and attention ...............................................1027
The human amygdala in social function ................................................................................1033
The human amygdala dysfunction ........................................................................................1037
The human amygdala in autism ............................................................................................1040
The human amygdala in schizophrenia ................................................................................1044
The human amygdala in Alzheimer’s disease .......................................................................1045
Chapter 13
OLFACTORY SYSTEM
Olfactory receptors ................................................................................................................1078
Olfactory transduction ...........................................................................................................1082
Olfactory bulb – secondary olfactory neurons........................................................................1084
Olfactory tract ........................................................................................................................1089
Olfactory striae ......................................................................................................................1090
Thalamic neurons ..................................................................................................................1094
Cortical neurons ....................................................................................................................1095
Olfactory cortex projections ...................................................................................................1095
Efferent olfactory connections ...............................................................................................1096
Disorders of the olfactory system ..........................................................................................1096
Chapter 14
GUSTATORY SYSTEM
Taste receptors ......................................................................................................................1103
Lingual taste buds .................................................................................................................1105
XVII
Extralingual taste buds ..........................................................................................................1107

Taste transduction .................................................................................................................1107
Primary neurons ....................................................................................................................1109
Secondary neurons ...............................................................................................................1110
The ascending gustatory path ...............................................................................................1112
Thalamic neurons ..................................................................................................................1112
Cortical neurons ....................................................................................................................1114
Disorders of the gustatory system .........................................................................................1116
Chapter 15
FRONTAL LOBES
Introduction ............................................................................................................................1122
PRECENTRAL DIVISION ......................................................................................................1125
Functional organization .........................................................................................................1128
Disorders due to lesions of the upper motor neurons ...........................................................1134
Pathological hyperreflexia .....................................................................................................1135
Spasticity ...............................................................................................................................1135
Loss of dexterity ....................................................................................................................1135
Weakness ..............................................................................................................................1136
Pseudobulbar (spastic bulbar) palsy .....................................................................................1136
PREMOTOR DIVISION .........................................................................................................1138
Broca’s aphasia .....................................................................................................................1144
Frontal-subcortical aphasias .................................................................................................1146
Brodmann’s area 8 .................................................................................................................1147
Supplementary motor area (SMA) .........................................................................................1150
Cingulate motor cortex ..........................................................................................................1153
Motor functions of somatosensory cortex ..............................................................................1154
PREFRONTAL DIVISION ......................................................................................................1155
Cytoarchitecture ....................................................................................................................1156
Connections ..........................................................................................................................1158
Neuropsychological functions of the prefrontal cortex ...........................................................1162
Dorsolateral prefrontal cortex (DLPFC) .................................................................................1162
Dorsomedial prefrontal cortex ...............................................................................................1163
Orbitofrontal cortex ................................................................................................................1165
Medial prefrontal cortex .........................................................................................................1169
Function and localization within rostral prefrontal cortex .......................................................1169
Motivation and cognitive control in the human prefrontal cortex ...........................................1175
Executive function, actions and plans ...................................................................................1176
Executive control ...................................................................................................................1179
Rostro-caudal axis of PFC ....................................................................................................1182
Response inhibition ...............................................................................................................1184
Monitoring ..............................................................................................................................1185
Attention ................................................................................................................................1185
Mental flexibility .....................................................................................................................1187
Affect .....................................................................................................................................1188
Depression ............................................................................................................................1188
XVIII
CONTENTS
Euphoria ................................................................................................................................1188
Hypokinesia ...........................................................................................................................1189
Ambiguity and decision .........................................................................................................1190
Planning ................................................................................................................................1193
Theory of mind: empathy .......................................................................................................1196
Memory of the future .............................................................................................................1199
Novelty and routine ...............................................................................................................1199
Memory .................................................................................................................................1200
Retrieval ................................................................................................................................1201
Temporal sequencing ............................................................................................................1201
Source of memory .................................................................................................................1201
Autobiographical memory .....................................................................................................1202
Working memory ...................................................................................................................1203
Social behavior ......................................................................................................................1206
Prefrontal cortex and intelligence ..........................................................................................1206
Prefrontal dysfunction ...........................................................................................................1209
Introduction ...........................................................................................................................1209
Frontal lobe syndromes .........................................................................................................1211
Dorsolateral frontal syndrome ...............................................................................................1211
Orbitofrontal syndrome ..........................................................................................................1213
Medial syndrome ...................................................................................................................1216
Reticulofrontal disconnection syndrome ...............................................................................1218
Attention deficit / hyperactive disorder (ADHD) .....................................................................1218
Disturbance in self-awareness ..............................................................................................1219
Lesions in Broca’s area .........................................................................................................1225
Lesions in the frontal eye field ...............................................................................................1226
Lesions in the motor cortex ...................................................................................................1226
Chapter 16
PARIETAL LOBE
Primary somatosensory cortex ..............................................................................................1256
Subdivisions of the Parietal Cortex .......................................................................................1258
Somatosensory association cortices .....................................................................................1259
High-order cortical representation .........................................................................................1263
Gustatory cortex ....................................................................................................................1264
Spatial information ................................................................................................................1265
Object recognition .................................................................................................................1265
Guidance of movement .........................................................................................................1265
Movement intention ...............................................................................................................1268
Human volition ......................................................................................................................1270
Brain circuits ..........................................................................................................................1271
Early gamma oscillations synchronize developing thalamus and cortex ..............................1273
Voluntary action and decision making ...................................................................................1273
Voluntary action as exploratory behavior ..............................................................................1276
Voluntary action as random behavioral noise .......................................................................1277
Voluntary action as conditioned responding ..........................................................................1277
XIX
Voluntary action as goal-directedness ..................................................................................1277

Volition and consciousness ...................................................................................................1278
Conclusions ...........................................................................................................................1280
Clinical somatosensory disorders .........................................................................................1280
The SI syndrome: astereognosis ..........................................................................................1281
Tactile agnosia ......................................................................................................................1282
Symptoms of posterior parietal damage ...............................................................................1283
Balint’s syndrome ..................................................................................................................1284
Symptoms of right parietal lesions ........................................................................................1286
Contralateral neglect (inattention) .........................................................................................1286
“Attention neurons” in the monkey parietal cortex .................................................................1288
Visual inattention ...................................................................................................................1289
Tactile inattention ..................................................................................................................1289
The Gerstmann syndrome and other left parietal symptoms ................................................1290
Neglect of one-half of the body .............................................................................................1291
Autotopagnosia .....................................................................................................................1292
Apraxia ..................................................................................................................................1293
Drawing .................................................................................................................................1294
Spatial attention ....................................................................................................................1295
Disorders of spatial cognition ................................................................................................1295
Body-part phantoms ..............................................................................................................1296
Left and right parietal lobes compared ..................................................................................1298
Summary ...............................................................................................................................1299
Lesions in the primary somesthetic area ...............................................................................1300
Lesions in the secondary somesthetic area ..........................................................................1300
Lesions in the supramarginal gyrus ......................................................................................1301
Lesions in the supramarginal and angular gyri of the dominant hemisphere ........................1302
Lesion in the parietal association area of the nondominant hemisphere ..............................1302
Lesions in the Wernicke’s area .............................................................................................1302
Lesions in the Wernicke’s and Broca’s area .........................................................................1303
Lesion in the superior longitudinal fasciculus ........................................................................1303
Lesions in other afferent fibres terminating in Broca’s or Wernicke’s areas ..........................1303
Chapter 17
TEMPORAL LOBES
Introduction ...........................................................................................................................1319
Anatomy ................................................................................................................................1321
The central auditory system ..................................................................................................1323
Auditory cortex ......................................................................................................................1325
Auditory cortical anatomy ......................................................................................................1326
Cytoarchitecture of auditory cortex .......................................................................................1328
Connectivity ...........................................................................................................................1329
Auditory association cortex ...................................................................................................1330
Anatomy ................................................................................................................................1330
Functional studies in monkeys ..............................................................................................1330
XX
CONTENTS
Functional studies in humans ................................................................................................1331

Unilateral lesions ...................................................................................................................1333
The left temporal lobe and verbal memory ............................................................................1335
The right temporal lobe, nonverbal memory, and musical perception ...................................1335
Neurophysiology ...................................................................................................................1336
Auditory processing ...............................................................................................................1338
The role of the primary auditory cortex .................................................................................1338
Spatial localization ................................................................................................................1338
Tonotopy ................................................................................................................................1339
Complex response properties ...............................................................................................1339
Binaural properties ................................................................................................................1340
The role of the planum temporale in sound decoding ...........................................................1340
Sound localization .................................................................................................................1340
Spatial attention ....................................................................................................................1341
Auditory object recognition and scene analysis ....................................................................1342
Speech perception ................................................................................................................1344
Introduction ...........................................................................................................................1344
History ...................................................................................................................................1346
Decoding speech ..................................................................................................................1346
Speech as a gestural language .............................................................................................1348
Mapping of speech and speech perception in the brain ........................................................1348
Music perception ...................................................................................................................1353
Intensity .................................................................................................................................1354
Timbre ...................................................................................................................................1354
Pitch ......................................................................................................................................1355
Consonance ..........................................................................................................................1358
Duration .................................................................................................................................1358
Disorder of music perception ................................................................................................1358
Plasticity and reorganization of the auditory cortex ...............................................................1361
Auditory awareness during sleep and sedation ....................................................................1363
Auditory imagery ...................................................................................................................1364
Cytoarchitecture of the temporal lobe cortex ........................................................................1364
Connections of the temporal cortex ......................................................................................1365
Asymmetry of temporal lobes ................................................................................................1366
Temporal-lobe functions ........................................................................................................1367
Organization and categorization ...........................................................................................1368
Emotion, affect and personality .............................................................................................1369
Klüver-Bucy syndrome ..........................................................................................................1370
Memory .................................................................................................................................1370
Memory allocation in neural circuits ......................................................................................1372
Synaptic selection and memory allocation ............................................................................1373
Allocation of episodic memories ............................................................................................1374
Spatial navigation ..................................................................................................................1376
Visual perception ...................................................................................................................1376
Facial recognition and biological motion ...............................................................................1377
Phonagnosia .........................................................................................................................1379
XXI
The superior temporal sulcus and biological motion .............................................................1379

Activation of inferior temporal neurons ..................................................................................1380
Selective attention to auditory input ......................................................................................1381
Clinical effects of temporal lobe lesions ................................................................................1382
Visual disorders .....................................................................................................................1382
Cortical deafness ..................................................................................................................1383
Auditory agnosia ...................................................................................................................1384
Apperceptive deficits .............................................................................................................1384
Associative deficits ................................................................................................................1384
Word deafness ......................................................................................................................1385
Behavioral aspects of auditory agnosia ................................................................................1385
Neurological substrate of the disorder ..................................................................................1385
Auditory hallucinations ..........................................................................................................1386
Disorder of memory, emotion and behavior ..........................................................................1387
Vestibular disturbances .........................................................................................................1388
Smell and taste .....................................................................................................................1388
Disturbances of time perception ............................................................................................1389
Nonauditory syndromes ........................................................................................................1389
Temporal lobe epilepsy .........................................................................................................1390
The interictal disorders ..........................................................................................................1395
The anterior temporal neocortex ...........................................................................................1395
Lesions in the auditory association area ...............................................................................1395
Lesions of the cortical vestibular area ...................................................................................1395
THIRD PART
Chapter 18
OCCIPITAL LOBE
Introduction ...........................................................................................................................1409
VISUAL PATHWAYS .............................................................................................................1409
Visual field topography ..........................................................................................................1412
Anatomy ................................................................................................................................1414
Cytoarchitecture ....................................................................................................................1415
Primary visual cortex .............................................................................................................1417
Extrastriate visual areas – outside of V1 ...............................................................................1419
The functional organization of extrastriate visual areas ........................................................1421
Connectivity ...........................................................................................................................1424
Visual input ............................................................................................................................1425
Intrinsic circuitry ....................................................................................................................1428
Corticocortical connectivity ....................................................................................................1431
Patterns of organization within the sensory cortices: Brain modules ....................................1432
The columnar organization of the striate cortex ....................................................................1434
Functional subsystem ...........................................................................................................1436
Motion perception ..................................................................................................................1436
Color ......................................................................................................................................1436
Form ......................................................................................................................................1437
XXII
CONTENTS
Cue invariance ......................................................................................................................1438

Figure-ground segmentation .................................................................................................1438
Complex forms ......................................................................................................................1438
Written words and dyslexia ...................................................................................................1439
Depth and the analysis of space ...........................................................................................1439
The ventral and dorsal pathways ..........................................................................................1440
Visual consciousness ............................................................................................................1443
Unconscious perception ........................................................................................................1443
Visual attention ......................................................................................................................1445
CLINICAL EFFECTS AND SYMPTOMS ...............................................................................1448
Visual field defects ................................................................................................................1448
Visual agnosia .......................................................................................................................1450
Associative agnosia ..............................................................................................................1451
Apperceptive agnosia ............................................................................................................1451
Simultanagnosia ....................................................................................................................1452
Prosopagnosia ......................................................................................................................1452
Visual object agnosia ............................................................................................................1454
Disorder of reading ................................................................................................................1455
Disorder of color processing .................................................................................................1456
Achromatopsia ......................................................................................................................1457
Color anomia .........................................................................................................................1458
Color agnosia ........................................................................................................................1458
Visual neglect ........................................................................................................................1459
Other visuospatial anomalies ................................................................................................1460
Cortical blindness and Anton’s syndrome .............................................................................1460
Topographical disorientation .................................................................................................1461
Defects in constructional skills ..............................................................................................1463
Visual illusions (metamorphopsias) .......................................................................................1465
Visual hallucinations ..............................................................................................................1466
Visual imagery .......................................................................................................................1467
Lesions in the primary visual area .........................................................................................1469
Lesions in the association visual areas .................................................................................1469
Chapter 19
WHITE MATTER OF CEREBRAL HEMISPHERE
Association fibres ..................................................................................................................1480
The short arcuate fibres ........................................................................................................1481
The long arcuate fibres .........................................................................................................1481
The uncinate fasciculus .........................................................................................................1481
The cingulum .........................................................................................................................1481
The superior longitudinal fasciculus ......................................................................................1482
The superior fronto-occipital fasciculus (subcalosal bundle) .................................................1482
The inferior longitudinal fasciculus ........................................................................................1482
The external capsule .............................................................................................................1482
Projection fibres ....................................................................................................................1482
Corticopetal fibres .................................................................................................................1483
XXIII
Corticofugal fibres ..................................................................................................................1484

Commissural fibres ...............................................................................................................1484
Anterior commissure .............................................................................................................1484
Posterior commissure ...........................................................................................................1485
Hippocampal commissure .....................................................................................................1486
Corpus callosum ...................................................................................................................1486
Internal capsule and corona radiata ......................................................................................1486
Chapter 20
CORPUS CALLOSUM
Anatomy of the corpus callosum ...........................................................................................1493
The rostrum ...........................................................................................................................1495
The genu ...............................................................................................................................1495
The body ...............................................................................................................................1495
The isthmus ...........................................................................................................................1497
The splenium .........................................................................................................................1498
The callous fibres ..................................................................................................................1499
The function of the corpus callosum .....................................................................................1504
The clinic of the corpus callosum ..........................................................................................1506
Specificity of callosal fibres ...................................................................................................1511
The disconnection syndrome ................................................................................................1511
The effects of complete disconnection ..................................................................................1513
The effects of partial disconnection .......................................................................................1513
The acute disconnection syndrome ......................................................................................1514
The chronic disconnection syndrome ....................................................................................1515
The transfer of sensorial information .....................................................................................1516
Visual effects .........................................................................................................................1516
Language ..............................................................................................................................1521
Postcallosotomy mutism .......................................................................................................1523
Corpus callosum and reading ...............................................................................................1526
Corpus callosum and the visual-spatial aptitudes .................................................................1527
Somesthesis ..........................................................................................................................1527
Audition .................................................................................................................................1530
Olfaction ................................................................................................................................1531
The transfer of motor information ..........................................................................................1532
Movement .............................................................................................................................1532
Praxic and graphometric activities ........................................................................................1534
Agnosia and alexia ................................................................................................................1537
Transfer of complex asymmetrically organized information ..................................................1537
Unilateral apraxia ..................................................................................................................1537
Alien hand syndrome ............................................................................................................1538
Corpus callosum and memory ..............................................................................................1540
Corpus callosum and attention ..............................................................................................1541
Corpus callosum and the emotional function ........................................................................1542
The interhemispheric transfer of elaborate behavior .............................................................1542
The median fusion .................................................................................................................1543
XXIV
CONTENTS
Interhemispheric transfer time ...............................................................................................1544

Syndromes after callosotomy ................................................................................................1544
Frontal commissurotomy .......................................................................................................1544
Midcallosal section ................................................................................................................1546
Splenial section .....................................................................................................................1546
Complete callosotomy ...........................................................................................................1554
Callosal agenesis ..................................................................................................................1557
The stroke of the corpus callosum ........................................................................................1561
Tumors and degenerative diseases of corpus callosum .......................................................1561
Marchiafava-Bignami disease ...............................................................................................1563
Anterior corpus callosum vascular malformations .................................................................1563
Summary ...............................................................................................................................1567
Conclusions ...........................................................................................................................1573
Chapter 21
CEREBRAL CORTEX
Introduction ...........................................................................................................................1592
Fissures, sulci, and gyri .........................................................................................................1597
Lateral organization ...............................................................................................................1597
Longitudinal organization ......................................................................................................1598
Point-to-point representation on the cortex ...........................................................................1599
Association areas of the cortex .............................................................................................1600
Connections between cortical areas and binding problems ..................................................1604
Histology of the cerebral cortex .............................................................................................1605
Inhibitory interneurons in the neocortex ................................................................................1609
Cortical layers ........................................................................................................................1611
Cortical connectivity ..............................................................................................................1614
Afferent connections .............................................................................................................1614
The thalamocortical fibres .....................................................................................................1614
The thalamocortical relationship ...........................................................................................1615
Efferent connections .............................................................................................................1616
Myeloarchitectonics ...............................................................................................................1617
Cortical columns spots and stripes (microarchitecture) ........................................................1619
The organization of the cells of the cortex ............................................................................1624
Cortical layers, afferents and efferents ..................................................................................1625
Mapping the human cortex ....................................................................................................1627
Neurotransmitters of the cerebral cortex ...............................................................................1630
Cortical areas ........................................................................................................................1632
Functional aspects of the cerebral cortex .............................................................................1634
The functional areas of the cerebral cortex ...........................................................................1639
Summary ...............................................................................................................................1640
Cortical areas controlling motor activity ................................................................................1640
THE PRIMARY MOTOR AREA .............................................................................................1641
The corticospinal tract ...........................................................................................................1645
Secondary motor cortex ........................................................................................................1648
XXV
PREMOTOR CORTEX ..........................................................................................................1649

Supplementary motor area (SMA) ........................................................................................1652
Posterior parietal motor area .................................................................................................1654
Frontal eye field .....................................................................................................................1654
Supplementary eye fields ......................................................................................................1661
Dorsolateral prefrontal cortex ................................................................................................1661
Motor speech region .............................................................................................................1664
The mirror system: ventral premotor and parietal cortex ......................................................1666
PREFRONTAL CORTEX ......................................................................................................1668
The lateral prefrontal cortex ..................................................................................................1668
The dorsolateral area ............................................................................................................1668
The ventrolateral prefrontal area ...........................................................................................1668
The cortex of the frontal pole ................................................................................................1669
The inferior or orbital prefrontal cortex ..................................................................................1669
The medial prefrontal cortex .................................................................................................1669
SENSORY AREAS OF THE CEREBRAL CORTEX .............................................................1670
Primary sensory areas ..........................................................................................................1670
Primary somatosensory cortex (S I) ......................................................................................1670
Secondary somatosensory cortex (S II) ................................................................................1676
Primary vestibular cortex .......................................................................................................1681
Awareness of voluntary action and the parietal cortex ..........................................................1684
Primary visual cortex (V1) .....................................................................................................1685
The output from the primary visual cortex .............................................................................1690
Secondary visual cortex (V2) ................................................................................................1690
The third visual area (V3) ......................................................................................................1692
The fourth visual area (V4) ....................................................................................................1692
The fifth visual area (V5) .......................................................................................................1695
Preoccipital areas involved in following ocular movements ..................................................1695
Auditory cortex ......................................................................................................................1697
Primary auditory cortex .........................................................................................................1697
Auditory association cortex ...................................................................................................1704
Area 21 ..................................................................................................................................1705
Area 20 ..................................................................................................................................1706
Descending auditory pathways .............................................................................................1706
Acoustic startle reflex, orientation, and attention ..................................................................1706
INSULA .................................................................................................................................1709
The insular cortex of the primates .........................................................................................1711
Connections ..........................................................................................................................1711
Functional aspects ................................................................................................................1713
CORTICAL LANGUAGE AREAS ..........................................................................................1714
Wernicke’s area ....................................................................................................................1714
Broca’s area ..........................................................................................................................1715
Cortical localization of music .................................................................................................1717
Ventral surface and midtemporal cortical areas ....................................................................1718
Illusions .................................................................................................................................1718
Hallucinations ........................................................................................................................1718
XXVI
CONTENTS
Automatisms .........................................................................................................................1718
Anomic aphasia .....................................................................................................................1720
Primary gustatory cortex .......................................................................................................1721
Chapter 22
VENTRICULAR SYSTEM AND MENINGES
Introduction ...........................................................................................................................1748
Lateral ventricle .....................................................................................................................1749
The frontal horn .....................................................................................................................1749
The body or the central portion .............................................................................................1749
The posterior (occipital) horn ................................................................................................1749
The inferior (temporal) horn ..................................................................................................1750
The choroid plexus ................................................................................................................1750
Third ventricle ........................................................................................................................1750
Anterior wall ..........................................................................................................................1751
The lamina terminalis ............................................................................................................1751
Roof .......................................................................................................................................1751
Floor ......................................................................................................................................1752
Posterior wall .........................................................................................................................1752
Lateral wall ............................................................................................................................1753
Aqueduct of Sylvius ...............................................................................................................1753
Fourth ventricle .....................................................................................................................1753
Floor of the fourth ventricle ...................................................................................................1754
Roof of the fourth ventricle ....................................................................................................1755
Production of the cerebrospinal fluid (CSF) ..........................................................................1756
CSF absorption .....................................................................................................................1757
CSF function .........................................................................................................................1758
Tanycites ...............................................................................................................................1758
Composition of CSF ..............................................................................................................1758
Meninges ...............................................................................................................................1759
Cranial dura mater ................................................................................................................1760
Reflections of the meningeal layer of the dura mater ............................................................1760
Falx cerebri ...........................................................................................................................1761
Tentorium cerebelli ................................................................................................................1761
Falx cerebelli .........................................................................................................................1762
Diaphragma sella ..................................................................................................................1762
Cavum trigeminale (Meckel’s cave) ......................................................................................1762
Vascular and nerve supply ....................................................................................................1762
Sinus pericranii ......................................................................................................................1763
Emissary veins ......................................................................................................................1763
Innervation of the cranial dura mater ....................................................................................1763
Leptomeninges and CSF space ............................................................................................1763
Cranial arachnoid ..................................................................................................................1764
Arachnoid cisternae ..............................................................................................................1765
Arachnoid granulations and villi ............................................................................................1766
Pia mater ...............................................................................................................................1770
XXVII
Chapter 23
CEREBRAL ASYMMETRY in nonhumans
Introduction ...........................................................................................................................1776
Asymmetry in rats .................................................................................................................1779
Asymmetry in birds ................................................................................................................1781
Asymmetry in nonhuman primates ........................................................................................1782
The evolution of handedness ................................................................................................1786
Theories of hand preference .................................................................................................1787
Environmental theories .........................................................................................................1787
Culture and language ............................................................................................................1788
Sensory or environmental deficits .........................................................................................1789
Brain organization in nonhearing people ...............................................................................1789
Environmental deprivation .....................................................................................................1790
Environmental accident .........................................................................................................1790
Functional cerebral organization of left-handers ...................................................................1790
Anatomical theories ...............................................................................................................1791
Hormonal theories .................................................................................................................1792
Genetic theories ....................................................................................................................1793
Sex differences in cerebral organization ...............................................................................1795
Sex differences in behavior ...................................................................................................1795
Motor skills ............................................................................................................................1796
Spatial analysis .....................................................................................................................1796
Mathematical aptitude ...........................................................................................................1796
Perception .............................................................................................................................1797
Verbal ability ..........................................................................................................................1797
Sex difference in the brain structure .....................................................................................1797
The influence of sex hormones .............................................................................................1798
Explanation of sex differences ..............................................................................................1802
Hormonal effects ...................................................................................................................1802
Genetic sex linkage ...............................................................................................................1803
Maturation rate ......................................................................................................................1803
Environment ..........................................................................................................................1804
Preferred cognitive mode ......................................................................................................1804
Anatomical studies ................................................................................................................1804
Handedness and the longevity ..............................................................................................1807
Effects of hemispherectomy ..................................................................................................1809
Ontogeny of asymmetry ........................................................................................................1811
ASYMMETRY BETWEEN THE HEMISPHERES in humans ................................................1814
Introduction ...........................................................................................................................1814
Historical aspects ..................................................................................................................1817
Bouillaud ...............................................................................................................................1817
Marc Dax ...............................................................................................................................1818
Gustav Dax ...........................................................................................................................1819
Broca .....................................................................................................................................1820
Wernicke ...............................................................................................................................1821
Pitres and amnesic aphasia ..................................................................................................1825
XXVIII
CONTENTS
Geschwind ............................................................................................................................1826
Aphasia and thought .............................................................................................................1826
ASYMMETRIES OF THE HUMAN FRONTAL LOBES .........................................................1827
Asymmetries in language ......................................................................................................1828
Morphological asymmetries ..................................................................................................1830
Functional imaging ................................................................................................................1831
Asymmetry of prosody and emotion ......................................................................................1833
Prefrontal cortex ....................................................................................................................1836
Premotor cortex .....................................................................................................................1839
Primary motor cortex .............................................................................................................1840
Medial wall (anterior cingulate cortex and SMA) ...................................................................1842
Anterior cingulate cortex .......................................................................................................1842
Supplementary motor area ....................................................................................................1844
Asymmetry in the motor system ............................................................................................1846
Direct observation .................................................................................................................1847
Interference tasks ..................................................................................................................1847
The left hemisphere as interpreter ........................................................................................1848
Asymmetries for the language in humans .............................................................................1848
Asymmetry in visuospatial functions .....................................................................................1852
Hemispheric isolation of visual and tactile information ..........................................................1852
Sharing of attention control ...................................................................................................1853
Asymmetries in processing spatial informations ...................................................................1854
Asymmetry in memory and learning ......................................................................................1856
Asymmetry in the information process ..................................................................................1858
Asymmetry in the attention ....................................................................................................1858
Asymmetry in the music ........................................................................................................1860
Musical perception ................................................................................................................1862
Asymmetry in the visual perception and language of temporal-lobe lesions ........................1863
Language ..............................................................................................................................1864
Asymmetry in the auditory system ........................................................................................1864
Asymmetry in the somatosensory system of parietal-lobe lesions ........................................1866
Somatosensory symptoms of parietal-lobe lesions ...............................................................1868
Blind touch ............................................................................................................................1869
Pseudocerebellar syndrome .................................................................................................1870
Somatosensory agnosias ......................................................................................................1870
Astereognosis .......................................................................................................................1870
Asomatognosia .....................................................................................................................1871
Left parietal syndrome ...........................................................................................................1873
Apraxia and the parietal lobe ................................................................................................1874
Ideomotor apraxia (IMA) .......................................................................................................1874
Ideational apraxia ..................................................................................................................1875
Conceptual apraxia ...............................................................................................................1875
Limb kinetic apraxia ..............................................................................................................1876
Conduction apraxia ...............................................................................................................1877
Dissociation apraxia ..............................................................................................................1877
XXIX
Facial-oral apraxia .................................................................................................................1878

Dressing apraxia ...................................................................................................................1878
Constructional apraxia ..........................................................................................................1879
Localization and lateralization of language ...........................................................................1880
Asymmetry in emotional system ...........................................................................................1881
Brain structures studied in emotional behavior in humans ....................................................1882
The right hemisphere ............................................................................................................1882
The left hemisphere ..............................................................................................................1884
The human amygdala ...........................................................................................................1886
Orbitofrontal cortex ................................................................................................................1888
Chapter 24
THE NEURAL BASIS OF CONSCIOUSNESS
Introduction ...........................................................................................................................1928
Patients and method .............................................................................................................1928
Results ..................................................................................................................................1931
BRAINSTEM .........................................................................................................................1931
The reticular formation ..........................................................................................................1932
Ascending (reticular) activating system (AAS) ......................................................................1932
Ascending (reticular) inhibitory system (AIS) ........................................................................1936
Clinical aspects .....................................................................................................................1939
Coma .....................................................................................................................................1939
Persistent vegetative state ....................................................................................................1939
Diffuse axonal injury (loss of consciousness in concussion).....................................................1939
Logorrhea syndrome with hyperkinesia ................................................................................1940
MIDBRAIN (Mesencephalon) ................................................................................................1941
Dorsal midbrain syndrome ....................................................................................................1941
DIENCEPHALON ..................................................................................................................1942
The hypothalamus .................................................................................................................1943
The thalamus ........................................................................................................................1944
The epithalamus ....................................................................................................................1946
LIMBIC SYSTEM AND HIPPOCAMPUS ..............................................................................1947
CEREBRAL CORTEX ...........................................................................................................1949
Unilateral and diffuse, bilateral cortical destruction ...............................................................1949
Discussion .............................................................................................................................1952
Conclusions ...........................................................................................................................1953
.............................................................................................................................................. i
XXX
Foreword
As a neurosurgeon who has performed over 40 000 surgeries on the central and
peripheral nervous system during my 50 years of continuous neurosurgical activity, I can
comprehend the structural and functional complexity of the brain.
In order not to disturb the highly functional areas of the central nervous system, I
was forced to get familiar with the details of the brain map, which, taking into
consideration my experience, varies from individual to individual, and I can say that each
person, healthy or sick, is unique.
I have been an assiduous reader of many books and papers in order to have a better
documentation in this area, but I could not find any manual or book to contain relatively
complete and up-to-date information on the anatomy and physiology of the brain. The
existing neuroanatomy textbooks are not thorough enough, in my opinion, as they do not
explain the morphological and neurophysiological complexity of white and grey matter.
That is why – and also because of practical reasons – I decided to gather information
from books and recent papers and make a precise and complete synthesis of the structure
and functions of the brain, the most complex system in the universe, without claiming
originality. I carefully and respectfully quoted from the works of great neuroanatomists
and I mentioned them in references.
So, this book is not written by a neuroanatomist, but it represents a textbook
assembled by me as a neurosurgeon, as I have often had to deal with a variety of known
or still unknown, normal or abnormal activities of the brain during my numerous years
of activity.
To keep up with the vast literature in this research field, and with the investigations
of the brain as a whole has been for me a real challenge or better said an impossible task,
an unreachable goal.
The clinical pre- and post-op information has been of great help in understanding
the basic scientific concepts and the way in which the central nervous system, especially
the brain, operates and interacts in the presence of various internal and external harmful
factors, or in abnormal, pathological situations.
The turmoil of my life as a neurosurgeon came with sacrifices, sleepless nights, but
also with the great satisfaction of saving many lives, which has helped keeping my
physical and moral tonus.
The struggle with the mentalities, with the hostility of people and especially that one
of my colleagues sometimes brought me down, but never made me give up.
I have lived desolation and bitterness of painful defeats, but I have also won
extremely tough battles with the diseases I fought. I considered neurosurgery to be a true
XXXI
religion to which I dedicated my entire life. I was selfish with myself but an offering
person to the ones around me. I have worked a lot without receiving help from anyone
and I became a well known name forgetting about my own life. I have always struggled
to conquer centimetre by centimetre the way I had chosen in life. But, in order to study
and write, I had to isolate myself from the surrounding reality and carry on with my
existence in a rather symbolic way.
Patients, beginning with the adult, paediatric or elderly population admitted into the
hospital with various cognitive disorders caused by cerebral tumours, vascular diseases,
parasites, traumatisms, developmental or psychiatric disorders and degenerative diseases
have always been thoroughly investigated and helped. The evaluation and diagnosis of
their cognitive topography represented the starting point for an early rehabilitating
treatment. In order to achieve this I carefully studied the neuropathology of different
morbid entities as well as their consequences upon the highly functional activities of the
cerebral cortex.
When I decided how to operate on a patient I have always considered the post-
surgical quality of life. The main goal of neurosurgical operations was to re-establish
patients’ possibility of going back to school, to work, and their ability to carry on their
own business, to drive and thus to have their own independence.
Publishing this book concurs with an enormous explosion of knowledge about the
morphology and physiology of the central nervous system and its vast reciprocal
connections and plasticity. Consequently, I found it hard to keep up with the multitude
of works published during the past ten years about functional neuroimaging,
neuropharmacology, computational modulation, rehabilitation methods, theories of
thinking, of memory, attention, frontal functions, language etc., as well as the structures
and the immense number of neural connections and columns that build them.
First, as a graduate of the Faculty of Psychology and then as a Professor in
neuropsychology at the same university, I had to prove accurate knowledge about the
central nervous system, its macroscopic, cellular and chemical architecture, primary and
associative areas for sight, hearing, taste, motion, sensibility, visceral, endocrine and
speech functions.
While psychology is the science that studies behavior, neuropsychology deals with
its neural and neuronal determinants. Modern neuroimagistics make the scanning of
healthy persons possible, clarifying the brain - behavior interrelationships. It also helps
us to comprehend the normal cerebral processes which concern language, recognizing
objects, attention, memory, thinking and control of movements.
These were the reasons that determined me for a period of 7 years, day by day, to
gather the most significant and up-to-date information regarding the activity of all areas,
structures, regions and cerebral connections – realizing, however, that I cannot exhaust
all subjects.
This book, which includes an immense material, starts with the history of
neuroscience, data and ideas referring to soul, mind and brain, the way they have been
imagined and conceived by healers, witches and philosophers since old times.
XXXII
FOREwORD
Nevertheless, the book aims at revealing some basic and recent data about mind and
brain, making them accessible to students, doctors, psychologists, biologists and all those
interested in this vast topic and research field – the brain – who are studying by
themselves.
The information included in the entire content of this book which comes from studies
on animals, primates and humans is non-exhaustive. Critics, comments, corrections and
suggestions from neuroanatomists, neurophysiologists, colleagues and all those who
come in contact and use this book are welcome.
No matter how much effort I made writing this book, from various reasons, objective
or subjective, I keep the doors open to corrections, additions and novelty and, why not,
to reinterpretation.
It’s me who will do it or maybe others will do it better than I did.
I wish to gratefully acknowledge the kind assistance of Mrs. Stela Georgescu in
typing and correcting the text on the computer and her great effort in arranging the
illustrations and the ample bibliography.
I also thank to Dorel Arsene, MD, for his generosity and attention during typing a
large part of the text on the computer, and to Mrs. Olga Dumitru, editorial assistant, for
her care and accuracy in correcting the entire text and references.
XXXIII
OCCIPITAL LOBE
Introduction
On the lateral surface of the brain, there are no definite boundaries between the
occipital lobes and the parietal and temporal lobes.
The occipital lobe encompasses the most posterior portion of the human cerebral
cortex and is primarily responsible for vision. The surface area of the human occipital
lobe encompasses approximately 12% of the total surface area of the neocortex of the
human brain. Vision begins with the spatial, temporal, and chromatic pattern of light
falling onto photoreceptors of the retina and culminates in the perception of the properties
of the objects and surfaces within the world around us (Deyoe, 2002). To permit these
more cognitive functions, the occipital lobe is heavily interconnected with other lobes of
the brain, especially the parietal and temporal lobes, as well as with an array of subcortical
structures. Through these connections, the results of visual processing in the occipital
lobe enter into and can be influenced by more general processes involved in goal-directed,
motivated behavior and “thinking” (Kaas, 1997).
Traditionally, occipital cortex has been subdivided into anatomically distinct regions
based on cytoarchitecture. Primary visual cortex is the most distinct region of the occipital
lobe. It is also known as striate cortex due to the stria of Gennari, a band of myelinated
axons running horizontally in layer 4B which demarcates the extent of striate cortex
within and adjacent to the calcarine sulcus.
VISUAL PATHWAYS
The retina arises as an evaginated portion of the brain, the optic pouch, which
secondarily is invaginated to form the two layered optic cup. The axons of ganglion cells,
at first unmyelinated, are arranged in fine radiating bundles which run parallel to the
retinal surface and converge at the optic disk (or optic papilla) to form the optic nerve.
This region of the retina contains no photoreceptors and, because it is insensible to light,
produces the perceptual phenomenon known as the blind spot. It is the site from which
the ophtalmic artery and veins enter (or leave) the eye. The subarachnoid space
1409
Leon DănăiLă – Functional neuroanatomy of the brain (iii)
surrounding the optic nerve is continuous with that of the brain. As a result, increases in
intracranial pressure can be detected as papilledema, a swelling of the optic disk.
Optic nerves enter the cranial cavity through the optic foramina and unite to form
optic chiasma, beyond which they are continued as the optic tracts. In humans, about
60% of these fibres cross in the chiasma, while the other 40% continue toward the
thalamus and midbrain targets on the same side. So, within the chiasma a partial
deccussation occurs, the fibres from the nasal halves of the retina crossing to the opposite
side, and those from the temporal halves of the retina remaining uncrossed. In binocular
vision each visual field, right or left, is projected upon portion of both retinae. Thus the
images of objects in the right field of vision are projected on the right nasal and the left
temporal half of the retina. In the chiasma the fibres from those two retinal portions are
combined to form the left optic tract, which represents the complete right field of vision.
By this arrangement the whole right field of vision is projected upon the left hemisphere,
and the left visual field upon the right hemisphere. Once past of the chiasma, the ganglion
cell axons on each side form the optic tract. Thus, the optic tract, unlike the optic nerve,
contains fibres from both eyes. The partial crossing of ganglion cell axons at the optic
chiasma allows information from corresponding points on the two retinas to be processed
by approximately the same cortical site in each hemisphere.
On each side the optic tract sweeps outward and backward, encircling the
hypothalamus and the rostral portion of the crus cerebri (Hubel, 1988).
The ganglion cell axons in the optic tract reach a number of structures in the
diencephalon and midbrain. The major target in the diencephalon is the dorsal lateral
geniculate nucleus of the thalamus. The lateral geniculate nucleus gives rise to the
geniculocalcarine tract which forms the last relay to the visual cortex. Neurons in the
lateral geniculate nucleus, like their counterparts in the thalamic relays of other sensory
systems, send their axons to the cerebral cortex via the internal capsule (Hubel and
Wiesel, 1968; Hubel, 1988).
The superior colliculus is concerned with detection of movement with the visual
fields and with the coordination of eye and head movements. The pretectal region is
concerned with the pupillary light reflex (Fig. 18.1).
Geniculocalcarine tract arises from the lateral geniculate nucleus, passes through
the retrolenticular portion of the internal capsule and forms the optic radiations, which
end in the striate cortex (also referred to as Brodmann’s area 17 or V1), which lies largely
along and within the calcarine fissure in the occipital lobe.
The retinogeniculostriate pathway, or primary visual pathway, convey information
that is essential for most of what is thought of seeing.
Thus, damage anywhere along this route results in serious visual impairment.
A second major target of the ganglion cell axons is a collection of neurons that lies
between the thalamus and the midbrain in a region known as the pretectum. The
pretectum is important as the coordinating center for the pupillary light reflex. The initial
component of the pupillary light reflex pathway is a bilateral projection from the retina
to the pretectum.
1410
18. Occipital lobe
Fig. 18.1. The circuitry

responsible for the pupillary light
reflex. The pathway includes
bilateral projections from the
retina to the pretectum and
projections from the pretectum to
the Edinger-Westphal nucleus.
Neurons in the Edinger-Westphal
nucleus terminate in the ciliary
ganglion, and neurons in the
ciliary ganglion innervate the
pupillary constrictor muscles.
Notice that the afferent axons
activate both Edinger-Westphal
nuclei via the neurons
in the pretectum
(after Purves et al., 2004).
Pretectal neurons, in turn, project to the Edinger-Westphal nucleus, a small group

of nerve cells that lie close to the nucleus of the oculomotor nerve (cranial nerve III) in
the midbrain. The Edinger-Westphal nucleus contains the preganglionic parasympathic
neurons that send their axons via the oculomotor nerve to terminate on neurons in the
ciliary ganglion. Neurons in the ciliary ganglion innervate the constrictor muscle in the
iris, which decreases the diameter of the pupil when activated. The reduction in the
diameter of the pupil occurs when sufficient light falls on the retina.
Under normal condition, the pupils of both eyes respond identically regardless of
which eye is stimulated; that is, light in one eye produces constriction of both the
stimulated eye (the direct response) and the unstimulated eye (the consensual response).
Comparing the response in the two eyes is often helpful in localizing a lesion (Horton,
1992; Hattar et al., 2002).
There are several other important targets of retinal ganglion cell axons. One is
suprachiasmatic nucleus of the hypothalamus. The retinohypothalamic pathway is the
route by which variation of light levels influences the broad spectrum of visceral functions
that are entrained to the day / night cycle. Another target is the superior colliculus, which
coordinates head and eye movements to visual (as well as other) targets (Horton, 1992;
Hendry and Reid, 2000; Hattar et al., 2002; Purves et al., 2004).
So there is a diversity of ganglion cell types that provide information appropriate to
the functions of these different targets. They include not only differences in ganglion cell
synaptic connections, but in the locus of the phototransduction event itself. Unlike the
majority of ganglion cells, which depend on rods and cones for their sensitivity to light,
the ganglion cells that project to the hypothalamus and pretectum express their own light-
1411
sensitive photopigment (melanopsin) and are capable of modulating their response to

changes in light levels in the absence of signals from rods and cones (Hattar et al., 2002).
Visual field topography

Traditionally, visual field topography has been a primary source of information used
to identify and map different visual areas in animals.
In general, there are two types of photoreceptors: cones and rods. Cones are color-
selective, less sensitive to dim light than rods, and important for detailed color vision in
daylight. Cones are densely packed into fovea, the central part of the retina that we use
to look directly at objects to perceive their fine details. Rods contain a different
photopigment that is much more sensitive to low levels of light. Rods are important for
night vision (dark adaptation). Curiously, there are no rods in the fovea, only cones, and
the proportion of rods increases in the periphery. The signals from photoreceptors are
processed by a collection of intermediary neurons, bipolar cells, horizontal cells, and
amacrine cells, before they reach the ganglion cells, the final processing stage in the retina
before signals leave the eye.
The actual cells bodies of ganglion cells are located in the retina, but those cells have
long axons that leave the retina at the blind spot and form the optic nerve. Each ganglion
cell receives excitatory inputs from a collection of rods and cones – the distillation of
information forms a receptive field (Tong and Pearson, 2007). Lateral inhibition (Kuffler,
1953) is important for enhancing the neural representation of edges, regions of an image
where the light intensity sharply changes.
As a general rule, information from the left half of the visual world, whether it
originates from the left or right eye, is represented in the right half of the brain, and vice
versa. Each eye sees a part of visual space that defines its visual field (Fig. 18.2).
A vertical line divides the retina into nasal and temporal division and the horizontal
line divides the retina into superior and inferior divisions. Vertical and horizontal lines
in visual space intersect at the point of fixation (the point of visual space that falls on the
fovea) and define quadrants of the visual field. So, objects in the temporal part of the
visual field are seen by the nasal part of the retina, and objects in the superior part of the
visual field are seen by the inferior part of the retina.
With both eyes open, the two foveas are normally aligned on a single target in visual
space, causing the visual fields of both eyes to overlap extensively. This binocular field
of view consists of two symmetrical visual hemifields (left and right). The left binocular
hemifield includes the nasal visual field of the right eye and the temporal visual field of
the left eye; the right hemifield includes the temporal visual field of the right eye and the
nasal visual field of the left eye.
The temporal visual fields are more extensive than the nasal visual fields, reflecting
the size of the nasal and temporal retinas respectively. As a result, vision in the periphery
of the field of view is strictly monocular, mediated by the most medial portion of the
nasal retina (Purves et al., 2004).
1412
18. Occipital lobe
Fig. 18.2. Pathways in the visual system: from the eye to V1. A schematic drawing of the pathways in binocular vision,
showing the visual input from left and right visual fields (top of figure) through the optic nerve and optic tract (center of
figure), continuing on through the LGN and onto V1 in the cortex (bottom of the figure). (Source: Standring, 2005).
Most of the rest of the field of view can be seen by both eyes; i.e., individual points
in visual space lie in the nasal visual field of one eye and the temporal visual field of the
other. However, the inferior nasal fields are less extensive than the superior nasal field,
1413
and consequently the binocular field of view is smaller in the lower visual field than in
the upper.
The topographic arrangement of photoreceptors in the retina is maintained in the central
connection. Neurons representing the vertical midline of the visual field are represented in
both hemispheres and are functionally linked by interhemispheric, callosal connections.
Anyhow, visual space is systematically distorted in the cortical representation.
Ganglion cells that lie in the nasal division of each retina give rise to axons that cross
in the chiasma, while those that lie in the temporal retina give rise to axons that remain
on the same side. Images of objects in the left visual hemifield fall on the nasal retina of
the left eye and the temporal retina of the right eye, and the axons from ganglion cells in
these regions of the two retinas project through the right optic tract. Thus, unlike the optic
nerve, the optic tract contains the axons of ganglion cells that originate in both eyes and
represent the contralateral field of view.
For the primary visual pathway, the map of the contralateral hemifield that is
established in the lateral geniculate nucleus is maintained in the projection of the lateral
geniculate nucleus to the striate cortex.
Functional neuroimaging (fMRI) has been used to chart the retinotopic organization of
visual areas in the human occipital lobe (Zilles and Clarke, 1997). The resulting flat maps
show bands of activation corresponding to alternating representations of quadrants of the
horizontal and vertical meridian. On the medial wall of the hemisphere, these bands are
oriented roughly parallel to the calcarine sulcus (Deyoe and van Essen, 1988; Deyoe, 2002).
From maps of the meridian representations, it is possible to estimate the locations
of the borders between different visual areas.
Thus the fovea is represented in the posterior part of the striate cortex, whereas the
more peripheral regions of the retina are represented in progressively more anterior parts
of the striate cortex. The upper visual field is mapped below the calcarine sulcus, and the
lower visual field above it. Like the representation of the hand region in the somatic
sensory cortex, the representation of the macula is therefore disproportionately large,
occupying most of the caudal pole of the occipital lobe.
Anatomy
The occipital lobes form the posterior pole of the cerebral hemispheres, lying under
the occipital bone at the back of the skull. Viewed from the medial surface of the cerebral
hemisphere, the occipital lobe is distinguished from the parietal lobe by the parieto-
occipital sulcus (Fig. 18.3). No clear landmarks separate the occipital cortex from the
temporal or parietal cortex on the lateral surface of the hemisphere, however, because
the occipital tissue merges with the other regions. For practical purposes, an imaginary
line running laterally from the dorsal tip of the parieto-occipital sulcus to the preoccipital
notch is considered the effective boundary separating the occipital lobe from the parietal
and temporal lobes.
The lack of clear landmarks makes it difficult to define the extent of the occipital
areas precisely and has led to much confusion about the exact boundaries.
1414
18. Occipital lobe
Fig. 18.3. Medical view of the occipital

lobe, illustrating the major landmarks
(Source: Kolb and Whishaw, 2003).
Within the visual cortex, there are three clear landmarks. The most prominent is the
calcarine sulcus, which is flanked above by the cuneus and below by the lingula, and
which contains much of the primary cortex. The calcarine fissure divides the upper and
lower halves of visual world. On the ventral surface of the hemisphere there are two gyri
(lingual and fusiform). The lingual gyrus, separated from the more laterally placed
fusiform gyrus by the collateral sulcus, includes part of visual cortical regions V2 and
VP, whereas V4 is in the fusiform gyrus.
The fusiform gyrus is then bounded laterally by the occipitotemporal sulcus,
although this sulcus tends to be variable and interrupted as it extends posteriorly toward
the occipital pole.
The lateral surface of the occipital lobe is especially variable from individual to
individual.
Consequently, the lateral occipital gyrus can be irregular and can be split by the
lateral occipital sulcus, which has several important variants, sometimes appearing as
one, two, or even three small sulci running approximately in the anterior-posterior
direction. Most dorsally on the lateral surface there is the transverse occipital sulcus,
which often forms the most posterior end of the intraparietal sulcus.
Cytoarchitecture
As for all neocortex, the occipital gray matter is laminated, though the criteria for
identifying and naming different layers have varied considerably. The monkey occipital
cortex was first divided by Brodmann into three regions (areas 17, 18, and 19), but studies
using imaging, physiological, and even anatomical techniques have produced much finer
subdivisions.
Although the map is still not complete, the consensus is that the occipital cortex
contains at least nine different visual areas (V1, V2, V3, VP, V3a, V4d, V4v, DP, and
MT also known as V5) (Tootell and Hadjikhani, 2001) (Fig. 18.4).
The precise locations of the human homologues are still not settled. In a map
constructed by Tootell and Hadjikhani there are included all the monkey areas as well as
an additional color-sensitive area (V8) (Fig. 18.5).
1415
Fig. 18.4. Topography of the visual cortex of the macaque

monkey.
(A) A nearly normal rendition of the lateral surface of the
brain in which the sulci are opened slightly. (B) A flattened
cortical surface showing both the lateral and medial regions.
The shaded areas represent regions that are normally
curved up (gyri) or down (sulci). The asterisks refer to the
foveal representation in areas B1 and V4. (after Tootell and
Hadjikhani, 2001.
Fig. 18.5. Tomography of the human visual cortex. (A) A

nearly normal rendition of the lateral surface of the brain in
which the sulci are opened slightly. (B) The medial surface in
which the sulci are opened slightly. (C) A flattened cortical
surface showing both the lateral and medial regions. The
shaded areas represent regions that are normally curved up
(gyri) or down (sulci). The asterisks refer to the foveal
representation in areas V11 and V4. (after Tootell and
Hadjikhani, 2001).
1416
18. Occipital lobe
Some of the areas contain a complete visual field, whereas others have only an upper
or lower visual field. This distinction is curious, and Previc (1990) has suggested that the
upper and lower fields may have different functions, with the upper more specialized for
visual search and recognition and the lower specialized for visuomotor guidance.
Primary visual cortex is the most cytoarchitecturally distinct region of the occipital
lobe. It is also known as striate cortex, due to the stria of Gennari, which can be identified
even in a cross section of freshly cut tissue (Fig. 18.6).
Fig. 18.6. The visual cortex is highly laminated, as can be

seen in a cell body stain (left) or a myelin stain (right) in
these sections from a monkey brain. Because of the distinct
stripes, the visual cortex is sometimes called the striate
cortex (after Kolb and Wishaw, 2003).
This band of myelinated axons running horizontally in layer 4B demarcates the

extent of striate cortex within, and adjacent to, the calcarine sulcus.
Cytoarchitectural differences among visual areas outside the striate cortex (known
as extrastriate cortex) tend to be less obvious and more inconsistent, perhaps accounting
for significant differences in the accounts of cytoarchitectonic parcellation of occipital
cortex by early investigators.
One of the most widely used cytoarchitectonic schemes for subdividing cerebral
cortex has been that of Brodmann. According to him, striate cortex is designated area 17
and is immediately surrounded by area 18, which in turn is bounded by area 19. And the
portion of Brodmann area 37 may also be included in what is defined here as occipital
cortex.
Except for visual areas 17 and 18, Brodmann’s areas often correspond poorly with
functional distinction identified by more modern techniques such as neuroimaging. This
has resulted in diminished use of Brodmann’s nomenclature as a basis for describing the
functional organization of visual cortex (Fig. 18.7).
Distribution of myelinated fibres within the cortical gray matter has been successful
in delineating some functionally defined visual areas. This is certainly the case for the
stria of Gennari, which distinguishes the primary visual cortex.
1417
Fig. 18.7. Cytoarchitectural map of human cortex. A, Convex surface; B, medial surface (after Brodmann, 1909).
So, from lateral geniculate nucleus (LGN), neurons send their signals to the primary
visual cortex, called V1, because it is the first cortical visual area. The left LGN projects to
V1 in the left hemisphere which contains a retinotopic map of the entire right visual field.
The right LGN project to the right V1 which contains a map of the entire left visual field.
Its complex laminar organization is probably the most distinct of all cortical areas.
Although we usually say that the cortex has six layers, it is possible to see many more in area
V1, partly because layer IV alone features four distinct layers (Kolb and Whishaw, 2003).
1418
18. Occipital lobe
Another surprising feature of area V1 is that, although it appears to be anatomically

homogeneous, it can be shown to actually be heterogeneous by staining it for the enzyme
cytochrome oxidase, which is crucial in making energy available to cells.
Regions of cytochrome-rich areas known as lobes take part in color perception and
the interlobes have a role in form and motion perception (Kolb and Whishaw, 2003).
Neurons in V1 are sensitive to a whole host of visual features, not seen in LGN. One
of the most important visual features is orientation (Hubel and Wiesel, 1962, 1968). Some
V1 neurons respond best to vertical lines, some to 20-degree tilted lined, others to
horizontal lines and so forth.
V1 neurons are also sensitive to many other visual features besides orientation
(Hubel and Wiesel, 1968). Some neurons respond best to a particular direction of motion,
such as upward, leftward or downward motions. Other neurons respond best to particular
colors or color differences.
Finally, some neurons respond best to particular binocular disparities (Barlow et al.,
1967; Cumming, 2002), which refer to the degree of alignment between images in the
two eyes. Small displacements between images in the two eyes are what allows us to
perceive stereo-depth when we look at objects with both eyes open.
V1 neurons provide a neural representation of the orientation of visual features that
comprise the contours and shapes of the object. From the LGN, V1, V4 to the ventral
temporal cortex, you can see that neurons gradually respond to motor complex stimuli
from one area to the next (Tong and Pearson, 2007).
So, to summarize, neurons from V1 have small receptive fields that are sensitive to
orientation, color, motion or binocular disparity. V1 is functionally heterogeneous.
After visual signals are analyzed in V1, they are sent to higher visual areas for further
processing.
Extrastriate visual areas – outside of V1

V1 sends feedforward signals to many higher visual areas including areas such as
V2, V3, V4 and motion-sensitive area MT, to name a few (Felleman and Van Essen,
1991).
Area V2 is also heterogeneous when stained with cytochrome oxidase, but instead
of lobes, stripes are revealed (Purves et al., 1992). One type, the “thin stripe”, takes part
in color perception. Two other types, known as thick stripes and pale stripes, have roles
in form and motion perception, respectively. The distinction of color function across
much of the occipital cortex and beyond (i.e., areas V1, V2, V4, V8) is important because,
until recently, the perception of form or movement was believed to be colorblind.
It has now become clear that color vision is integral to analysis of position, depth,
motion, and structure of objects (Tanaka et al., 2001). Although the relative amount of
color processing certainly varies across occipital regions, with area V4 having color
processing as its major function, the processing of color-related information does more
than simply allow us to tell red from green. The appreciation of color also enriches our
capacity to detect motion, depth, and position.
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An example of the advantage of color vision can be seen in the type of

photoreceptors in primates.
Sumer and Mollan (2000) found that the color system of primates is optimized for
differentiating edible fruits from a background of leaves.
This ability to differentiate is an important advantage when having to select edible
fruits from a complex scene and is especially important when the fruits are partly
occluded by leaves, which is fairly common. In fact, color provides important information
for object recognition in such cases.
According to Zilles and Clarke (1997), dense myelin staining characterizes the
middle temporal visual area hMT+, located in the lateral occipital cortex near the
confluence of the occipital, temporal, and parietal lobes. In macaque monkeys the third
visual area, V3, can also be identified by heavy myelin staining, though it is not clear
whether this is also in humans. Human visual areas in lateral cortex appear to be displaced
posteriorly toward the occipital pole or onto the medial occipital surface. For example,
the hMT+ complex is located posterior to the superior temporal sulcus (STS) in human
but it is buried deep within the STS in macaque. Most of the human retinotopic visual
areas (V1, V2, V3-VP, V4, V3A) are located entirely or partially on the medial and
ventral aspects of the occipital lobe. In macaques, they are located partly or completely
on the lateral surface of the brain. This displacement of human visual areas places the
foveal representation of the visual field at the occipital pole. Maps of visual field
topography provide a good organizational framework for understanding the contributions
of different areas to specific visual function such is color or movement perception.
The discovery of circumscribed zones of high cytochrome oxidase activity in striate
cortex (puffs, blobs) and extrastriate cortex (V2 “stripes”, V4 “patches”) triggered the
identification and characterization of functionally distinct “modules” within occipital
visual areas that had previously been thought to be functionally homogeneous.
So, areas V1 and V2 are functionally heterogeneous and both segregate processing
for color, form, and motion. In a sense, areas V1 and V2 appear to serve as little mail-
boxes into which different types of information are assembled before being sent on to
the more specialized visual areas.
From areas V1 and V2 flow three parallel pathways that convey different attributes
of vision. The information derived from the blob area V1 goes to area V4, considered to
be a color area. Cells in area V4 are not solely responsive to color, however; some cells
respond to both form and color (Farah, 1984; Clarke and Miklossy, 1990; Barbur et al.,
1993; Farah, 2000; Goodale, 2000; Kosslyn and Thompson, 2000).
Other information from area V1 (the magnocellular input) also goes to area V2 and then
to area V5, which is specialized to detect motion. Finally, an input from area V1 and V2 to
area V3 is connected with what Zeki calls “dynamic form” – that is, the shape of objects in
motion. Thus, we see that vision begins in the primary cortex (V1), which has multiple
functions, and then continues in more specialized zones (Zeki, 1993; Zeki et al., 1999).
It is not surprising to discover that selective lesions up the hierarchy in areas V3, V4,
and V5 produce specific deficits in visual processing. People who suffer damage to area
V4 are able to see only in shades of gray. Patients not only fail to perceive colors but also
1420
18. Occipital lobe
fail to recall colors from before their injuries or even to imagine colors. The loss of area V4
results in the loss of color cognition, or the ability to think about color (Meadows, 1974;
Sacks and Wasserman, 1987; Tanaka et al., 2001; Tootell and Hadjikhani, 2001).
Similarly, a lesion in area V5 produces an inability to perceive objects in motion.
Objects at rest are perceived but, when the objects begin to move, they vanish. In
principle, a lesion in area V3 will affect from perception but, because area V4 also
processes form, a rather large lesion of both V3 and V4 would be required to eliminate
form perception (Zihl et al., 1983; Servas et al., 1993; Ungerleider and Haxby, 1994).
An important constraint of the function of areas V3, V4, and V5 is that all these areas
receive major input from area V1. People with lesions in area V1, act as though they are
blind, but visual input can still get through to higher levels-partly through small projections
of the lateral geniculate nucleus to area V2 partly through projections from the colliculus
to the thalamus (the pulvinar) to the cortex. This is the tectopulvinar pathway.
So, projections to the superior colliculus can reach the cortex through relays in the
lateral posterior-pulvinar complex of the thalamus. Because this so-called tectopulvinar
pathway constitutes the visual system in fish, amphibians and reptiles, we can expect it
to be capable of a reasonably sophisticated vision. Because there are two visual pathways
to the neocortex, complete destruction of the main pathway, the geniculostriate pathway,
does not render a subject completely blind (Poggio, 1968; Kaas, 1987; Livingston and
Hubel, 1988).
People with V1 lesions seem not to be aware of visual input and can be shown to
have some aspects of vision only by special testing.
Area V1 thus appears to be primary for vision in yet another sense: V1 must function
for the brain to make sense out of what the more specialized visual areas are processing.
So, people with significant V1 damage are capable of some awareness of visual
information, such as motion. Barbur and colleagues (1993) suggested that the integrity
of area V3 may allow this conscious awareness, but this suggestion remains a hypothesis.
The functional organization of extrastriate visual areas

Anatomical and electrophysiological studies in monkeys have led to the discovery
of multiple areas in the occipital, parietal, and temporal lobes that are involved in
processing visual information (Fig. 18.8). Each of these areas contains a map of visual
space, and each is largely dependent on the primary visual cortex for its activation
(Felleman and Van Essen, 1991; Maunsell, 1992). Neurons in some of these regions are
specialized for different aspects of the visual scene.
For example, the middle temporal area (MT) contains neurons that respond
selectively to the direction of a moving edge without regard to its color. In contrast,
neurons in another cortical area called V4 respond selectively to the color of visual
stimulus without regard to its direction of movement.
So, damage to area MT leads to a specific impairment in a monkey’s ability to
perceive the direction of motion in a stimulus pattern, while other aspects of visual
perception remain intact (Zihl et al., 1983; Schiller and Logothetis, 1990; Maunsell, 1992;
Zeki, 1993; Chalupa and Werner, 2004).
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Fig. 18.8. Subdivisions of the extrastriate cortex in the macaque monkey. (A) Each of the subdivisions indicated contains
neurons that respond to visual stimulation. Many are buried in sulci, and the overlying cortex must be removed in order to
expose them. Some of more extensively studied extrastriate areas are specifically identified (V2, V3, V4 and MT).
V1 is the primary visual cortex; MT is the middle temporal area. (B) The arrangement of extrastriate and other areas of
neocortex in a flattened view of the monkey neocortex. There are at least 25 areas that are predominantly or exclusively
visual in function, plus 7 other areas suspected to play a role in visual processing.
(A after Maunsell and Newson, 1987; B after Felleman and Van Essen, 1991).
Functional MRI studies have indicated a similar arrangement of visual areas within
human extrastriate cortex (Sereno et al., 1995). Using retinotopically restricted stimuli it has
been possible to localize at least 10 separate representations of the visual field (Fig. 18.9).
One of these areas exhibits a large motion-selective signal, suggesting that it is the
homologue of the motion-selective middle temporal area described in monkeys. Another
area exhibits color-selective responses, suggesting that it may be similar to V4 in non-
human primates.
So, in clinical description, a well-studied patient, who suffered a stroke that damaged
the extrastriate region thought to be comparable to area MT in the monkey, was unable
to appreciate the motion of objects. The neurologist who treated her noted that she had
difficulty in pouring tea into a cup because the fluid seemed to be “frozen”. In addition,
she could not stop pouring at the right time because she was unable to perceive when the
fluid level had risen to the rim. The patient also had trouble following a dialogue because
she could not follow the movement of the speaker’s mouth. Crossing the street was
potentially terrifying because she could not judge the movement of approaching cars.
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18. Occipital lobe
Fig. 18.9. Localization of multiple visual areas in the human brain using fMRI. (A, B) Lateral and medial views
(respectively) or the human brain, illustrating the location of primary visual cortex (V1) and additional visual areas V2, V3,
VP (ventral posterior area), V4, MT (middle temporal area), and MST (medial superior temporal area). (C) Unfolded and
flattened view of retinotopically defined visual areas in the occipital lobe. Dark grey areas correspond to cortical regions
that were buried in sulci; light regions correspond to regions that were located on the surface of gyri. Visual areas in
humans show a close resemblance to visual areas originally defined in monkeys (after Sereno et al., 1995).
Her ability to perceive other features of the visual scene, such as color and form, was
intact (Ungerleider and Mishkin, 1982; Zihl et al., 1983; Sereno et al., 1995; Tootell et
al., 1996; Courtney and Ungerleider, 1997; Purves et al., 2004).
Another example of a specific visual deficit as a result of damage to extrastriate
cortex is cerebral achromatopsia. These patients lose the ability to see the world in color,
although other aspects of vision remain in good working order. The normal colors of a
visual scene are described as being replaced by “dirty” shades of gray, much like looking
at a poor quality black-and-white movie (Purves et al., 2004).
When achromatopsic individuals are asked to draw objects from memory, they have
no difficulty with shapes, but are unable to appropriately color the objects they have
represented (Purves et al., 2004).
It is important to distinguish this condition from the color blindness that arises from
the congenital absence of one or more cone pigments in the retina. The discovery of the
1423
three human cone types and their different absorption spectra is correctly regarded,
therefore, as the basis for human color vision. Nevertheless, how these human cone types
and higher-order neurons they contact produce the sensation of color is still unclear.
A fundamental problem has been that, although the relative activities of three cone
types can more or less explain the colors perceived in color-matching experiments
performed in the laboratory, the perception of color is strongly influenced by the context.
The phenomena of color contrast and color constancy led to a heated, modern debate
about how color percepts are generated that now spans several decades. For Land (1986),
the answer lay in a series of ratiometric equations that could integrate the spectral returns
of different regions over the entire scene. In achromatopsia, the three types of cones are
functioning normally; it is damage to specific extrastriate cortical areas that renders the
patient unable to use the information supplied by the retina (Purves et al., 2004).
Extrastriate cortical areas are organized into two largely separate systems that eventually
feed information into cortical association areas in the temporal and parietal lobes.
One system, called the ventral stream, includes area V4 and leads from the striate
cortex into the inferior part of the temporal lobe. This system is responsible for high-
resolution form vision and object recognition. Neurons in the ventral stream exhibit
properties that are important for object recognition, such as selectivity for shape, color,
texture, and faces.
Lesions of the inferotemporal cortex produce profound impairments in the ability
to perform recognition tasks but no impairment in spatial tasks.
The dorsal stream, which includes the middle temporal area, leads from striate cortex
into the parietal lobe. This system is responsible for spatial aspects if vision such analysis of
motion and positional relationships between objects in the visual scene (Purves et al., 2004).
Neurons in the dorsal stream show selectively for direction, and speed of movement.
Lesions of the parietal cortex severely impair an animal’s ability to distinguish
objects on the basis of their position, while having little effect on its ability to perform
object recognition tasks.
These effects are remarkably similar to the syndrome associated with damage to the
parietal and temporal lobes in humans.
These discoveries led to the concept that individual cortical visual areas can contain
multiple, distinct processing pathways or streams, thereby extending (though not
necessarily reiterating) the organizational principle of multiple processing pathway found
in the retina and lateral geniculate nucleus.
Connectivity
By the late 1960s, the consensus was that the visual cortex is hierarchically
organized, with visual information proceeding from area 17 to areas 18 and 19.
Each visual area was thought to provide some sort of elaboration on the processing
of preceding area. This strictly hierarchical view is now considered too simple, and has
been replaced by the notion of a distributed hierarchical process, with multiple parallel
and interconnecting pathways at each level (Kolb and Whishaw, 2003).
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18. Occipital lobe
So, the primary visual pathway from the retina to the dorsal lateral geniculate nucleus
in the thalamus and on the primary visual cortex is the most important and certainly the
most thoroughly studied. Different classes of neurons within this pathway encode the
varieties of visual information-luminance, spectral differences, orientation, and motion.
The parallel processing of different categories of visual information continues in
cortical pathways that extend beyond primary visual cortex, supplying a variety of visual
areas in the occipital, parietal and temporal lobes.
Visual areas in the temporal lobe are primarily involved in object recognition,
whereas those in the parietal lobe are concerned with motion. Normal vision depends on
the integration of information in all these cortical areas.
So, distinct population of retinal ganglion cells sends their axons to a number of
central visual structures that serve different functions. The most important projections
are to the pretectum for mediating the pupillary light reflex, to the hypothalamus for the
regulation of circadian rhythms, to the superior colliculus for the regulation of eye and
head movements, and – most important at all – to the lateral geniculate nucleus for
mediating vision and visual perception.
The primary visual pathway (retinogeniculostriate projection) is arranged topo-
graphically such that central visual structures contain an organized map of the
contralateral visual field.
Visual input
According to Deyoe (2002) visual input from the retina is relayed through the lateral
geniculate nucleus (LGN) of the thalamus to terminate in the primary visual cortex
(striate, cortex, area 17, V1).
A second major pathway arises from retinal projections that bypass the LGN and
project to the superior colliculus. The superior colliculus then projects to the thalamic
pulvinar nucleus, which in turn distributes widely to the cortex of the occipital lobe. The
layers in the lateral geniculate are distinguished on the basis of cell size. The
geniculocortical pathways are subdivided into three main components associated with
different neuronal subclasses in the retina and LGN (Maunssell, 1992).
Two ventral layers are composed of large neurons and are referred to as the
magnocellular layers, while more dorsal layers are composed of small neurons and are
referred to as the parvocellular layers. The axons of the relay cells in the magno- and
parvocellular layers of the lateral geniculate nucleus terminate on distinct populations of
neurons located in separate strata within layer 4 of striate cortex.
One pathway originates from small P-cells in the retina and is relayed through the
parvocellular layers of the LGN to terminate in the layer 4Cβ of V1 and more sparsely
in layers 4A and 6. A second pathway to striate cortex begins with large M-type retinal
ganglion cells and is relayed through the magnocellular layers of the LGN to terminate
in layer 4Cα accompanied by a light projection to layer 6.
The response properties of P and M ganglion cells provide important clues about
the contributions of the magno- and parvocellular streams to visual perception.
1425
M ganglion cells have larger receptive fields than P cells, and their axons have faster
conduction velocities.
M and P ganglion cells also differ in ways that are not so obviously related to their
morphology. M cells respond transiently to the presentation of visual stimuli, while P
cells respond in a sustained fashion. Moreover, P ganglion cells can transmit information
about color, whereas M cells cannot. P cells convey color information because of their
receptive field centers and surroundings are driven by different classes of cones (i.e.,
cones responding with greatest sensitivity to short-, medium-, or long-wavelength light).
For example, some P ganglion cells have centers that receive inputs from long wavelength
(“red”) sensitive cones and surrounds that receive inputs from medium-wavelength
(“green”) cones. Others have centers that receive inputs from “green cones” and surrounds
from “red cones”. As a result, P cells are sensitive to differences in the wavelengths of light
striking their receptive field center and surroundings (Ungerleder and Mishkin, 1982; Purves
and Lotto, 2003). Although M ganglion cells also receive inputs from cones, there is no
difference in the type of cone input to the receptive field center and surroundings; the center
and surroundings of each M cell receptive field is driven by all cone types.
A third source of projections to V1 comes from a class of small cells within the
koniocellular (K) or intercalar layers of the LGN.
These neurons typically receive input from both the retina and the superior colliculus
and terminate in the supragranular layers (above layer 4) of striate cortex. These afferents
tend to cluster into “pufflike” regions of layers 2-3 that are also unique for their high
levels of metabolic enzyme cytochrome oxidase (co).
Afferents to striate cortex via the alternate tectopulvinar pathway terminate most
heavily in laminae 1 and upper 2-3 (Horton, 1992; Kaas, 1997; Zilles and Clarke, 1997).
So, neurons contributing to the K-cell pathway reside in the interlaminar zones that
separate lateral geniculate layers. These neurons receive inputs from fine-caliber retinal
axons and project in a patchy fashion to the superficial layers (layers II and III) of striate
cortex. Although the contribution of the K-cell pathway to perception is not understood,
it appears that some aspects of color vision, especially information derived from short-
wavelength-sensitive cones, may be transmitted via the K-cell rather the P-cell pathway
(Hubel and Wiesel, 1962; Hubel, 1988; Ungerleider and Mishikin, 1982; Berson, 2003;
Chalupa and Werner, 2004).
Neurons of the P, M, and K pathways differ in their visual response properties. Neurons
of the parvocellular path have smaller receptive fields, are often color opponents, and are
well-suited for conveying information about fine spatial detail and color. Magnocellular
neurons tend to have larger receptive fields, prefer low spatial frequencies, and have more
transient responses. They tend to have the greatest sensitivity to luminance contrast,
especially at low spatial frequencies and low luminance levels. They are optimized for
processing rapid temporal changes such as flicker and movement (Fig. 18.10).
The function of K-pathway neurons has appeared to be a major determinant of co-
puff cell properties and may play a key role in the modulation of responses evoked by
the M and P pathways (Felleman and Van Essen, 1991; Casagrande and Kaas, 1994).
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18. Occipital lobe
Fig. 18.10 (A) Distribution of thalamic inputs to the occipital lobe and nearby portions of the parietal and temporal
lobes. (From Zilles and Clarke, 1997). (B) Concurrent input to V1 from K, M, and P retinogeniculate pathways
with schematic of intrinsic circuitry and cytochrome oxidase defined puffs (dashed ellipses). V2 receives segregated
input from different sets of output neurons in V1 and distributes projections to the different sets of extrastriate visual
areas via distinct populations of output neurons in different cytocrome oxidase defined compartments. Such circuitry
forms the anatomical basis of multiple concurrent processing pathways within and among occipital visual areas
(Adapted from Casagrande and Kaas, 1994). (C) Functional interpretation of V1 circuitry
(Adapted from Callaway, 1989). Abbreviations: LGN, lateral geniculate nucleus; sc, superior colliculus;
K, konicellular; M, magnocellular; P, parvocellular.
So, although these three pathways are distinct, their functional capabilities can
overlap significantly. It is primarily at the extremes of spatial and temporal frequencies
that the M- and P-cell capabilities are most different.
Both M and P pathways may contribute to processing intermediate spatial and
temporal frequencies, but P-cell will tend to dominate for high spatial frequencies that
are slowly varying. Conversely, magnocellular neurons will respond better than P-cells
at low spatial frequencies that are rapidly varying. Chromatically, P-cell color opponency
appears to be critical for hue discrimination, but M-cells can respond more strongly to
some wavelengths than others, though they are not opponent and their tuning is typically
broader than that of P-cells. Under natural viewing conditions, all three inputs to the
visual cortex are likely to be concurrently active. Under extreme visual conditions, the
specialized capabilities of one or another of the pathways may take over and thereby
extend the range of useful sight (Horton, 1992; Callaway, 1998; Deyoe, 2002).
Thus the retinogeniculate pathway is composed of parallel magnocellular and
parvocellular streams that convey distinct types of information to the initial stages of
cortical processing. Damage anywhere along the primary visual pathway which includes
the optic nerve, optic tract, lateral geniculate nucleus, optic radiation, radiation, and striate
cortex, results in a loss of vision confined to the predictible region of visual space.
1427
Damage to the magnocellular layers has little effect on visual acuity or color vision,
but sharply reduces the ability to perceive rapidly changing stimuli. In contrast, damage
to the parvocellular layers has no effect on motion perception, but severely impairs visual
acuity and color perception.
Visual information conveyed by the parvocellular stream is particularly important
for high spatial resolution vision – the detailed analysis of the shape, size, and color of
objects. The magnocellular stream, on the other hand, appears critical for tasks that
require high temporal resolution, such as evaluating the location, speed and direction of
a rapidly moving object (Zihl et al., 1983; Rodieck, 1998; Purves et al., 2004).
– In sum, primary visual pathway is composed of separate functional streams that
convey information from different types of retinal ganglion cells to the initial stages of
cortical processing. The magnocellular stream conveys information that is critical for
detection of rapidly changing stimuli, the parvocellular stream mediates high acuity vision
and appears to share responsibility for color vision with the konicellular stream. Beyond
the striate cortex, parcellation of function continues in the ventral and dorsal streams that
lead to the extrastriate and association areas in temporal and parietal lobes, respectively.
Areas in the inferotemporal cortex are especially important in object recognition, whereas
areas in the parietal lobe are critical for understanding the spatial relations between objects
in the visual field.
Intrinsic circuitry
The retinal information relayed through the LGN is processed further by the intrinsic
circuitry of V1 and then distributed to other cortical areas via output neurons in layers 2-3
(Callaway, 1998) (Fig. 18.11). Subcortical projections to the superior colliculus and
feedback projection to LGN originate from layers 5 and 6 respectively.
It is through this selective distribution of visual information combined with the
characteristics of local processing that different visual areas achieve their functional
uniqueness.
Hubel and Wiesel (1962) used microelectrode recording to examine the properties of
neurons in more central visual structures. The responses of neurons in the lateral geniculate
nucleus were found to be remarkably similar to those in the retina, with a center-surrounded
receptive field organization and selectivity for luminance increases or decreases. However,
the small spots of light that were so effective at stimulating neurons in the retina and LGN
were largely ineffective in the visual cortex. Instead, most cortical neurons in cats and
monkeys responded vigorously to light-dark bars or edges, and only if the bars were
presented at a particular range of orientations within the cell’s receptive field.
The responses of a large number of single cells, Hubel and Wiesel (1962),
demonstrated that all edge orientation was roughly equally represented in visual cortex.
As a result, a given orientation in a visual scene appears to be “encoded” in the activity
of a distinct population of orientation-selective neurons.
Hubel and Wiesel (1962) also found that there are subtly different subtypes within
a class of neurons that preferred the same orientation. For example, the receptive field of
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18. Occipital lobe
some cortical cells, which they called simple cells, were composed of spatially separate
“on” and “off” response zones, as if the “on” and “off” centers of lateral geniculate cells
that supplied these neurons were arrayed in separate parallel bands. Other neurons,
referred to as complex cells, exhibited mixed “on” and “off” responses throughout their
receptive fields as if they received their inputs from a number of simple cells. Further
analysis uncovered cortical neurons sensitive to the length of the bar of light, decreasing
their rate of response when the bar exceeded a certain length. Still other cells responded
selectively to the direction in which an edge moved across their receptive field. Anyhow,
there is little doubt that the specificity of the receptive field properties of neurons in the
striate cortex (and beyond) play an important role in determining the basic attributes of
visual scenes (Purves et al., 2004).
Fig. 18.11. Central projections of retinal ganglion cells. Ganglion cell axons terminate in the lateral geniculate nucleus
of the thalamus, the superior colliculus, the pretectum, and the hypothalamus. For clarity, only the crossing axons of
the right eye are shown (view is looking up at the inferior surface of the brain) (after Purves et al., 2004).
Another feature is the binocularity. Most cortical neurons have binocular receptive
field, and these fields are almost identical, having the same size, shape, preferred
orientation, and roughly the same position in the visual field of each eye.
Bringing together the inputs from the two eyes at the level of the striate cortex
provides a basis for stereopsis, the special sensation of depth that arises from viewing
nearby objects with two eyes instead of one. Because the two eyes look at the world from
slightly different angles, objects that lie in front of or behind the plane of fixation project
to noncorresponding points on the two retinas. For a small disturbance on either side of
1429
the plane of fixation, where the disparity between the two views of the world remains
modest, a single image is perceived; the disparity between the two eye views of objects
nearer or farther than the point of fixation is interpreted as depth (Purves et al., 2004).
An important advance in studies of stereopsis was made in 1959 when Julesz (1971,
1995) discovered an ingenious way of showing that stereoscopy depends on matching
information seen by the two eyes without any prior recognition of what object(s) such
matching might generate.
Although the neurophysiological basis of stereopsis is not understood, some neurons
in the striate cortex and in other visual cortical areas have receptive field properties that
make them good candidates for extracting information about binocular disparity.
Unlike many binocular cells whose monocular receptive fields sample the same
region of visual space, these neurons have monocular fields that are slightly displaced
(or perhaps differ in their internal organization) so that the cell is maximally activated
by stimuli that fall on noncorresponding parts of the retinas (Purves et al., 2004).
Some of these neurons (so-called far cells) discharge to disparities beyond the plane
of fixation, while others (near cells) respond to disparities in front of the plane of fixation.
The pattern of activity in these different classes of neurons seems likely to contribute to
the sensation of stereoscopic depth (Julesz, 1995; Tootell et al., 1996).
So, the intrinsic processing of V1 can be divided into two major levels. Input from
LGN terminates at the first level in the different subdivisions of layer 4C. Information is
then distributed primarily to level 2 output neurons within layers 2-3, and 4B. The latter
output signals are modified by neurons in layers 5 and 6 that combine information about
the inputs and outputs of each processing level and feed it back onto neurons at the same
level (Zilles and Clarke, 1997; Kaas, 1997).
The laminar organization of V1 circuitry is complemented by horizontal connections
that tend to connect functionally similar zones distributed within specific laminae.
In layers 2-3, long horizontal projections preferentially interconnect puff-like zones
containing cells that have similar visual response properties and that are rich in the
metabolic enzyme cytochrome oxidase.
Likewise, interpuff zones tend to be interconnected most strongly with other interpuff
zones. In V2, a similar pattern of specific horizontal connections link co-defined
compartments termed the thick-, thin-, and interstripe zones (Kaas, 1997; Callaway, 1998).
Together, the laminar specificity of vertical intrinsic connections and the functional
specificity of horizontal connections provide an anatomical substrate for creating different
subsets of output neurons whose visual response properties reflect different combinations
of the P, M, and K afferent pathways, as well as modulatory effects of cortical feedback
pathways and other subcortical inputs (Felleman and Van Essen, 1991; Zilles and Clarke,
1997; Kaas, 1997; Callaway, 1998).
Output neurons in layer 4B of V1 are dominated by M-pathway characteristics, as
are the responses of the extrastriate visual areas, such as V2 thick stripes and area MT,
to which the 4B cells project.
In contrast, output neurons in the interpuff regions of V1 tend to be strongly biased
by P-cell characteristics, which are subsequently imparted to downstream visual areas
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18. Occipital lobe
such as V2 (thin- and interstripe compartments), VP, and V4. Output neurons in co-puff
subdivisions tend to exhibit characteristics that appear to reflect a mixture of influences.
As a result, later processing stages, such as V4, can also be shown to exhibit a
mixture of influences.
Overall, then the intrinsic circuitry of V1 acts to process, combine, and redistribute
the visual information available in the different afferent pathways, thereby creating a new
set of output signals that reflects the afferent inputs, but that also encodes more complex
visual properties or features. Intrinsic circuitry within subsequent cortical processing
stages, though less well-studied, presumably functions in a similar manner (Callaway,
1998; Deyoe, 2002).
Corticocortical connectivity
The output neurons of layers 2-3 and 4B of V1 selectively distribute different types of
visual information to subsequent processing stage in extrastriate visual cortex. Each
extrastriate visual area itself has unique feedforward and feedback connections within and,
often, outside the occipital lobe. These patterns of selective connectivity are a primary
determinant of the functional specificity of each visual area. Finally, interhemispheric
projections through the corpus callosum connect the left and right halves of each visual
area into a functionally integrated whole (Kaas, 1997; Callaway, 1998; Deyoe, 2002).
In monkey, connections among cortical visual areas tend to follow a consistent
pattern of laminar distribution that differentiates forward, backward, and lateral types of
connectivity (Felleman and Van Essen, 1991).
Generally, forward connections arise from neurons in layers 2-3 of the lower area
and distribute to layer 4, tapering off into the lower reaches of layer 3 in the higher visual
area. In some visual areas, however, forward projections can also originate in subgranular
layers (below layer 4), though the terminal distribution remains targeted at layer 4 of the
recipient area (Felleman and Van Essen, 1991; Callaway, 1998; Deyoe, 2002).
In contrast, backward-type projections tend to originate in layer 6 of the higher area
and distribute outside the layer of the lower area, though some feedback projections can
have a bilaminar origin. Finally, some visual areas have interconnections, whose terminal
fields engage nearly all laminae. This distribution pattern is thought to characterize lateral
connections between visual areas at approximately the same processing level. On the
basis of these patterns of connectivity, it is possible to arrange the various occipital visual
areas into a processing hierarchy (Felleman and Van Essen, 1991).
The extent to which this plan applies to human visual cortex is not known, though
the overall scheme is likely to be similar (Deyoe and Van Essen, 1988).
This connectional hierarchy incorporates several important organizational features.
First, it is generally consistent with the concept that successively more complex visual
response properties are represented at successive processing stages, though a detailed
comparison of the response properties of efferent neurons at one stage with the properties of
recipient neurons at the next stage are generally lacking. Another key aspect of this cortico-
cortical network is that nearly every forward connection is matched by a corresponding
backward connection, thereby establishing reciprocity between visual areas.
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Alternate connectivity schemes based on the strength of response correlation among

visual areas rather than anatomical connectivity have stressed this reciprocity and suggest
that a less hierarchical, more dynamic, processing network may also provide a useful
model of occipital connectivity. A third important principle is that multiple, parallel
pathways exist within, and between, each processing level (Felleman and Van Essen,
1991).
The arrangement of multiple parallel pathways within the cortex thereby provides a
basis for concurrent processing of different aspects of the incoming visual information.
Thus, the M, P, and K pathways that provide concurrent processing within the retina and
LGN are further modified in V1 to yield a new set of signals.
These are then passed on to subsequent stages of processing via distinct sets of
corticocortical output neurons. This same process is then reiterated at each successive
processing stage (Felleman and Van Essen, 1991; Deyoe, 2002).
Not long ago, it seemed that these intracortical pathways were simply a continuation
of the geniculostriate pathways – that is, the magnocellular pathway provided input to
the dorsal stream and the parvocellular pathway provided input to the ventral stream.
More recent work has indicated that the temporal pathway has clearly access to the
information conveyed by both the magno- and parvocellular stream; and the parietal
pathway, while dominated by inputs from the magnocellular stream, receives inputs from
the parvocellular streams. Thus, interaction and cooperation between the magno- and
parvocellular stream appear to be the rule in complex visual perception.
Patterns of organization within the sensory cortices: Brain modules

Observations over the last 40 years have made it clear that there is an iterated
substructure within the sensory cortical maps. This substructure takes the form of units
called modules, each involving hundreds or thousands of nerve cells in repeating patterns
(Purves et al., 2004).
The observation that the somatosensory cortex comprises elementary units of
vertically linked cells was first noted in the 1920s by Lorente de No (1949) based on his
studies in the rat.
Mountcastle (1957, 1988) found that vertical microelectrode penetrations in the
primary somatosensory cortex of the monkeys encountered cells that responded to the
same sort of mechanical stimulus presented at the same location on the body surface.
Soon after Mountcastle’s pioneering work, Hubel and Wiesel (1977) discovered a similar
arrangement in the cat primary visual cortex. These and other observations (Woolsey and
Van der Loos, 1970; Hubel, 1988; Purves et al., 1992) led Mountcastle (1988) to the
general view that “the elementary pattern of organization of the cerebral cortex is a
vertically oriented column or cylinder of cells capable of input-output functions of
considerable complexity”. Since these discoveries, the view that modular circuits
represent a fundamental feature of mammallian cerebral cortex has gained wide
acceptance, and many such entities have now been described in various cortical regions
(Figures 18.12 and 18.13).
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18. Occipital lobe
Fig. 18.12. Examples of iterated, modular substructures in the

mammallian brain. (A) Ocular dominance columns in layer IV in the
primary visual cortex (V1) of a rhesus monkey. (B) Repeating units
called “blobs” in layers II and III in V1 of the squirrel monkey. (C) Stripes
in layers II and III in V2 of squirrel monkey. (D) Barrels in layer IV in A
primary somatic sensory cortex of a rat. (E) Glomeruli in the olfactory
bulb of a mouse. (F) Iterated units called “barreloids” in the thalamus of
a rat. These and other examples indicate that modular organization is
commonplace in the brain. These units are of the order of one hundred
to several hundred microns across. (From Purves et al., 1992).
B
E
Fig. 18.13. Columnar organization of orientation selectivity in the monkey
striate cortex. Vertical electrode penetrations encounter neurons with the
same preferred orientations, whereas oblique penetrations show a
systematic change in orientation across the cortical surface. The circles
denote the lack of orientation-selective cells in layer IV. (after Purves et F
al., 2004).
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This patterned circuit has led to conclude that modules are a fundamental feature of
the cerebral cortex, essential for perception, cognition, and perhaps even consciousness.
Although modular circuits of a given class are readily seen in the brains of some
species, they have not been found in the same brain regions of other, sometimes closely
related, animals. Second, not all regions of the mammillian cortex are organized in a
modular fashion. And third, no clear function of such modules has been discerned (Purves
et al., 2004).
The columnar organization of the striate cortex

In general, the responses of neurons are qualitatively similar at any one point in
primary visual cortex, but tend to shift smoothly across its surface. With respect to
orientation, all the neurons encountered in an electrode penetration perpendicular to the
surface at a particular point will very likely have the same orientation preference,
formatting a “column” of cells with similar response properties (Weliky et al., 1996).
Adjacent columns usually have slightly different orientation preference; the sequence of
orientation preferences encountered along a tangential electrode penetration gradually
shifts as the electrode advances (Obermayer and Blasdel, 1993; Purves et al., 2004).
Thus, orientation preference is mapped in the cortex, much like receptive field
location (Blasdel and Salma, 1986).
Unlike the map of visual space, however, the map of orientation preference is iterated
many times, such that same orientation preference is repeated at approximately 1 mm
intervals across the striate cortex.
This iteration presumably ensures that there are neurons for each region of visual
space that represent the full range of orientation values (Bonhoefer and Grinvald, 1993,
1996). The orderly progression of orientation preferences accommodated within the
orderly map of visual space by the fact that the mapping is relatively coarse.
Each small region of visual space is represented by a set of neurons whose receptive
fields cover the full range of orientation preferences, the set being distributed over several
millimeters of the cortical surface (Bonhoeffer and Grinvald, 1996; Weliky et al., 1996;
Purves et al., 2004).
The availability of optical imaging techniques has made it possible to visualize how
response properties, such as the selectivity for edge orientation or ocular dominance, are
mapped across the cortical surface. These methods generally rely on intrinsic signals
(changes in the amount of light reflected from the cortical surface) that correlate with
levels of neural activity. Such signals are thought to arise at least in part from local
changes in the ratio of oxyhemoglobin and deoxyhemoglobin that accompany such
activity, more active areas having a higher deoxyhemoglobin / oxyhemoglobin ratio.
This change can be detected when the cortical surface is illuminated with red light
(605-700 nm). Under these conditions, active cortical regions absorb more light than the
less active ones. With the use of sensitive video camera, and averaging over the number
of trials (the changes are small, 1 or 2 parts per thousand) it is possible to visualize these
differences and use them to map cortical patterns of activity (Bonhoeffer and Grinvald,
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18. Occipital lobe
1993; Obermeyer and Blasdel, 1993). This approach has now been applied to both striate
and extrastriate areas in both experimental animals and human patients undergoing
neurosurgery (Purves et al., 2004). The results emphasize that maps of stimulus features
are general principle of cortical organization.
This powerful technique can also be used to determine how maps for different
stimulus properties are arranged relative to one another, and to detect additional maps
such as that for direction of motion. A comparison of ocular dominance hands and
orientation preference maps shows that pinwheel centers are generally located in the
center of ocular dominance bands, and that the iso-orientation contours that emanate from
the pinwheel centers run orthogonal to the border of ocular dominance bands (Bonhoeffer
and Grinvald, 1993; Obermeyer and Blasdel, 1993).
These systematic relationships between the functional maps that coexist within
primary visual cortex are thought to ensure that all combinations of stimulus features
(orientation, direction, ocular dominance, and spatial frequency) are analyzed for all
regions of visual space (Bonhoeffer and Grinvald, 1993; Obermeyer and Blasdel, 1993).
Although most neurons in the striate cortex respond to stimulation of both eyes, the
relative strength of the inputs from the two eyes varies from neuron to neuron. At the
extremes of this continuum are neurons that respond almost exclusively to the left or
right eye; in the middle are those that respond equally well to both eyes. As in the case
of orientation preference, vertical electrode penetrations tend to encounter neurons with
similar ocular preference (or ocular dominance), whereas tangential penetrations show
gradual shifts in ocular dominance (Tootell et al., 1996; Hubel and Wiesel, 1977; Tootell
et al., 1996; Chalupa and Werner, 2004; Purves et al., 2004). These shifts in ocular
dominance result from the ocular segregation of the inputs from lateral geniculate nucleus
within cortical layer IV (Horton, 1992).
In short, the striate cortex is composed of repeating units, or modules, that contain
all the neuronal machinery necessary to analyze a small region of visual space for variety
of different stimulus attributes.
A number of other cortical regions show a similar columnar arrangement of their
processing circuitry.
Compared to retinal ganglion cells, neurons at higher levels of the visual pathway
become increasingly selective in their stimulus requirements. Thus, most neurons in the
striate cortex respond to light-dark edges only if they are presented at a certain orientation;
some are selective for the length of the edge, and others to movement of the edge in a
specific direction. Indeed, a point in visual space is related to a set of cortical neurons,
each of which is specialized for processing a limited set of the attributes in the visual
stimulus. The neural circuitry in the striate cortex also brings together information from
the two eyes; most cortical neurons (other than those in layer IV, which are segregated
into eye-specific columns) have binocular responses. Binocular convergence is
presumably essential for the detection of binocular disparity, an important component of
depth perception (Purves et al., 2004).
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Functional subsystem
The incoming visual information is relayed from the retina through the lateral
geniculate nucleus to V1 and then to V2 and other extrastriate visual areas.
So, V1 (the striate cortex) is the primary vision area: it receives the largest input
from the lateral geniculate nucleus of the thalamus and it projects to all other occipital
regions. V1 is the first processing level in the hierarchy.
V2 also projects to all other occipital regions. V2 is the second level.
After V2, three distinct parallel pathways emerge on route to the parietal cortex,
superior temporal sulcus, and inferior temporal cortex, for further processing.
As we shall see in more detail shortly, the parietal pathway, or dorsal stream, has a
role in the visual guidance of movement, and the inferior temporal pathway, or ventral
stream, is concerned with object perception (including color).
The middle pathway along the superior temporal sulcus is probably important in
visuospatial functions.
At hierarchical levels beyond V1 and V2, part of the visual information goes to areas
V3 and VP (Horton, 1992).
Motion perception
Human hMTS+ respond selectively to moving vs. stationary stimuli, but also responds
to other aspects of motion stimuli in ways that appear to parallel reported single-unit
response properties or perceptual effects. Motion produces a significant change in activation
within hMT+, yet it can result in little or no change in activation V1-V2 (Deyoe, 2002).
Though retinal image motion often indicates the movement of objects (or self),
motion cues can also be used to identify the boundaries and 3-dimensional shape of
objects rather than their trajectories.
In summary, the middle-temporal area, or what is commonly called area MT, is
important for motion perception. Almost all of the neurons in area MT are direction-
selective, meaning that they respond selectively to a certain range of motion directions
and do not respond to directions beyond that range (Zeki, 1974; Albright, 1984).
Moreover, some of these neurons respond well to the pattern of motion (Albright, 1992),
meaning that these neurons can integrate many different motion directions and calculate
what the overall direction of an object might be. The activity in this region seems to be
closely related to motion perception and, when activity in this region is disrupted, motion
perception may be severely impaired (Tong and Pearson, 2007).
Color
The most studies have identified several distinct foci within human visual areas VP
and V4 that are activated somewhat more strongly by chromatic than by archromatic
stimuli. Anyhow, greater selectivity and task specificity are found anterior to V4v. Such
selectivity has been shown to be associated with visual area V8 and, in some tasks, with
a more anterior site. V8 is retinotopically distinct from V4v and contains a representation
of both superior and inferior visual fields.
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18. Occipital lobe
Color-selective activation sites in dorsal occipital cortex have also been observed
on occasion, but their location and identity remain poorly defined.
The presence of occipitotemporal color-related sites is consistent with human lesion
studies in which damage to ventral cortex results in diminished or absent color
discrimination (achromatopsia) (Zeki, 1990). Often, color perception losses in both upper
and lower visual fields, even though the lesion appears to be confined to ventral cortex.
In contrast, area V8, which is located within the lesion-sensitive zone, does have both
upper and lower field representations, thereby making it a prime candidate for the
achromatopsia site (Zeki, 1990). Moreover, V8 is located adjacent to the fusiform face area
(FFA). This juxtaposition of V8 and FFA is likely to account for the fact that prosopagnosia
(inability to recognize face) is commonly associated with cerebral achromatopsia.
In humans, cerebral achromatopsia does not arise from lesions of V4v but from more
anterior lesions encompassing V8 and / or additional neighboring areas. This does not
necessarily imply that V8 or any single visual area is solely responsible for color vision
or for all color-related deficits. In fact, moving stimuli consisting of pure chromatic
contrast can readily activate human hMT+.
So, to summarize, area V4 is known to be especially important for the perception of
color (Zeki, 1997) and some neurons in this area respond well to more complex features
or combination of features (Pasupathy and Connor, 2002). For example, some V4 neurons
are sensitive to curvature of two lines that meet at a specific angle. These neurons might
signal the presence of a curving contour or of a corner (Tong and Pearson, 2007).
Area V4 sends many outputs to higher visual areas in the ventral visual pathway,
which is important for object recognition (Ungerleider and Mishkin, 1982). The anterior
part of ventral visual pathway consists of the ventral temporal cortex, which is especially
important for object recognition.
Form
There is general agreement that a major portion of the form processing system is
located in the ventral occipitotemporal cortex.
Passive viewing of luminance-based contour and edges readily activates retinotopic
visual areas of the medial and ventral occipital cortex in humans. The size of a detectable
increment in the contrast of a plaid grating was quite precisely tracked by a proportional
increment in fMRI response of visual area V1, V2d, V3 and V4A. In area hMT+, the
fMRI response tends to saturate above a few percent contrast, consistent with the high
contrast sensitivity of MT neurons studied in animals (Kaas, 1997).
Single-cell recording in animals has shown that neurons in V2, but less in V1, are
capable of responding selectively to these contours, thereby suggesting a hierarchical
processing mechanism. Neuroimaging studies with human subjects have shown that some
types of illusory contours may preferentially activate later processing stages including
V3A, V4v, V7, V8 and LO (lateral occipital visual complex).
The most selective responses to motion-defined contours and shapes have been
associated with a region termed the kinetic-occipital area (KO).
It is located approximately 1.5 cm posterior to hMT+ in the lateral occipital cortex.
1437
Cue invariance
In humans, several neuroimaging studies have tested for cue-invariant responses to
contours, edges, or outline figures defined by luminance, color, texture, binocular
disparity, or motion. In the most comprehensive study, similar responses were observed
for luminance-, texture-, and motion-defined figures in lateral occipital cortex posterior
to hMT+ (labeled LO) and in, or near, area V3A. The cue-invariant representation of
contour information in LO and V3A may represent an important stage of abstraction in
influence of object attributes from the available retinal information (Deyoe, 2002).
Figure-ground segmentation
It has been proposed that a swath of cortex located posterior to area hMT+ forms a
complex specialized for the segmentation and processing of object information. This area,
labeled LO, is more strongly activated by discrete objects than by gratings, textures, or
motion fields (Deyoe, 2002).
In summary, lateral occipital (LO) cortex seems to have a general role in object
recognition and responds strongly to a variety of shapes and objects (Malach et al., 1995).
LO prefers intact shapes and objects more than scrambled visual features.
This region seems to represent the particular shapes of objects.
Presumably, different neurons in this region respond best to different kinds of
objects. A method to test object selectivity is to measure neural adaptation to a particular
shape. This is exactly what LO does, even when the repeated object is presented in a new
location or in a different format so that retinotopic visual areas (V1-V4) will not adapt to
the image (Grill-Spector et al., 1999; Kourtzi and Kanwisher, 2001).
Parahippocampal place area (PPA) is another strongly category-selective region that
responds best to houses, landmarks, indoor and outdoor scenes (Epstein and Konwisher,
1998).
In comparison, this brain area responds more weakly to other types of stimuli such
as faces, bodies or inanimate objects. Because this region responds to very different
stimuli than the fusiform face area, many studies have taken advantage of the different
response properties of the FFA and PPA to study the neural correlates of visual awareness
(Tong and Pearson, 2007).
Complex forms
Regions of cortex in the collateral sulcus and adjacent lingual gyrus that is similar to
retinotopically defined V4 and / or VP, the fusiform gyrus or adjacent inferior temporal
gyrus, sometimes extending into area LO, encompass a swath of cortex that extends from
the occipital lobe into ventral temporal cortex. This swath not functionally homogeneous
is perhaps most consistently apparent for the analysis and recognition of face. The posterior
extent of this region is lateral to the area activated during color processing (V8) or during
the presentation of “scrambled” faces and has been termed the fusiform face area (FFA).
Face stimuli and face discrimination have been studied extensively. In the human
studies it has been shown that the fusiform gyrus from the occipital junction forward to
midtemporal lobe is activated by tasks requiring face recognition.
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18. Occipital lobe
This region responds more to human, animal, and cartoon faces than to a variety of
non-face stimuli, including hands, bodies, eyes shown alone, back views of heads,
flowers, buildings and inanimate objects (Kanwisher et al., 1997; Mc Carthy et al., 1997;
Tong et al., 2000; Schwarzlose et al., 2005).
In a recent study, Tsao et al. (2006) recorded the activity of single neurons in this
face area and discovered that 97 per cent of the neurons in this region responsed more to
face than to other kinds of objects.
This region seems to be important for the conscious perception of face.
Lesions that cause prosopagnosia tend to have common involvement of the fusiform
gyrus within the general vicinity of the FFA (Fig. 18.4).
In summary, single unit recordings in monkeys have revealed that many neurons in
the ventral temporal cortex respond best to contour, simple shapes, or complex objects.
Same neurons in this region are highly selective and respond to only a particular kind of
object, such as a hand, a face shown from a particular viewpoint, a particular animal, a
familiar toy or an object that the monkey has learned to recognize and so forth (Desimone
et al., 1984; Gross, 1992; Logothetis et al., 1995; Tanaka, 1996).
Human neuroimaging studies have revealed many brain areas involved in processing
objects. These object-sensitive areas, which lie just anterior to early visual areas V1-V4,
respond more strongly to coherent shapes and objects, as compared to scrambled,
meaningless stimuli.
The lateral occipital complex lies on the lateral surface of the occipital lobe, just
posterior to area MT. Because this region is strongly involved in object recognition, Tong
and Pearson (2007) consider it as part of the ventral pathway.
The fusiform face area lies on the fusiform gyrus, on the ventral surface of the
temporal lobe. The parahippocampal place area lies on the parahippocampal gyrus, which
lies medial to the fusiform gyrus on the ventral surface of the temporal lobe.
Written words and dyslexia

Because this function is most highly developed in humans, it may distinguish us
from other primates. Some neuroimaging studies have implicated ventral occipitotem-
poral cortex near, but distinct from the FFA, in the analysis of visual word form, though
other studies have obtained different results.
Specifically, dyslexics appear to have an impaired function of magnocellular-
dominated pathways extending into dorsal occipital cortex, especially through hMT+ to
the parietal cortex (Kaas, 1997).
Depth and the analysis of space

The analysis of space involves the assignment of distances of objects and surfaces
relative to the self and each other, the representation of spatial maps for navigation, the
extraction of locations and orientations of objects relative to the limbs for purposes of
manipulation, and, finally, the computation of object positions relative to the center of
gaze or relative to the current focus of attention.
1439
Visual information allows us to direct our movements to objects in space and to

assign meaning to objects. But spatial location is not a unitary characteristic. Objects
have location relative to an individual (egocentric space) and relative to one another
(allocentric space).
Egocentric visual space is central to the control of your actions toward objects. It
therefore seems likely that visual space is coded in neural systems related to vision for
action. In contrast, allocentric properties of objects are necessary for you to construct a
memory of spatial location (Kolb and Whishaw, 2003).
The available evidence indicates that the cortical analysis of space heavily involves
parietal and medial temporal lobe structures that receive direct or indirect projection from
occipital lobe visual areas. Under passive viewing, the 3-dimensional stimuli evoked
stronger fMRI activation in hMT+ and in several other foci, which included LO, V3A,
and several parietal foci that are likely to receive projections from hMT+ or V3A (Zilles
and Clarke, 1997).
Visual areas involved in the extraction of spatial information may be involved in
the analysis of eye movements. This is supported by the observation that parietal visual
areas such as VIP and LIP in macaques contain cells that are active during different types
of eye movements and may be capable of compensating for such movements.
Other aspects of spatial processing such as the representation of mental maps of
space appear to involve visual areas in the parietal, frontal, and medial temporal cortices
outside the occipital lobe.
Given that there are a number of functionally distinct areas in macaque parietal
cortex (e.g., VIP, LIP, MIP, PRR), it is likely that a similar multiplicity related, in part,
to spatial processing will be described for human parietal cortex in the near future.
The ventral and dorsal pathways

The distinction between the ventral and the dorsal streams can be seen clearly in a
series of patients studied by Milner and Goodale (1995). They first described D.F., a
patient who was blind but who nevertheless shaped her hand appropriately when asked
to reach for objects. Her dorsal stream was intact, as revealed by the fact that she could
“unconsciously” see location, size, and shape.
On the other hand, Milner and Goodale noted that patients with dorsal-stream
damage consciously reported seeing objects but could not reach accurately or shape the
hand appropriately when reaching. Milner and Goodale proposed that the dorsal stream
should be thought of as a set of systems for the one-line visual control of action. Their
argument is based on three main lines of evidence.
1) The predominant characteristic of the neurons in posterior parietal regions is that
they are active during a combination of visual stimulation and associated behavior. For
example, cells may be active only when a monkey reaches out to a particular object.
Looking at an object in the absence of movement does not activate the neurons. Thus,
these “visual” neurons are unique in that they are active only when the brain acts on
visual information.
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18. Occipital lobe
2) These posterior parietal neurons can therefore be characterized as an interface

between analysis of the visual world and motor action taken on it. The demands of action
have important implications for what type of information must be sent to the parietal
cortex – information such as object shape, movement, and location. Each of these visual
features is likely to be coded separately, and at least three distinct pathways within the
dorsal stream run from area V1 to the parietal cortex. One pathway goes from area V1
directly to area V5 to parietal cortex, a second goes from area V1 to areas V5 and V3a
and then to parietal regions, and a third goes from area V1 to area V2 to the parietal
cortex. These three pathways must certainly be functionally dissociable.
3) Most of the visual impairment associated with lesions to the parietal cortex can
be characterized as visuomotor or orientational (Jakobson et al., 1991; Goodale et al.,
1991; Felleman and van Essen, 1991; Goodale, 1993; Kosslyn and Thompson, 2000).
The Milner-Goodale model is an important theoretical advance in understanding
how our visual brain is organized (Fig. 18.14).
Fig. 18.14. A summary of the visual processing
hierarchy. The dorsal stream, which takes part
in visual action, guides movements such as the
hand postures for grasping a mug or pen, as
illustrated. The ventral stream, which takes
part in object recognition, identifies object such
as mugs and pens in our visual world. The
dorsal and ventral stream exchange
information through polysensory neurons in the
superior temporal sulcus stream, as shown by
doubleheaded arrows. (after Goodale, 1993).
So, the two distinct visual streams have evolved to use visual information in two
fundamentally different ways: the dorsal stream for guiding movements and the ventral
for identifying objects.
Anyhow, according to Kolb and Whishaw (2003), the third stream of visual
processing, which originates from structures associated with both the parietal and the
temporal pathways and flow to a region of the temporal lobe is buried in the superior
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temporal sulcus. The superior temporal sulcus is characterized by polysensory neurons-

neurons that are responsive to both visual and auditory or both visual and somatosensory
input. The interaction of the parietal and temporal streams in the superior temporal sulcus
is probably due to the interaction between the dorsal and the ventral -the “action” and
“recognition”-streams (Kolb and Whishaw, 2003).
Brain regions associated with specific visual pathways were identified by measuring
the regional blood flow (Ungerleider and Haxby, 1994; Haxby et al., 1999, 2000). In
their studies subjects were given two tasks. In the first, the subjects indicated which of
two faces was identical with a sample face. In the second, the subjects were asked to
identify which of two stimuli had a dot (or square) in the same location as in a sample.
The results showed activation of the temporal regions for the facial stimuli and activation
of the posterior parietal region for the location task. Note, in addition, the activation of
frontal areas for the spatial task supporting the idea that the frontal lobe plays a role in
certain aspects of visual processing. Anyhow, in that time subjects have to make eye
movements, which activate regions in the dorsal stream; so, whether the spatial or the
movement components activate the parietal region is not clear. A similar dissociation
was identified among the processes that detect motion, color, and shape (Campbell et al.,
1986; Kingdom et al., 2001; Kolb and Whishaw, 2003). Detection of motion activates
regions in the vicinity of area V5, whereas detection of shape activates regions along the
superior temporal sulcus and the ventral region of the temporal lobe. The perception of
color is associated with activation of the region of the lingual gyrus, which is the location
of area V4. One study also found activation of a lateral occipital region, which is difficult
to interpret in the light of lesion studies.
In sum, studies of regional blood flow in normal subjects show results consistent
with the general notion of two separate visual streams, one to the parietal lobe and the
other to the temporal lobe (Kolb and Whishaw, 2003).
The ventral pathway leading from V1 to the temporal lobe that is important for
representing “what” object are and a dorsal pathway leading from V1 to the parietal lobe
that is important for representing “where” objects are located. This important organi-
zational principle of the visual system was proposed by Ungerleider and Mishkin (1982).
In the dorsal pathway, signals from V1 travel to dorsal extrastriate areas, such as
areas MT and V3A, which then send major projections to many regions of the parietal
lobe. The dorsal pathway is important for representing the locations of objects, so that
the vision system can guide actions towards those objects (Goodale and Humphrey,
1998). This type of vision requires detailed information about the precise location, size,
and orientation of the object.
Areas MT and V3A are important for processing visual motion and stereo-depth.
In the ventral pathway, many signals from V1 travel to ventral extrastriate areas V2,
V3 and V4 and onward to many areas of the temporal lobe. The ventral or “what”
pathway is important for processing information about the color, shape, and identity of
visual objects, processing which emphasizes the stable, invariant properties of objects.
The parietal and temporal lobes send projections to some common regions in the
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18. Occipital lobe
prefrontal cortex, where information from each pathway can also be reunited (Tong and
Pearson, 2007).
Visual consciousness
In the brain there are a lot of areas responsible for consciousness. These areas work
together to achieve this remarkable feat. Primary visual cortex seems to be important for
our ability consciously to perceive any visual feature, while higher visual areas may have
a more specialized role in perceiving certain visual features or objects (Tong, 2003).
Different cortical visual areas and neurons involved in processing a specific kind of
visual stimuli (color, orientation, motion, faces, objects, etc.), together with other cortical
areas and subcortical structures (thalamus, hypothalamus, reticular formation, etc.) seems
to play different roles in our conscious visual experience.
According to one theory of visual consciousness, called hierarchical theory (Crick
and Koch, 1995; Rees et al., 2002), higher visual areas respond to more complex stimuli,
such as entire objects, and can integrate information about many visual features, which
are processed in early visual areas. The interactive theory of visual consciousness
emphasizes a different idea. It turns out that the signals entering the brain do not simply
travel up the visual hierarchy: higher visual areas send feedback signals back down to
early visual areas, especially to area V1 (Bullier, 2001). There are as many feedback
projections as feedforward projections in the visual system, neurons projecting from
higher visual areas to lower visual areas.
According to the interactive theory, once a stimulus is presented, feedforward signals
travel up the visual hierarchy, activating many neurons in its path, but this feedforward
activity is not enough for consciousness. Instead, high-level areas must send feedback
signals back to lower-level areas where the feedforward signals come from, so that neural
activity returns full circle, forming a neural circuit (Pollen, 1999; Lamme and Roclfsema,
2000).
This combination of feedforward - feedback signals is important for awareness,
because higher areas need to check the signals in nearly areas and confirm if they are
getting the right message, or perhaps to link neural representation of an object to the
specific features that make up the object (Tong and Pearson, 2007).
Unconscious perception
According to Tong and Pearson (2007) the term unconscious perception refers to
situations when subjects report not seeing a given stimulus, but their behavior or brain
activity suggests that specific information about the unperceived stimulus was indeed
processed by the brain.
Neurons may fire in a stimulus-specific way at many levels of the brain, but this
activity may not be strong enough, last long enough, or involve enough neurons or brain
areas to lead to awareness. One of the best examples of this comes from neural recordings
in animals under anesthesia; visual neurons in many brain areas still show strong
stimulus-selective responses (Tong and Pearson, 2007). If you become conscious of a
1443
particular stimulus, then neurons in your brain that represent that pattern will become
highly active.
Anyhow, without enough activity in the right brain areas, awareness may simply
fail: the result is unconscious perception. When two different stimuli are flashed briefly
enough in quick succession, the visual system can no longer separate the two stimuli.
Instead, what people perceive is a mix, or a fused blend of the two images.
For example, if we were to expose you to a red square, then quickly follow it with
a green square, what you might experience is a combination of the two – a yellow square
(Tong and Pearson, 2007). This method can be used to present invisible patterns, such as
a face or a house, by flashing red contours on a green background to one eye and the
opposite colors to the other eye.
When subjects were presented with such images in the fMRI scanner, the fusiform
face area responded more strongly to faces and the parahippocampal place area responded
more to house, even though subjects were no longer aware of the images (Moutoussis
and Zeki, 2002). This is an example of unconscious perception. The activity in ventral
temporal parts of the brain could differentiate, to some degree, whether a face or house
was presented, even though the subject could not verbally report a difference.
Area MT, a brain area specialized for processing motion, also responds to
unperceived motion. When moving stimulus is presented far out in the periphery of the
visual field and is crowded by other stimuli, area MT still responds to motion, even when
subjects are not aware of the motion (Moutoussis and Zeki, 2006). In this experiment,
the motion stimulus was flanked on two sides by flickering stimuli, making the visual
space so busy and cluttered that subjects could not see the motion in the display. Although
MT responded somewhat to the perceived motion stimulus, it responded much more
strongly when the surrounding flickering stimuli were removed and motion stimulus was
clearly perceived.
In other studies, researchers used binocular rivalry to render pictures of fearful faces
invisible.
The expression of the faces carried emotional content, although the subjects were
never aware of seeing the faces. The amygdala that normally responds to emotional
stimuli also responded to the invisible fearful faces (Pasley et al., 2004).
It is clear that many brain areas may continue to show stimuli-specific activity
despite the fact that we are unaware of that stimulus.
In most of these studies, greater activity was found when subjects were aware of a
stimulus than when they were not, suggesting that a minimum level of activity may be
needed to make the difference between no awareness and awareness. A low level of
neural activity below a specific threshold might not be adequate to result in being aware
of a stimulus (Tong and Pearson, 2007).
In sum, Tong and Pearson (2007) can conclude that at least two things are needed
for visual awareness: (1) activity in the right neurons or brain areas; and (2) activity that
exceeds a critical threshold.
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18. Occipital lobe
Visual attention
Visual attention refers to the ability to prepare for, select, and maintain awareness
of specific locations, objects, or attributes of the visual scene (or an imagined scene)
(Deyoe, 2002).
The center of gaze typically follows the focus of attention, but the observer can
intentionally dissociate the two, thereby demonstrating that the neural systems controlling
eye movements and attention are at least partially distinct (Deyoe, 2002). Some visual
attributes are:
– enhance the detection of subtle changes in brightness, color, or virtually any other
attribute;
– require focused attention to be perceived correctly. In a crowded visual
environment directed attention may be required if different attributes of the same object
are to be correctly associated. Certain behaviors can be performed with little, if any,
focused attention, whereas others are highly sensitive to the allocation of attention.
Automatic processes direct behavior that occurs without intention, involuntarily, without
conscious awareness, and without producing interference with ongoing activities.
Automatic processing may be an innate property of the way in which sensory information
is processed or it can be produced by extended training (Logan, 1992, Bargh and
Ferguson, 2000).
Operations that are not automatic have been referred to by various terms, including
controlled, effortful, attentive, and conscious. Conscious operations differ fundamentally
from automatic processing in that they require focused attention. A person stopping at a
red light is an example of bottom-up processing, whereas a person actively searching for
a street at which to turn is an example of top-down processing (Treisman, 1986).
Bottom-up processing is data driven; that is, it relies almost exclusively on the
stimulus information being presented in the environment. In contrast, top-down
processing is conceptually driven. It relies on the use of information already in memory,
including whatever expectation might exist regarding the task at hand. So, automatic and
conscious processing can reasonably be presumed to require at least some different
cortical circuits (Logan, 1992; Naatanen, 1992; Neibur, 2002).
Treisman (1986) and Treisman and Gormican (1988) concluded that, although
practice can speed up feature processing, it remains dependent on specific automatic
neural associations between features and a serial-processing pathway. Feature processing
appears to be innate to the visual system.
Posner and Raichle (1993) suggest that, in a sense, the attentional process provides
the “glue” that integrates features into a unitary object. When features have been put
together, the object can be perceived and held in memory as a unit. A clear prediction
from Treisman’s theory is that neurons in the visual areas outside area V1 and probably
outside area V2 should respond differentially, depending on whether attention is focused
on the corresponding receptive field. Treisman (1986) presumes that features are the
properties that cells in the visual system are coded to detect. But features may perhaps
be biologically significant stimuli, as illustrated in an experiment by Eastwood and
1445
colleagues (2001). The task was to identify the odd face, which could be a happy face in
a sea of sad ones or vice versa. Before you try to do so, turn your book upside down.
Subjects were faster at detecting sad faces, whereas they were upside down or right
side up. Furthermore, when Eastwood and colleagues redid the experiment with abstract
targets that signified either a happy or sad state, subjects still found the sad-related feature
faster.
Given that the features should be equally conspicuous in the happy and sad
conditions, it follows that there is something biologically more important to detecting
sad (negative) than happy (positive) stimuli.
It appears that negative stimuli (potentially dangerous or threatening features as well
as sad ones) are attended to very efficiently and demand attention more than to targets
for positive features.
From an evolutionary perspective, favoring the nervous system that attends to stimuli
that can make a difference to an animal’s survival makes sense. The evolution of
biological targets is likely more important to survival than are the simplest targets detected
by cells in area V1.
How and where attention exerts its effects over the processing of incoming visual
information are becoming clearer. Ample evidence from animals and humans now shows
that attention can modulate the responses of neurons in occipital visual cortex.
Moran and Desimone (1985) trained a monkey to hold a bar while it gazed at a
fixation point on a screen. A sample stimulus (for instance, a vertical blue bar) appeared
briefly at one location in the receptive field, followed about 500 ms later by two stimuli:
one at the same location and another in a separate one. The key point is that both targets
were in the cell’s receptive field, but only one target was in the correct location. When
the test stimulus was identical with the sample and in the same location, the animal was
rewarded if it released the bar immediately. In this way, the same visual stimulus could
be presented to different regions of the neurons’ receptive field, but the importance of
the information varied with its location.
– As the animal performed the task, the researchers recorded the firing of cells in
the area V4. Cells in area V4 are color and form sensitive; so, different neurons responded
to different conjunctions of features. Thus, a given cell might respond to one stimulus
(for example, a horizontal green bar) and not to another (for example, a vertical red bar).
These stimuli were presented either in the correct location or in an incorrect location for
predicting reward.
So, when effective stimulus was presented in the correct location, the cell was highly
active. When the same stimulus was presented in an incorrect location, however, the cell
was not responsive. It appears that, when attention is focused on a place in the visual
world, the cell responds only to stimuli appropriate to that place.
Moran and Desimone (1985) considered the possibility that visual area activated
earlier (V1) or later (TE) in visual processing might also show attentional effects.
Presumably the features detected in area V1 were too pimple to direct attention, whereas
those in area TE could.
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18. Occipital lobe
So, the cells showing constraints in spatial attention were in the areas V4 and TE,
both parts of the object-recognition stream. Neurons in this system are coding spatial
location.
Moran and Desimone’s monkeys did not make a movement in space. If they did,
we would predict that cells in the posterior parietal cortex would be significant to
attentional demands.
In fact, Mountcastle (1995) reported just such results. These cells are responding
not to the features of the stimuli but rather to the movements needed to get to them. Thus,
there appear to be two types of visual attention, one related to the selection of stimuli
and the other to the selection and direction of movements.
Kahneman (1973) noted that perceptual system does not always work at peak
efficiency. He proposed that the capacity to perform mental activity is limited and that
this limited capacity must be allocated among concurrent activities. Thus, for Kahneman,
one aspect of attention is the amount of effort that is directed toward a particular task.
When you attempt a difficult maneuver with a car, such as parking in a tight spot,
you turn down your car radio.
Spitzer and colleagues (1988) wandered if cells in area V4 might vary their firing
characteristics in accord with the amount of effort to solve a particular visual problem.
Spitzer and colleagues (1988) reasoned that it should be easy for cell to discriminate
between a stimulus within its preferred orientation or color and a stimulus outside this
orientation of color. Animals’ performance confirmed that the finer discrimination was
more difficult: 93% of their responses were correct under the easy conditions as compared
with 73% under the difficult conditions.
The change in response characteristics of the area V4 cells is intriguing. First, under
the difficult conditions, the cells increased their firing rate by an average of about 20%.
Second, the tuning characteristics of the cells changed.
The more difficult task appears to have required increased attention to the
differences between the stimuli, as manifested in a change in the stimulus selectivity of
neurons in area V4.
It is not known how this attentional effect can alter the cell’s activity. The result of
studies using monkeys have led to the idea that the critical region may be the pulvinar,
which is a thalamic nucleus that projects to secondary visual areas in the tectopulvinar
system.
Petersen and his colleagues (1987) found that neurons in the pulvinar respond more
vigorously to stimuli that are targets of behavior than they do to the same stimuli when
they are not targets of behavior. That is, when a visual stimulus is present but has no
meaning for the animal, the cells have a low firing rate. When the same stimulus now
signifies a reward, the cells become more active.
Because the pulvinar complex projects to the posterior parietal cortex, temporal
cortex, and prefrontal cortex, it may play same role in directing Treisman’s “spotlight”
to different parts of space.
Petersen and his colleagues tested this prediction by finding that disrupting the
pulvinar does disrupt spatial attention. The pulvinar receives visual inputs from the
1447
colliculus, which is known to play a role in orienting to visual information; so it may be

a collicular-pulvinar spotlight that is at work.
PET measurements showed that the selective-attention task activated specific visual
regions, the region varying with the feature detected (Corbetta et al., 1991, 1993). Thus,
attention to color activated a region probably corresponding to area V4, whereas attention
to shape activated regions corresponding to areas V3 and TE. The selective task also
activated the insula, the posterior thalamus (probably, pulvinar), the superior colliculus,
and the orbital frontal cortex (Corbetta et al., 1991, 1993).
Taken together, the results of the Corbetta studies show that different coortical areas
are activated in different attentional tasks:
The parietal cortex is activated for attention to location; the occipital-temporal cortex
is activated for attention to features such as color and form.
The anterior cingulate and prefrontal areas show activation during both visual tasks.
Thus, attention appears to generally require the activation of anterior cingulate and some
prefrontal areas in addition to the activation of specific sensory areas related to a particular
sensory modality, such as vision or touch.
So, tactile stimulation activated areas S1 and S2, but in addition, during the
attentional task, there was activation in the posterior parietal cortex, like in Brodmann’s
area 7. Thus, distinct regions in the posterior parietal cortex appear to have roles in
attention to different types of sensory inputs (Burton et al., 1999).
CLINICAL EFFECTS AND SYMPTOMS
Visual field defects

Brain lesions studies are important for understanding what brain areas may be
necessary for certain kind of visual awareness – awareness of color, motion, faces,
objects, or the capacity to be aware of seeing anything at all! (Tong and Pearson, 2007).
Brain lesions may be investigated in humans who have suffered from unfortunate
injury to certain parts of the brain, which may result from strokes, tumors, trauma, or
neurodegenerative disease.
Different visual deficits can result from neural damage at different levels of the visual
processing hierarchy.
Because a spatial relationship in the retinas is maintained in central visual structures,
a careful analysis of the visual fields can often indicate the site of neurological damage.
Relatively large visual field deficits are called anopsias and smaller ones are called
scotomas.
Damage to the retina or one of the optic nerves before it reaches the chiasma results
in a loss of vision that is limited to the eye of origin.
The main causes of unilateral and bilateral optic neuropathy are: demyelinative,
ischemic, parainfectious, toxins and drugs, deficiency states, heredofamilial and
developmental, compressive and infiltrative.
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18. Occipital lobe
Observable changes in the optic disc are, therefore, of particular importance. They
may reflect the presence of raised intracranial pressure (papilledema or “choked disc”),
infarction of the optic nerve head (disc edema), congenital defects of the optic nerves
(optic pits or colobomas), hypoplasia and atrophy of the optic nerves, and glaucoma.
Lesions of the chiasma, optic tract and geniculocalcarine pathway cause bitemporal
hemianopsia, homonymous hemianopsia or superior homonymous quadrantanopsia
(contralateral temporal and ipsilateral nasal quadrants) (Meyer’s loop).
Parietal lobe lesions are said to affect more the inferior quadrants of the visual field
than the superior ones, but this is difficult to document; with a lesion of the right parietal
lobe, the patient ignores the left half of space, and with a left parietal lesion, the patient
is often aphasic.
Damage in the region of the optic chiasma results in specific types of deficits that
involve the visual field of both eyes. For example, damage to the middle portion of the
optic chiasma can affect the fibres that are crossing from the nasal retina of each eye,
leaving the uncrossed fibres from the temporal retinas intact. The resulting loss of vision
is confined to the temporal visual field of each eye and is known as bitemporal
hemianopsia. It is also called heteronomous hemianopsia to emphasize that the parts of
the visual field that are lost in each eye do not overlap. Individuals with this condition
are able to see in both left and right visual fields, provided both eyes are open (Fig. 18.15).
Damage to structures that are central to the optic chiasma, including the optic tract, lateral
geniculate nucleus, optic radiation, and visual cortex, results in deficits that are limited
to the contralateral visual hemifield.
Because such damage affects the corresponding parts of the visual field in each eye,
there is a complete loss of vision in the affected region of the binocular visual field, and
the deficit is referred to as a homonymous hemianopsia.
Fig. 18.15. A 56-years-old female patient

harboring a very large nonfunctioning
macroadenoma with suprasellar extension
and bitemporal hemianopsia.
1449
Damage along the optic radiation in its course from the lateral geniculate nucleus to
the striate cortex is rarely complete. Some of the optic radiation axons run out into the
temporal lobe on their route to the striate cortex, a branch called Meyer’s loop. Meyer’s
loop carries information from the superior portion of the contralateral visual field. More
medial parts of the optic radiation, which pass under the cortex of the parietal lobe, carry
information from the interior portion of the contralateral visual field. So, superior fibres
that leave the lateral geniculate body go straight back to the primary visual cortex; inferior
fibres loop anteriorly around the superior temporal horn of the lateral ventricle (Meyer’s
loop). Because these fibres are approximately 5 cm from the top of the temporal lobe,
they are sometimes damaged during temporal lobectomy, can thus result in a superior
homonymous quadrantanopsia. Damage to the optic radiation underlying the parietal
cortex results in an inferior homonymous quadrantanopsia.
Macular vision is represented most posteriorly at the occipital tips. Each fovea appears
to project in both occipital lobes. Injury to central visual structures can lead to a phenomenon
called macular sparing. Macular sparing is commonly found with damage to the cortex,
but can be a feature of damage anywhere along the length of the visual pathway.
The nonoverlapping part of the most peripheral temporal field (monocular temporal
crescent) represents unpaired crossed axons from the nasal retina, which project to the
most anteromedial part of the visual cortex. The primary visual cortex has inter-
connections with numerous visual association areas (Zeki, 1993).
Visual agnosia
The disorder of vision and higher visual functions are common in many patients
with neurological disease. The visual system is the most widely researched and best
understood higher order sensory system in the brain.
Object agnosia is a rare condition first described by Lissauer in 1890. It consists of
a failure to name and indicate the use of a seen object by spoken or written words or by
gesture. The patient cannot even tell the generic class of the seen object. Visual acuity is
intact, the mind is clear, and the patient is not aphasic – conditions requisite for the
diagnosis of agnosia. If the object is palpated, it is recognized at once, and it can also be
identified by smell or sound if it has an odor or makes noise. Moving the object or placing
it in its customary surroundings facilitates recognition. Lissauer conceived the visual
object recognition as consisting of two distinct processes – the construction of a
perceptual representation from vision (apperception) and the mapping of this perceptual
representation onto stored percepts or engrams of the object’s functions and associations.
Lissauer proposed that impairment of either of these processes could give rise to a defect
in visual object recognition.
Teuber was credited in 1968 with the classic definition of agnosia – that is, a normal
percept stripped of its meaning. In the setting of visual agnosia, such a definition implies
normal or near normal sensory perception in the context of impaired recognition of the
object being perceived. Most patients with visual agnosia can be shown to have
abnormality of perception.
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18. Occipital lobe
The traditional way to classify visual-object agnosia is to distinguish two broad

forms: associative agnosia and apperceptive agnosia (Lissauer, 1888).
Associative agnosia
Associative agnosia corresponds to a “pure” visual agnosia, as reflected in Teuber’s
definition, and means the ability to recognize an object despite any apparent perception
of the object. Thus, the associative agnostic can copy a drawing rather accurately,
indicating a coherent percept, but he cannot identify it.
Failure of object recognition is a defect in memory, that affects not only past
knowledge about the object, but also the acquisition of new knowledge. Associative
agnosias are more likely with damage to region in the ventral stream that are farther up
the processing hierarchy, such as the anterior temporal lobe. So, associative agnosia
usually results from damage to the ventral temporal cortex.
Apperceptive agnosia
Apperceptive visual agnosia refers to an abnormality of visual recognition in which
perceptual features are so prominent as to dominate the clinical picture. Basic visual
functions (acuity, color, motion) are preserved. The fundamental deficit is an inability to
develop a percept of the structure of an object or objects. In the simplest case, patients
are simply unable to recognize, copy, or match simple shapes.
Many patients have another unusual symptom, too-often referred to as simultan-
agnosia. In this case patients can perceive the basic shape of an object, but they are unable
to perceive more than one object at a time. Such patients often act as though they were
blind, possibly because they are simply overwhelmed by the task at hand. Such patients
can still recognize objects by using other senses such as touch, hearing or smell, so the
loss of function is strictly visual.
Apperceptive agnosia does not result from a restricted lesion but usually follows
gross bilateral damage to the lateral parts of the occipital lobes including regions sending
outputs to the ventral stream. Such injuries are probably most commonly associated with
carbon monoxide poisoning, which appears to produce neuronal death in “watershed”
region – that is, regions lying in the border areas between territories of a different arterial
system (Kolb and Whishaw, 2003).
In the course of assessing patients with possible agnosia, it is important to distinguish
between defects in naming and defects in recognition. This is a distinction that is
commonly either blurred or completely unappreciated in the scientific and clinical
literature on agnosia. The key is to understand that an object can be recognized without
being named but cannot be named without being recognized. Thus, if a patient is asked
to identify an object and fails to produce its name, it is important to probe the patient
regarding features of the object to establish that a true recognition defect exists.
Visual agnosia does not appear to result from damage to the dorsal stream. The most
affected region is the tissue at the occipitotemporal border, which is part of the ventral
visual pathway.
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James et al. (2003) propose that the dorsal system is not only responsible for
processing “where” objects are, but also “how” action can be performed toward a
particular object, such as pointing at or reaching for that object. Apparently, visual
processing in the dorsal system is not accessible to consciousness – the patient cannot
report the orientation of the slot – yet the dorsal system can guide the right action.
Complementary studies of patients with optic ataxia have revealed the opposite pattern
of visual deficits, indicating a double dissociation between conscious visual perception
and visually guided action. Optic ataxia typically results from damage to the parietal lobe,
which is part of the dorsal pathway. These patients can perceive visual orientations and
recognize objects well, but have great difficulty in performing visually guided actions.
Simultanagnosia
Wolpert (1924) originally described a patient who demonstrated a “spelling
dyslexia” (an inability to read all but the shortest words, spelled out letter by letter) and
a failure to perceive simultaneously all the elements of a scene and to properly interpret
the scene. In the framework of gestalt psychology, the patient could recognize the parts
but not the whole. A cognitive defect of synthesis of the visual impressions was thought
to be the basis of this condition, which Wolpert called simultanagnosia. Some of the
patients with this disorder have a right homonymous hemianopsia; in others, the visual
field is full. This is part of the Balint syndrome, the other components of which are faulty
visual scanning (ocular apraxia) and visual reaching (optic ataxia), suggesting that a fault
in ocular scanning might underlie all the defects.
Through tachistoscopic testing, Kinsbourne and Warrington (1963) have noted that
reducing the time of stimulus exposure permits single objects to be perceived in an instant,
but not two objects. Rizzo and Robin (1990) have proposed that the primary defect is in
sustained attention to incoming visual-spatial information. Nielsen (1946) has attributed
this disorder to a lesion of the inferolateral part of the dominant occipital lobe (area 18).
In a patient who presented with an isolated “spelling dyslexia” and simultanagnosia,
Kinsbourne and Warrington (1963) found a localized lesion within the inferior part of
the left occipital lobe. In other instance, the lesions have been bilateral in the superior
part of the occipital association cortices.
Prosopagnosia
The earliest mention of the symptom was made by Quaglino, an Italian
ophthalmologist, who, in 1867, reported a patient suffering from left hemianopsia,
achromatopsia, and inability to recognize familiar faces – problems caused by a
cerebrovascular accident.
The symptom had to await Bodamer’s report in 1947 to be identified as a distinct
form of agnosia, deserving a distinctive name (prosopagnosia, from the Greek word
prosopon, meaning “face”).
Since the 1940’s, more than a hundred case reports (Farah, 1990) have been
published, and some patients have been extensively and repeatedly investigated.
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18. Occipital lobe
The clinical picture. Prosopagnosia refers to an impairment in familiar face

recognition. Patients with facial agnosia cannot recognize any previously known faces,
including their own as seen in a mirror or photograph. They can recognize people by face
information, however, such as a birthmark, moustache or characteristic hairdo, by voice,
gait, context or other nonface cues.
With a few exceptions, they can discriminate its gender, race, and approximate age,
although finer age estimation may be impaired (De Renzi et al., 1989). Face recognition
disorders do not extend to the identification of emotional expressions, which is preserved
in the great majority of prosopagnosics, while it may be impaired in patients who do not
have problems in recognizing familiar faces (Kurucz and Feldmar, 1979), providing
evidence that discrete neural structures subserve the two abilities. It has been shown that
patients with prosopagnosia demonstrate nonconscious recognition of familiar faces.
Patients with prosopagnosia, particularly those of the associative type, often have
normal judgments of facial emotional expressions.
That is, despite the inability to identify the face, judgments related to facial emotional
expression (e.g., happy, sad, angry, and surprised) are similar to those of controls.
The opposite dissociation has been described. In these studies, it was demonstrated
that patients with bilateral damage to amygdala were unable to judge emotional facial
expressions accurately, despite normal recognition of identity (Adolphs et al., 1994, 1995,
1998). Patients with bilateral amygdala damage were significantly impaired in judging
faces that looked “unapproachable” or “untrustworthy”. These findings were interpreted
to support the proposition that the amygdala was involved in social judgment as well as
judgment of emotion based on facial features (Jones and Tranel, 2001, 2002). The
findings indicate the complex, complimentory and reciprocal relationship between
multiple areas of the brain, in the processing of different aspects of face information (e.g.,
identity, emotion, and social valence) (Jones and Tranel, 2002). In patients with proso-
pagnosia caused by acquired brain damage (e.g., by stroke, tumor, or other lesion), there
may be some visual field defect, usually a superior quadrantanopsia of one or both visual
fields. Such patients have otherwise normal neurologic and neuropsychological exams
and do not evidence aphasia, amnesia, dementia, or disorders of executive functions.
Visual acuity and visual perception may be normal or near normal in associative
prosopagnosia, although many cases with clear visual perceptual defects have been
described (and probably correspond to an apperceptive type).
It was demonstrated that patients with acquired prosopagnosia show that the
recognition defect often extends to objects other than faces. Anyhow, there are some
remarkable exceptions that have been reported. Patients with prosopagnosia are still able
to recognize objects well, but have great difficulty in recognizing or telling apart faces
(Bodamer, 1947; Meadows, 1974).
Studies have revealed a few patients who can discriminate between subtle differences
in objects but can no longer distinguish between faces (McNeil and Warrington, 1993).
Another patient could no longer recognize upright faces accurately and was actually better
at recognizing upside-down faces, which is just the opposite of normal subject
performance (Farah et al., 1995).
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A study of a very unusual object agnosic patient, who was very impaired at recognizing
objects could recognize upright faces just as well as normal subjects (Moscovitch et al.,
1997). Remarkably, if the face were turned upside-down, the patient became severely
impaired, performing six times worse than normal participants under these conditions.
Apparently the patient has an intact system for processing upright faces, but the system
responsible for processing objects and upside-down faces is badly damaged (Valentine,
1988). Taken together, evidence from that patient and prosopagnostic patients provide
evidence of a double dissociation between the visual processing of upright faces as compared
to objects and upside-down faces (Tong and Pearson, 2007). Prosopagnosics may not accept
the fact that they cannot recognize their own faces, probably because they know who must
be in the mirror and thus see themselves. According to Damasio and colleagues, most facial
agnosics can tell human from nonhuman faces and can recognize facial expression normally
(Damasio et al., 1982; 1989).
Scientists have also described a third form of prosopagnosia termed “developmental
prosopagnosia” (De Haan and Campbell, 1991; Kracke, 1994; De Haan, 1999; Jones and
Tranel, 2001). Developmental prosopagnosia refers to a selective face recognition defect
that begins in childhood and is not associated with any identifiable structural lesion. In
general, such cases have shown significant apperceptive features, although one reported
case was believed to be an essentially associative prosopagnosia. Similar to cases of
acquired prosopagnosia, such patients recognize individuals by gait, voice, or other
nonface features. In one case there were features of a broader visual object agnosia. In
those cases in which neuroimaging has been completed, no structural brain abnormalities
have been identified. Functional imaging has not been done in such cases. These patients
appear to manifest the face recognition disability over many years. Although first
identified in childhood, in at least one case the disorder persisted into adulthood.
Similar to cases of acquired prosopagnosia, in at least one case nonconscious
electrodermal recognition of familiar faces was demonstrated.
Prosopagnosia can result from bilateral damage around the regions of the lateral
occipital cortex, inferior temporal cortex and the fusiform gyrus (Meadows, 1974;
Bouvier and Engel, 2006). In some cases, unilateral damage to the right hemisphere may
lead to this impairment. Because lesions are usually quite large and might damage fibre
tracts leading to a critical brain region, it is difficult to identify a precise site. Nonetheless,
the brain lesion sites associated with prosopagnosia appear to encompass the fusiform
face area and extend much more posteriorly (Tong and Pearson, 2007).
All postmortem studies on facial agnosias have found bilateral damage, and the results
of imaging studies in living patients confirm the bilateral nature of the injury in most
patients, with the damage centered in the region below the calcarine fissure at the temporal
junction. These results imply that the process of facial recognition is probably bilateral, but
asymmetrical (Kolb et al., 1983; Boussaud et al., 1990; Hancock et al., 2000).
Visual object agnosia

The term visual object agnosia is reserved for patients who have difficulty with
identification of entities at basic object level. Thus, visual object agnosia refers to a visual
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18. Occipital lobe
recognition defect at the level of nonunique objects rather than at the level of specific
members of a category (Damasio et al., 2000). For example, a patient with visual agnosia
may not know that a violin is a violin, that a dog is a dog, or that a car is a car (Jones and
Tranel, 2002). Memory is normal, and there is defect in judgment, basic verbal intellectual
skills, or language.
Associated conditions often include defects in color recognition and naming and
defects in reading. Lesions associated with visual object agnosia are typically more
extensive than those in case of prosopagnosia, including occipitotemporal cortex
bilaterally, extending dorsally into visual association cortex, and almost always involving
underlying white matter. There is evidence that the left hemisphere plays a more critical
role than the right in the development of visual object agnosia (Jones and Tranel, 2002).
Disorder of reading
The study of alexia dates at least to the contributions of Déjérine, who in 1891 and
1892 described two patients with quite different patterns of reading impairment.
Déjérine’s first patient (Déjérine, 1891) developed an impairment in reading and
writing subsequent to an infarction involving the left parietal lobe. Déjérine termed this
disorder “alexia with agraphia” and attributed the disturbance to a disruption of the
“optical image for words”, which he thought to be supported by the left angular gyrus.
Déjérine concluded that reading and writing required the activation of these “optical
images” and that the loss of the images resulted in an inability to recognize or write
familiar words.
Déjérine’s second patient (Déjérine, 1892) was quite different. This patient was
unable to read aloud or for comprehension but could write, a disorder that Déjérine
designated “alexia without agraphia” (also known as agnosic alexia and pure alexia). The
patient had a right homonymous hemianopsia from a left occipital lesion, which included
the fibres carrying visual information from the right to the left hemisphere. Déjérine
explained alexia without agraphia in terms of a “disconnection” between visual
information confined to the right hemisphere and the left angular gyrus, which he
assumed to be critical for the recognition of words.
The study of acquired dyslexia was revitalized by Marshall and Newcombe (1973).
These investigators described a patient (GR) who read approximately 50 percent of
concrete nouns but was severely impaired in the reading of abstract nouns and all other
parts of speech. The most striking aspect of GR’s performance, however, was his
tendency to produce errors that appeared to be semantically related to the target word
(e.g., speak read as “talk”). Marshall and Newcombe (1973) designated this disorder
“deep dyslexia”. These investigators also described two patients whose primary deficit
appeared to be an inability to derive the pronunciation of irregularly spelled words, such
as “yacht”. This disorder was designated “surface dyslexia”.
Pure alexia refers to the inability to read with preserved ability to write. These
patients are not aphasic, nor is there a defect in memory, orientation, basic intellectual
skills, or verbal arithmetic skills. The neurologic exam is normal apart from a typical
finding of a right homonymous hemianopsia.
1455
An inability to read has often been seen as the complementary symptom to facial-
recognition deficits.
Alexia is most likely to result from damage to the left fusiform and lingual areas.
Either hemisphere can read letters, but only the left hemisphere appears able to combine
the letters to form lexical representations (that is, words). The lesion typically abuts the
splenium. Thus, visual information is regarded only by the right occipital lobe, and such
information is blocked from passing to the left hemisphere by virtue of the retrosplenial
lesion. This information thus cannot be decoded into lexically meaningful words by
association areas in the left parietal cortex, specifically surrounding the left angular gyrus
(Jones and Tranel, 2002). In the instance, when a patient is asked to trace letters with his
or her hand, there is no such disconnection between sensorimotor cortex on the left and
the left angular gyrus. The key in this case is that the visual system is bypassed (Jones
and Tranel, 2002).
Alexia can be conceived as a form of object agnosia in which there is an inability to
construct perceptual wholes from parts or to be a form of associative agnosia, in which
case word memory (the lexical store) is either damaged or inaccessible (Farah, 1990;
1998; Behrmann et al., 1992).
In evaluating patients with pure alexia, it is useful to ask them to copy printed
material, to write a sentence by dictation, and to write a sentence spontaneously.
However, such patients will have difficulty in copying sentences, given their inability to
read. If the examiner asks the patient to trace letters with the patient’s finger, the patient
may be able to discern the meaning of the written word (Jones and Tranel, 2002).
Disorder of color processing

Normal color vision depends on the integrity of cone cells, which are most numerous
in the macular region. When activated, they convey information to special columns of
cells in the striate cortex. Three different cone pigments with optimal sensitivities to blue,
green, and orange-yellow wavelengths are said to characterize these cells; presumably
each cone possesses only one of these pigments. Transmission to higher centers for the
perception of color is believed to be effected by neurons and axons that encode at least
two pairs of complementary colors. In the optic nerve and tracts, the fibres for color are
of small caliber and are preferentially sensitive to noxious agents and pressure. The
geniculostriate fibres for color are separate from but course along with fibres that convey
information about form and brightness; hence there may be a homonymous color
hemianopsia (hemiachromatopsia). The visual fields for blue-yellow are smaller than
those for white light, and the red and green fields are smaller than those for blue-yellow.
Assessment of color imagery depends primarily on the self-report on the patient.
Patients may complain that they cannot “remember” the colors that various objects should
have (this complaint may also indicate color agnosia).
The patients may note that, following a brain lesion, they no longer dream in color.
Interestingly, it has been suggested that recall of most personal memories depends on
color and other visual imagery (Ogden, 1993).
1456
18. Occipital lobe
Achromatopsia
Diseases may affect color vision by abolishing it completely (achromatopsia) or
partially by quantitatively reducing one or more of the three attributes of color –
brightness, hue and saturation. Or, only one of the complementary pairs of color may be
lost, usually red-green. The disorder may be congenital and hereditary or acquired. The
commonest form, and the one to which the term color blindness is usually applied, is a
male sex-linked inability to see red and green while normal visual acuity is retained.
Patients with achromatopsia complain that colors appear to be black and white,
washed out, gray or dirty. Such patients may also demonstrate some color desaturation
and dyschromatopsia rather than complete lack of color.
Lesions associated with achromatopsia are characteristically found in the
infracalcarine medial occipital lobe, typically involving the lingual and fusiform gyri.
When the lesion is unilateral, the color defect is in the contralateral visual space. When
the lesion is bilateral, the color defect subsumes the entire visual field. There may well
be visual field cuts, typically involving superior quadrants.
Damasio (1985) has drawn attention to a group of acquired deficits of color
perception with preservation of form vision, the result of focal damage (usually,
infarction) of the visual association cortex and subjacent white matter. Color vision may
be lost in a quadrant, half of the visual field, or the entire field. The latter, or full-field
achromatopsia, is the result of bilateral occipitotemporal lesions involving the fusiform
and lingual gyri, a localization that accounts for its frequent association with visual
agnosia (especially, prosopagnosia), and some degree of visual field defect. A lesion
restricted to the inferior part of the right occipitotemporal region, sparing both the optic
radiation and striate cortex, causes the purest form of achromatopsia (left hemiachro-
matopsia). With a similar left-sided lesion, alexia may be associated with the right
hemiachromatopsia.
In addition to the losses of perception of form, movement, and color, lesions of the
visual system may also give rise to a variety of positive sensory visual experiences. The
simplest of these are called phosphenes, i.e., flashes of light and colored spots in the
absence of luminous stimuli. Mechanical pressure on the normal eyeball may induce
them at the retinal level, as every child discovers.
In patients with migraine, ischemia of nerve cells in the occipital lobe gives rise to
the bright zigzag lines of a fortification spectrum.
Formed or complex visual hallucinations are observed in a variety of conditions,
notably in the withdrawal state following chronic intoxication with alcohol and other
sedative-hypnotic drugs, in Alzheimer disease, and in disease of the occipitoparietal or
occipitotemporal regions or the diencephalon (“peduncular hallucinosis”). In color
blindness a genetic abnormality of cone pigments is postulated, but the defect cannot be
seen by inspecting the retina. A failure of the cones to develop or a degeneration of cones
may cause a loss of color vision, but in the latter condition visual acuity is often
diminished, a central scotoma may be present, and, although the macula appears to be
normal ophthalmoscopically, fluorescein angiography shows the pigment epithelium to
1457
be defective. Congenital color visions are usually protan (red) or detan (green), leaving
yellow-blue color vision intact; acquired lesions may affect all colors.
Lesion of the optic nerves usually affects red-green more than blue-yellow; the
opposite is true of retinal lesions. An exception is a dominantly inherited optic atrophy,
in which the scotoma mapped by a large blue target is larger than that for red.
Color anomia
The term color anomia refers to an inability to name colors in the context of normal
performances on tests of matching color or of color generation. This disorder is usually
associated with pure alexia and right homonymous hemianopsia.
Color naming can be affected independently of color perception, imagery, and
recognition (Geschwind and Fusillo, 1966; Damasio et al., 1979; Rizzo and Damasio,
1989; Rizzo et al., 1993).
Color anomia is relatively rare, and, in fact, naming of color is often relatively spared
in patients who have severe naming defects for other classes of stimuli. Goodglass and
coworkers (1986) found that color naming was very infrequently impaired in various
aphasic patients and was, in fact, one of the categories that tended to stand out as being
especially intact – a finding consistent with an older case study (Yamadori and Albert,
1973). Such patients are able to match same-color chips and associate colors with objects.
When shown a specific color, such patients are unable to name it with appropriate verbal
tag. This defect seems to be exacerbated when less contextual information is available.
Given the site of the lesion in color anomia, there is some suggestion that this may
represent a disconnection syndrome. That is, in the left visual field (ipsilateral to the
lesion) color perception is normal, but perception is limited to primary visual cortex in
the right hemisphere only. This elementary perceptual information is blocked by a
retrosplenial lesion in the mesial left occipital lobe, thereby rendering such information
unavailable to the left hemisphere (Jones and Tranel, 2002).
Color agnosia
Following the Teuber (1968) definition of agnosia as a “normal percept stripped of
its meaning”, color agnosia refers to the loss of the ability to retrieve color knowledge
pertinent to a given stimulus that is not caused by deficient color perception. So, color
agnosia is a rare condition defined as an inability to retrieve color information in the
context of normal perception and language. Color agnosia is often associated with visual
object agnosia and may be associated with category-related recognition defects,
particularly for living entities as opposed to artifactual entities. The defect should also
be distinguished from color anomia and from color imagery impairment. In the latter
condition, the patient cannot bring into mind’s eye a particular color, but the patient still
knows what the color is and can give verbal or nonverbal testimony to that knowledge –
for instance, by performing normally on tasks requiring matching of color or names with
objects. A patient with color agnosia, by contrast, has lost the “knowing” of colors and
will not perform such tasks normally (Tranel, 1997). For example, a patient with color
agnosia will be unable to remember the color of common entities (e.g., “what color is a
1458
18. Occipital lobe
banana?”) and will be unable to provide a list of objects that come in various colors (e.g.,
“name things that are red”) (Jones and Tranel, 2002). Some authors have argued that
especially in cases in which the defect is “two-ways” – i.e., when the patient cannot name
colors from color stimuli and cannot point the colors given the color names – the
designation of agnosia is accurate. Color agnosia is rare. Only a few well-studied cases
have been reported (Kinsbourne and Warrington, 1964; Farah et al., 1988; Schnider et
al., 1992; Luzzatti and Davidoff, 1994, etc.). Based on a handful of well-studied patients,
the neuroanatomical correlates of color agnosia include the occipital-temporal region
either unilaterally on the left or bilaterally.
Functional imaging studies suggest that areas associated with color knowledge are
probably anterior and lateral to areas associated with color perception.
Visual neglect
Neglect can be defined as “the failure to report, respond, or orient to novel or
meaningful stimuli, presented to the side opposite a brain lesion, when this failure cannot
be attributed to either sensory or motor defects”. In the visual modality, the most common
form of neglect is hemispatial neglect. The essential feature of spatial neglect is that the
patient ignores objects in the visual hemifield contralateral to the lesion, in the absence
of a visual field cut.
Such neglect is commonly associated with right hemisphere lesions resulting in left
hemispatial visual neglect.
Right hemispatial visual neglect, though rare, can be seen during the acute period in
some cases of left hemisphere lesions. The typical lesion is in the occipital-temporal-
parietal border zone (Jones and Tranel, 2002).
So, damage to the dorsal pathway can lead to optic ataxia (impairments in visual
guided actions) or visual neglect. Damage to the ventral temporal cortex can lead to
impairments in visual perception, object recognition or face recognition. Patients with
brain injuries in the ventral and dorsal pathways reveal a dissociation between the
conscious perception of basic shapes and orientations and the ability to perform visually
guided actions.
The finding of neglect is often not restricted to the visual modality and may be
demonstrated in both sensorimotor and auditory systems concurrently with visual neglect.
One of the ways to evaluate hemispatial visual neglect in affected patients is to
perform a double simultaneous stimulation task, in which the examiner introduces a visual
stimulus to the left visual field, to the right visual field, and then to both fields
simultaneously. The most clear evidence of neglect from this procedure is that the patient
will identify each stimulus individually, but when presented simultaneously the patient
will identify only the stimulus presented ipsilateral to the lesion.
Furthermore, methods of detecting hemispatial neglect include drawing tasks, line
bisection-tasks, or line cancellation tasks (Jones and Tranel, 2002).
So, material in one visual field – usually the left – can be seen but remain unnoticed
unless the patient’s attention is drawn to it (Chaves and Caplan, 2001). This form of
1459
visual inattention, also known as unilateral sensory or spatial neglect, typically occurs
when there is right parietal lobe involvement as well as occipital lobe damage. Right
occipital lesions are less likely to give rise to inattention. The so-called “visual
inattention” associated with occipital lobe damage is similar to simultaneous agnosia in
that the patient spontaneously perceives only one thing at a time. It differs from
simultaneous agnosia in that the patient will see more than one object if others are pointed
out: this is not the case in a true simultaneous agnosia.
In addition to demonstrating neglect in other modalities (sensorimotor and auditory),
associated signs observed in neuropsychological testing of patients with neglect include
constructional dyspraxia, anosodiaphoria, and anosognosia.
Other visuospatial anomalies

Occasionally, patients with an attention hemianopsia may displace an image to the
nonaffected half of the field of vision (visual allesthesia), or visual image may persist for
minutes to hours, or it may reappear episodically, after the exciting stimulus has been
removed (palinopsia or paliopsia); the later disorder also occurs in defective but not blind
homonymous fields of vision. Polyopia (polyopsia), the perception of double or multiple
images when a single stimulus (object) is presented, is said to be associated predominantly
with right occipital lesions and can occur with either eye. Usually there is one primary
and a number of secondary images, and their relationships may be constant or changing.
Bender and Krieger (1951), who described several such patients, attributed the
polyopia to unstable fixation. Oscillopsia, or illusory movement of the environment,
occurs mainly with lesions of the labyrinthine-vestibular apparatus and is described with
disorder of ocular movement.
Other visuospatial anomalies associated with occipital lesions include astereopsis
(loss of stereoscopic vision), metamorphopsias (visual distortions), optic allesthesia
(misplacement of percepts in space), and palinopsia (persevered visual percept)
(Damasio, 1988; Benson, 1989; Zihl, 1989; Barton and Caplan, 2001; Dănăilă and Golu,
2006). These are very rare conditions but of theoretical interest as they may provide clues
to cortical organization and function. Lesions associated with these conditions tend to
involve the parietal cortex as well.
Cortical blindness and Anton’s syndrome

With bilateral lesions of the occipital lobe (destruction of area 17 of both
hemispheres), there is a loss of sight and a loss of reflex closure of the eyelids to a bright
light or threat. The degree of blindness may be equivalent to that which follows
enucleation of the eyes or severance of the optic nerves. The pupillary light reflexes are
preserved, since they depend upon visual fibres that terminate in the midbrain, short of
the geniculate bodies. Usually no changes are detectable in the retinas, though van Buren
(1963) has described slight optic atrophy in monkeys long after occipital ablation. The
eyes are still able to move through a full range, but optokinetic nystagmus cannot be
elicited. Visual imagination and visual imagery in dreams are preserved. With very rare
1460
18. Occipital lobe
exceptions, no cortical potential can be evoked in the occipital lobes by light flashes or
pattern changes (visual evoked response), and the alpha rhythm is lost in the EEG. There
may also be visual hallucinations of either elementary or complex types. The usual cause
of cortical blindness is occlusion of the posterior cerebral arteries (embolic or thrombotic).
The infarction may also involve the medial temporal regions and thalami with a resulting
Korsakoff amnesic defect and a variety of other neurologic deficits referable to the high
midbrain and diencephalon. Hypoxic-ischemic encephalopathy, Schilder disease and
other leukodystrophies, Creutzfeldt-Jakob disease, progressive multifocal leukoence-
phalopathy, and bilateral gliomas are other causes of cortical blindness.
A commonly associated phenomenon with cortical blindness is Anton’s syndrome,
in which the patient with cortical blindness denies all visual difficulties. Anton’s
syndrome is considered a special form of anosognosia and is frequently seen only in the
acute epoch (within 2 or 3 months following the event).
The main characteristic is denial of blindness by a patient who obviously cannot see.
The patient acts as though he could see, and when attempting to walk, he collides with
objects, even to the point of injury. He may offer excuses for his difficulties: “I lost my
glasses”, “The light is dim”, etc., or there may be only an indifference to the loss of sight.
The lesion in cases of negation of blindness extend beyond the striate cortex to
involve the visual association areas.
Cortical blindness and Anton’s syndrome may also result from subcortical lesions
to optic radiations. Pupillary responses are preserved, but visual evoked potential cannot
be demonstrated (Jones and Tranel, 2002).
Bilateral lesions of primary visual cortex result in cortical blindness, a condition
commonly caused by bilateral infarction of the posterior cerebral arteries.
Rarely, the opposite condition may arise: a patient can see small objects but claims
to be blind. This individual walks about avoiding obstacles, picks up crumbs or pills from
the table, and catches a small ball thrown from a distance. Damasio et al. (1980) suggests
that this might be a type of visual disorientation but with sufficient residual visual
information to guide the hand, and that the lesion will be in the visual association areas
superior to the calcarine cortex.
Topographical disorientation
The term topographical disorientation refers to an acquired inability to navigate the
environment in daily life (Tranel et al., 1997; Barrash, 1998; Damasio et al., 2000).
The most striking manifestation of spatial memory deficit is topographic
disorientation – namely, the inability to find one’s way in a familiar environment and to
learn new paths, in the absence of global amnesia, severe mental deterioration, or
disorders of visual perception and exploration. Förster (1890) and Meyer (1900) must be
credited with having provided the first exhaustive description of its features. With
restitution of function or in milder cases from the beginning, navigation is impaired only
in environments that the patient has first experienced since the onset of disease (Habib
and Sirigu, 1987).
1461
Two broad types of topographical disorientation can be discerned. The first may be
termed anterograde topographical disorientation, which involves a defect in new learning.
Patients with this disorder will complain that they become lost in new places, cannot
learn new routes, or cannot retrace their path in real life. Associated clinical findings may
include left hemispatial neglect, left visual field cuts, and constructional dyspraxia. The
site of lesion associated with the disorder is the medial occipitotemporal area, particularly
on the right and including the posterior parahippocampal gyrus and lingual gyrus.
Anterograde topographical agnosia has been described in cases of right parietal
dysfunction, and of left mesial occipitotemporal dysfunction but in these cases the clinical
phenomenon appears to be more transient and less severe.
Retrograde topographical disorientation refers to the inability to recognize previously
well-known spatial / topographical routes. The patient with retrograde topographical
disorientation will be unable to recognize either previously known visual scene (e.g.,
rooms in their home and the street on which they lived) or landmarks (e.g., their house
and the local grocery). Patients with retrograde topographical disorientation are unable
to describe in verbal terms from memory familiar scenes or routes. The lesion most
commonly associated with this disorder is in the mesial occipitotemporal cortices of the
right hemisphere, thus disconnecting primary visual cortex from higher order association
cortices (Jones and Tranel, 2002).
It is apparent that the basic deficit underlying the patient’s difficulty is the inability
to retrieve and abstract map of the route, which specifies the spatial relationships defining
the position of a place with respect to other places and the subject and to transform them
in guidelines for walking.
Landmark recognition and spatial map construction are the main mental operations
that assist navigation through familiar surroundings and their discrete disruption underlies
two forms of route-finding disability, topographic agnosia and topographic amnesia
(Paterson and Zangwill, 1945). The failure to identify a specific building might result
from perceptual impairment that prevents the appreciation of the small distinctive features
identifying an exemplar of a category whose elements are similar or from the inability to
match the perceived building with its representation stored in memory. Prosopagnosia is
a frequent, but not necessarily concomitant, topographic agnosia. Landis and coworkers
(1986) found prosopagnosia in only 7 of 16 patients suffering from what they called
“environmental agnosia”.
Failure to recognize familiar environments is by no means a constant feature of
patients with topographic disorientation. De Renzi and Scotti (1969) who were unable to
identify famous building did not improve in taking his bearing when their names were
provided by the examiner because he could not remember their position with respect to
other sites of the city. The amnestic nature of this form of topographic disorientation is
confirmed by the patient’s failure to give a verbal description of the route, to trace it on
a road map, and to draw a map of a familiar place.
The dissociation between topographic amnesia and topographic agnosia is
exemplified by patient 5 of Aimard et al. (1981) who was unable to find a room in his
apartment but, when he eventually opened its door, immediately recognized it. Of course,
1462
18. Occipital lobe
agnosic and amnesic disorders can coexist in the same patient, as both are dependent on
right hemispheric damage.
The study of the anatomic correlates of topographic disorientation has pointed out
the crucial role played by the posterior regions of the brain, especially of the right
hemisphere. In some cases damage is bilateral (Förster, 1890; Wildbrand, 1892; Dunn,
1895; Peters, 1896; Meyer, 1900), but in others it is confined to the right side, where the
areas more frequently involved are the parietal lobe (Paterson and Zangwill, 1945; Hécaen
et al., 1956; Assal, 1969; Aimard et al., 1981; Newcombe and Ratcliff, 1990) and the
medial occipitotemporal cortex (Gloning, 1965; Whitty and Newcombe, 1973; Hécaen
et al., 1980; Aimard et al., 1981; Landis et al., 1986; Habib and Sirigu, 1987). The most
frequent etiology is an infarction in the territory of the right posterior cerebral artery,
which supplies blood to the medial surface of the occipital and temporal lobe. Habib and
Sirigu (1987) argued that the crucial lesion is located in the right parahippocampal gyrus
(posterior to the uncus and anterior to the subsplenial region), but it is difficult to reconcile
this assumption with the lack of topographic disorientation found in patients submitted
to right temporal ablation, although they showed psychometric signs of spatial learning
impairment (Milner, 1965; Milner, 1971; Smith and Milner, 1981).
In the animal, parietal area 7, corresponding to the inferior parietal lobule in humans,
has strong connections with the posterior parahippocampal gyrus, but the evidence that
its damage results in route-finding impairment is meager and based only on the report
that monkeys are hesitant and slow in finding their way to the cage after bilateral
(Ettlinger and Wegener, 1958; Bates and Ettlinger, 1960) and also unilateral ablation
(Sugishita et al., 1978) of areas 5 and 7.
Episodes of topographic disorientation are frequently seen in the advanced stages
of degenerative dementia of Alzheimer type.
Eleven cases have been reported (Moretti et al., 1983; Stracciari, 1992; Stracciari et
al., 1994). During the attack which lasted from 5 to 40 min, the patients were perfectly
aware of what was happening to them and retained the ability to recognize places, shops,
streets, and so on, but they could not find their way out. None of them showed signs of
mental deterioration, or of verbal and spatial dysmnesia when the episode was over. This
reflects a transient dysfunction of unknown origin of the right occipitotemporal region.
Defects in constructional skills

Constructional ability can be defined as the ability to manipulate materials to form
an intended final construction (Jones and Tranel, 2002).
Copying drawings is a task that enjoys particular popularity in clinical practice because
it is easy to administer at the bedside and is the simplest way to bring out constructional
apraxia. This ability is well known to most practitioners, examples of tests of constructional
ability are the Draw a Clock test, the block design subtest from the Wechsler Adult
Intelligence Test, and the intersecting pentagons from the Mini Mental State Examination.
The test of constructional ability presumes that the patient has adequate visual acuity to see
the test and that motor skills are adequate to complete the test.
1463
The mechanisms whereby a patient manifests defects in constructional abilities may

be determined by examination of the process of construction or by examination of the
final product.
The symptoms known by the neurologists for more than seventy years (Kleist, 1934)
consist in the inability to assemble the elements of a bidimensional or tridimensional
whole, respecting their orientations and spatial relationship. For example, visual neglect
may be determined by a drawing task in which the item to be drawn (or copied) is placed
far to the side of the page (usually the right side, indicating left hemispatial visual neglect).
Hemispatial neglect may also be shown in a case in which one side of the object is
distorted or missing. Finally, in the absence of neglect, there may be a lack of appreciation
of visual spatial relationships apparent in the production of a drawing by the patient, in
which elements of the object to be constructed are present but are distorted in their spatial
relationship to one another (Jones and Tranel, 2002).
Kleist (1934) viewed constructional apraxia as a left parietal deficit, due to the
disruption of a center (tentatively localized in the left angular gyrus) that would represent
the interface between the analysis of visuospatial information and the planning of hand
movements. On this assumption, the deficit would be attributable to neither a perceptual
nor an executive impairment but to the stage where movement programs, which are
organized by the left hemisphere, must be monitored by spatial analysis. This hypothesis
was abandoned when it was shown that constructional apraxia is by no means limited to
left parietal damage and is indeed as frequent or even more frequent following right brain
damage.
The evidence that constructional apraxia reflects the disruption of different abilities,
depending on the damage side, is most suggestive but has not been unequivocally
demonstrated. Although an executive impairment remains a possible component of the
defective performance of left brain-damaged patients, visuospatial disorders are likely
to be influential in both hemispheric groups. Parietal damage is a frequent anatomic
correlate of constructional apraxia after damage to either hemisphere, although the
association is closer in right brain-damage patients than in left brain-damage patients
(Ajuriaguerra et al., 1960).
Reproduction of a structured model is a sequential task that requires a certain degree
of planning and is, therefore, liable to be sensitive to the functioning of frontal structures
(Luria and Tsvetkova, 1964; Benton, 1968).
Supportive of the idea that different mechanisms underlie parietal and frontal
constructional apraxia is the finding that the disorder is associated with poor performance
on a line bisection task in right brain-damaged patients having damage to the
parietooccipital cortex but not in those with frontal, subcortical damage (Pillon, 1981;
Marshall et al., 1994).
In conclusion, the site of lesion associated with defects in constructional skills is
typically the right occipital cortices and adjacent visual association cortex. There may
be a greater perceptual component to the defect with more ventral lesions and a greater
defect of spatial relationship with more dorsal lesions. In some cases, constructional
1464
18. Occipital lobe
disabilities can be observed in left-sided lesions in these same sites, but such patients
often have a fluent aphasia, a lesser or more transient constructional defect, and the defect
is more likely to show a lack of appreciation of spatial relationships and preserved
visuoperception (Jones and Tranel, 2002). Since the introduction of imaging techniques
in clinical practice, it has been increasingly recognized that subcortical structures
contribute to cognitive functions, and disorder of language, praxis, lateralized attention,
and so on, have been reported following damage to basal nuclei.
Visual illusions (metamorphopsias)

According to Adams and colleagues (1997), these may present as distortions of form,
size, movement, or color; also visual images may fail to arouse visual memories and their
associated effect, resulting in a sense of strangeness or inexplicable familiarity, as it
occurs in the “dreamy state” of temporal lobe epilepsy.
Visual illusions take the form of objects seeming too small (micropsia) or too large
(megalopsia or macropsia) or that appear to be moving toward or away from the patient.
In other cases, objects may appear elongated, swollen, or run together or the vertical and
horizontal orientation of the image may shift (metamorphopsia). Inverted vision,
irradiation of contour, disappearance of color (achromatopsia), illusional coloring
(erythropsia), polyopia (one object appearing as two or more objects), monocular
diplopia (vertical, concentric, especially triplopia), illusions of movement of stationary
objects, too rapid displacement of moving objects or imperception of movement are other
form of illusory visual experience. Also, there may be a loss of stereoscopic vision,
perseveration or periodic reappearance of visual images long after the cessation of the
visual stimulus (palinopsia or paliopsia), or a false orientation of objects in space (optic
allesthesia) (Hécaen, 1962).
Illusions of these types have been reported with lesions of the occipital,
occipitoparietal, or occipitotemporal regions, and the right hemisphere appears to be
involved more often than the left one. Illusions of movement occur more frequently with
posterior temporal lesions, polyopia (polyopsia) more frequently with occipital lesions
(although it may occur in hysteria), and palinopsia with both parietal and occipital lesions.
Visual field defects are present in many of the cases.
Hoff and Potzl (1935) have insisted that an element of vestibular disorder underlies
the metamorphopsias of parieto-occipital lesions (the vestibular and proprioceptive
systems are represented in the right parietal lobe and lesions there are responsible for
misperceptions of movement and spatial relations). The illusion of tilting of the
environment or upside-down vision occurs more often with lesions of the vestibular nuclei
than with those of the occipital-parietal cortex.
Pharmacological agents like atropine, lysergic acid, and mescaline cause many of
the afore-mentioned illusory phenomena.
1465
Visual hallucinations
A hallucination is a perception in the absence of an adequate peripheral stimulus; it
must be distinguished from an illusion, which is a misinterpretation of a perception.
Illusions occur in normal people, especially when they are tired, inattentive, or in states
of high expectation.
Visual hallucinations are less frequent in schizophrenia than auditory ones, but when
they are present, they often occur in association with other hallucinations. Visual hallu-
cinations of small animals are noted in delirium, especially delirium tremens, and
fornication, the sensation that animals are crawling under the skin or over the body, have
been associated with cocaine psychosis.
Traditionally it has been taught that the lesions responsible for visual hallucinations,
if identifiable, are usually situated in the occipital lobe or posterior part of the temporal
lobe, and that elementary hallucinations have their origin in the occipital cortex, and
complex ones, in the temporal cortex. However, the complexity of visual hallucinations
has only limited diagnostic value; in some cases, formed hallucinations are localizing
with lesions of the occipital lobe and unformed ones with lesions of the temporal lobe
(Weinberger and Grant, 1941).
Also, as emphasized by these authors, lesions that give rise to visual hallucinations,
simple or elaborate, need not be confined to central nervous structures but may be caused
by lesions at every level of the neuro-optic apparatus (retina, optic nerve, chiasma, etc.).
So, visual hallucinations caused by a neurological disease are attributable to lesions
anywhere in the visual system from the retina (macular degeneration, cataracts,
enucleations), optic nerve and tract, midbrain, geniculocalcarine radiation (multiple
sclerosis, ischemia, compression, stroke, tumors), to the occipital or temporal cortex
(stroke, tumors, seizures). They sometimes reflect sensory deprivation.
Other visual hallucinations appear in migraine, narcolepsy, Alzheimer’s disease,
diffuse Lewy body disease, Parkinson’s disease with dopaminergic treatment, drug
intoxication or withdrawal, metabolic encephalopathies (delirium), schizophrenia, and
depression or mania (mood congruent). The clinical setting for the occurrence of visual
hallucinations varies. The simplest black and white moving scintillations are part of
migraine. Others, some colored, can occur as a seizure aura. Often they are associated
with a homonymous hemianopia, as indicated earlier. Frequently they occur as part of a
confusional state or delirium. In the “peduncular hallucinosis” of Lhermitte (1971), the
hallucinations are purely visual, appear natural in form and color, sometimes in pastels,
move about as in an animated cartoon, and are usually considered to be unreal, abnormal
phenomena (preserved insight). Similar phenomena may occur as part of hypnagogic
hallucinations in the narcolepsy-cataplexy syndrome.
In their material, McKee and associates (1990) emphasize that so-called peduncular
hallucinosis has been associated mainly with high mesencephalic lesions and, more
particularly in one case, with lesions of the pars reticulata of the substantia nigra. The
hallucinations in this disorder are purely visual; if hallucinations are polymodal, the lesion
is always in the occipitotemporal parts of the cerebrum.
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18. Occipital lobe
Visual hallucinations may be elementary or complex, and both types have sensory
as well as cognitive aspects.
Elementary (or unformed) hallucinations include flashes of light, colors, luminous
points, stars, multiple lights (like candles), and geometric forms (circles, squares, and
hexagons). They may be stationary or moving (zigzag, oscillations, vibrations, or
pulsations). They are much the same as the effects that Foerster and Penfield (1930)
obtained by stimulating the calcarine cortex in a conscious person. Complex, or formed,
hallucinations include objects, persons or animals. They are indicative of lesions in the
visual association areas or their connections with the temporal lobe. They may be of
natural size, lilliputian, or grossly enlarged.
With hemianopsia, they may appear in the defective field or move from the intact
field toward the hemianopsic one. The patient may realize that the hallucinations are false
experiences or may be convinced of their reality. Patient’s response is usually in accord
with the nature of the hallucination or he may react with fear to a threatening vision.
A special syndrome of ophthalmopathic hallucinations occurs in the blind person.
The visual images may be of elementary or complex type, usually of people or animals,
and are polychromic (vivid colors). The hallucinations may occupy all of the visual field,
the field of one eye, or corresponding blind fields in the patient with homonymous
hemianopia (hemianopsia). Moving the eyes or closing the affected eye has variable
effects, sometimes abolishing the hallucinations. A similar phenomenon in the elderly
(with preserved vision) has been called the “syndrome of Bonnet”, following the report
by this author of visual hallucinations occurring in a “sane” person. The topic of senile
hallucinations has been extensively reviewed by Gold and Robin (1989).
The hallucinatory phenomena of delirium are nonlocalizable, but sometimes the
evidence points to an origin in the temporal lobe. In ophthalmopathic hallucinations, there
is visual loss from retinal, optic nerve or tract, or occipital lobe lesions, and, with the
latter locations, a slight impairment of mental function as well.
Visual imagery
Visual mental imagery refers to the evocation of visual images in the “mind’s eye”
in the absence of sensation through the retina.
Early studies demonstrated that patients with various types of deficits in higher order
visual functions (e.g., achromatopsia and spatial neglect) tended to show similar deficits
in mental imagery. For example, when asked to imagine walking down a familiar street,
a patient with left hemispatial visual neglect would describe only the buildings on the right
side of the street. When asked to imagine turning around and walking the other direction
up the street, the same patient would describe buildings on the other side of the street that
had previously been neglected (Heilman et al., 1993; Farah, 2001; Tranel, 2001).
Similarly, patients with deficits in color perception due to cerebral lesions have been
shown to have deficits in imaging colors of objects (Temple, 1992; Farah, 2001). So,
visual perceptual deficits in patients can often be demonstrated in some way by similar
deficits in visual imagery.
1467
Visualization is crucial in problem-solving tasks such as mental arithmetic, map

reading, and mechanical reasoning.
Behrmann and colleagues (1992) described a patient, CK. The curious thing about
CK is that, although he cannot recognize objects, he can imagine them and can draw
them in considerable detail from memory. This ability implies some dissociation between
the neural system dealing with object perception and that dealing with the generation of
images. Kolb and Whishaw (2003) conclude that neural structures mediating the
perception and visualization of objects are unlikely to be completely independent, but it
is clear that a deficit in object perception cannot be due simply to a loss of mental
representations (that is, memory) of objects.
Farah (1984, 1990) and Kosslyn and Thompson (2000) proposed that mental rotation
of objects probably entails both hemispheres, with some degree of right-hemisphere
superiority.
Nonetheless, it does seem likely that mental rotation implicates structures related to
the dorsal stream. We can imagine that, before a brain could visualize rotating an object,
it would first have to have actually rotated it manually. This requires the activation of at
least part of the motor cortex – the region needed to actually do it. Farah (1984, 1990)
concluded that, although the data designed to identify the natural events underlying the
generation of a mental image are noisy, a reasonably consistent answer is emerging from
the results of imaging studies.
D’Esposito and colleagues (1997) addressed this question in an fMRI study by
asking subjects to generate mental images from memory, cued by an aurally presented
word such as “tree”. The subjects kept their eyes closed throughout the experiment so
that any neural activation could be attributed to imagery rather than to direct activation
of the visual pathways. The results show that visualizing concrete words increases
activation in the left posterior temporo-occipital region corresponding to the fusiform
gyrus (area 37). There was no activation in area V1, the fMRI data are consistent to those
of other imaging studies, as well as to a case history of a patient with a left-occipital
lobectomy (including area 37) who had hemianopia in both real and imagined stimuli.
The pronounced asymmetry is consistent with Farah’s hypothesis that, in most people,
the left hemisphere is specialized for image generation.
Mental imagery appears to be a top-down activation of a subset of the brain’s visual
areas. In other words, at least some cortical areas are used both for perception and for
visualization.
These common areas carry the same representational functions for both purposes,
carrying information specifically about color, shape, spatial location, and so on. There is
evidence for a distinct mechanism for image generation as well, one separates from the
processes needed for perception. Farah notes that the evidence, although mixed, points
to a region in the left temporo-occipital region as the key location for this mechanism.
Anyhow, the neural underpinnings of deficits in visual imagery have been located
primarily in visual association cortex (areas 8 and 19) and more anterior association
cortices. However, data from functional MRI studies suggest that primary visual cortex
1468
18. Occipital lobe
(area 17) may be more actively involved in mental imagery than there had previously
been suspected.
Summary
Lesions in the primary visual area
A unilateral lesion in the primary visual area (Brodmann’s area 17) results in
blindness of the contralateral visual field, referred to as a contralateral homonymous
hemianopsia. If distruction of the primary visual cortex is the result of a vascular lesion,
macular sparing may occurs, that is, central vision is unaffected.
It is believed that this due to the presence of collateral anastomotic channels between
the middle and posterior cerebral arteries.
A bilateral lesion in the primary visual area results in complete blindness, also
referred to as cortical blindness.
The usual cause of cortical blindness occlusion of the posterior cerebral arteries
(embolic and thrombotic). A transitory form of cortical blindness may occur with head
injury, migraine, or the antiphospholipid antibody syndrome of lupus erythematous, and
as a consequence of intravascular dye injection and administration of a number of drugs
such as interferon-alpha or cyclosporine.
Lesions in the association with visual areas

A lesion in the association with visual areas (Brodmann’s areas 18 and 19) (usually,
bilaterally) results in visual agnosia. Since the visual pathways and primary visual cortex
are intact, the individual is able to “see” an object or person. However, although he may
be locking at a familiar object or person, he is unable to identify them, or describe the
function of it.
Selective disorders of form discrimination (including depth perception and the
integration of features into a whole) as well as disorders affecting the surface properties
of objects (such as their texture or color) have been documented.
An individual with visual agnosia may recognize an object one day but not the next.
Also, he may recognize certain familiar objects but not others. Interestingly, an object
may be identified by other senses, such as touch.
Dyslexia is a type of visual agnosia. Four patterns of dyslexia have been recognized:
letter-by-letter, deep, phonological, and surface dyslexia.
Letter-by-letter dyslexia is equivalent to pure alexia without agraphia. Deep dyslexia
is a severe reading disorder in which patients recognize and read aloud only familiar
words, especially concrete, imageable nouns and verbs. Phenological dyslexia is similar
to deep dyslexia, with poor reading of nonwords, but single nouns and verbs are read in
a nearly normal fashion and semantic errors are rare. The fourth type, surface dyslexia,
involves spared ability to read laboriously by grapheme-phoneme conversion but inability
to recognize words at a glance.
Individuals with dyslexia are unable to read and write words, although they can see
and recognize letters.
1469
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WHITE MATTER
OF CEREBRAL HEMISPHERE
The central nervous system (CNS) is composed of white and gray matter.
White matter consists mostly of nerve cell axons, whereas gray matter consists
mostly of nerve cell bodies.
Gray matter is arranged into nuclei or cortex. The cerebral cortex consists of 50-
100 billion nerve cell bodies arranged into a three to six layered sheet that laminates the
brain surface.
All information entering (afferent fibres) or leaving the cerebral cortex (efferent
fibres) or connecting one part of the cortex with another must pass through the subcortical
white matter. Thus, the cerebral cortex receives the following afferent (input) fibres:
corticocortical (association and commissural) excitatory fibres (which release glutamate
or aspartate) from ipsilateral and contralateral areas, thalamocortical excitatory fibres
from thalamus nuclei, cholinergic excitatory fibres from the basal forebrain nuclei,
noradrenergic inhibitory fibres from the brain stem locus ceruleus, and serotonergic
inhibitory fibres from the brain stem raphe nuclei (Patestas and Gartner, 2008). Cortical
efferent fibres arise from the output neurons of the cerebral cortex: the pyramidal and
fusiform cells. Their myelinated axons course deep, pass into the subcortical white matter,
and then are distributed to widespread regions of the CNS.
The central core white matter of the cerebral hemispheres is composed of myelinated
nerve fibres of varied sizes and their supporting neuroglia. These nerve fibres which make
up the white matter of the cerebral hemispheres are either association fibres which link
different cortical areas in the same hemisphere; commissural fibres, which link
corresponding cortical areas in the two hemispheres; or projection fibres, which connect
the cerebral cortex with the corpus striatum, diencephalon, brain stem and the spinal cord.
Association fibres
The association fibres interconnect various areas of the cortex within the same
hemisphere. Association fibres also known as arcuate fibres are axons of small pyramidal
cells and fusiform neurons primarily from cortical layers II and III. Association fibres that
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19. White matter of cerebral hemisphere
connect various cortical areas make up most of subcortical white matter. These fibres gather
to form fasciculi that connect different lobes, but like a two-way highway, fibres merge into
and exit these fasciculi all along their course. These arcuate fibres restricted to a single
hemisphere are subdivided into two major categories, short and long fibres (Fig. 19.1).
The short arcuate fibres connect adjacent gyri (U-shaped fibres). These fibres leave
the cortex of one gyrus, enter the underlying white matter, and then loop around the pit
of a sulcus and project into the cortex of an adjacent gyrus. Thus, many pass subcortically
between adjacent gyri, some merely pass from one wall of sulcus to the other, and most
of them are confined to cortical gray matter.
The long arcuate fibres which connect distant nonadjacent gyri, and different lobes
of the same hemisphere consist of the following fibre tracts; the uncinate fasciculus,
cingulum, superior longitudinal fasciculus, inferior longitudinal fasciculus, and the
superior and inferior fronto-occipital fasciculus.
The fibres follow a sharply curved course across the stem of the lateral sulcus, near
the anteroinferior part of the insula.
The uncinate fasciculus which extends from the anterior temporal to motor speech
(Broca’s) area and orbital gyri, forms fronto-temporal interconnections.
The cingulum which extends from medial cortex below the rostrum to
parahippocampal gyrus and parts of the temporal lobe is located internal to the cingulate
gyrus continuing into the parahippocampal gyrus. The cingulum is a prominent
association bundle in the cingulate gyrus. This bundle of long and short association fibres
carries impulses to and from the parahippocampal gyrus.
Fig. 19.1. The organization of the principal association fibres projected upon a sagittal section of the left cerebral
hemisphere. (after Crossman, 2008).
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The superior longitudinal fasciculus extends from anterior frontal lobe to occipital,
parietal, and temporal lobes and is located in the core of the hemisphere. It is the largest
of long association fasciculi. It starts in the anterior frontal region and arches back, above
the insular area contributing fibres to the occipital cortex (areas 18 and 19). It curves
down and forwards, behind the insular area, to spread out in the temporal lobe.
The superior longitudinal fasciculus contains a group of fibres, the arcuate fasciculus
that forms a distinct arch posterior to the insula. This fasciculus links Broca’s area (the
frontal lobe motor area for speech) with Wernicke’s area (the temporal lobe area for
language comprehension).
The superior fronto-occipital fasciculus (subcalosal bundle) interconnects the
frontal lobe with the occipital lobe.
The fronto-occipital fasciculus starts at the frontal pole. It passes back deep to the
superior longitudinal fasciculus, separated from it by the projection fibres in the corona
radiata. It lies lateral to the caudate nucleus near the central part of the lateral ventricle.
Posteriorly, it fans out into the occipital and temporal lobes, lateral to the posterior and
inferior horns of the lateral ventricle (Crossman, 2008).
The inferior longitudinal fasciculus extends from posterior region of the parietal
and temporal lobes to anterior region of occipital lobe. Its fibres, probably derived mostly
from areas 18 and 19, sweep forward, separated from the posterior horn of the lateral
ventricle by the optic radiation and tapetal commissural fibres, and are distributed
throughout the temporal lobe (Crossman, 2008).
The inferior fronto-occipital fasciculus, which like their superior counterpart also
interconnects the frontal and occipital lobes, radiates in the frontal lobe, passes through
the temporal lobe inferior to the insula, to also radiate in the occipital lobe. Some of its
fibres curve around on the deep aspect of the lateral sulcus, interconnecting the frontal
and temporal lobes, as a result of their hook-like path are referred to as the uncinate
fasciculus (Patestas and Gartner, 2008).
The external capsule is insinuated between the claustrum and putamen, and the
extreme capsule is located between the claustrum and the insular cortex (Haines and
Mihailoff, 2006).
Projection fibres
Projection fibres include ascending fibres from lower centers to the neocortex, such
as projections from the thalamus, and descending fibres from the neocortex to the brain
stem and spinal cord.
Projection fibres are restricted to a single hemisphere and connect the cerebral cortex
with lower levels, namely the corpus striatum, diencephalon, brain stem, and spinal cord.
The majority of these fibres are axons of pyramidal cells and fusiform neurons.
These fibres are component part of the internal capsule, which is subdivided into
the anterior limb (Fig. 19.2), genu (Fig. 19.3), posterior limb (Fig. 19.4), restrolentiform,
and sublentiform regions. The projection fibres may be subdivided into corticopetal and
corticofugal fibres.
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Fig. 19.2. A coronal section of

the rostral part of the human
cerebral hemispheres at the
level of the anterior limb of the
internal capsule where it
separates the caudate nucleus
from the putamen (after
Augustine, 2008).

the human cerebral
hemispheres at the level of
genu of the internal capsule
(after Augustine, 2008).

the human cerebral
hemispheres at the level of the
posterior limb of the internal
capsule. The cortical origin and
partial course of the projection
fibres that form the internal
capsule are illustrated
including fibres of the corona
radiata (after Augustine, 2008).
Corticopetal fibres are afferent fibres that bring information from the thalamus to
the cerebral cortex. They consist of thalamocortical fibres.
Thus corticopetal fibres include: (1) thalamocortical fibres arising from the VPL,
VPM, ventral lateral (VL), and ventral anterior (VA) nuclei of the thalamus relaying
sensory information such as touch, pressure, conscious proprioception, two-point tactile
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sensation, as well as pain and temperature sensation from the body and head to the sensory
cortex; (2) the MGN (medial geniculate nuclei) of the thalamus relaying auditory
information via the auditory radiation to the auditory cortex; and (3) the LGN (lateral
geniculate nuclei) of the thalamus relaying visual information via the optic radiation to
the visual cortex. Although these afferent fibres terminate in layers I-IV of the cerebral
cortex, most terminate in layers IV. The cholinergic and serotonergic afferents of the
cerebral cortex function in the control of the sleep and arousal.
Corticofugal fibres are efferent fibres that transmit information from the cerebral
cortex to lower centers of the brain and spinal cord.
These fibres consist of axons arising from large pyramidal cells that course in the
corona radiata and internal capsule to terminate in the basal ganglia, the brain stem, and
the spinal cord.
Corticofugal fibres consist of the corticothalamic, corticoreticular, corticorubral,
corticotegmental, corticopontine, corticobulbar and corticospinal tracts.
Commissural fibres
The commissural fibres ensure the anatomical and functional connections of the two
cerebral hemispheres. Therefore, it is possible to coordinate their integrative-reflex
actions.
Commissural fibres arise in one cerebral hemisphere and cross the midline to
terminate in the corresponding cortical area of the contralateral hemisphere. These fibres
provide an avenue of communication between corresponding cortical areas of the two
hemispheres which is essential in the integration of information in the two sides of the
brain. Commissural fibres consist of the myelinated axons of medium-sized pyramidal
neurons residing in various layers of the cerebral cortex. Cortical commissural fibres
emerge mainly from the pyramidal cells residing in the cortical superficial layers and the
external granular (layer II) and external pyramidal (layer III) layers.
In the adult brain there are four major hemispheric commissures: the anterior
commissure, the posterior commissures that bridge the temporal lobes, the hippocampal
commissure (commissure of the fornix) connecting hippocampal formation of two
hemispheres, and the corpus callosum.
Anterior commissure
The anterior commissure is a compact bundle of myelinated nerve fibres located
caudal to the rostrum of the corpus callosum but rostral to the main part of the fornix.
Here it is embedded in the lamina terminalis where it is part of the anterior wall of the
third ventricle (Fig. 19.5).
In sagittal suction it is oval. Its long (vertical) diameter is approximately 1.5 mm.
Laterally it splits into anterior and posterior bundles. The smaller anterior bundle curves
forwards on each side to the anterior perforated substance and olfactory tract. The
posterior bundle curves posterolaterally on each side in a deep grove on the anteroinferior
aspect of the lentiform complex, and subsequently fans out into the anterior part of the
1484
Fig. 19.5. A coronal section

of the human cerebral
hemispheres, at the level of
the anterior commissure.
Some commissural fibres
that form the corpus
callosum and the anterior
commissure are illustrated
(after Augustine, 2008).
temporal lobe, including the parahippocampal gyrus (Crossman, 2008). It connects the
right and left amygdala, the olfactory bulb and anterior olfactory nucleus, the anterior
perforated substance, olfactory tubercle and diagonal band of Broca; the prepyriform
cortex; the entorhinal area and adjacent parts of the parahippocampal gyrus; part of the
amygdoid complex (especially the nucleus of the lateral olfactory stria); the bed nucleus
of the stria terminalis and the nucleus accumbens; the anterior regions of the middle and
inferior temporal gyri.
Thus, anterior commissure is a relatively small one in the basal forebrain lying above
the optic chiasma and anterior to the main columns of the fornix that connects
homologous areas of the middle and inferior temporal gyri, including parts of the
olfactory cortices (Mendoza, 2011).
Posterior commissure
The posterior commissure which is of unknown constitution in man is a small
fasciculus that crosses the midline at the base of the pineal gland and just posterior
(dorsal) to the cerebral aqueduct.
Various small nuclei are associated with it. Among these are the interstitial nuclei
of the posterior commissure, the nucleus of Darkschewitscz in the periaqueductal grey
matter, and the interstitial nucleus of Cajal near the upper end of the oculomotor complex,
closely linked with the medial longitudinal fasciculus. Fibres from all these nuclei and
the fasciculus cross in the posterior commissure. It also contains fibres from thalamic
and pretectal nuclei and the superior colliculi, together with fibres that connect the tectal
and habenular nuclei. The destinations and functions of many of these fibres are obscure
(Crossman, 2008).
Thus, the posterior commissure connects the right and left pretectal region and
related cells group of the mesencephalon.
1485
The habenular commissure which is a small fascicle running along the upper aspect
of the posterior commissure, interconnected the habenular nuclei. However, the pretectal
area and pretectal nuclei are parts of the epithalamus, that are three fibre bundles: the
posterior commissure, habenular commissure, and the habenulo-interpeduncular tract.
Hippocampal commissure
The hippocampal commissure (commissure of the fornix) is formed by fibres that
originate in the hippocampal formation and cross the midline as a thin layer inferior to
the splenium of the corpus callosum. Thus, this commissure joins the right and left
hippocampi to one another.
Corpus callosum
The corpus callosum is the most massive commissure in the entire nervous system.
It is the largest axonal tract of the adult brain that provides symmetrical connections
between the two hemispheres. It provides a bridge for the passing of information from
one cerebral hemisphere to the other by 200-300 million myelinated and unmyelinated
axons (Dupree, 2011).
Although the corpus callosum is the largest white matter tract of the brain, it is not
essential for life.
The corpus callosum begins development around the 11th week of gestation and
continues through adolescence. Initially, the corpus callosum is composed of astrocytic
processes which serve as conduits for growing axons extending to the contralateral
hemisphere (Paul et al., 2007).
Corpus callosum is composed of four parts: the rostrum, the genu, the body (also
known as the trunk), and the splenium. Each portion of the corpus callosum is responsible
for connecting symmetrical regions of the two hemispheres, with the rostrum and genu
connecting portions of the prefrontal and premotor cortices, the body interconnecting the
premotor, motor, supplementary motor, and the posterior parietal cortices, while the
splenium connects portions of the temporal, occipital, and parietal lobes.
Internal capsule and corona radiata

Projection fibres are organized into a large, compact bundle called the internal
capsule, which has intimate structural associations with the diencephalon and basal
ganglia. In an axial plane through the hemisphere, the internal capsule appears as a
prominent “V”-shaped structure with the “V” pointing mediatelly (Fig. 19.6).
Thus, the internal capsule is a massive, fan-shaped collection of fibres (white matter)
that connect the thalamus to the cerebral cortex, and another which descends to the lower
portion of the brain stem and the spinal cord.
Fibres which reciprocally connect the thalamus and the cortex constitute the
thalamic radiation. These thalamocortical and corticothalamic fibres form a continuous
fan that emerges along the whole lateral extent of the caudate nucleus. Fibre bundles
radiating forward, backward, upward, and downward form large portions of various parts
of the internal capsule.
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Fig. 19.6. Schematic diagram of the right internal capsule as seen in a horizontal section (after Carpenter, 1979).
Although the radiations connect with practically all parts of the cortex, the richness
of connections varies considerably for specific cortical areas. Most abundant are the
projections of the frontal granular cortex, the precentral and postcentral gyri, the calcarine
area and the gyrus of Heschl. The posterior parietal region and adjacent portions of the
temporal lobe also have rich thalamic connections, but relatively scanty radiations go to
other cortical areas (Walker, 1938).
The thalamic radiation are grouped into four subradiations designated as the thalamic
peduncles.
The anterior or frontal peduncle connects the frontal lobe with the medial and
anterior thalamic nuclei.
The superior or centroparietal peduncle connects the Rolandic area and adjacent
portion of the frontal and parietal lobes with the ventral tier thalamic nuclei. The fibres,
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carrying general sensory impulses from the body and head, form part of this radiation
and terminate in the postcentral gyrus.
The posterior or occipital peduncle connects the occipital and posterior parietal
convolutions with the caudal portions of the thalamus. It included the optic radiations
(geniculocalcarine) from the lateral geniculate body to the calcarine cortex (striate area).
The inferior or temporal peduncle is small and includes the scanty connections of
the thalamus with the temporal lobe and the insula. Includes in this are the auditory
radiations (geniculotemporal) from the medial geniculate body to the transverse temporal
gyrus of Heschl (Carpenter, 1979).
Thalamocortical and corticofugal fibres within the internal capsule occupy a
comparatively small, compact area.
The cerebral hemisphere is connected with the brain stem and spinal cord by the
extensive projection system of the internal capsule. Thus, descending motor fibres arising
from the motor cortex destined for the brain stem and the spinal cord also descend in the
internal capsule.
Fibres of the internal capsule flare out into the hemisphere as they pass distal to the
caudate and putamen. This abrupt divergence of internal capsule fibres forms the corona
radiata (“radiating crown”), which contains converging corticofugal fibres, as well as
diverging corticopetal fibres (Haines, 2006). Thus, fibres arise from the whole extent of
the cortex, enter the while substance of the hemisphere and appear as a radiating mass of
fibres, the corona radiata, which converges toward the brain stem (Fig. 19.7). On
reaching the latter they form a broad compact fibre band, the internal capsule, flanked
medially by the thalamus and caudate nucleus and the lateral by the lenticular nucleus.
Thus, the internal capsule is composed of all the fibres, afferent and efferent, which
go to, come from, the cerebral cortex. A large part of the capsule is obviously composed
of the thalamic radiation described above. The rest is composed mainly of corticofugal
fibre systems (efferent cortical fibres) which descend to the lower portion of the brain
stem and the spinal cord.
In an axial plane through the hemisphere the internal capsule can be divided into an
anterior limb, a genu (L “knee”) and a posterior limb. The two limbs converge toward
the genu, the angle between the anterior and posterior limb.
The anterior limb is interposed between the head of the caudate nucleus and the
lenticular nucleus. This anterior limb contains the anterior thalamic radiation (thalamocortical
/ corticothalamic fibres) or peduncle, and the prefrontal corticopontine tract.
These frontopontine fibres, which arise from the cortex in the frontal lobe, synapse with
cells of the pontine nuclei. Axons of these cells enter the opposite cerebellar hemisphere
through the middle cerebellar peduncle. Anterior thalamic radiations interconnect the medial
and anterior thalamic nuclei and limbic structures with the frontal cortex.
The genu, located at the intersection of the anterior and posterior limbs, is situated
approximately at the level of the interventricular foramen. The genu abuts the third ventricle
medially and the globus pallidus forms its lateral border. The genu of internal capsule
contains corticonuclear (corticobulbar) fibres that arise in the frontal cortex just rostral to
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precentral sulcus (area 4), form the precentral gyrus (primary motor cortex) and terminate
mostly in the contralateral motor nuclei of cranial nerves. Anterior fibres of the superior
thalamic radiation, between the thalamus and cortex, also extend into the genu.
Lesions of these fibres give rise to motor deficits of cranial nerves, most notably
deficits related to the facial and hypoglossal nerves (Haines, 2006).
The posterior limb of the internal capsule is larger, more complex and includes the
corticospinal tract. The fibres concerned with the upper limb are anterior. More posterior
regions contain fibres representing the trunk and lower limbs.
Other descending axons include frontopontine fibres, particularly from areas 4 and
6 and corticorubral fibres, which connect the frontal lobe to the red nucleus. Most of the
posterior limb also contains fibres of the superior thalamic radiation (the somaesthetic
radiation) ascending to the postcentral gyrus (Crossman, 2008).
This posterior limb is divided into a thalamolenticular part (which lies between
the lenticular nucleus and the dorsal thalamus), a sublenticular part (fibres passing
ventral to the lenticular nucleus) and a retrolenticular part (fibres extend caudally for
a short distance behind the lenticular nucleus). In this caudal region a number of fibres
passing beneath the lenticular nucleus to reach the temporal lobe collectively form the
sublenticular portion of internal capsule.
Fig. 19.7. Diagram of the blood supply of the internal capsule and corpus striatum. The putamen and globus pallidus
are shown rotated ventrally away from their normal position adjacent to the internal capsule. Regions supplied by
branches of the middle and anterior cerebral arteries are shown in black and portions of the internal capsule
and corpus striatum supplied by the anterior choroidal artery. Direct branches of the internal carotid artery supply
the genu of internal capsule (Alexander, 1942).
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However, contemporary terminology and common usage refer to the “thalamo-

lenticular part” as the posterior limb, and the “sublenticular part” as the sublenticular
limb. By this scheme the internal capsule consists of five parts: an anterior limb, genu,
posterior limb, sublenticular limb, and retrolenticular limb (Haines, 2006).
Thus, the posterior limb of the internal capsule contains: (1) corticospinal fibres, (2)
frontopontine fibres, (3) the superior thalamic radiation, and (4) a relatively smaller
number of corticotectal, corticorubral and corticoreticular fibres. Corticospinal fibres are
organized in a specific manner so that those closest to the genu are concerned with
cervical portions of the body, while succeeding, more caudal regions are related to the
upper extremity, trunk and lower extremity, respectively.
Fibres of superior thalamic radiation, located caudal to the corticospinal fibres,
project impulses concerned with general somatic sense to the postcentral gyrus
(Carpenter, 1979).
The retrolenticular portion of the posterior limb contains the posterior thalamic
radiations and the optic radiation and interconnections between the occipital and parietal
lobes and caudal parts of the thalamus, especially the pulvinar. These include the optic
radiation, parietal and occipital corticopontine fibres and fibres from the occipital cortex,
to the superior colliculi and pretectal region.
Visual input from the lateral geniculate body to the occipital cortex is conveyed via
geniculocalcarine radiation (optic radiations) through the retrolenticular limb. Optic
radiations form a distinct lamina of fibres immediately lateral to the tapetum as they
course caudally into the occipital lobe. It sweeps backwards, intimately related to the
superolateral aspect of the inferior horn and the lateral aspect of the posterior horn of the
lateral ventricle, from which it is separated by the tapetum.
The sublenticular part of the internal capsule contains temporopontine and some
parietopontine fibres, the auditory radiation from the medial geniculate body to the
superior temporal and transverse temporal gyri (areas 41 and 42), and a few fibres that
connect the thalamus with the temporal lobe and insula. Fibres of the auditory radiation
sweep anterolaterally below and behind the lentiform complex to reach the cortex.
Thus, geniculotemporal radiation (auditory radiations) convey auditory information
from the medial geniculate nucleus to the transverse temporal gyri through the
sublenticular limbs.
Vascular supply. The anterior limb of the internal capsule is supplied by the anterior
cerebral artery, and anterior choroidal artery.
The posterior limb is supplied by penetrating branches of the middle cerebral artery
(De Piero, 2011) (Fig. 19.8).
Function. Descending fibres of the corticobulbar and corticospinal tracts travel
through the internal capsule. Corticobulbar fibres, controlling facial musculature, larynx,
and tongue, are located in the genu. Posterior to the genu there are corticospinal tracts
controlling arm, followed by leg. The most posterior part of the internal capsule contains
ascending axons of the spinothalamic tract, carrying sensory input from the body to the
thalamus.
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Fig. 19.8. Diagrammatic

representation of the
arterial supply of the
corpus striatum and
thalamus
(modified from Aitken,
1909).
The anterior limb of the internal capsule contains axons to and from frontal
association cortex (Martin, 2003; Fix, 2008; De Piero, 2011).
Pathology. The posterior limb of the internal capsule is a frequent site for lacunar
strokes. The most common syndrome is that of pure motor hemiplegia. The lenticulo-
striate arteries, penetrating branches of the middle cerebral artery, are frequently damaged
by hypertension, diabetes, and aging, and can be occluded, causing strokes.
Less commonly small aneurysms (Charcot-Bouchard aneurysms) may develop, and
cause intracerebral hemorrhage, sometimes referred to as intraparenchymal hemorrhage
(De Piero, 2011).
Thrombosis or hemorrhage of the anterior choroidal, striate or capsular branches of
the middle cerebral arteries are responsible for most injuries to the internal capsule.
Vascular lesions in the posterior limb of the internal capsule may result in
contralateral hemianesthesia of the head, trunk, and limbs due to injury of thalamocortical
fibres en route to the sensory cortex. There is also a contralateral hemiplegia due to injury
of the corticospinal tract (Aitken, 1909; Alexander, 1942).
If the genu of the internal capsule is involved in the injury, corticobulbar fibres are
also destroyed. Lesions in the posterior third of the posterior limb may include the optic
and auditory radiations.
In such instances there may be a contralateral triad consisting of hemianesthesia,
hemianopsia and hemihypoacusia. More extensive vascular lesions may include the
thalamus or corpus striatum, so that affective changes and symptoms due to injury of the
basal ganglia may be added to those characteristic of injury to the internal capsule
(Alexander, 1942; Dănăilă and Păiş, 1988, 2004). Thus, lesions in this area produce more
widespread disability than lesions in any other region of the nervous system.
Lesions in cerebral white matter sever connections between lower and higher centers
or between cortical areas. White matter lesions are found in many dementing disorders
and appear to be specifically associated with attentional impairments (Junkué et al., 1990;
Filley, 2001).
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REFERENCES
Aitken HF, A report on the circulation of the lobar ganglia: made to Dr. James B. Ayer. Boston
Med Surg J Suppl 160; 25, 1909.
Alexander L, The vascular supply of the striopallidum. A Res Nerv & Ment Dis Proc 21; 77-132,
1942.
Augustine JR, Human Neuroanatomy. An Introduction. Academic Press, Amsterdam, Boston,
Heidelberg etc.; 316-318, 2008.
Carpenter MB, Human Neuroanatomy. Seventh Edition. The Williams and Wilkins Company,
Baltimore; 162-165, 1979.
Crossman AR, Basal ganglia. In: S Standring (ed.), Gray’s Anatomy. Fortieth Edition. Churchill
Livingstone, Elsevier; 354-359, 2008.
Dănăilă L, Păiş V, Ateroscleroza cerebrală din sistemul carotidian, ed. Ştiintifică şi enciclopedică,
Bucureşti, 1988.
Dănăilă L, Păiş V, Ateroscleroza cerebrală ischemică. editura: editura Medicala, Bucureşti, 2004.
De Piero TJ, Internal Capsule. In: JS Kreutzer, J De Luca, B Caplan (eds) Encyclopedia of Clinical
Neuropsychology. Vol. 2, Springer, New York, Dordrecht, Heidelberg, London; 1343, 2011.
Dupree J, Corpus Callosum. In: JS Kreutzer, J De Luca, B Caplan (eds.), Encyclopedia of Clinical
Neuropsychology. Vol. 1, Springer , New York, Dordrecht, Heidelberg, London; 709, 2011.
Filley CM, The Behavioural Neurology of White Matter. Oxford: Oxford University Press, 2001.
Fix JD, Neuroanatomy (3rd ed.), Baltimore, MD: Lippincott, Williams and Wilkins, 2008.
Haines DE, Fundamental neuroscience for basic and clinical applications. 3rd ed, Philadelphia,
PA: Churchill Livingstone, Elsevier; 2006.
Haines DE, Mihailoff GA, The telencephalon. In: DE Haines (ed.), Fundamental neuroscience
for basic and clinical applications. Philadelphia. Churchill-Livingstone-Elsevir; 244-259,
2006.
Junqué, C, Pujol, J, Vendrell P, et al., Leuko-araiosis on magnetic resonance imaging and speed
of mental processing. Arch Neurol 47; 151-156, 1990.
Mendoza JE, Anterior Commissure. In: JS Kreutzer, J De Luca, B Caplan (eds) Encyclopedia of
Clinical Neuropsychology. Vol. 1, Springer, New York, Dordrecht, Heidelberg, London;
187, 2011.
Martin J, Neuroanatomy: Text and atlas (3rd ed). New York, Mc Graw-Hill, 2003.
Patestas AM, Gartner LP, A Textbook of Neuroanatomy. Blackwell Publishing, USA, 2009.
Paul LK, Brown WS, Adolphs R, et al., Agenesis of the corpus callosum: genetic, developmental
and functional aspects of connectivity. Nature Review Neuroscience 8; 287-299, 2007.
Walker AE, The thalamus of chimpanzee. IV. Thalamic projection of the cerebral cortex. J Anat
73; 37-93, 1938.
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CORPUS CALLOSUM
Anatomy of the corpus callosum

The midline longitudinal cerebral fissure, occupied in life by the falx cerebri,
incompletely separates the two cerebral hemispheres from one another.
The link between the hemispheres is provided by the corpus callosum. This large
arch of white matter constitutes the floor of the cerebral fissure.
The corpus callosum is the largest fibre tract in the brain, and it contains over 200
million axons originating from layers 2 and 3 of both hemispheres (Aboitiz et al., 1992).
The corpus callosum (from the Latin callus, meaning “hard body“) is the largest
structure on the medial surface of each hemisphere.
This enormous bundle of myelinated fibres forms an anatomical and functional
connection between the right and left hemispheres.
The corpus callosum links mainly corresponding areas of the neocortex of the two
cerebral hemispheres. It, however, also contains commissural fibres that arise in certain
cortical areas of one cerebral hemisphere and cross to the opposite side to terminate in
noncorresponding areas of the contralateral hemispheres.
This is true for fibres arising in the primary visual cortex of one cerebral hemisphere
that cross to the opposite side to terminate in the visual association cortex of the
contralateral hemisphere.
Similarly, parts of the motor and somesthetic cortical areas where the hand is
represented, do not receive commissural fibres from the corresponding motor and sensory
cortical areas of the contralateral hemisphere.
However, the somesthetic association areas receive commissural fibres that connect
the two cerebral hemispheres, thus each hemisphere samples information available to the
contralateral hemisphere.
While the left and right hemispheres have some different functions, the corpus
callosum has the same 200 million fibres, constantly trafficking back and forth, which
serves to integrate information from both sides.
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The corpus callosum has fibres that project between the hemispheres in an orderly
way, with regions in the anterior portion connecting similar brain areas in the frontal lobes
and regions in the posterior portion connecting similar brain areas in the occipital lobe.
A variety of individual differences in callosal size and pattern are suggested to exist.
For example, Witelson (1986) reported that the corpus callosum is larger in left-handers
than in right-handers and in the women than in the man.
Thus, the size and the shape of the corpus callosum vary greatly from individual to
individual, and there are sex differences in the shape of the callosum. The splenium is
more bulbous shaped in women and has a greater maximum width but it is more tubular
shaped in men. There are age related changes in the corpus callosum during childhood
and adulthood. In some cases, the corpus callosum is lacking, a condition termed agenesis
of the corpus callosum.
The corpus callosum originates from the area of the lamina terminalis as a structure
initially composed of astrocytic processes. Axons from developing neurons in each
hemisphere traverse this glial structure across to the contralateral side. As this takes place
the corpus callosum enlarges in a caudal direction to form the prominent structure found
in adults.
The corpus callosum is located superior to the diencephalon and forms the roof of
much of the lateral ventricles, and the floor of the longitudinal fissure.
Its antero-posterior length is of 96 mm in men and 98 in women when measured
through by projecting the farthest anterior and posterior points on a horizontal line (Velut
et al., 1998). The anterior end is located 4 cm away from the frontal pole, and the posterior
end is found at 6 cm from the occipital pole. However, the corpus callosum is organised
with a great deal of regularity (Brodal, 1981; Colonier, 1986; Witelson, 1995; Clarke et
al., 1998)
This huge bundle of commissural fibres, the corpus callosum, consists, from rostral
to caudal, of five segments: the anteriormost region, the rostrum, the curved genu, the
relatively flattened body (also called the trunk) forming the roof of the lateral ventricle,
the isthmus, and its posteriormost region, the splenium (Fig. 20.1).
Fig. 20.1. The aspect of corpus callosum

on a sagital section: 1. Rostrum; 2. The
genu of the corpus callosum; 3. The line
that separates the genu from the body
(trunk); 4. Trunk (body) of the corpus
callosum; 5. The line that unites the point
located 5 cm anterior from the central
sulcus with the superior margin of
intraventricular foramen; 6. The isthmus of
corpus callosum; 7. Splenium; 8. Fornix;
9. Anterior commisure.
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20. Corpus callosum
The rostrum represents the most anterior part and it forms a curve downwards. It
continues towards the posterior with a lamina of white matter of various widths. This
horizontal lamina descends in a beak-like shape that reaches the superior margin of the
white anterior commissure.
The peaked posterior extremity of the rostrum is located between the subcallous area
downward and the septum pellucidum upwards. Consequently, the posterior elongation of
this white lamina separated, from the subcallous area by the posterior paraolfactory sulcus,
locates itself above the paraterminal gyrus which covers the septal nuclei (Velut et al., 1998).
The genu of the corpus callosum which presents a significant anterior convexity is
situated anterior to the rostrum. Thus, the anterior extent of the corpus callosum, known
as the genu, bends inferiorly and turns posteriorly where it forms a slender connection,
the rostrum, with the anterior commissure.
Inferior to the genu and rostrum is the subcallosal area – a collective term including
the subcallosal gyrus and, inferior to it, the septal area. The term, rhinencephalon (Greek,
nose brain) refers to cerebral structures related to olfaction, particularly in lower animals.
In humans, this area of the brain consists of many structures on the medial and inferior
surfaces of each cerebral hemisphere.
One, the anterior perforated substance, is posterior to the olfactory trigone and best
visualised on the inferior surface of the brain.
Another, the subcallosal area, is on the medial surface of each cerebral hemisphere
inferior to the genu and rostrum of the corpus callosum. It includes a dorsally located
subcallosal gyrus and a ventrally located septal area. As the cingulate gyrus turns into
the subcallosal area, it is continued with the subcallosal gyrus that is inferior to the
rostrum of the corpus callosum.
The virtual separation of the genu from the rostrum and body consists of a vertical
line that crosses through the most posterior area of the genu. The genu is located between
the septum pellucidum, which is inserted in a posterior medial line and the gyrus cinguli
which is located anteriorly.
The insertion of the septum pellucidum is frequently doubled (in 83% of cases
according to Winkler et al., 1997) resulting in a double septum and septal cavity (Fig. 20.2).
The septum pellucidum is bilaminar with a potential space between its layers (cavum
septi pellucidi) that is normally absent at birth but may remain open as a median cleft.
There is an enormous variability in the reported incidence of cavum septi pellucidi (from
2% to 71.5%).
Enlargement of the cavum, though rare in healthy individuals, has been reported in
patients with schizophrenia (Augustine, 2008).
Many of the fibres passing through the rostrum and genu arch rostrally to
interconnect the anterior cortical areas of the frontal lobes; these form the minor (or
frontal) forceps.
The body (trunk) of the corpus callosum is continued behind the genu and consists
of most of the commissural fibres that interconnect the remaining frontal lobe, parietal
lobe, and part of the temporal lobe. Thus, midcallosal areas contain a mixture of fibres
coming from both anterior and posterior regions.
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Fig. 20.2. Diagram of the medial view of a sagital section of the brain.
20. Corpus callosum
Either rectangular or upwards in a convex shape, its larger axis is horizontal or a

little ascending in an antero-posterior direction.
According to Winkler et al. (1997), the average width of the corpus callosum is
6.12 mm but ranges between 4 and 8 mm.
The body is located between the cingular gyrus (from which it is separated by the
callous sulcus), which is located upwards, and the septum pellucidum, downwards. Thus,
throughout its entire length, the convex facet of the corpus callosum is separated from
the cingular gyrus by a deep callous sulcus.
Thus, dorsal to, and following the contours of the corpus callosum, is the cingulate
gyrus that then passes behind the splenium, narrows into the cingulate isthmus, before
becoming continuous with the parahippocampal gyrus. Separating the cingulate gyrus
from the corpus callosum is the sulcus of the corpus callosum. The cingulate gyrus is
continued rostrally with the subcallosal gyrus (the dorsal part of the subcallosal area).
On the superior aspect of the body there are two bundles of fibres which form the
medial and lateral longitudinal striae.
The former is better identified. It passes on each side of the median line and is
adherent to the surface of the corpus callosum.
The lateral longitudinal striae is more difficult to identify because it is located deeper
in the callosum sulcus and is marked through a small shape located between the inferior
facet of the cingular gyrus and the superior facet of the corpus callosum.
Between these two striae, the plane surface of the corpus callosum is covered with
a grey matter lamina called indusium griseum. Anteriorly it passes around the knee and
rostrum in order to reach the paraterminal gyrus. Inferiorly it continues with Broca’s
diagonal band and then with the anterior perforated substance and the periamygdaloid
area. Posteriorly it leaves the surface of the splenium of the corpus callosum. It elongates
through the subsplenial gyrus and then the fasciolar gyrus into the hyppocampal region
between the fimbria upwards and the dentate gyrus downwards. The origin and structure
of the medial and lateral longitudinal striae are uncertain (Duvernoy, 1998). They are
considered to be aberrant fibres of the fornix (the medullar stria blends with the fasciola
cinerea, a posterior extension of the dentate gyrus and the lateral stria blends with the
fasciolar gyrus).
The isthmus of corpus callosum is located in the posterior area of the body.
Anteriorly it is thinner than the body, and posteriorly it is larger, thus its name. According
to Witelson (1989) the anterior limit is given by the vertical line that passes through the
junction between the anterior 2/3 and the posterior 1/3 of the corpus callosum. The
posterior limit is given by another vertical line located between the anterior 4/5 and the
posterior 1/5 of the corpus callosum. According to Velut et al. (1998) the inferior limit
corresponds to the adhesion point of the fornix, and the posterior limit is given by the
vertical line that passes through the anterior facet of the splenium.
The most important particularity of the isthmus is represented by its adhesion to the
superior facet of the fornix body. This adhesion of the corpus callosum to the fornix
creates the risk of sectioning the interhyppocampal commissure of the fornix while
performing a low posterior callosotomy.
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For Winkler et al. (1997) the distance between the M line (the line that unites the
point located 5 cm anterior from the central sulcus with the superior margin of the
interventricular foramen) and the most anterior point of the adhesion of the corpus
callosum to the fornix varies between 10 and 40 mm (the average is 23.79 mm). One
must also take notice of the fact that the antero-posterior length of this adhesion is highly
variable. Its maximum is greater than 10 mm.
Finally, Winkler et al. (1997) highlights the fact that the separation of the corpus
callosum from the fornix is very easy in 77% of cases and difficult or impossible in the
remaining cases. These variations highlight the importance on an MRI scan before every
callosotomy.
The splenium is the region located in the most posterior area of the corpus callosum,
and closes the “callous C“. The fibres interconnecting the occipital lobes, loop through
the splenium of the corpus callosum forming the major (or occipital) forceps. Fibres from
the visual cortex at the posterior pole of the cerebrum occupy the posterior end portion
of the callosum.
The tapetum, which is located in the lateral wall of the atrium and posterior horn of
the lateral ventricle, is also composed of fibre bundles that cross in the splenium and
separate the ventricle from the optic radiation.
Thus, the posterior extent of the corpus callosum, known as the splenium, is bullous
in shape. This portion of the corpus callosum consists of commissural fibres
interconnecting the posterior parietal, posterior temporal and occipital cortices. Lesions
in this area are associated with the well-known neurobehavioral disconnection syndrome
of alexia without agraphia.
Contrary to the rest of the corpus callosum that is hidden between the two
hemispheres, the splenium emerges in the ambient cistern or the superior cerebellar lake
surrounded in its posterior region by the falco-tentorial junction. The splenium forms a
thicker area which is the superior limit of this cistern through its inferior convexity.
The anterior limit is given by the medial pineal body and the lateral pulvinar, and
downwards and forwards there is the mesencephalic tectum. Downwards, the cistern is
limited by the culmen of the vermis, and in its posterior area it is limited by the free
margin of the cerebellar tentorium, which curves upwards and internally in order to bond
with the free margin of the cerebral falx. This falco-tentorial junction forms the original
triangle of the right sinus. At this level the width of the cingular gyrus, which moulds on
the posterior region of the splenium, decreases and forms the isthmus. This isthmus forms
away from the median line and is continued interiorly by the parahippocampal gyrus.
The subsplenial gyrus, which is between the isthmus and the splenium, is continued
with the fasciolar gyrus. Above and ahead of the splenial formation, there is the body of
the fornix which contains in its posterior area the interhyppocampal fibres of its
commissure. It is called the psalterium. In the lateral area, each lateral margin of this
body is continued by the fornix cross which becomes the fimbria that roles around the
pulvinar area.
Then, the fimbria emerges above the fasciolar gyrus and away from the splenium,
which remains above these structures.
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20. Corpus callosum
In sum, in humans, the different regions of the corpus callosum described on the
medial sagittal section are: the rostrum, the genu, the body or the trunk, the isthmus and
the splenium.
Callosal fibres radiating to the frontal lobe (radiations of the corpus callosum) form
the genu from the frontal forceps; those radiating from the splenium in the occipital lobe
form the occipital forceps. Attached to the inferior border of the corpus callosum is the
thin septum pellucidum – a transparent, membranous partition that separates the right
and left cerebral ventricles and forms their medial wall.
The callous fibres

The nervous fibres of the corpus callosum radiate into the white matter of each
hemisphere. Afterwards they disperse into the cerebral cortex. The dissection of the
posterior extremity of the rostrum does not allow the identification of some commissural
fibres, but the white median tissue unites in the posterior with the anterior commissure
(Velut et al., 1998).
In the lateral region, the fibres of the rostrum blend with the lateral fibres of the
anterior commissure. These are located in the posterior area and make a loose curve with
the concavity towards the posterior. The fibres located in the most posterior region of
the rostrum pass in the anterior region below the putamen. Internally there is the
accumbens nucleus which continues the head of the caudate nucleus in its inferior and
lateral area (Nieuwenhuys and Meek, 1990).
The fibres of the genu draw a perfect horseshoe shape with an anterior concavity –
an assembly named the minor forceps. The inferior fibres of this forceps appear above
the gyrus rectus. These are fibres coming from the ventral and median regions of the
prefrontal cortex, which cross through the rostrum and the ventral area of the genu of
the corpus callosum (Pandya and Seltzer, 1986; Habib and Pelletier, 1994).
The fibres which come from the prefrontal dorso-lateral cortex are located in the dorsal
area of the genu of the corpus callosum. The fibres of the genu are arched by the cingular
fibres and have a sagittal direction. These are located below the cortex of the gyrus holding
the same name. These cingular fibres are connected in their posterior area with the septal
nuclei. The fibres of the corpus callosum are arched by the cingular fibres (Fig. 20.3).
Laterally, the callous fibres spread in the white substance, forming a curve with its
concavity located in its superior area. The more they are located towards the dorsal area
of the corpus callosum, the larger the concavity.
They cross the fibres of the corona radiata in the core of this white matter and form,
according to Klingler (1956), an arched line, which Velut et al. (1998) did not find.
Nevertheless, the callous fibres and those of the corona radiata are oriented so that they
crisscross in an oblique angle. This makes it difficult to identify them. The fibres of the
corona radiata condense in the lower internal capsule. The angle in which the callous
fibres and those of the corona radiata connect is located immediately above the body of
the caudate nucleus, and below the subependymal layer it forms the lateral margin of the
body of the lateral ventricle (Velut et al., 1998).
1499
Fig. 20.3. (A) Horizontal schematic representation of the brain showing the fibre connections of the genu and
splenium of the corpus callosum. (B) Coronal schematic representation of the brain showing the fibres of the anterior
comissure and the body of the corpus callosum. (Modified from Young PA and Young PH, 1997.
Basic Clinical Neuroanatomy. Williams and Wilkins, Baltimore).
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20. Corpus callosum
Fig. 20.4. Patterns of commissural connections. (A) The areas shaded show regions of the cortex of a rhesus monkey
that receive projection from the contralateral hemisphere through the corpus callosum.
(B) Regions of the corpus callosum showing zones through which a radioactive label was transported
after injections into specific locations in the cortex (after Pandya and Seltzer, 1986).
The fibres of the anterior half of the callous body connect to the premotor
dorsolateral cortex and the median supplementary motor area. The middle area of the
body connects to the motor area M1, the insula and the anterior cingulate cortex (Pandya
and Seltzer, 1986; Habib and Pelletier, 1994).
More towards its posterior region, the callous areas connect to the somatosensory
areas S1 and S2. The posterior area of the body connects to the associative parietal cortex,
and more towards the posterior it connects to the superior temporal areas (including the
hearing area), the insula and the posterior cingulum. The areas M1, S1 and S2 related to
the foot and hand are not connected. Thus, the motor and sensory areas for distal parts of
the limbs (mainly the hands and feet) lack connections. It could be argued that, because
their essential function is to work independently of one another, connections are not
necessary. Among the areas that do receive interhemispheric connections, the density of
projections is not homogeneous (Fig. 20.4 A) (Pandya and Seltzer, 1986).
Areas of the cortex that represent the midline of the body – such as the central
meridian of the visual fields, auditory fields, and trunk of the body on the somatosensory
and motor cortex – have the densest connections. The functional utility of this
arrangement is that movements of the body or actions in central space require
interhemispheric cooperation.
Thus, the corpus callosum bonds together the representations of the midpoints of
the body and space that are divided by the longitudinal fissure. The corpus callosum
1501
connects identical points in the contralateral hemisphere. One group of projections goes
to areas to which the homotopic areas on the contralateral side project. Another group of
projections has a diffuse terminal distribution. The pattern of connections between the
hemisphere in the rhesus monkey is illustrated in figure 20.4B (Pandya and Seltzer, 1986).
Thus the fibres passing through the body of the corpus callosum are proceeding from
front to back, from the premotor, motor, somatosensory, and posterior parietal cortex.
Many studies proved that the transfer of somato-sensitive information needs to
integrate the trunk of the corpus callosum (Diamond et al., 1977; Bogen, 1987). In
particular, the fibres that pass through the posterior area of the trunk are crucial to
finishing the tasks that need the crisscross location of a tactile stimulus. Geffen et al.
(1985) showed that if the trunk of the corpus callosum is the regular path for the sensitive
information, the splenium can maintain up to 50% of this function.
The fibres of the splenium form a posterior concavity that is larger than the one of
the genu which is called the major forceps (Young and Young, 1997).
Outside and at a distance from the median line, the splenium is arched by the isthmus
of the cingulate gyrus. The fibres from the superior area of the splenium connect to the
inferior temporal cortex and the parahippocampal gyrus. In its anterior area (and the
superior one) the fibres connect to the superior parietal lobules and the juxtastriate region
(Pandya and Seltzer, 1986; Habib and Pelletier, 1994) (Fig. 20.5).
The dissection of the fibres located in the splenium really demonstrates that the
inferior fibres that are located in the splenial area go towards the striate regions and form
the major forceps. Areas 17 are not connected. The more these fibres are located in the
posterior region of the splenium, the closer they are to the median line of the occipital
lobe. So, fibres in the posterior part, or splenium, are from the superior temporal, inferior
temporal, and visual cortex (Pandya and Seltzer, 1986).
The superior splenial fibres go towards the occipito-temporal and temporal regions
(Velut et al., 1998). This location of the special fibres forms the tapetum.
Initially, the fibres are located on the roof of the ventricular atrium. Afterwards they
form into a fan like shape from back to front, and spread in an anterior direction below
the lateral ependymal area of the atrium and the inferior horn of the lateral ventricle.
Thus, the tapetum is located between this ependyma and the optic radiations.
In order to reveal the optic radiations at the level of the roof of the inferior horn in
the lateral ventricle it is necessary to perform the ablation of the fibres located in the
tapetum. Finally, the fibres located mostly towards the anterior area of the anterior
tapetum are next to the tail of the caudate nucleus, which is located above the stria
terminalis. Thus, according to Pandya and Seltzer (1986), most of the primary visual
cortex (area V1) is devoid of interhemispheric connections, except for that part
representing the midline of the visual world, the visual meridian. The lack of such
connections has been explained in functional terms: this cortex represents the visual world
topographically, and there is no need for one half of the representation to be connected
to one other.
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20. Corpus callosum
Fig. 20.5. Functions associated with the dominant and nondominant cerebral hemispheres. (Modified from Noback,
CR et al. (1996), The Human Nervous System, 5th edn. Williams and Willkins, Baltimore).
Klingler’s method allows the dissection of fibres in each of these areas and the
establishment of their connections to the corona radiata and the optic radiations.
Finally each segment of the corpus callosum takes part in forming the walls of the
lateral ventricle.
Despite the size and the large number of commissural fibres, the information
regarding the functional role of the corpus callosum is limited. In humans the total number
of fibres is approximately 200 million. However, there is detailed data missing regarding
1503
the callous connections of many regions. The first investigations have been done in the
visual area. The somatic and sensitive areas are connected to the contralateral ones, but
the right and left areas related to the hand and foot lack commissural callous
connections (Powell, 1981).
It is not well defined if there are callous connections between the visual cortex and
the two hemispheres. They exist only to represent the vertical meridian (or visual area)
of the retina. It can be claimed that the connected cortical areas are in relation with a
medium retinal region which is very narrow and from which the ganglion cells send axons
that spread and send collaterals in the optic tract on both sides. The commissural bonds
are specific because they gather together cortical columnar units in a bilateral function.
The function of the corpus callosum

The description of this structure was made by Galen in the second century BC, but
the hypothesis of its involvement in the functional connection of the two hemispheres
dates from 1543 and belongs to Vesalius. However, in 1739 the corpus callosum was
considered by La Peyronie to be the centre of the soul (Brion and Jedynak, 1975).
During the seventeenth century Schmidt (1676) called attention to the rather striking
phenomenon of loss of reading ability with preservation of the capacity to write as a sequel
to stroke. Many descriptions of the condition which was by then called “pure word
blindness“ and which was often attributed on theoretical grounds to the destruction or
dysfunction of a “reading centre” in the angular gyrus appeared during the 1870’s and
1880’s (Benton, 2000). No clinicopathologic correlations were made, however, until 1892,
when Déjérine published his famous post-mortem study of a case of pure alexia following
a stroke. His patient, an educated man and an accomplished musician, suddenly lost the
ability to read musical scores as well as conventional written material. He had a right visual
field defect – in all probability a hemiachromatopsia, not a hemianopsia (Damasio, 1983).
The autopsy study disclosed infarctions in the territory of the left posterior cerebral artery,
specifically, the medial occipital area and the splenium of the corpus callosum. Déjérine
inferred that the lesions had the effect of preventing the transmission of visual information
to the language centres of the left hemisphere, thus making reading impossible while leaving
the interpretation of nonverbal visual stimuli intact. Déjérine claimed that the lesion of the
splenium led to a disconnection of the speech areas located in the left hemisphere, from the
intact cortical areas in the right hemisphere, therefore the impossibility of the patient to
decode the verbal visual stimuli (Brion and Jedynak, 1975).
His concept of pure word blindness as a disconnection symptom, and not as a result
of destruction of a “reading centre“, was validated by later investigators. This theory was
later confirmed by Trescher and Ford (1937), Maspes (1948), Geschwind (1965).
Thus, most of our knowledge related to the callous function comes from studying
adult subjects which suffered spontaneous or surgical lesions of the corpus callosum.
Although the corpus callosum is the largest of the interhemispheric commissures,
relatively little has been known of its functions until recently. According to Carpenter
(1979), the first convincing evidence regarding its function was the demonstration of its
importance in interhemispheric transfer of visual discrimination learning in cats with a
longitudinal section of the optic chiasma (Fig. 20.6) (Meyers, 1956).
1504
20. Corpus callosum
Fig. 20.6. A top view of the two hemispheres. Schematic drawing of the two halves of the cerebral cortex,
showing some major functions of the right and left hemispheres. Note the massive bridge of the corpus callosum
connecting the two sides. The eyes on top focus on converging lines in order to enable stereoscopic depth
perception. (Standring, 2005).
Following the section of the optic chiasma and corpus callosum, cats trained with one
eye masked were unable to remember simple visual discriminations learned with the first eye.
The untrained eye could be trained to make reverse-type discrimination without
interfering with the patterned discrimination learned on the opposite side. This functional
independence of the surgically separated cerebral hemispheres with respect to learning,
memory and other gnostic activities has been the stimulus for considerable investigations
(Mountcastle, 1962).
Thus, interhemispheric connections function to allow each hemisphere to work as a
coordinated unit.
Callosal disconnections of either inter- or intrahemispheric connections can produce
a variety of neurological syndromes including apraxia, aphasia, agnosia, alexia, and
unilateral agraphia.
The most systematic investigation of hemispheric specialisation and hemispheric
integration in cases of callosal disconnection has been carried out with patients who have
undergone callosotomy in order to control their intractable epilepsy.
1505
These so-called split-brain patients are the focus of most studies.

Akelaitis (1941, 1944) failed to discover cognitive sequelae of the surgery using
standard neuropsychological procedures.
It was the Bogen group that recognised the importance of providing a nonverbal
means of response to demonstrate the presence of two independent cognitive systems
within the same subject (Bogen and Gazzaniga, 1965; Sperry et al., 1969).
Initial studies confirmed the neurologists’ assertion that the left hemisphere was
dominant for language whereas the right could neither name nor describe objects
presented to it visually or tactually, although it could perform certain visuospatial tasks.
The left hemisphere is dominant for conceptual similarities, for detail and for a
gestalt synthesizer. The right hemisphere perceives forms but is lacking a phonological
analyser.
However, interactive processes between hemispheres in the normal undivided brain
may further modulate such strategic differences, in some cases reducing them, in others
enhancing them.
Moreover, even in the divided brain, undivided subcortical processes may provide
a surprising degree of interhemispheric cross-talk.
However, the corpus callosum plays an important role in the interhemispheric
transfer of learned discrimination, sensory experience and memory.
Further – refined experiments continue to develop our understanding of perceptual
cognitive, mnemonic, and linguistic processes and their integration into coherent thought
and behavior (Baynes and Gazzaniga, 1997).
The clinic of the corpus callosum

The clinical effects of disconnection were first seriously considered by Wernicke in
1874 and were very much a part of early neurology. He predicted the existence of an aphasic
syndrome (conduction aphasia) that would result from severing fibre connections between
the anterior and posterior speech zones. Later, in 1892 Déjérine was the first to demonstrate
a distinctive behavioral deficit resulting from the pathology of the corpus callosum.
The first real description of a callous syndrome had been made by Raymond in 1893
(Lassonde et al., 1996).
In a series of papers published in about 1900, Liepmann (1900, 1905) and Liepmann
and Maas (1907) most clearly demonstrated the importance of severed connections as an
underlying factor in the effects of cerebral damage. Liepmann wrote extensively on the
principle of disconnection, particularly about the idea that same apraxias might result
from disconnection. He reasoned that, if a patient were given a verbal command to use
the left hand in a particular way, only the verbal left hemisphere would understand the
command. To move the left hand, a signal would then have to travel from the left
hemisphere through the corpus callosum to the right hemispheric region that controls
movement of the left hand.
By interrupting the part of the corpus callosum that carries the command from the
left hemisphere to the right, one disconnects the right hemisphere’s motor region from
1506
20. Corpus callosum
the command. Thus, although the subject would comprehend the command, the left hand
would be unable to obey it. Necessarily then, callosal interruption would result in an
inability to follow verbal commands with the left hand although there would be no loss
of comprehension (as expected from a left hemisphere lesion) and there would be no
weakness or incoordination of the left hand (as expected from a right hemisphere lesion).
We now recognise the notion that spatial or pictorial instructions understood by the right
hemisphere may require a callosally mediated interhemispheric communication for
correct left hand execution.
In humans, the highlighting of many callous related symptoms was done in patients
with tumors, degenerative disease, partial vascular lesions and agenesis of the corpus
callosum.
The study of epileptic patients, where the ablation of a commissure (anterior,
posterior, hippocampal) or a callosotomy (sectioning of corpus callosum) had been
performed as therapy, allowed the description of the main components of the callous
disconnection syndrome.
One should keep in mind that callosal lesions, surgical as well as naturally occurring,
are often accompanied by damage to or pressure upon neighbouring structures, resulting
in several distinct types of signs: (a) signs of hemisphere disconnection, (b) neigh-
bourhood signs, and (c) nonlocalising signs such as meningismus or signs of increased
intracranial pressure. Here, attention is given mainly to signs of the first type.
Thus, the earliest clinical report of a surgical division of commissural pathways to
prevent the spread of an epileptic attack was made by Van Wagenen and Herren in 1940,
coincident with Erickson’s report of the experimental observations in primates of seizure
spread via the corpus callosum (Erickson, 1940). Van Wagenen and Herren (1940) were
inspired to perform the surgery on patients with severe intractable epilepsy after observing
that one of their epileptic patients experienced considerable relief after developing a tumor
in his corpus callosum. Epileptic seizures are caused by abnormal electrical discharges
that reverberate across the brain from one hemisphere to the other. Severing all or part
of the corpus callosum can reduce seizure activity by 60-70% in 80% of the patients. Van
Wagenen and his colleagues feared that one of the side effects of the surgery would be
that it might produce a split personality, or a dual consciousness.
However, after 20 of the surgeries were conducted in the 1940’s, researchers like
Akelaitis never found psychological side effects (Akelaitis, 1941, 1945). The surgery did
not appear to create two minds, each with its own personality and consciousness, fighting
over the control of the body. The absence of a dual consciousness continued to be
observed when the surgery was revived by Bogen, in the early 1960’s, and Sperry.
In 1965, Bogen advocated this approach as a surgical treatment for epilepsy, and
further reports appeared in the 1970’s (Luessenhop, 1970; Wilson et al., 1975). However,
despite the phenomenal academic interest generated by the function of the corpus
callosum and lateralised hemispheric function in humans, this therapeutic approach did
not arouse much clinical interest until several reports appeared in the mid-1980’s. The
procedure was medically beneficial, leaving some patients virtually seizure-free after-
wards, with minimal effects on their everyday behavior.
1507
However, more extensive, psychological testing by Sperry, Gazzaniga and Bogen

(1969) soon demonstrated a unique behavioral syndrome that has been a source of new
insights into the nature of cerebral asymmetry.
Although the callosotomy is not as dangerous as it was in the 1940’s, given the
advent of microsurgery technique, it is still a treatment of last resort. And the procedure
is even rarer now, since pharmacological treatments have greatly improved, as well as
presurgical techniques to localise the origin of seizure (Gazzaniga and Miller, 2009). But
the callosotomy surgery offers a lot of hope to patients with no other treatment options,
and in the 1940’s those other options were much fewer.
This right-to-left aspect of callosal function was not part of Liepmann’s original
callosal concept although, in retrospect, it seems a natural corollary. Liepmann himself
considered the left hemisphere to be the organiser of complex (particularly learned) motor
behavior. Whether and in what way the left hemisphere is dominant for skilled
movements generally (and not just those linguistically related) are currently matters of
active controversy (Kimura and Archibald, 1974; Zaidel and Sperry, 1977; Haaland and
Delaney, 1981; Jason, 1983; Hampson and Kimura, 1984; Bogen, 1987).
Liepmann’s deduction, although brilliant, was ignored by a number of neurologists.
The earliest systematic studies of the effects of commissural sections in humans are those
of Akelaitis (1943). Very few behavioral deficits were observed, such as in jocular
despair.
Lashley (1950) declared that the corpus callosum served only to keep the
hemispheres from sagging. Testing procedures at the time were far from subtle, but more
importantly we now know that, rather far from the anterior commissure, enough of the
splenium may have been spared to permit transfer of some visual information.
An important series of papers by Myers (1956) and Sperry (1974, 1976, etc.), revived
interest in the effects of disconnecting neocortical regions.
Their work confirmed others’ earlier observations that the animals were virtually
indistinguishable from their surgically intact counterparts and indeed appeared normal
under most testing and training conditions.
Unlike those of earlier studies, however, the results of their studies revealed that,
under special training procedures, the animals could be shown to have severe deficits.
Thus, if the sensory information were allowed to separate access to each hemisphere,
each could be shown to have its own independent perceptual, learning, and memory
processes (Mishkin, 1979). The corpus callosum does indeed serve important functions.
This conclusion has been confirmed in subsequent studies on the effects of surgical
disconnection of the human cerebral hemispheres as a treatment of intractable epilepsy
(Kolb and Whishaw, 2003).
The examination of the callous disconnection syndrome also depends on the age at
which the callosotomy is performed. According to Ptito and Lepore (1983), a callosotomy
that had been performed on an animal before the end of myelinisation of the corpus
callosum allows at least a partial interhemispheric visual transfer. It is well known that
the myelination of fibres is one of the last events in the maturation of the neural system.
1508
20. Corpus callosum
Mitchel (1987) found that human infants younger than about 1 year are like split-brain
patients in that they are unable to transfer information about objects obtained by touch.
Rudy and Stadler-Morris (1987) found that rats trained on spatial-navigation tasks
learned the task with one hemisphere at 22 days of age but could not learn it with the
other.
By the time they were 25 days old, they did display interocular equivalence. The
researchers suggest that the 22-day-old rat behaves like a split-brain animal. After the
end of myelinisation no transfer can be performed. In cats, the period of myelinisation in
callous fibres begins around the age of 28 days (Elberger, 1982), and in humans it extends
until the end of the tenth year of existence (Yakovlev and Lecours, 1967).
Due to this reason, a callosotomy performed before the age of 10 should remain
almost asymptomatic.
Transfer tests in children with a callosotomy performed before the age of ten,
revealed minor or no deficit (Geoffroy et al., 1983, 1986; Lassonde et al., 1986). The
reaction time, much longer than in normal persons, confirms the limits of the
compensation mechanisms in these subjects (Sauerwein and Lassonde, 1983; Lassonde
et al., 1991, 1996).
A commissurotomy performed between age ten and fifteen leads to not very severe
signs of callous disconnection (ideomotor apraxia, unilateral anomia, etc.), similar to the
ones in adults. It is possible that this mildness is based on certain forms of plasticity that
determines a cerebral reorganisation. Its quality and efficacy depends on how early the
lesion was produced (Lassonde et al., 1996).
Related to different aspects of the interhemispheric disconnection syndrome in
children, youth and adults, Ramackers and Nijokiktjien (1991) released theirs concept of
development.
Young children may be considered subjects with a physiological split-brain. In the
first decade, the transfer capacity of tactile information is limited, but it increases with
age (Quinn and Geffen, 1986).
The fact that the physiological disconnection syndrome disappeared is an ontogenetic
phenomenon (Galin et al., 1977) that corresponds to a degree of myelinisation (Ptito and
Lepore, 1983).
Thus, some authors stress about the hypothesis of a dysfunction in the corpus
callosum in some dyslexic subjects (Ramackers and Nijokiktjien, 1991). This
phenomenon of plasticity in subjects with no corpus callosum or subjects, who underwent
an early callosotomy, was related to the critical period of development that coincides
with synaptic hyperproduction (Hommet and Billard, 1998).
However, the precise relation between the callous malformation and the
interhemispheric dysfunction is suspected but not yet proved in the development
pathology.
We performed callosotomies (Fig. 20.7) for intractable seizures in four patients.
They were 17, 19, 25 and 27 year-old. After surgery we obtained remission of 8-43
months and a decrease in the number and severity of the epileptic seizures. The routine
1509
A B
Fig. 20.7. Postoperative CT-scan shows a partial disconnection (A + B) in a patient with contractable seizures.
Control clips have been fixed in order to see the location and extension of the colostomy.
The postoperative results were very good.
neurological examination did not record any significant change in walking, orthostatism,
cutaneous and myotatic reflexes, cranial nerves, sight, hearing and smell. The extraocular
movements of the face, tongue, mandible and those of each limb were normal. However,
the coordination of the hands was affected if a task that needed both hands was performed
without seeing.
When studied under more stringent experiment condition where sensory input was
limited to one hemisphere, the consequences of callosal disconnection readily became
apparent. Thus, when deprived of visual feedback, the commissurotomised participant
was unable to name an object held in the left hand because the left (naming) hemisphere
no longer had access to information in the right hemisphere. For the same reason, when
deprived of visual input, one hand was unable to select an object held by the other. While
the left hand was unable to write an intelligible sentence, it may surpass the efforts of the
right in copying a complex geometric design. If emotionally charged images are restricted
to the left visual field, a split-brain patient may evidence an appropriate affective
response; however, because the speaking left hemisphere is disconnected from the
hemisphere that saw the image, he or she may be unable to explain their reaction.
On rare occasions, patients have been dismayed that one hand (usually the left) might
be carrying out some activity of which the left (speaking hemisphere) is unaware or find
that one hand is working in a counter-productive fashion to the other (e.g., one hand
pulling pants up and the other pushing them down) (Mendoza, 2011).
However, according to Kolb and Whishaw (2003), for dualists who hold that the
brain has a separate corresponding mental representation (the mind), these are compelling
reasons to consider that a split-brain person possesses two brains and two minds. For
materialists, who hold that behavior is explained as a function of the nervous system,
without recourse to mind, the philosophical implications are not so weighty. But for
1510
20. Corpus callosum
everyone, there is a challenge to understand how persons with separated hemispheres

function in a seemingly integrated way (Kolb and Whishaw, 2003).
Further on, we will describe the disconnection syndrome in direct relation with the
disruption of communication between the motor and sensorial areas. Because of the
crossing of these tracts, each hemisphere controls the contralateral half of the body. The
operational efficacy of the two hemispheres is based on the transfer of information that
takes place between them and on their bilateral integration (Jeeves, 1990).
Specificity of callosal fibres

It has long been noted that separating up to two-thirds of the anterior callosum leads
to little if any changes in ability (Risse et al., 1989). The symptoms of callous
disconnection may vary depending on the location of the lesion. Thus, located lesions
allowed determining these commisural areas that play a primary role in producing each
of the elements of the callous disconnection syndrome. Commissurotomies and
callosotomies disrupt the interhemispheric transfer of many types of information.
However, both cerebral hemispheres are believed to make significant contributions to
most routine daily functions, including language-based activities being carried out
primarily by the left hemisphere and the right hemisphere apparently being more
important for certain perceptual and emotional functions.
If the anterior split continues far enough, a disruption of the ability to transfer sensory
and position information from hand to hand will be observed. In contrast, the section of
the splenium disrupts the transfer of visual information between the hemispheres, which
isolates lateralised visual input. After a posterior section, although explicit identification
and naming of left visual field stimuli is not possible, some transfer of higher-order
information may occur (Sidtis et al., 1981).
In cases with inadvertent surgical sparing, very specific transfer of information has
been found (Gazzaniga et al., 1989). Occasionally, strokes yield partial callosal lesions
as well; one such patient with damage to the body of the corpus callosum demonstrates
left-hand tactile anomia and agraphia (Baynes and Gazzaniga, 1997).
The disconnection syndrome

Most of our knowledge related to the function of the corpus callousum comes from
studying adult subjects who suffered spontaneous or surgical lesions of the corpus
callosum.
Classically, the syndrome of interhemispheric disconnection or the callous syndrome
consists of a series of symptoms of variable complexity in which one can include transfer
defects of elementary sensorial information that is symmetrically organised in the two
hemispheres.
One might also include dysfunctions of elaborate cognitive functions (speech,
praxias) in which one hemisphere is more or less exclusively specialised, and even
psychic symptoms with a dissociative character.
1511
Thus, the complete section of the corpus callosum, which has come to be used
increasingly as a treatment for medically intractable epilepsy (Reeves, 1985) is regularly
followed by a wide variety of neurological and neuropsychological deficits. The deficits
that are most apparent immediately after operation make up the acute disconnection
syndrome (Wilson et al., 1977). Those deficits that persist make up the stabilised
syndrome of hemisphere disconnection (Sperry et al., 1969; Bogen, 1978; 1985 a, b).
A partial section of the corpus callosum may produce a fraction of the full syndrome,
depending upon the part of the corpus callosum that has been cut as well as the amount
and nature of any associated extracallosal damage.
In general, most of the disconnection deficits, both acute and chronic, are not present
as long as the splenium is spared (Apuzzo et al., 1982; Gordon et al., 1971; Dănăilă and
Golu, 2002). But certain partial sections do entail a few inevitable deficits, as well as
some common complications, whose recognition is important for the surgeon utilising
transcallosal approaches.
Sperry, Gazzaniga and others have extensively studied the effects of hemispheric
disconnection on behaviours related to both motor and sensory systems.
The patients with divided brain (split-brain) operated by Akelaitis (1943 and 1944)
and Bogen and Vogel (1962) for epileptic seizures, have been examined by Sperry et al.
(1969) and Sperry (1986). Thus, with the exception of several transitory postoperatory
phenomena observed just in some of the patients (mutism, left hemiapraxia, etc.), the
respective patients did not seen to stand out in any way compared to the ones who did
not undergo surgery. However, when these patients went through adequate psychological
tests, they showed some particular signs and symptoms.
Afterwards, they have been grouped under the name “callous disconnection
syndrome“ (Bogen and Vogel, 1962; Bogen and Gazzaniga, 1965; Gazzaniga, 1970;
Hécaen and Assal, 1973; LeDoux and Gazzaniga, 1978; Bogen, 1985; Sperry, 1986).
The signs of callous disconnection are based upon the principle of a specialised left
hemisphere involved in the verbal behavior and a right hemisphere involved in spatial
and visual-perceptive abilities.
The communication between the two hemispheres is based upon the registration of
sensorial or motor information coming from the callous commissure in each of them. Or,
in some cases, it is based upon the bilateral transport of information.
Thus, signs of disconnection may be observed when the callous commissure is
sectioned, and the motor or sensorial information is limited to a single hemisphere
There are four conditions in which the hemispheres become completely or partial
separated.
First, in humans, the interhemispheric fibres are sometimes cut as a therapy for
intractable epilepsy.
Second, people are born with congenitally reduced or completely missing
interhemispheric connections.
Third, in animals, disconnections are performed to trace functional systems, to model
human conditions and to answer basic questions about interhemispheric development.
Four, a stroke involving the anterior and / or posterior cerebral artery.
1512
20. Corpus callosum
The effects of complete disconnection

Epileptic seizures may begin in a restricted region of one hemisphere (most often
the temporal lobes) and then spread through the fibres of the corpus callosum or anterior
commissure to the homologous location in the opposite hemisphere.
In some cases the medication is of little value, and the seizures may actually become
life threatening because they recur often, sometimes several times in an hour.
To relieve this seizure condition, the corpus callosum and anterior commissure can
be surgically sectioned. In these patients we can obtain substantial relief from their
epilepsy and often show marked improvements in personal well being, competence, and
intelligence.
As a result of the surgery, each hemisphere retains fibres that allow it to see only
the opposite side of the visual world. Likewise, each hemisphere predominantly receives
information from the opposite side of the body and controls movements on the opposite
side of the body. The surgery also isolates speech in those persons with lateralised speech.
About a year or so is required for recovery from the surgical trauma. Within 2 years,
the typical patient is able to return to school or work.
Specific tests, however, can show differences between the functioning of split-brain
patients and that of people with normal cerebral connections. In the split-brain, each
hemisphere can be shown to have its own sensations, percepts, thoughts, and memories
that are not accessible to the other hemisphere (Purves et al., 1988).
Thus, after hemisphere disconnection in the human, unilateral tactile anomia, left
hemialexia, and unilateral apraxia are typical. That is a right-hander with complete cerebral
commissurotomy cannot name aloud objects correctly manipulated (hence, recognised) with
the left hand, cannot read aloud written material presented solely to the left half-field of
vision, and cannot execute with the left hand actions verbally named or described by the
examiner, although these actions are readily imitated when demonstrated.
The apraxia usually recedes within a few months, whereas the hemialexia and
unilateral anomia can persist for years (Bogen, 1987).
Finally, the subjects with total callosotomy still have the possibility to transfer a
piece of this information probably through extracallous interhemispheric tracts (or
through ipsilateral projections of tactile information) (Habib, 1998). The absence of direct
callous connections between primary sensitive areas of the distal extremity of the limbs
makes one suppose that the transfer of sensitive information is performed through
associative areas rich in callous connections, therefore after processing the signal to some
extend (Cusik and Kaas, 1986).
The effects of partial disconnection

According to Kolb and Whishaw (2003), surgeons have experimented with partial
surgical disconnection of the hemispheres, hoping to attain the same clinical relief from
seizures but with fewer neuropsychological side effects.
Thus, partial disconnection, in which the posterior part of the corpus callosum is left
intact, appears to combine markedly milder effects than those of a complete
commissurotomy and the same therapeutic benefits.
1513
Sperry (1974) and Sperry et al. (1979) have found that patients with partial
disconnection are significantly better at motor tasks such as those needed to use the
Etch-a-Sketch.
The results of research on monkeys with partial commissurotomies suggest that the
posterior part of the corpus callosum (splenium) subserves visual transfer, whereas the region
just in front of the splenium affects somatosensory transfer (Pandya and Seltzer, 1986).
Acute disconnection syndrome

During the first few days after a complete cerebral commissurotomy, the patients
commonly respond reasonably well, to simple commands, with their right limbs. But
they are easily confused by three- or even two-part commands, each part of which is
obviously understood. The patients often lie quietly and may seem mildly “akinetic”,
although cooperating when stimulated (Bogen, 1987).
There is sometimes an “imperviousness” resembling the one often seen with
naturally occurring genu lesions (Alpers and Grant, 1931; Bogen, 1978, 1987). The
patients are often mute even when willing to write short (usually one-word) answers.
The left-side apraxia to verbal command is usually severe and can be mistaken for
hemiplegia. Similarly, a disregard for the left half-field of vision can be mistaken for a
hemianopsia.
Left side weakness in the first week or so due to retraction edema in the right
hemisphere sometimes confounds the picture. There may be competitive movements
between the left and right hands. Moreover, some patients have focal motor seizures,
manifested by clonic contractions on alternating sides of the body and without loss of
consciousness, occasionally followed by transient unresponsiveness of whichever limbs
were involved.
The patients commonly have bilateral Babinski signs as well as bilateral absent
superficial abdominal reflexes (Bogen, 1987).
Well-coordinated but repetitive reaching, groping, and grasping with the left hand
sometimes resembles a grasp reflex. The left arm hypotonia, the responses bilaterally to
plantar stimulation, and the mutism were regularly observed.
One of Bogen’s patient’s condition worsened at the end of the first week associated
with an alkalotic hyponatremia present on days 5 to 7. When the hyponatremia was
corrected the patient rapidly improved with respect to alertness and left side coordination.
But some degree of mutism persisted for another month. The duration of mutism seems
to be related to the extent of extracallosal damage (Bogen, 1987). There was also, as in
every one of Bogen’s 12 right-handers tested after complete commissurotomy, a
persistent anomia in the left hand.
A positive Babinski sign can be found not only contralateral to the retracted
hemisphere but also, for at least a day or two, on the ipsilateral side. The best explanation
for this ipsilateral Babinski sign is probably that the diaschistic shock effect on the
unexposed hemisphere after an extensive callosal section is sufficient to depress for a
few days the corticofugal inhibition of the primitive extensor response (Bogen, 1974;
1514
20. Corpus callosum
Van Gijn, 1977). In any event, the Babinski signs rapidly subside bilaterally and are not
present over a long term (Botez and Bogen, 1976).
As the severity of the acute disconnection syndrome subsides in a week or so, a
phenomenon variously called “intermanual conflict” or “the alien hand” appears (Bogen,
1987). Almost all complete commissurotomy patients manifest some degree of
intermanual conflict during the early postoperative period.
Intermanual conflict was observed after commissurotomy by Wilson et al. (1977)
and by Akelaitis (1944-1945), who called it “diagnostic dyspraxia”.
While doing the block design test unimanually with his right hand, his left hand
came up from beneath the table and was reaching for the blocks when he slapped it with
his right hand and said, ”That will keep it quiet for a while”. Examples of intermanual
conflict have been reported in detail by Rayport et al. (1983) and Ferguson (1985). In
rare instances, the intermanual conflict may reappear even years later.
One of Bogen’s patients remained seizure-free for 8 years and then had a status
epilepticus a few months after her family physician discontinued her anticonvulsant
medication (Bogen, 1985). Her seizures were readily controlled when her medication
was reinstituted. Her left-handed anomia was still readily demonstrable 21 years postope-
ratively. This persistence of unilateral tactile anomia was also true of all their other
patients (Bogen et al., 1981).
Chronic disconnection syndrome

According to Bogen (1987), within a few months after surgery, the symptoms of
acute hemisphere disconnection become compensated to a remarkable degree. In
personality and social situations the patient appears much as before.
When input is lateralised, each hemisphere seems to have its own learning processes
and its own separate memories.
Split-brain patients soon accept the idea that they have capacities of which they are
not conscious such as left-hand retrieval of objects not nameable. They may quickly
rationalise such acts, sometimes in a transparently erroneous way (Gazzaniga and
LeDoux, 1978). But even many years after operation the patients will occasionally be
quite surprised when some well-coordinated or obviously well-informed act has just been
carried out by the left hand. This is particularly common under conditions of continuously
lateralised input (Zaidel, 1983).
In sum, split-brain is a condition resulting from surgical lesioning of all or a
substantial portion of the corpus callosum, thus interrupting the normal flow of
information between the two hemispheres of the brain (Mendoza, 2011).
Geschwind and Kaplan (1962) discovered that their patient produced lucid writing with
the right hand (left hemisphere, but “aphasic” writing with the left hand (right hemisphere).
They also reported anomia for objects placed in the left hand but not the right.
By the middle of the 20th century, Sperry and his associate noted that if both the
corpus callosum and the optic chiasma were lesioned in animals (thus, restricting visual
information from each eye to the ipsilateral hemisphere), dramatically different results
1515
were obtained. Not only could the animal not carry out a discrimination task previously learned
by one eye (cerebral hemisphere) when only the opposite eye was left uncovered, but each
eye (cerebral hemisphere) could learn conflicting tasks, depending on which eye was used.
In other classic series in the 1960s, Gazzaniga, Boegen and Sperry clearly
demonstrated the effects of split-brain preparations in human subjects (Mendoza, 2011).
Following commisurotomy, behavioral deficits were not always obvious. This is
probably due to the extensive cross-cueing that normally takes place, especially through
vision where the right hand sees what the left one is doing and vice-versa.
Although in cases of naturally occurring callosal lesion in humans, or even more
surprisingly in cases of callosal agenesis, there is typically a failure to evidence the signs
of a disconnection syndrome (Mendoza, 2011).
The psychological examination emphasised discrete elements of unilateral agraphia
on the left side, unilateral constructive apraxia on the right side, tactile anomia of the left
hand, disorder in naming objects presented in the left visual area and amnestic elements.
In addition to providing insights into how the two hemispheres normally interact
and their respective strengths, studies of split-brain patients have raised some intriguing
questions about the presumed unitary nature of consciousness.
The transfer of sensorial information

Visual effects
The organisation of the tract in the visual system directs the information coming
from each hemi-field towards the opposite hemisphere. As far as the transfer of visual
information is concerned, the data pleads for its location to be at the level of the enlarged
splenial area, a region dedicated for the passage of interoccipital fibres.
In the visual system, connections in each hemisphere run from area V1 to area V2
and to area V3, V4 and V5 in the same hemisphere (Mishkin, 1979). Connections from
V3, V4 and V5 cross the corpus callosum to the analogous area on the opposite side, and
also connect with area TE on the same side (Fig. 20.8). Area TE connects to the anterior
temporal cortex and the amygdala on the same side and connects, through the anterior
commissure, to these structures on the opposite side.
By using different tasks, Mishkin (1979) has demonstrated that bilateral lesions in
area V1, V2 or TE result in an impaired or abolished ability to solve visual-discrimination
problems in monkeys.
Because unilateral lesions do not have such an effect, what seems to be necessary is
one intact trio of areas V1, V2 and TE. There is, however, one constraint: the remaining
cortical regions must be connected to. Thus, as illustrated in figure 20.8 B, a lesion in
area V1 on the right and in area TE on the left does not disturb performance, because an
intact system still functions.
If the connection between the hemispheres is severed, the neocortical areas are still
intact but are not connected, and the result is failure of the visual-discrimination ability
(Fig. 20.8 C). Clearly, the neocortical regions do not function properly if they are not
connected to one another.
1516
20. Corpus callosum
Fig. 20.8. Disconnection

effects in the visual system of
monkeys.
(A) The visual system is
intact.
(B) After lesioning (dark gray
areas), the left visual cortex
still has access to the visual
association cortex of the right
hemisphere, and so vision is
still possible.
(C) The intact components of
the visual system are
disconnected (jagged line)
after lesioning, producing
major visual deficits. (After
Mishkin, 1979).
Mishkin (1979) studied area TE, thinking of it as the final step in the neocortical
visual system. He later studied the problem of how visual stimuli might gain what he
calls “motivational” or “emotional” significance. Monkeys with bilateral temporal
lobotomies including the amygdala attach no significance to visual stimuli. That is, they
will repeatedly eat nasty-tasting objects or place inedible objects in the mouth.
In 1965, Geschwind proposed that this symptom represents a disconnection of the
amygdala from the visual system. Area TE connects with the amygdala on the same side
and the amygdala on the opposite side through the anterior commissure.
The result of Mishkin (1979) and Nakamura and Mishkin (1980) point to an
important role of the nonvisual cortex in visual perception and demonstrate the
importance of studying the connections to a functional system as well as its areas. If an
animal cannot move in response to visual information, it appears to be essentially blind,
even though the visual system may be processing the sensory input.
We can speculate at this point that it is an extreme example of a disconnection
syndrome because the brain is disconnected from both its inputs and outputs. It seems
1517
likely that, although the brain could still function, it would be unconscious in the absence
of inputs or outputs (Kolb and Whishaw, 2003).
In human beings, visual material can be presented selectively to a single hemisphere
by having the patient fix his gaze on a projection screen onto which pictures of objects
or symbols are projected to the right, left or both visual half-fields using exposure times
of 0.1 second or less (Bogen, 1987).
In short, the visual system is crossed, so information flashed to one visual field
travels selectively to the contralateral hemisphere. By using this fact, researchers have
demonstrated left- and right-visual-field superiority for different types of input.
For example, verbal material is perceived more accurately when presented to the
right visual field, presumably because the input travels to the left, linguistic hemisphere.
On the other hand visuospatial input (such as a map) produces a left-visual-field
superiority, because the right hemisphere appears to have a more important role in
analysing spatial information (Kolb and Whishaw, 2003).
However, words presented to the left visual field, and hence right hemisphere, are
sometimes perceived, not as accurately or consistently as when they are presented to the
right visual field. These relative effects occur because either hemisphere potentially has
access to input to the opposite hemisphere through the corpus callosum, which connects
the visual areas. Thus, the visual-field superiority observed in normal subjects is relative
(Myers, 1956; Sperry, 1974; Nakamura and Mishkin, 1980; Lepore et al., 1986; Lassonde
1986; Lassonde et al., 1986; Fantie and Kolb, 1989).
A commissurotomy patient no longer has such access, because the connection is
severed. Given that speech is usually housed in the left hemisphere of right-handed
patients, visual information presented to the left visual field will be disconnected from
verbal associations because the input goes to the right, nonlinguistic hemisphere.
Similarly, complex visual material presented to the right visual field will be
inadequately processed, because it will not have access to the visuospatial abilities of the
right hemisphere. It follows that, if material is appropriately presented, it will be possible
to demonstrate aphasia, agnosia, alexia, and acopia (the inability to copy a geometric
design) in a patient who ordinarily exhibits none of these symptoms, as Kolb and
Whishaw (2003) demonstrated.
If verbal material is presented to the left visual field, the commissurotomy patient
will be unable to read it or to answer questions about it verbally, because the input is
disconnected from the speech zones of the left hemisphere.
Presentation of some verbal material to the right visual field presents no difficulties,
because the visual input projects to the verbal left hemisphere (Downer, 1961; Geschwind,
1965; Gazzaniga, 1970; Schrift et al., 1986; Fabri et al., 2001; Kolb and Whishaw, 2003).
Similarly, if an object is presented to the left visual field, the patient will be unable
to name it and thus will appear agnosic and aphasic. If presented to the right visual field,
this same object will be correctly named, because the left visual cortex perceives the
object and has access to the speech zones. Thus, we can see that the split-brain patient is
aphasic, alexic, and agnosic if verbal material or an object requiring a verbal response is
1518
20. Corpus callosum
presented visually to the right hemisphere, but this person appears normal if material is
presented to the left hemisphere (Downer, 1961; Geschwind, 1965; Gazzaniga, 1970;
Schrift et al., 1986; Fabri et al., 2001; Kolb and Whishaw, 2003).
A further deficit can be seen if the patients are asked to copy a complex visual figure.
Because the right hemisphere controls the left hand, we might predict that the left hand
will be able to copy the figure but right hand being deprived of the expertise of the right
hemisphere, will be severely impaired. This result is indeed the case: the left hand draws
the figure well, whereas the right hand cannot and is, thus, acopic (Kolb and Whishaw,
2003).
The complete splenial sections are exceptional. There are only few documented
observations of spontaneous lesions that led to splenial destruction with no previous
lesions (Damasio et al., 1980; Degas et al., 1987; Habib et al., 1990). The typical behavior
of subjects with callous disconnection, in the case of a short tachistoscopic projection of
a stimulus representing an image, a letter, a word etc., in the lateral region of this visual
area refers only to reporting a light or a “flash” in the left side. The same stimulus
presented on the right side leads to its immediate recognising. In case of subjects with
cerebral division, a simultaneous bilateral projection of stimuli in each visual hemifield
shows that it is difficult to distinguish them and that the images cannot overlap. Each
hemisphere responds independently to its respective stimulus (Lassonde et al., 1996). In
the case of chimerical figures (faces of people, shapes etc.), formed by two unpaired
halves, each of the elements in a compound pair was projected in a single hemisphere.
Under these conditions, if a verbal answer is required, the subject communicates only
the stimulus directed towards the left hemisphere. When he is asked to point with the left
hand, the subject indicates the stimulus analysed by the right hemisphere (Levy et al.,
1972).
With the help of this test it is possible to confirm the difference between specific
functions for each hemisphere. So, the stimuli presented in the right hemifield which is
controlled by the left hemisphere can be read and described verbally. The right
hemisphere could not name, neither verbally, nor in writing, the visual material presented
in the left hemifield.
With the left hand the subject can indicate with no difficulty, in a collection of things,
the object that is presented to him as an image or verbally.
The failure of the right hand is due to the fact that the left hemisphere, on which it
depends, is not informed about the stimulation exerted exclusively upon its homologue
(LeDoux and Gazzaniga, 1978).
Thereinafter, it was proved that patients with callosotomy, too, have a superior
visuospatial function of their hemisphere, while their left hemisphere uses electively
visual imagery that consists of letters.
The use of tactile information in order to form representations of abstract shapes is
better developed at the level of the parietal lobe in the right hemisphere. The analysis of
information from unfamiliar facial figures, too, belongs to the right hemisphere, while
the left hemisphere is more able to generate voluntary expressions. However the facial
1519
mimic, which is part of a spontaneous emotion, is the result of both hemispheres.

Consequently, the right hemisphere has proved its superiority in analysing perceptual
and spatial performances, while the left hemisphere is essential for finding solutions to
complex visual problems, speech, tasks that involve deductions, generalisation, and
intelligent behaviours.
In the case of a callosotomy, visual and tactile perceptions remain isolated in each
hemisphere. Even though the subjects are able to report independently the visual material
that was received and saved in one of the two hemispheres, they cannot compare the two
hemifields because the perception remains isolated in each hemisphere (Baynes and
Gazzaniga, 1997).
These facts correspond to the concept of a specialised left hemisphere for treating
significant information.
Besides the infraconscious treatment of information received in the right hemisphere,
it has proved that subjects with callosotomy are able to transfer messages related to
movement, light, and location of targets in the lateral area of the visual field, between
the two hemispheres (Habib, 1998). Sergent (1990) proved that “split-brain” subjects are
capable of a certain level of conscious treatment, in particular a semantic one of some
stimuli (numbers, facial expressions) that are addressed to the right hemisphere. It is
supposed that the subcortical commissures are responsible for the transfer of this
information. The fact was proved in rats but they were considered to be accessories or
inexistent in primates (Berlucchi, 1990). Consequently, the subcortical commissures, in
particular the anterior commissure, are able to maintain a part of the visual information
transfer that is depending on the splenium.
The loss of the ability to transfer information from the left hemisphere to the right
hemisphere and vice-versa seems to have no impact on their overall psychological state.
In sum, although individuals seem normal following callosotomy, postoperative studies
have revealed some interesting findings. Thus, when patients were asked to read words that
were presented in their right visual field, they were able to see and to read the words.
However, when words were presented in their left visual field, they could not read them as
they were not even aware that the words were there. One explanation is as follows: visual
information from the right visual field is relayed to the left cerebral hemisphere (via the
visual pathway, which was not affected when the corpus callosum was sectioned), which is
the dominant hemisphere in the processing of language in most individuals.
Thus the patients were able to see and read the words. In contrast, visual input from
the left visual field is relayed to the right cerebral hemisphere (again, via the visual
pathway, which was not affected when the corpus callosum was sectioned), the
nondominant hemisphere for language.
As a result of the bisection of the corpus callosum, the visual input relayed to the
right cerebral hemisphere has no way of also reaching the left hemisphere containing the
language area.
Consequently, patients could not see or read the words, as if they had a left
homonymous hemianopsia. These individuals are not blind.
1520
20. Corpus callosum
When they were asked to select with their hand an object that corresponds to the
object that was presented in their left visual field, they selected the matching object. This
showed that the visual system is functioning properly, and that it is the language function
that is not.
Although the above studies support the finding that the left cerebral hemisphere is
the “dominant” hemisphere in the processing of language, other studies indicate that the
right hemisphere may also be involved to some extent in language comprehension
(Patestas and Gartner, 2008).
Language
The most striking observation regarding split-brain subjects is the presence of
complex generative language in only one hemisphere. Nonetheless, the series of patients
operated on by Bogen demonstrated a well-developed right hemispheric lexicon in the
majority of patients examined, although that lexicon appeared to be limited to simple
auditory and visual comprehension and some written output (Gazzaniga et al., 1962;
Sperry et al., 1969; Levy et al., 1971).
Assessing the scientific significance of the data obtained after the examination of the
four left-handed patients with face localised in the right hemisphere, we may state that:
a. they confirm other studies of this kind which pointed out the poorer lateralisation
of the speech structure in left-handed patients as compared with right-handed ones
(Gazzaniga, 1983).
b. they demonstrated the role of the right hemisphere in the integration and
production of speech in left-handed patients. It extends its competence in performing
impressive speech. On the other hand it begins to directly control the articulating
apparatus and, implicitly, to participate in the production of expressive speech;
c. correlated with the data supplied by the analysis of right-handed patients with
lesions in the right hemisphere, they show that the linguistic dominance of the left
hemisphere does not completely eliminate but only limits the participation of the right
hemisphere in the production of verbal behavior (Dănăilă and Golu, 1987).
The Wilson-Roberts series, demonstrated much less frequent right hemispheric
participation in even rudimentary language processing. By 1983, of the 28 completed
callosotomies, only 3 patients had a documented right hemispheric lexicon (Gazzaniga,
1983). Moreover, there was considerable variation in the quality and sophistication of
the language available to the right hemisphere (Sidtis et al., 1981).
The visual and auditory lexicons of the right hemisphere appear to be similar, albeit
somewhat smaller than the corresponding left hemispheric lexicons (Gazzaniga et al., 1984).
Both hemispheres can make a variety of semantic judgments, recognising cate-
gorical, functional and associative relations. The ability to discriminate words from
nonword letter strings is limited but possible, which suggest that the visual word form is
represented in the right hemisphere of the patients (Reuter-Lorenz and Baynes, 1992).
Phonologic information is difficult for the right hemisphere to manipulate, although
it may possess limited phonologic competence and be able to produce speech. Sidtis et
1521
al. (1981) assessed discrimination of phonemes (such as “ba” versus “pa”) in two
callosotomy patients. The right hemisphere of one patient was able to discriminate but
not identify phoneme contrasts and was also able to identify rhyming words. However,
this patient was able to produce some verbal responses to left visual field stimuli within
a year of her completed surgery (Gazzaniga et al., 1984).
The other patient remained mute until more than 10 years after the surgery; he has now
gained rudimentary control of speech within the right hemisphere (Baynes et al., 1995).
Although he remained unable to make accurate judgments that require moving from
letter to sound, he was able to integrate visual and auditory phonologic information within
his right hemisphere (Baynes et al., 1994, 1995). This remarkable development has
implications for the limits of functional plasticity and for the role of the right hemisphere
in long-term recovery from aphasia (Baynes and Gazzaniga, 1997).
The linguistic prowess of the right hemisphere does not appear to extend to the use
of grammatical rules for comprehension or the production of sentences.
In a left-handed patient with right hemispheric language dominance, comprehension
of grammatical relations appears to be possible only for the right hemisphere (Lutsep et
al., 1995).
Right hemispheric reading proceeds more slowly than the left hemispheric reading
and may use a different mode of processing as has been reported for some deep dyslexic
patients (Reuter-Lorenz and Baynes, 1992).
Likewise, a right hemispheric lexicon with a more diffuse or associative organisation
than that of the left hemisphere has been suggested as the source of certain reading errors
in deep dyslexic (Coltheart, 1980; Schweinger et al., 1989) and pure alexic patients
(Coslett and Saffran, 1989).
The language profile seen in callosotomy patients is more consistent with the profile
reported by Coslett and Saffran (1989) for the preserved reading of their pure alexic
patient than with that reported for deep dyslexic patients (Baynes and Gazzaniga, 1997).
Thus, auditory comprehension of words by the disconnected right hemisphere is
suggested by the subject’s ability to retrieve with the left hand various objects if they are
named aloud by the examiner. Visual comprehension of printed words by the right
hemisphere is often present: after a printed word is flashed to the left visual half-field,
the subject is often able to retrieve with the left hand the designated item from among an
array of hidden objects. Control by the left hemisphere is excluded in these tests because
incorrect verbal descriptions given immediately after a correct response by the left hand
show that only the right hemisphere knew the answer.
While the disconnected right hemisphere’s receptive vocabulary can increase
considerably over the years, single word comprehension is rarely accompanied by speech.
The most extreme cases of right hemisphere language ability in right-handed (and left
hemisphere-speaking) split-brain subjects include two patients with right hemisphere
speech, both with an intact anterior commissure (Sidtis et al., 1981; McKeever et al., 1982).
Right hemisphere language in the split-brain subject has other limitations, with the
syntactic ability being rudimentary at best. Whereas phonetic and syntactic analysis seems
1522
20. Corpus callosum
to specialise heavily in the left hemisphere, there is a rich lexical structure in the right
hemisphere (Zaidel, 1978).
However, after a commissurotomy, each hemisphere can be tested separately,
demonstrating in a positive way those things that each hemisphere can do better than the
other, rather than inferring from its loss of function what a hemisphere is able to do if injured.
Representative reviews are included in the references (Bogen and Bogen, 1969;
Levy, 1974; Nebes, 1974; Sperry, 1974; Zaidel, 1983; Bradshaw and Nettleton, 1983;
Trevarthen, 1984).
Right-handers can write legibly, albeit not fluently, with the left hand. This ability
is commonly lost with callosal lesions, especially those that cause unilateral apraxia. An
inability to write to dictation is common with left hemisphere lesions, almost always
affecting both hands. The left hand may be dysgraphic if affected by a right hemispheric
lesion, such as a frontal lesion causing forced grasping (Bogen, 1978).
That the left dysgraphia after callosal sectioning is not simply attributable to an
incoordination or paresis can be established if one can demonstrate other abilities in the
left hand requiring as much control as would be required for writing. The left hand may
spontaneously doodle or it may copy various designs or diagrams. It is not so much the
presence of a deficit but rather the contrast between certain deficits and certain retained
abilities that is most informative (Bogen, 1987).
Simple or even complex geometric figures previously made with the patient’s own
right hand can often be copied by a left hand that cannot write or even copy writing
(Bogen and Gazzaniga, 1965; Bogen, 1969; Kumar, 1977; Zaidel and Sperry, 1977).
Postcallosotomy mutism
After a complete section of the cerebral commissures, there was in almost every case
a postoperative period of mutism, of varying duration, during which speech was absent
or extremely sparse, although comprehension and writing were retained.
In these cases, there was little if any paraphasia: when the ability to talk returned
there was no nominal amnesia; in some cases there was a definite lack of bodily
spontaneity and motor initiative for a time, but only partially correlated in duration with
the loss of speech.
As the mutism subsided, there was a stage of partial recovery that usually included
hoarseness or whispering, but without paraphasia, anomia, or novel semantic or syntactic
errors, except for 1 right-hander (corpus callosum was operated from the left) (Bogen, 1987).
However, postcommissurotomy deficits depend mainly upon the nature and amount
of preexisting extracallosal damage (Sperry et al., 1969; Gordon et al., 1971; Bogen, 1976).
Postcommissurotomy mutism was originally considered a simple neighbourhood
sign, a partial akinetic mutism from the retraction affecting the anterior end of the third
ventricle (Cairns, 1952; Ross and Stewart, 1981). In contrast to the cases of complete
commissurotomy in other patients all of the same structures (including the massa
intermedia and the anterior commissure) were severed, except the splenium, and there
was no immediate postoperative mutism (Gordon et al., 1971).
1523
Such cases are evidence not only against a third ventricle origin for mutism, but also
against a right supplementary cortex origin. On the other hand, Ross et al. (1984) reported
mutism after anterior callosal sections but not after posterior callosal sections.
After a complete callosotomy in two stages, Rayport et al. (1985) observed in three
of eight cases a marked decrease in spontaneous speech unaccompanied by paraphasia
or a comprehension deficit or inability to sing. The authors suggested that, in these most
affected cases, mixed hand dominance may have been an important consideration.
Of particular importance was the absence of any language or speech problems after
the first stage of callosotomy (rostrum, genu, and most of the trunk). The mutism appeared
only after the second stage of the callosotomy (the splenium and remainder of the trunk).
This result does not totally eliminate the retraction on the supplementary motor
cortex as a partial contributory cause.
Rayport et al. (1985) have suggested that mutism could result from an interhe-
mispheric conflict. But they emphasize more the aspect of mixed dominance, which might
indicate a greater role than usual of the corpus callosum in the production of speech.
A diaschisis secondary to differentiation of speech areas accounts for deficits in
terms of left hemisphere dysfunctions even when the left hemisphere in unmolested.
So, the diaschisis of the left hemisphere (from a complete section) must affect the
speech “centres” or “circuits” more than it affects writing “centres“ or “circuits”. This
implies, in turn, that the writing function is more robust or resistant in some sense than
that for speech, in spite of having developed later in both phylogeny and ontogenesis
(Bogen, 1978).
A more speculative possibility is that speech usually requires interhemispheric
integration in order to control the larynx and other midline structures in the following
sense: One can suppose that left hemisphere speech ordinarily includes a corollary
discharge (Sperry, 1950) to the other hemisphere.
When the commissures are completely severed a downstream interhemispheric
conflict occurs at the level of the motor nuclei for the larynx, which results in dysphonia
(Bogen, 1987).
Those concerned with the normal physiology of speech will be more interested in the
temporary (several weeks to months) mutism after splenial sections (either as part of a total
callosotomy or as a second stage) than the long-lasting mutism (many months to years) of
those whose anomalous laterality is associated with long-standing cortical lesions. But for
the surgeon using a transcallosal approach to the third ventricle, neither of these is apt to be
as important as transient mutism (several days to weeks) after the section of callosal
segments (such as the trunk) well anterior to the splenium (Bogen, 1987).
However, the lack of speech could be considered a mutism of the type often
associated with akinesia of either cingulate or subfrontal origin. Ross et al. (1984) think
of the postcommissurotomy state as a sort of “forme fruste“ of akinetic mutism, in which
mutism is much more evident than is akinesia.
The occurrence of mutism in callosotomy cases without entry into the third ventricle
could be explained as the result of a subfrontal retraction while sectioning the rostrum.
1524
20. Corpus callosum
Arguing against this is the paucity of postoperative mutism in four of Ross et al. (1984)
patients whose splenium was spared but who underwent a section of both the rostrum
and the anterior commissure under direct vision. Thus, transitory mutism (for a few days
or months) immediately after surgery (commissurotomy) is classic but not completely
explained.
For Bogen (1987), keeping an intact splenium of the corpus callosum was sufficient
in order to avoid such a disorder.
In case of sectioning the intermediary area between the genu and the trunk of the
corpus callosum, the transitory mutism would be due to the inclusion of interhemispheric
fibres from the cingular area 24, which are associated, to the elemental mechanisms of
speech (Ross et al., 1984). According to Reeves (1991), an anterior callosotomy produces
a speech disorder which evokes an “adynamic” aphasia of variable gravity (from a simple
bradyarthria to complete mutism). The reasons for this type of disorder still remain
unknown but there probably are multiple ones: preparatory associated lesions, the
phenomenon called diaschisis of the hemisphere that dominates speech, a functional
imbalance between the two hemispheres in relation to the brutal disruption of an
assembly of cortical and cortico-subcortical connections.
Reeves (1991) shows that these disorders are associated with a certain number of
symptoms which evoke a dysfunction of the medial regions in the non-dominant frontal
cortex.
They manifest through a deficit of the inferior left limb and grasping of the left hand
which indicates a lesion of the right SMA.
In such situations the author invokes a surgical injury of the right internal frontal
region.
Long-term dysphasic disorders after a callosotomy are very rare and debatable. After
a complete callosotomy, Fergusson et al. (1985) and Spencer et al. (1988) reported
multiple cases of an important and long-term lack of variability in spontaneous speech,
with no disorders in understanding or repetition. The respective authors suggest that such
a disorder occurs mainly in patients whose speech depends on the interhemispheric
interaction and very large bilateral representations. This is why before every
commissurotomy there is a mandatory test with amobarbital. We can probably be
reassured with respect to the risk of severe postoperative mutism by a favorable response
to carotid amobarbital testing. This test can give ambiguous results, but it can be used to
exclude critical dependence upon the commissures. That is, if the patient continues to
speak intelligibly when the hemisphere minor for speech is narcotised, then the
disconnection of this minor hemisphere will probably not deprive the patient of an
essential resource with respect to speech production.
Except these particular cases, the callous disconnection is considered to be an
intervention that does not affect speech.
However, in “split-brain” cases, there are some very subtle disorders of speech as
for instance an influence on very elaborate or pragmatic speech. Zaidel (1990) shows
that the most obvious pragmatic deficits appear in subjects whose right hemisphere has
1525
a rather important role in speech development. One of Zaidel’s (1990) “split-brain”

subjects used subtlety of speech and clinch in a pertinent manner. They were formally
correct from a lexical and semantic point of view. In normal subjects, they are dependent
on the right hemisphere, and are disturbed by its lesions (Hannequin et al., 1987).
Zaidel (1990) affirms that the respective functions are sensible to transcallous
inhibition.
Corpus callosum and reading

In patients with verbal capacities controlled by the right hemisphere there is more
conceptual and semantic information in that hemisphere compared to syntactic and
phonologic information.
However, the ability of discrimination of words from a row of letters is limited,
which proves that the visual shape of words is represented in the right hemisphere
(Eviator and Zaidel, 1991; Reuter-Lorentz and Baynes, 1992; Baynes and Gazzaniga,
1997). The left hemisphere is dominant not only for speech but also for the possibility of
deduction, interpreting of behavior and emotions and giving a rational meaning for events
we are confronted with.
The interhemispheric mechanism involved in reading can be approximated due to a
tachistoscopic method.
If a visual-linguistic stimulus (letter or word) is projected for a short period of time
in a visual field, the stimulus at first reaches only the contralateral hemisphere. In subjects
with an intact corpus callosum, the letter or words that are projected on the left side are
perceived in the right hemisphere, and are immediately recognised by the left hemispheric
circuits that are responsible for decoding the visual-linguistic information and transformed
in oral language.
On the contrary, in “split-brain” subjects the information remains stored in the right
hemisphere that has a variable decoding capacity according to individual and decoding
material. However, it cannot achieve a complete processing of information. Consequently,
its capacity of expressive formulation is considered to be quasi-nil and leads to an
incapacity of the individual to name the respective oral stimulus (Habib, 1998).
This left hemialexia that is characteristic to the callous disconnection syndrome is
thoroughly documented in literature. Sidtis et al. (1981) discuss the case of a patient with
commissurotomy in the posterior half of the corpus callosum. When significant stimuli
have been projected in his right hemisphere he could not name, but could describe them,
a phenomenon called “bout de langue”. This fact suggested that a lesion of the posterior
area of the corpus callosum is responsible of the absence of perceptive characteristic
transfers of the stimulus, while the anterior area is intact and capable of transferring
whichever level of significant representation. On the other hand, Sergent (1987) interprets
this phenomenon to be a result of an extracallous transfer through the profound
subcortical structures of the brain stem.
One of the first neurologic syndromes related to an interhemispheric disconnection
is the syndrome of pure alexia (Déjérine, 1892). People suffering from alexia following
1526
20. Corpus callosum
a lesion of the left occipital region, lesion which is frequently vascular, are incapable of
understanding or reading words.
However, after a period of total alexia they can decipher the words by splitting them
into syllables (“letter by letter dyslexia”). Messages coming from the right hemisphere
(the only one receiving information due to a right homonymous hemianopsia) are
interrupted by a lesion of the splenial fibres at the level they enter the left hemisphere,
consequently to an occipital lesion, spread the forward and into depth.
Therefore, the absence of interhemispheric transfer leads to some speech disorder
directly related to the dominance of the left hemisphere.
In right-handed “split-brain” patients, the deficits manifest through left tactile
anomia, left lateral homonymous pseudohemianopsia, left ideomotor apraxia to verbal
orders and agraphia of the left hand.
The linguistic potential of the right hemisphere in a patient with cerebral division,
seems to be limited to verbal, heard or read understanding but only for certain categories
of words, and his capacity of expressing himself is extremely limited, but not quite
inexistent (Bogen, 1985).
The analysis of subjects with callous lesions consists of a privileged pattern for
understanding the role of the right hemisphere in reading (Michel et al., 1996).
Corpus callosum and the visual-spatial aptitudes

A unilateral constructive apraxia was reported for patients with callosotomy (Bogen
and Gazzaniga, 1965). A drawing made with the left hand is inaccurate but the three
dimensional characteristics are conserved because of the fact that the right hemisphere is
dominant in treating spatial data necessary for building three-dimensional shapes.
On the other hand, the drawing made with the right hand, although it has correct
graphics, it lacks several of the spatial attributes, particularly the three-dimensional ones,
making it difficult to identify it. Consequently, the right hand is apraxic because of the
isolated left hemisphere that is not completely adapted for visuospatial tasks.
The location of the callous lesion that is responsible for the right constructive apraxia
is not precisely known. Degas et al. (1987) and Habib (1998) assume that right
hemisphere information that is necessary for the hemisphere borrow the fibres in the
junction between the splenium and the trunk of the corpus callosum in order to allow the
right hand to perform visual-constructive tasks.
The lesions located before this region are not accompanied by a constructive apraxia
(Kazuis and Sawanda, 1993), and keeping the splenium does not involve it happening.
Somesthesis
The somatosensory system is completely crossed. Thus, an object placed in the left
hand can be named because the tactile information projects to the right hemisphere,
crosses to the left, and subsequently has access to the speech zones. Similarly, if a subject
is blindfolded and the right hand is moulded to form a particular shape, the left hand is
able to copy the shape. The tactile information goes from the right hand to the left
1527
hemisphere and then across the corpus callosum to the right hemisphere, and the left hand
forms the same shape (Kolb and Whishaw, 2003).
The lack of interhemispheric transfer after hemisphere disconnection can be
demonstrated with respect to somesthesis (including touch, pressure, and proprioception)
in a variety of ways. The somatosensory functions of the left and right parts of the body
become independent.
Consequently, unseen objects in the right hand are handled, named, and described
in a normal fashion but the subjects with total callosotomy cannot do so if the object is
placed in the left hand, because the sensory input is disconnected from the left (speech)
hemisphere.
Thus, the most useful single sign of hemisphere disconnection is unilateral tactile
anomia: this is an inability to name or describe an object when it is left by one hand
whereas it is readily named (or well described if the name is unknown) when it is placed
into the other hand or when it is presented either to vision or to audition.
This unilateral tactile anomia was present in every patient with complete
commissurotomy studied by Gazzaniga and LeDoux (1978), McKeever et al. (1981) and
Bogen (1978), despite sparing the anterior commissure. Although there are many signs
of brain bisection, one of the most convincing ways to demonstrate hemisphere
disconnection is to ask the patient to feel with one hand then name various small, common
objects such as a button, coin, safety pin, paper clip, pencil stub, a rubber band or key.
Vision must be excluded (Bogen, 1987).
The patient with a hemisphere disconnection is generally unable to name or describe
an object in the left hand although he readily names objects in the right hand. Sometimes
the patient will give a vague description of the object although unable to name it, but
there is a contrast with the ability to name the object readily when it is placed into the
right hand.
The most certain proof that the object has been identified is for the subject to retrieve
it correctly from a collection of similar objects.
However, astereognosis can be reasonably excluded.
Specific posture impressed on one (unseen) hand by the examiner cannot be mimicked
in the opposite hand. A convenient way to test for lack of interhemispheric transfer of
proprioceptive information is as follows: the patient extends both hands beneath the opaque
screen (or vision is otherwise excluded) and the examiner impresses a particular posture
on one hand. For example, one can put the tip of the thumb against the tip of the little finger
and have the other three fingers fully extended and separated. The split-brain patient cannot
mimic with the other hand a posture being held by the first hand.
This procedure should be repeated with various postures and in both directions. After
complete commissurotomy there is a partial loss of the ability to name exact points
stimulated on the left side of the body.
This defect is least apparent, if at all, on the face and it is most apparent on the distal
parts, especially the finger tip. This deficit is not dependent upon language; it can be
shown in a nonverbal (picture identification) fashion, in which case the deficit is present
in both directions (right-to-left and vice versa) (Bogen, 1987).
1528
20. Corpus callosum
According to Bogen (1987), an easy way to demonstrate cross localisation of the

defect is to have the subject’s hand extended, palms up (with vision excluded). One
touches the tip of one of the four fingers with the point of a pencil, asking the patient to
then touch the same point with the tip of the thumb of the same hand. Repeating this
manoeuvre many times produces a numerical score, about 100% in normal people, for
either hand. In the absence of a parietal lesion, identification of any of the four finger
tips by putting the thumb tip upon the particular finger can be done at nearly 100% level
by the split-brain patient.
One then changes the task so that the finger tip is to be indicated, not by touching it
with the thumb of the same hand, but by touching the corresponding finger tip of the
other hand with the thumb of that (other) hand. Sometimes the procedure should be
demonstrated with the patient’s hand in full vision until the patient understands what is
required. This cross localisation cannot be done by the split-brain patient at much better
than chance level (25%), whereas most normal adults do better than 90%.
An incompetence to cross localize or cross match has been found in young children
(Galin et al., 1979) possibly because their commissures are not yet fully functioning
(Yakovlev and Lecours, 1967).
Nociceptive and thermal information is transmitted from the extra lemniscal
spinothalamic system through partially bilateral paths, which are not significantly
damaged by the disconnection following the callosotomy. Nevertheless, the hemispheric
disconnection might be highlighted as far as the fine tactile actions are concerned, as well
as in cases that need an active exploration (stereognosia, the recognition of physical
characteristics of stimuli, localizing of tactile areas) (Lassonde et al., 1996).
A right handed patient with a split-brain cannot, without seeing a familiar object
(spoon, fork, pencil, key, etc.) that he can touch with the left hand, but after numerous
manipulations he can give hints about the nociceptive character of the tip of the scissors,
the thermal aspect (cold metal), weight, and other attributes that help him identify the
object. The use of these hints, called “cross-cueing” or crisscross naming, is highly
common in patients with callosotomy, who try, consciously or not, to compensate their
deficits ( Lassonde et al., 1996 ).
Gazzaniga et al. (1962), Brion and Jedinak (1975) and McKeever et al. (1981)
described the details of anomia, but it is important to mark the fact that a left unilateral
anomia cannot be related to astereognosia, because the patient must choose a series of
stimuli that he perceives with the left hand.
Neither is it aphasia because he correctly names these objects with the right hand
(Barbizet and Duizabo, 1985). Consequently, a left tactile anomia is due to the fact that
the sensitive information that allows the recognition of an object reaches the right
hemisphere but cannot reach the speech area of the left hemisphere. A left visual anomia
is due to the fact that visual information coming from the left temporal visual area reaches
the right occipital region, but cannot reach the speech area located in the left hemisphere.
Finally, the patient with a divided brain cannot perform tasks that include
intermanual comparison. Without seeing, he cannot reproduce with one arm or hand the
specific postures of the opposite limb.
1529
According to Bentin et al. (1984) and Gaffen et al. (1985), one of the most sensitive
tests for evaluating the callous disconnection is that of crisscross tactile localisation. It
consists of applying light pressure upon the extremity of the finger, outside the visual
area of the patient. With the help of the thumb of the same hand, the patient indicates
without difficulty which of the fingers had been stimulated. If the tests are performed
separately with the fingers from the opposite hand the patient will be constantly wrong.
Audition
The auditory system is more complex than the other sensory system because it has
both crossed and uncrossed connections.
A naturally occurring lesion near the callosal trunk can result in the suppression of
one ear when tested dichotically. Hence, one might accept similar changes after a section
of the callosal trunk. However, several authors showed the place of the callosal transfer
of audible information.
Springer and Gazzaniga (1975) were the first to report a left dichotic extinction in a
case of a parietal callosotomy in which the splenium had been preserved. Musier and
Reeves (1986) noticed that complete callosotomies lead to an alteration of performance
of the left ear when undergoing dichotic tests. This fact explains the disruption of transfer
for verbal information that was initially received from the left ear / right hemisphere.
On the other hand, the two ears have a deficit in tests of pattern recognition for sound
frequency. This suggests that the test needs both hemispheres (Habib, 1998).
However, the performance of subjects with an anterior callosotomy are very variable,
therefore the conclusion that pertinent fibres for audible information transfer are located
in the posterior half of the commissurotomy. This fact had been confirmed in some cases
with spontaneous parietal lesions of the corpus callosum (Damasio et al., 1980; Degas et
al., 1987; Habib et al., 1990).
According to Damasio et al. (1980) and Degas et al. (1987), the splenial lesion had
been accompanied by an alteration of the dichotic hearing test. This fact suggests that
the passage of pertinent intertemporal fibres for audible transfer is located in the splenium.
Alexander and Warren (1988) came to the conclusion that the interhemispheric
passage of audible information is located near the somatosensorial information from the
posterior area of the trunk, i.e., the isthmus. Damasio and Damasio (1979), Poncet et al.
(1987) point out that in order to finish the extinction of the left ear it is necessary for the
callous fibres to be touched in general in the interior of the left hemisphere and not at the
level of the corpus callosum itself.
This “paradoxical extinction” of the left ear accompanied by a moderate aphasia
became the classic sign of a lesion of the profound white matter in the left hemisphere,
similar to the sensitive differentiation or ideomotor apraxia to which it is associated
(Poncet et al., 1987).
Therefore, the audible attributes are bilateral, but each sound stimulus is analysed
by both hemispheres due to the interhemispheric transfer through the corpus callosum.
Because the contralateral tracts are more important due to the number of fibres they
1530
20. Corpus callosum
contain, they are dominant over the information directed through the ipsilateral tracts.
Nevertheless, the patient with a split-brain can report with no difficulty the verbal or
nonverbal stimuli that are present in one ear only.
However, the verbal stimuli perceived by the right ear are analysed mainly by the
left temporal region (linguistic). Due to the fact that the right hemisphere is responsible
for musicality, the musical material is analysed with less difficulty in the left ear, from
where it is massively directed towards the right temporal area. However, after a cerebral
commissurotomy, the patient readily identifies single words (and other sounds) if they
are presented to one ear at a time.
But if different words are presented to the two ears simultaneously (“dichotic
listening”), only the words presented to the right ear will be reliably reported (Milner et
al., 1968; Sparks and Geschwind, 1968; Efron et al., 1977). Therefore, words played into
the left ear can travel directly to the hemisphere or can go to the right hemisphere and
then to the left through the corpus callosum. However, the direct access does not appear
to exist when the hemispheres are disconnected.
This large advantage of the right ear is usually considered the result of two concurrent
circumstances: (a) the ipsilateral pathway (from the left ear to the left hemisphere) is
suppressed by the presence of simultaneous but differing inputs, as it is in intact individuals
during dichotic listening (Kimura, 1967; Teng, 1981). (b) the contralateral pathway from
the left ear to the right hemisphere has now been severed and conveys information that
ordinarily reaches the left (speaking) hemisphere by the callosal pathway. Although left
ear words are rarely reported, their perception by the right hemisphere is occasionally
evidenced by appropriate actions of the left ear (Gordon, 1973).
Contralateral ear suppression commonly appears after hemispherectomy or the
creation of another large hemispheric lesion. Because there is usually suppressed by left
hemisphere lesions, the suppression of the left ear by a left hemisphere lesion has been
called “paradoxical ipsilateral extinction”. Further observations have led to the conclusion
that, whether the lesion is in the left or the right hemisphere, or if it is close to the midline,
the suppression of left ear stimuli is probably attributable to an interruption of
interhemispheric pathways (Sparks et al., 1970; Michel and Peronnet, 1975; Damasio
and Damasio, 1979).
In any case, the auditory effects are unlikely to be of clinical importance, although
one can anticipate certain patients in whom slight auditory alterations might be quite
important.
Olfaction
The olfactory tract is not essentially crisscrossed. The interhemispheric commu-
nication between the cortical areas responsible for the olfactory analysis is ensured rather
through the anterior commissure, than thorough the corpus callosum.
According to Bouchet and Cuilleret (1983), areas 23 and 24 of the anterior and
posterior region of the cingular circumvolution could be responsible for olfaction. Their
interhemispheric communication fibres transit, at least in monkeys, through the dorsal
facet of the corpus callosum.
1531
Fig. 20.9. Anosmia. (A) In the normal condition, olfactory input to the right nostril transvers directly back into the right
hemisphere and crosses the anterior commissure, thus gaining access to the left (speech) hemisphere. (B) Anosmia
results from section of the anterior commissure. (The jagged line indicates the lesion.) When the pathway is severed.,
the information is blocked, and the left hemisphere has no way of knowing what odor the right hemisphere perceived.
(after Kolb and Whishaw, 2003).
In humans no such fact could be confirmed. Therefore, there are no symptoms of

disconnection shown for this sensorial attribute, other than patients whose
commissurotomy included the anterior commissure (Risse et al., 1978). These patients
could not perceive smell presented in the right nostril with their right hemisphere to which
it was transmitted. Right anosmia does not hinder the left hand to find the object that
produces the sensation in a collection of stimuli (Gazzaniga et al., 1975). However, if
smell perceived by the right nostril is unpleasant, the subject may be disgusted, but cannot
verbally express the feeling (Gordon and Sperry, 1968).
A patient whose anterior commissure is severed cannot name odour presented to the
right nostril because the speaking left hemisphere is disconnected from the information.
The right hemisphere has the information but has no control of speech (Fig. 20.9) (Kolb
and Whishaw, 2003).
Thus, unlike all the other senses the olfactory system is not crossed. Input from the
left nostril goes straight back to the left hemisphere, and input from the right nostril goes
to the right hemisphere. Fibres travelling through the anterior commissure join the
olfactory regions in each hemisphere, just as fibres travelling thorough the corpus
callosum join the motor cortex of each hemisphere (Kolb and Whishaw, 2003).
The transfer of motor information

Movement
Observations by Akelaitis (1943) about the first patients with surgical callosotomies
show an extraordinary discretion of the neuropsychological changes induced by callous
sections.
1532
20. Corpus callosum
The most obvious change consists of the impossibility to perform two simultaneous
actions with each hand (Gazzaniga et al., 1967).
In fact, the most certain functional correlation in matter of the topographic anatomy
of the corpus callosum refers to the existence of important difficulties in bimanual
coordination consequent to sectioning the anterior half of the callous commissure.
Zaidel and Sperry (1977) observed that in 5-10 years after surgery an important
quantitative and qualitative alteration of bimanual coordination still persists during tasks
that involve either a rapid alternative movement of both hands, or a complex bimanual
coordination.
Kreuter et al. (1972) also demonstrated that during the synchronised or alternant
bimanual tapping test, the “split-brain” subjects cannot perform the task unless they
significantly slow down the rhythm of motor act.
Preilowski (1990), who studied the role of commissural fibres in bimanual
coordinated movements, believes one needs an unharmed anterior area of the corpus
callosum in order to complete these actions.
The information coming from a hemisphere needs to be transferred to the con-
tralateral hemisphere as an interhemispheric exchange of “motor corollary discharges”.
This role normally belongs to the premotor frontal cortex or more specifically to the
supplementary motor area (SMA) or the medial premotor system (Goldberg, 1985).
Through the genu of the corpus callosum, in the anterior area of the body, the SMA
is richly connected to the contralateral SMA as well as to the primary motor area. The
connections between the two motor and premotor systems of the corpus callosum are
crucial for performing coordinate actions with the two superior limbs.
However, a total callous section alters the synchronisation of the two hands more
severely than an anterior section. This fact suggests the partially compensatory role of
regions located more posterior which transmit proprioceptive information through the
presplenial region (Ellenberg and Sperry, 1979).
If a hand performs rapid alternative movements of pronation-supination one can
notice, particularly in children, the natural tendency of performing mirror movements
with the other hand (Njiokiktjien et al., 1986) when the subject is involved in a bimanual
activity. This tendency is found in subjects with callous agenesis, but is more severe.
Dennis (1976) supposes that this tendency of performing mirror gestures generally means
the callous transfer systems are immature.
Here, the corpus callosum has an inhibitory action that suppresses mirror involuntary
movements which disturb the coordinated bimanual movements.
For Dennis (1976), these inhibitory systems borrow the posterior region of the corpus
callosum. The callous connections may also play an important role in some motor
activities such as moving a hand during learning a particular motor action (Habib, 1998).
Therefore, patients with callosotomy present many disorders of interhemispheric
disconnections when a monomanual answer is expected. Thus, in right-handed patients,
writing with the left hand results in a unilateral left agraphia which is characterised by
drawing illegible letters of the alphabet, paragraphia, and the impossibility of copying
words if not written in printed form.
1533
These symptoms presented by the left hand (in right-handed patients) are
consequent to the fact that the right hemisphere is essentially aphasic, while writing
with the right hand (which depends on the left hemisphere) is normal. In the preoperatory
phase a unilateral left ideomotric apraxia appears, but only for verbal orders (Lassonde
et al., 1996).
However, according to Kolb and Whishaw (2003), because the motor system is
largely crossed, we might predict that the disconnection of the hemispheres will induce
a form of apraxia and agraphia, because the left hand would not receive instructions from
the left hemisphere. These disabilities would not be seen in the right hand because it has
access to the speech hemisphere.
So, if a patient was asked to use the right hand to copy a geometric design, it might
be impaired (acopia) because it is disconnected from the right hemisphere, which
ordinarily has a preferred role in rendering.
Preilowski (1975) and later Zaidel and Sperry (1977) stated that the severity of the
deficit declines significantly with the passage of time after surgery, possibly because the
left hemisphere’s ipsilateral control of movements is being used.
A second situation that might produce severe motor deficits in commissurotomy
patients is one in which the two arms must be used in cooperation.
Thus, patients were severely impaired at alternating tapping movements of the index
finger.
A high degree of manual cooperation is required to trace a diagonal line smoothly.
If the hemispheres have been disconnected, the cooperation is severely retarded, because
the left and right motor systems cannot gain information about what the opposite side is
doing, except indirectly by the patient’s watching them.
Dramatic illustrations of conflict between hands abound (Kolb and Whishaw, 2003).
It is of interest to note that while inhibiting these episodes of intermanual conflict
were able to use their left hands in a purposeful and cooperative manner when “not
thinking of what they were doing (Preilowski, 1975).
Praxic and graphometric activities

When there is a major disconnection between the two hemispheres, the language-
linked dominant hemisphere agent that maintains its primary control over the contralateral
dominant limb effectively loses its direct and linked control over the separate “agent”
based in the nondominant hemisphere (and, thus, the nondominant limb), which had been
previously responsive and “obedient” to the dominant agent. The possibility of purposeful
action in the nondominant limb occurring outside the realm of influence of the dominant
agent thus can occur (Goldberg and Goodwin, 2011).
Disturbing some general activities that reach only the left hemi-body following
surgical or spontaneous disconnection represents the most obvious test for specific praxic
functions in the left hemisphere. The locations of two lesions are capable of inducing it.
One affects the genu of the corpus callosum, probably through the disconnection of fibres
that interconnect the premotor areas (Geschwind and Kaplan, 1962) and another located
1534
20. Corpus callosum
in the posterior, at the level of the callous isthmus, engrams through the disconnection of
the left hemispheric motor (Heilman, 1979).
Therefore, one can distinguish two types of callous agraphies of the left hand: one
related to the disruption of premotor fibres from the anterior area of the corpus callosum,
characterised not only by affecting the handwriting but also the capacity of typewriting
or the use of letters on a mobile phone with the left hand.
The other one is related to the presplenial lesion which disconnects the left angular
gyrus and affects only handwriting.
Thus, the left hemisphere, which lacks the spatial support of the right hemisphere,
becomes apraxo-agnosic. The drawing or copying of a drawing which had been well
executed with the right hand before surgery becomes unrecognisable after operation. The
left hand may however reproduce the drawing. In this case, Bogen and Gazzaniga (1965)
speak about a constructive apraxia, and Preilowski (1975) and Zaidel and Sperry (1977)
speak about a dysfunction of the ability of bimanual motor coordination. The situation
becomes more dramatic when a task must be performed without seeing.
According to Watson and Heilman (1983), at the level of the left hemisphere, in
right handed people, there are two types of programs or engrams: a verbal-motor one,
that controls the linguistic nature of the written message, and another one named video-
kinaesthetic, that controls the graphic aspects that allow a spatial-temporal structure.
Finally, Sugishita et al. (1980) and Gersh and Damasio (1981) insist upon the
dissociated character of callous apraxia and agraphia. Degas et al. (1987) consider that a
lesion of the splenium, and of the posterior fourth of the body of the corpus callosum,
provoked agraphia without left apraxia.
Kazuis and Sawada (1993) had a patient with a lesion located in the posterior half
of the body of the corpus callosum leaving the juxta-splenial area of the isthmus intact.
They observed this patient showed left apraxia without agraphia.
These data show that the interhemispheric fibres that allow the transfer of graphic
information from the left to the right hemisphere are located in the posterior area of the
body of the corpus callosum and those that control the gestures of the left hand are located
in its anterior region.
Thus, if a lesion of the corpus callosum disconnects the left hand from the left
hemisphere, that hand is unable to respond to verbal commands and is considered apraxic.
Suppose, however, that the right hand is unable to respond to verbal commands.
Geschwind (1965) speculated that this deficit results from a lesion in the left hemisphere
that disconnects its motor cortex (which controls the right hand) from the speech zone
(Fig. 20.10). Thus, the right hand cannot respond to verbal commands and is considered
apraxic.
Although Geschwind’s model can explain bilateral apraxia in some patients, it must be
emphasized that disconnection is not the only cause of apraxia. Because the posterior cortex
has direct access to the subcortical neural mechanisms of arm and body movements, parietal
input need not go through the motor cortex, except for the control of finger movements.
Further, patients with sections of the corpus callosum are initially apraxic but show substantial
recovery despite a disconnection of the motor cortex of the left and right hemisphere.
1535
Fig. 20.10. Frontal commissurotomy: Sketched here are the structures sectioned during a frontal commissurotomy.
This includes most of the corpus callosum (sparing the splenium), the ventral hippocampal commissure
(between the fornices), and the anterior commissure (after Bogen, 1987).
A diagnosed apraxia is a rare manifestation, but a more spectacular one of this

intercortical disconnection (Brion and Jedynak, 1975; Poncet, 1983; Bogen, 1985). The
cited example is of a female patient who was struggling to button her shirt with the right
hand, while she was doing the opposite with the left one.
This complex, variable behavior showed that what appears to be the effect of the
callous lesion is due to a self and contradictory activity of the right hemisphere that is
freed by the control of the left hemisphere which is normally dominant.
Tanaka et al. (1996) compared through MRI the callous lesions of three patients
suffering from this syndrome and noticed that the diagnosed dyspraxia appears after a
lesion that specifically affects the most posterior area of the callous body, which passes
through a region of fibres that unite the left and right superior parietal areas.
Authors came to the conclusion that a diagnosed apraxia is due to the disconnection
between the superior left parietal lobe, which is dominant for voluntary control of
movement, and the right hemisphere, which controls the movements of the left hand.
Even though it is tempting, this hypothesis has not yet been confirmed (Habib, 1998).
Consequently, a diagnosed apraxia is a complex behavior in which the left hand or even
the assembly of the left hemi-body performs elaborate actions which come against the
free will of the patient.
1536
20. Corpus callosum
Agnosia and alexia

Geschwind (1965) theorized that agnosia and alexia can disconnect the posterior
speech area from the visual association cortex. Both symptoms can be produced by a
lesion that disconnects the visual association region on the left from the speech zone or
by a lesion that disconnects the right visual association cortex from the speech zone by
damaging the corpus callosum. Thus, the patient, although able to talk, is unable to
identify words or objects, because the visual information is disconnected from the
posterior speech zone in the left hemisphere (Kolb and Whishaw, 2003).
Transfer of complex asymmetrically organized information

What best differentiates the human brain from that of other mammals is mainly its
asymmetrical way of functioning. Diverse functions known as cognitive functions mainly
depend on either one or the other hemisphere. A lesion of the corpus callosum may disrupt
the access of a certain function of the so called “minor” hemisphere to the contralateral
hemisphere which is able to better or even exclusively treat the given information.
Unilateral apraxia
In 1907, Liepmann and Maas described a patient with a right hemiparesis from a
lesion of the pons. The patient also had a lesion of the corpus callosum. This patient was
unable to correctly pantomime to command with his left arm. Because he had a right
hemiparesis, his right hand could not be tested.
Since the work of Broca, it has been known that right-handers’ left hemisphere is
dominant for language. Liepmann and Maas could have attributed their patient’s inability
to pantomime to a disconnection between language and motor areas so that the left
hemisphere that mediates comprehension of verbal commands could not influence the
right hemisphere’s motor areas that are responsible for controlling the left hand.
However, this patient also could not initiate gestures or correctly use actual tools or
objects, therefore, a language-motor disconnection could not account for these findings.
Liepmann and Maas posited that the left hemisphere of right-handers contains movement
formulas and that the callosal lesion in this patient disconnected these movement formulas
from the right hemisphere’s motor areas.
Geschwind and Kaplan in 1962, Geschwind in 1965, and Gazzaniga et al. (1967)
also found that their patients with callosal disconnection could not correctly pantomime
to command with the left hand. Unlike the patient reported by Liepmann and Maas,
however, their patients could imitate and correctly use actual tools and objects with the
left hand. The preserved ability to imitate and use actual tools and objects suggests that
the inability to gesture to command in these patients with callosal lesions was induced
by a language-motor disconnection rather than a movement formula-motor disconnection.
In addition, a disconnection between the movement formula and motor areas should
produce spatial and temporal errors, but many of the errors made by Liepmann and Maas’
patient appeared to be content errors. In 1983, Watson and Heilman described a patient
with an infarction limited to the body of the corpus callosum. Their patient had no
1537
weakness in her right hand and performed all tasks flawlessly with her right hand. With
her left hand, however, she could not correctly pantomime to command, imitate, or use
actual tools. Immediately after her cerebral infarction she made some content errors, but
later on, she made primarily spatial and temporal errors.
Her performance indicated that not only language but also movement representations
were stored in her left hemisphere and that her callosal lesion disconnected these
movement formulas from the right hemisphere.
Thus, left limb dispraxia can be attributed to the simultaneous presence of two
deficits: poor comprehension by the right hemisphere (which has good control over the
left hand) and poor ipsilateral control by the left hemisphere (which understands the
commands).
Failure to correctly position a limb, to move the limb correctly in space, and to
properly orient the limb is called ideomotor apraxia. Apraxia has been subclassified
into ideational apraxia, and limb-kinetic apraxia (Liepmann, 1900).
Ideational apraxia is a loss of the conception of a gesture or skilled movement. In
this form, the patient does not seem to know what to do, and the motor activity is not
facilitated by the use of actual objects.
Ideomotor apraxia affects the implementation of movement, producing spatial and
timing errors. The patient seems to know what to do but cannot carry movement out
properly.
Limb-kinetic apraxia refers to clumsiness, awkwardness of a limb in the perfor-
mance of a skilled act that cannot be accounted for by paresis, ataxia, or sensory loss.
This apraxia manifested by the inability to make finely graded, precise limb movements.
Apraxia may be differentiated by the body elements involved in the impaired
movement, using the term limb apraxia, oral or buccofacial apraxia, trunk or axial apraxia.
The terms dressing apraxia and constructional apraxia are sometimes used to
describe certain symptoms of unilateral extinction or neglect (amorphosynthesis) that
characterize partial lobe lesions.
These patients also make temporal errors and may fail to correctly imitate
movements, but some patients imitate worse than they gesture in response to command.
In right-handed individuals, ideomotor apraxia is almost always associated with left
hemisphere lesions, but in left-handers, ideomotor apraxia is usually associated with right
hemisphere lesions. Ideomotor apraxia is associated with lesions in a variety of structures,
including the corpus callosum, the inferior parietal lobe, and the premotor areas.
Ideomotor apraxia has also been reported with subcortical lesions that involve the
basal ganglia and white matter.
Alien hand syndrome. Symptoms: anarchic hand, callosal apraxia, diagnostic
dyspraxia, Dr. Strangelove syndrome, intermanual conflict, magnetic apraxia, wayward hand.
Alien hand syndrome is a relatively rare manifestation of damage to specific brain
regions involved in voluntary movement (Goldberg and Goodwin, 2011). The core
observation is the patient’s report that one of his / her hand is displaying purposeful,
coordinated, and goal-directed behavior over which the patient feels he / she has no
1538
20. Corpus callosum
voluntary control. The hand seems to possess the capability of acting autonomously,
independent of their conscious voluntary control.
The patient fails to recognize the action of one of his hands as his own. The hand,
effectively, appears to manifest a “will of its own” (Goldberg and Goodwin, 2011).
This definition excludes disordered, non-purposeful, and dyskinetic movements
associated with other involuntary movement disorders.
Three forms of alien hand syndrome have been described: frontal, callosal, and
posterior.
The frontal form is associated with damage to the medial surface of the cerebral
hemisphere in the frontal region. The frontal variant involves the medial aspect of the
premotor cortex anterior to the primary motor cortex including the supplementary motor
area and anterior cingulate cortex. Generally, these alien behaviours appear in the hand
contralateral to the damaged hemisphere regardless of hemispheric dominance.
The posterior or “sensory” form appears most often with a parietal or parieto-
occipital focus of circumscribed damage (Pack et al., 2002). As in the frontal variant, the
alien behavior appears in the hand contralateral to the damaged hemisphere. The
movement of the affected alien limb is typically less organized and often has an ataxic
instability particularly with visually guided reaching. The limb may also show pro-
prioceptive sensory impairments with hypaesthesia, so that the kinaesthetic impairment
limits the monitoring of limb position. Visual field deficits as well as hemi-inattention
may be seen on the same side as the alien hand (Goldberg and Goodwin, 2011).
Alien hand behavior has also been reported in association with a subcortical thalamic
infarction.
The fMRI study of cortical activation patterns associated with alien and non-alien
movement has demonstrated that alien movement is in fact characterized by the isolated
activation of the primary motor cortex in concert with the activation of interhemispheric
premotor regions (Assal et al., 2007).
The callosal form is seen with an isolated lesion of the corpus callosum.
The voluntary motor systems of the two hemispheres are isolated from each other
due to lost interhemispheric communication following callosotomy.
In the “callosal” variant of alien hand syndrome, the appearance of “intermanual
conflict” or “self-oppositional” behaviours is the predominant feature (Goldberg and
Goodwin, 2011). In the callosal variant, the problematic alien hand is consistently the
nondominant hand, while the dominant hand is the identified “good”, controlled hand.
The patient may express frustration and bewilderment at the conflicting and disruptive
behavior of the alien hand whose motivations remain inaccessible to consciousness
(Goldberg and Goodwin, 2011).
There may be an attentional component that modulates the appearance of these episodes
of self-oppositional behavior since intermanual conflict is observed more frequently when
the patient is fatigued, stressed, or is engaged in effortful multitasking activity.
1539
Occasionally, the two hands are observed to be engaged in two different and entirely
unrelated activities as if being guided by completely separate and independent intentions
(Goldberg and Goodwin, 2011).
The callosal and frontal variants are often seen in combination with a corresponding
overlap of observed behavior. However, a clear differentiation between an apparent
intermanual conflict due to attempts to restrain alien behaviours associated with the
frontal variant, and a true intermanual conflict, in which the two hands are directed
towards an independently contradictory purpose, may be difficult to make (Biran and
Chatterjee, 2004).
The patient may become fearful that they will be held accountable for consequences
of an action of the alien hand over which they do not feel control (Giovannetti et al., 2005).
The patient may display “auto-criticism” complaining that the alien hand is not doing
what it has been “told to do” and is therefore characterized as disobedient, wayward, or
“evil”. Given the predicament created, the patients may develop depersonalization and
dissociate themselves from the unintended actions of the hand (Biran and Chatterjee,
2004; Giovannetti et al., 2005; Assal et al., 2007; Sumner and Husain, 2008; Goldberg
and Goodwin, 2011).
In alien hand syndrome, different regions of the brain are able to command purposeful
limb movements, without generating conscious feeling or self-control over these
movements. This process, impaired in alien hand syndrome, normally produces the
conscious sensation that movement is being internally initiated and produced by an active
self (Frith et al., 2000; Scepkowski and Cronin-Golomb, 2003; Sumner and Husain, 2008).
However, an evaluation of callosal apraxia and impairment of interhemispheric
transfer of information should be included. There is no definitive treatment for the alien
syndrome but a number of different rehabilitative approaches have been described.
Corpus callosum and memory

Changes in mnemonic capacity after callosotomy are due to lesions of the discrete
processing capacities in the isolated hemispheres.
Loss of general memory capacity as measured by standardised tests has been
reported for same patients (Zaidel and Sperry, 1974; Zaidel, 1990). Clark and Geffen
(1989) suggested that discrepancies in memory function reported after callosotomy might
be due to the involvement of the hippocampal commissure.
Phelps et al. (1991) observed a decrease in verbal and visual recall following a
posterior callosal section, which may damage the hippocampal commissure, but preserved
or even improved memory after an anterior callosal section. Recognition memory was
relatively intact in both groups.
The left hemisphere appears to make greater use of general knowledge schemas to
explain perceptions and experiences and to use them to “interpret“ events, than does the
right hemisphere, and this predilection has an impact on the accuracy of memory
(Gazzaniga, 1985; Phelps and Gazzaniga, 1992). A left hemisphere “interpreter” constructs
theories to assimilate perceived information into a comprehensible whole. By doing so,
1540
20. Corpus callosum
however, the elaborative processing involved has a deleterious effect on the accuracy of
perceptual recognition.
This result extended to include verbal material (Metcalfe et al., 1995).
However, this predilection has an important role in memory accuracy (Baynes and
Gazzaniga, 1997). Thus, the left hemisphere interprets the theoretical constructions by
assimilating information in a comprehensible whole with the help of verbal material.
Corpus callosum and attention

The cerebral substrate of attention mechanisms as well as that of other cognitive
functions is now considered to be overlapping an assembly of interconnected neurons that
are organized in a distributive network. Part of it is functionally lateralized in the right
hemisphere of the human brain (Mesulam, 1990). Several authors proved that the corpus
callosum does not possess a primary role in the distribution of attention resources in the
two hemispheres; therefore it acts as a regulator that is capable to distribute cognitive energy
to each hemisphere according to the existence of each situation and task.
According to Levy (1974), the regulation of the awakening function and its
distribution between hemispheres depends on the reciprocal inhibition from the level of
the brain stem and the reciprocal facilitation in the corpus callosum.
In “split-brain” subjects, there were reports about certain attention disorders both
during general awakening (Diamond et al., 1977) and during the distribution of attention
in the outside space of the body (Ellenberg and Sperry, 1979).
In Kinsbourne’s model, the regulation of attention involves the existence of an
interaction between the controlled activity of one hemisphere by mesencephalic structures
and the reciprocal inhibiting or facilitating relation achieved through the corpus callosum
(Kinsbourne, 1970 and 1973). Each hemisphere controls the attention from the
contralateral perceptive area and the activity balance between hemispheres appears to be
a result of the interaction between the activity of the mesencephalic systems and the
inhibition / facilitation game with the callous fibres (Habib, 1998).
According to this model, the most competent hemisphere in a certain task increases
its level of activity in a specific manner, while the opposite hemisphere decreases it.
Therefore, the role played by the corpus callosum is essential in ensuring the modulation
of equilibrium depending not only on the cognitive attributes of the task, but also on non-
specific factors such as motivation, the difficulty of the task or a voluntary attention path.
A particular case is the one of two competing tasks. In this situation, the capacity of the
receptor hemisphere for one task can be rather active than inhibited, which depends on
the attributes of the competing task (Kinsbourne, 1973). This reveals the attention control
through hemisphere interaction.
In subjects with a commissurotomy, the observed symptoms are interpreted by
Kinsbourne not as an interruption of a path that allows passage of information, but as the
inactive hemisphere being incapable of ensuring the treatment of information that it is
less specialized for.
1541
A similar explanation is given by Mayer et al. (1988) in a subject with a spontaneous

callous lesion who presented an extinction of the left hand in the task of dichaptic
palpation. However, with the help of sight the authors managed to attract the patient’s
attention to the left hand.
Concerning this tactile-kinaesthetic model, scientists came to the conclusion that
attracting attention towards the tactile recognition of the left hand by changing the
procedure suggests the special role played by the corpus callosum in the attention
mechanisms.
Corpus callosum and the emotional function

Amongst the cerebral functions that are asymmetrically organized, the emotional
functions are, without doubt, the ones with a very uncertain anatomical substrate.
Neuropsychologists admit that the right hemisphere is specialized in the treatment of
emotional information, both at a perceptive level and at an expressive level. In case of a
lesion of the right hemisphere, revealing emotional control disorders (anosodiaphoria,
anosognosia, hemiasomatognosia, affective indifference) and disorders of the prosody
of speech, represent two more valid examples.
On an intact brain it is difficult to measure the importance of the corpus callosum in
the support mechanisms of these functions. In patients with commissurotomy, Sperry et
al. (1979) presented emotional stimuli to the right hemisphere of “split-brain” subjects.
They noticed that the “affective aura”, meaning the poorly defined feeling of an affective
event immediately goes to the left hemisphere, through subcallous connections that unite
the limbic structures, the place where the emotional experience is probably built. The
only role in this field presently given to the corpus callosum is that of allowing an
individual who has an affective stimulus with characteristics best analysed by the right
hemisphere, to give a cognitive judgment and a verbal meaning to the stimulus.
Hoppe and Bogen (1977) and then Ten Houten et al. (1986) suggested applying the
concept of alexithymia (characterizing some difficulties in verbalizing emotions presented
to psychosomatic patients) to subjects with commissurotomy. The degree of ease or
difficulty the subject encounters in the verbal test of expressing emotion as well as
expressing the richness or purpose of his fantastic world are highly discriminative
between normal subjects and “split-brain” subjects. This fact suggests how a high degree
of alexithymia appears after a callous section and the important role of the corpus
callosum in the respective transfer of information.
The interhemispheric transfer of elaborate behavior

In this model of connectivity for premotor systems, Goldberg (1985) suggests that
each of the two median premotor systems (SMA and the neighbouring cortex), have,
among other functions, the role of volitional control of movements in the opposite
hemibody.
In lesions of the median facet of the frontal lobe, which also simultaneously involve
the SMA and the callous fibres, the author often observed an unusual behavior of the
1542
20. Corpus callosum
hemi-body that is opposite to the lesion, in which the superior limb has the tendency of
performing movements without voluntary control of the subject.
Thus, most often appear movements of attraction to a certain visual target with the
purpose of grabbing the objects that are close. Goldberg associates this behavior to an
excessive addiction of the motor cortex to the environment, because the motor cortex is
freed of the premotor median cortical control and left under the influence of only the
lateral system (its role is to control movements oriented as a response to stimuli from the
environment).
Goldberg calls this “foreign hand sign” behavior, which is often misinterpreted.
This is why Poncet et al. (1987) replaces the term with “stubborn hand“. This
symptom must be differentiated from the motor behavior observed after a callous lesion,
which is called apraxia.
In practice, it is important to make a difference between the stubborn hand sign and
the apraxia. The first is related to a double lesion, both median frontal and callous, which
affects the hand opposite to the harmed frontal lobe, and the latter appears only after a
callous lesion that affects exclusively the superior left limb (Habib, 1998).
The median fusion

The median fusion is the process that ensures the continuity of the proprio- and
exteroceptive space, beyond the median line (Lassonde et al., 1996). Thus, the stimuli of
a hemi-body or a hemi-visual field stimulate the neurons in one hemisphere, and after
passing through the median line they also stimulate the ones in the opposite hemisphere,
without recording any discontinuity, because the second hemisphere had already been
prepared to receive this information through the corpus callosum (Guillemot et al., 1987,
1988). Most callous connections of the motor and sensitive cortical regions from the
anterior area of the corpus callosum are designed, from a functional point of view, for
the median line of the corpus (the trunk) and to a smaller extend they are designed for
the proximal regions of the limbs (Manzoni et al., 1980; McKenna et al., 1981; Pandya
and Seltzer, 1986; Innocenti, 1986; Lepore et al., 1986; Guillemot et al., 1988).
Exploring the somato-sensorial sensitivity thresholds through the discrimination test
for two points, shows that the thresholds are indeed higher for the axial corporal region
(trunk) both in subjects with no corpus callosum and in those with callosotomy. In the case
of visual testing, the receptor fields of the callous neurons are found near the vertical
meridian, which they reach and sometimes cross (Berlucchi, 1972, 1983; Lepore et al., 1983).
Subjects with no corpus callosum are incapable of evaluating the distance between
stimuli if they must use the parallax movement index in their central vision (Rivest et
al., 1996). It even seems that cells from the primary additive cortex that are tight to the
corpus callosum functionally correspond to the omnidirectional cells involved in the
analysis of sound in the central area of the hearing field or in the perception of sounds
presented in front of the subject (Imig et al., 1986).
In tests of indicating the location of fixed sound and in those that simulate movement,
the results showed an inferior performance of subjects with no corpus callosum compared
1543
to the witnesses, both for sounds transmitted for the pericentral region and for sounds
transmitted for the lateral region. These data do not seem to support the hypothesis of a
privileged relation of the corpus callosum with the median line (Poirier et al., 1993).
Consequently, the entire pathology of the callous system should affect the median fusion
process because it is certain that the corpus callosum participates in the making of this
median fusion.
However, participation is more important for the systems that are certainly contra-
lateralized (visual, and lemniscal somatosensorial (Lepore et al., 1994; Lassonde et al., 1996).
Interhemispheric transfer time

The interhemispheric transfer time, which is tributary to the integrity of the callous
commissure, is prolonged (30 – 87 milliseconds) (Sergent and Myers, 1985; Di Stefano et
al., 1992), in people with commissurotomy compared to normal subjects (2 milliseconds)
(Berlucchi et al., 1977; Berlucchi, 1990).
A longer reaction period of 12.7 to 50.5 milliseconds had also been noticed with the
help of simple tests of video-motor reaction in persons with no corpus callosum (Milner
and Lines, 1982; Rugg et al., 1984).
Syndromes after callosotomy

Frontal commissurotomy
By “frontal commissurotomy”, Gordon et al. (1971) refer to a section of the anterior
two-thirds of the corpus callosum together with the anterior commissurotomy. A section
of the anterior commissure was done under direct vision and the third ventricle was entered
between the two fornices so the section also included the ventral hippocampal commissure
(Fig. 20.10). The same operation was used on a few occasions by Wilson et al. (1977).
Because these patients had retraction within the third ventricle to allow section of
the anterior commissure under direct vision, mutism in cases with more extensive sections
was not likely of third ventricular origin (Bogen, 1987). All of these patients had
retraction of the medial aspect of the right frontal lobe, comparable with that in the
complete cases: therefore the retraction on the supplementary motor cortex does not seem
to be a sufficient explanation for mutism after callosotomy (Bogen, 1987).
In the long term, Preilowski (1972) could show some deficits of motor coordination
in two patients with frontal commissurotomy. But exhaustive testing for usual
disconnection deficits has shown that, with retention of splenium, such deficits should
not be expected (Gordon et al., 1971; Gazzaniga et al., 1975; Greenblatt et al., 1980;
Bogen et al., 1981).
The patient of Geschwind and Kaplan (1962) that presented on operated left frontal
glioma and an accidental lesion of the anterior cerebral artery, was writing normally with
the right hand according to dictation, but had an aphasic behavior of the left hand. This
patient could not recognize the objects he was holding with the left hand, although he
could do it with the same hand put in front of a group of objects. The authors imagined
a lesion of the corpus callosum (confirmed by autopsy) that did not affect the splenium,
1544
20. Corpus callosum
but led to an interruption of the callous tract between the motor centres in the right
hemisphere which controls the left hand and the speech areas located near the left
hemisphere.
Gersh and Damasio (1981) reported cases of people with apraxia but no agraphia of
the left hand that followed the sectioning of the anterior region of the trunk in the corpus
callosum. The authors came to the conclusion that praxic impulses use fronto-frontal
tracts, thus the apraxia, but no agraphia of the left hand, appear when the section affects
exclusively the anterior area of the trunk in the corpus callosum.
Risse et al. (1989) noticed that the sectioning of the two-thirds located in the anterior
area of the corpus callosum leads to small or no changes. Here an example (Fig. 20.11).
Fig. 20.11. Anterior callosotomy. This sketch shows how anterior callosotomy differs from frontal commissurotomy.
There are two principal differences: the anterior commissure is spared, and third ventricle is not entered
by separating the fornices (after Bogen, 1987).
In the case of a larger anterior section there appears a disruption of the ability to
transfer sensorial and position information from one hand to the other. On the contrary,
a section of the splenium disrupts the transfer of visual information between hemispheres
and isolates the lateral visual inputs.
Thus, a section of the corpus callosum that spares the splenium (as well as the
anterior commissure) but is otherwise complete can be readily accomplished via an
1545
exposure anterior to the rolandic bridging vein (Bogen, 1987). This procedure which
avoids entry into the third ventricle has come to be the most popular version of
commissural section for epilepsy or tumors. After this operation one does not observe
most of the acute disconnection syndrome. This smoother postoperative course is not
surprising because the acute disconnection syndrome does not usually occur after frontal
commissurotomy, which is essentially the same procedure plus a section of the anterior
commissure and massa intermedia.
Absence of significant mutism with callosotomy sparing the splenium has been
reported by Rayport et al. (1985) and Bogen (1987).
Ross et al. (1984) reported transient (1- to 10- day) mutism with this procedure. This
difference could depend upon the amount of retraction particularly if there has been a
retraction of the left hemisphere below the falx as well as the usual right hemisphere
retraction. Even a lesser callosal section may be followed by mutism when it is associated
with a concurrent thalamic lesion (Bogen, 1987).
Midcallosal section
A midcallosal section is an incision through the trunk sparing not only the splenium
but also most of the genu. Such an incision affords ready access to the foramina of Monro
with practically no obligatory physiological cost as presently assessable (Gordon et al.,
1971; Ozgur et al., 1977; Shucart and Stein, 1978; Winston et al., 1979; Long and Leibrock,
1980; Antunes et al., 1980; Apuzzo et al., 1982). I operated on 115 cases of tumors of the
third ventricle. The clinical picture was dominated by the signs of intracranial hypertension.
Neuropsychological signs (40%) were sometimes under-estimated, revealing the disease
in only 17% of cases. Ophthalmologic signs and endocrine disorders have been found in
32% of these cases. In planning the surgical approach, we took into account the localization
and size of the tumors: transcallosal approach for the third ventricle, primary tumors (58,2%)
(Figures 20.12, 20.13, 20.14, 20.15).
Microsurgery has been used in all cases – Laser with CO2 and Nd: YAG was used
in 12 (10,4%) cases.
The somesthetic nontransfer has not been detected in most cases of midcallosal
section. But if the task is made more difficult, so that normal individuals commonly make
mistakes, some deficits (as compared with normal subjects) have been elicited.
Splenial section
In the case of a section of the posterior half of the trunk, the agraphia of the left hand
with no associated apraxia is due to the fact that the graphic impulses transit over the
posterior area, through parietal tracts.
The visual interhemispheric transfer is done especially through the splenium. A
lesion at this level leads to alexia without agraphia (Figures 20.16, 20.17, 20.18, 20.19,
20.20, 20.21).
1546
20. Corpus callosum
A B
C D
Fig. 20.12. (A and B) Preoperative coronal and sagittal T1-weighted gadolinium-enhanced MRI demonstrating details
of an anterior giant cystic craniopharyngioma with sellar enlargement, and suprasellar component and cystic
extension into the third ventricle. (C and D) images were obtained after almost complete removal of tumor with very
good results. Excision was accomplished through a midline anterior transcallosal and interfornicial corridor.
Thus, whereas more anterior section of the corpus callosum entails minimal long
term physiological cost, a section of the splenium commonly causes a left hemialexia
(Trescher and Ford, 1937; Maspes, 1948; Wechsler, 1972; Iwata et al., 1974; Damasio
et al., 1980). This inability to read in the left visual half-field may be accompanied by a
so called colour anomia, an inability to give the names of colours presented to the
patient’s view although the colours can be matched and the patient can give (speak or
write) the colour names of objects, for example “yellow“ when asked the colour of a
banana (Geschwind and Fusillo, 1966).
When the hemialexia and associated deficits are more severe they can be mistaken
for a left homonymous hemianopsia.
1547
A B
Fig. 20.13. (A) A contrast enhanced axial CT-scan of a 32-year-old man with a large third ventricle tumor
(craniopharyngioma). (B) Axial CT-scan, 6 months, postoperatively, confirming total removal of the tumor with
excellent results. Excision was accomplished through a midline anterior transcallosal corridor.
A B
Fig. 20.14. (A) Sagittal MRI demonstrating details of a big third ventricular tumor (dermoid cyst) who was excized
transcallosal with very good results. (B) Sagittal MRI after complete removal of the tumor.
In a review (Sugishita et al., 1985), hemialexia is considered of two types: an

inability to match written words with objects and an inability to read aloud written words
or letters. Both of these are said to be mimicked by the condition of visual hemineglect.
The splenial disconnection can be quite crippling for almost any literate person when
the callosal lesion is combined with left occipital lesions or indeed any lesion causing a
right hemianopsia.
Such individuals typically have alexia without agraphia: that is, they can write but
are unable to read, even what they have just written correctly to dictation. This remarkable
dissociation of reading from writing has been known for nearly a century (Déjérine, 1892;
Benson, 1985).
1548
20. Corpus callosum
A B
C D
Fig. 20.15. (A and B) Preoperative coronal and sagittal T1-weighted gadolinium-enhanced MRI demonstrating of an
anterior third ventricle tumor (astrocytoma). (C and D). Images were obtained after complete removal of the tumor
with excellent results. Excision was accomplished through a midline transcallosal approach.
In splenial lesions the right occipital cortex is disconnected from the left hemisphere.
Thus, the left hemisphere retains competence to write to dictation but no longer has access
to information arriving in the right occipital lobe from the left visual half-field.
Generally, alexia is a cortical disorder of reception in which there is a loss of the
ability to comprehend written material manifested as an impairment of reading. Those
afflicted with alexia have at one time the ability to read but no longer comprehend written
material.
1549
A B
Fig. 20.16. (A) Contrast enhanced axial CT-scan in a 39-year-old woman shows a large, well-delimitated pineal
region tumor (meningioma). (B) Postoperative CT-scan after total removal of the tumor.
A B
Fig. 20.17. (A) CT-scan showing a large pineal region tumor with involvement of the third and lateral ventricle.
(B) Postoperative CT-scan after the excision of that pineal region tumor (germinoma).
Hemialexia is the loss of reading ability in the nondominant visual field as the result
of a surgical section of the corpus callosum.
Alexia without agraphia (visual verbal agnosia) is a syndrome, in which a literate
person loses the ability to read aloud, to understand written script, and, often, to name
colours, i.e., to match a seen colour to its spoken name – visual verbal colour anomia.
Such a person can no longer name or point on command to words, although he is
sometimes able to read letters or numbers (Adams et al., 1997).
1550
20. Corpus callosum
A B
C D
Fig. 20.18. (A and B) Sagittal and coronal T1-weight gadolinium-enhanced MRI, demonstrating a medium-sized
pineocytoma. (C and D) Postoperative MRI after total removal of the tumor.
Understanding spoken language, repetition of what is heard, writing spontaneously

and to dictation, and conversation are all intact. The ability to copy words is impaired
but is better preserved than reading, and the patient may even be able to spell a word or
to identify a word by having it spelled to him or by reading one letter at a time (letter-by-
letter reading). In some cases, the patient manages to read simple letters but not join them
together (asyllabia).
The most striking feature of the syndrome is the retained capacity to write fluently,
after which the patient cannot read what has been written (alexia without agraphia).
When the patient with alexia or dyslexia also has difficulty in auditory
comprehension and in repeating spoken words, the syndrome corresponds to Wernicke’s
aphasia (Adams et al., 1997).
1551
A B
Fig. 20.19. (A) Contrast enhanced axial CT-scan shows a large germinoma of the pineal region with involvement of
the third ventricle. (B) Postoperative CT-scan (five month after operation) shows total removal of the tumor.
A B
Fig. 20.20. (A) Sagittal T1-weight gadolinium-enhanced MRI in a 31-year-old male patient, shows a pineal tumor.
(B) Postoperative MRI after removal of a germinoma. The tumor was removed by the infratentorial
supracerebellar approach.
Autopsies of such cases have usually demonstrated a lesion that destroys the left
visual cortex, and underlining white matter, particularly the geniculocalcarine tract, as
well as the connection of the right visual cortex with the intact language areas of the
dominant hemisphere.
In the case originally described by Déjérine (1892), the disconnection occurred in
the posterior part (splenium) of the corpus callosum, wherein lie the connection between
the visual association areas of the two hemispheres.
1552
20. Corpus callosum
A B
Fig. 20.21. (A) Contrast enhanced axial CT-scan in a 27-year-old woman shows a medium-sized pineoblastoma.
(B) Postoperative CT-scan after total removal of the tumor.
More often, the callosal pathways are interrupted in the forceps major or in the
paraventricular region (Damasio and Damasio, 1983). In either event, the patient is blind
in the right half of each visual field by virtue of the left occipital lesion, and visual
information reaches only the right occipital lobe; however, this information cannot be
transferred, via the callosal pathways, to the cingular gyrus of the left (dominant)
hemisphere.
A lesion deep in the white matter of the left occipital lobe at its junction with parietal
lobe interrupts the projection from the intact visual cortex to the language areas but spares
the geniculocalcarine pathway (Greenblatt, 1973).
This lesion, coupled with the one in the splenium, prevents all visual information
from reaching the language areas, including the angular gyrus and Wernicke’s area.
In yet other cases, the lesion is confined to the cingular gyrus, or the subjacent white
matter. In such cases a right homonymous hemianopsia will also be absent but the alexia
may be combined with agraphia, with anomic aphasia and other elements of the
Gerstmann syndrome, i.e., right-left confusion, acalculia, and finger agnosia. The entire
constellation of symptoms is referred to as the syndrome of the angular gyrus.
Alexia, with agraphia, is an acquired inability to read and write. The lesion is
probably localised in the left angular gyrus of the parietal lobe (the left cerebral
hemisphere is dominant for language in 95% of humans), corresponding to Brodmann’s
area 39. Such patients can comprehend spoken words. Alexia without agraphia is a rare
and uncommon disorder, in which patients write fluently, but cannot read what they have
written. They cannot read words or letters, but can read numbers. The injury usually
involves the dominant medial occipital lobe. The intact right primary visual cortex has
probably lost its connection with the intact dominant visual language area, particularly
1553
the angular gyrus. Patients see words, but cannot make the associations necessary for
their identification. Some patients are able to learn to trace letters with their fingers or
use ocular movements to identify these letters, and thus read, though slowly and
inefficiently. Thus, the visual interhemispheric transfer is done especially through the
splenium. A lesion of the splenium leads to alexia without agraphia (Geschwind, 1965).
After the posterior sectioning of the corpus callosum, although naming the stimuli
in the left visual field is not possible, there are many high-degree informational transfers
(Sidtis et al., 1981) as well as the possibility to integrate audio and visual information.
Cerebral vascular strokes that produce partial callous lesions can lead to a tactile anomia
and agraphia, which reveals the importance of fibres in the corpus callosum during
language transfer between the two hemispheres (Baynes and Gazzaniga, 1997).
Pandya and Seltzer (1986) highlighted in monkeys a tract for interparietal fibres
located just before the splenium (the isthmus of the corpus callosum), which, if sectioned,
is enough to lead to disorders of a crisscross tactile localisation (Volpe et al., 1982). This
area would also be critical for transferring audible information (Gazzaniga et al., 1975).
Complete callosotomy
When the corpus callosum is entirely sectioned at one sitting, the acute disconnection
syndrome appears in about all respects as it is seen after a complete cerebral commissurotomy
including the anterior commissure and massa intermedia (Bogen, 1987). This state after
callosotomy includes transient mutism, hence, when this symptom follows a complete section
it is not reasonably ascribed to the molestation of third ventricular structures.
Moreover, mutism does not necessarily follow a frontal commissurotomy that
includes molestation of the third ventricular structures but spares the splenium. Thus,
postcommissurotomy mutism requires an explanation on some other parts than third
ventricle retraction. Staying out of the third ventricle does avoid same problems, including
transient diabetes insipidus.
Experiments with monkeys have shown that if the anterior commissure is left intact
it can compensate for the loss of the splenium with respect to interhemispheric transfer
of certain kinds of visual information (Hamilton, 1982).
But the anterior commissure cannot compensate completely for splenial loss in
humans because hemialexia usually is present after splenial section.
Indeed, most of the stabilized syndromes seen after a complete cerebral commis-
surotomy are also seen (i.e., have not been compensated) after a callosotomy sparing the
anterior commissure (Gazzaniga and LeDoux, 1978; McKeever et al., 1981).
This is perhaps not surprising, because the anterior commissure is only 1/100 the
size of the corpus callosum. On the other hand, we can appreciate how significant it might
be when we consider the wealth of information that is conveyed over one optic nerve –
the diameter of which is about the same as that of the anterior commissure.
This question is complicated by the fact that the size of the anterior commissure is quite
variable; a diameter difference of 3 or 4 times has been reported (Yamamoto et al., 1981).
1554
20. Corpus callosum
This discrepancy between monkeys (transfer of learning by the anterior commissure)

and humans (inability of the anterior commissure to compensate for callosotomy) may
reflect differences between recently acquired memories as opposed to long-standing ones.
Current evidence suggests that memory deficits can be expected after a commissurotomy
that includes the anterior commissure even when the splenium is spared (Zaidel and
Sperry, 1974; Campbell et al., 1980; Milner, 1985).
The results originally suggested that a section of the corpus callosum prevented the
spread of learning and memory from one hemisphere to the other. Each hemisphere existed
independently and had a complete amnesia for the experience of the other (Sperry, 1962).
Extensions of these transfer studies in monkeys from visual to somesthetic and motor
learning (Sperry, 1961, 1962; Gazzaniga, 1970) have indicated that the independence of
the surgically separated hemispheres may be less clear cut than originally supposed.
Thus, both hemispheres may learn to discriminate simultaneously, one via a con-
tralateral sensory system and the other by an ipsilateral sensory system (Gazzaniga, 1970).
Observations of the functional effects of surgical separation of the hemispheres in
men (Gazzaniga et al., 1965; Gazzaniga and Sperry, 1967) by complete transection of
the corpus callosum, anterior and hippocampal commissures, and of the thalamic adhesion
(massa intermedia) have been reported.
These patients show a striking functional independence of the gnostic activities of
the two hemispheres. Perceptual, cognitive, mnemonic, learned and volitional activities
persist in each hemisphere, but each can proceed outside the realm of awareness of the
other hemisphere.
Subjective experiences of each hemisphere are known to the other only indirectly
through lower level and peripheral effects.
Disconnection of the hemispheres produces little disturbance of ordinary, daily
behavior, temperament or intellect.
Functional deficits tend to be compensated for by the development of bilateral motor
control from each hemisphere, as well as by the bilateralism of some sensory pathways.
Information perceived exclusively, or generated exclusively, in the minor (right)
hemisphere could not be communicated in speech or in writing; it was expressed entirely
by nonverbal responses.
There was no detectable impairment of speech or writing with reference to
information processed in the major (left) hemisphere.
These authors found linguistic expression to be organized almost exclusively in the
dominant hemisphere.
In contrast to the above, comprehension of language, both spoken and written, was
found to be represented in both hemispheres, with the minor hemisphere a little less
proficient.
In an analysis of the visual fields, with fixation assured, subjects verbally described
only those small spots of light presented in the right half of the visual field (Gazzaniga,
1970). A similar light stimulus present in the left half of the visual field produced no
verbal response.
1555
With double field stimulation, only spots of light falling in the right visual field were
reported. In these subjects, the visual fields stopped exactly in the midline and no macular
sparing was evident.
Thus, it would appear that no visual information can be transferred from one
hemisphere to the other after a section of the corpus callosum.
Certain lesions involving portions of the corpus callosum, or association areas of
the cortex which give rise to commissural fibres, produce disturbances of higher brain
functions collectively recognized as the disconnection syndrome (Geschwind, 1965,
1965a, 1970).
Word blindness without agraphia presumably results from lesions which interrupt
fibres from the visual association area which cross in the splenium of the corpus callosum
and project to the left angular gyrus.
Pure word deafness may result from subcortical lesions located in the left temporal
lobe and which interrupt the left auditory radiation as well as callosal fibres from the
contralateral auditory region. A similar syndrome manifested by various forms of agnosia
or apraxia may result from lesions involving portions of the corpus callosum and the
association fibre system (Carpenter, 1979).
Thus, after sectioning the corpus callosum, the two hemispheres are independent;
each receives sensory input from all sensory systems, and each can control the muscles
of the body, but the two hemispheres can no longer communicate with each other.
Because the functions in these separate cortices, or “split brain“, are thus isolated,
sensory information can be presented to one hemisphere and its function can be studied
without the other hemisphere having access to the information.
So, information seen in a particular part of the visual world by both eyes is sent to
only one hemisphere: input from the left side of the world (the left visual field) goes to
the right hemisphere, whereas input from the right side of the world (the right visual
field) goes to the left hemisphere. The two sides of the world are joined by a connection
thorough the corpus callosum.
With the corpus callosum severed, the brain cannot relate the different views of the
left and right hemispheres.
When the left hemisphere of a split-brain patient has access to information, it can
initiate speech and hence communicate about the information. The right hemisphere
apparently has reasonably good recognition abilities but is unable to initiate speech,
because it lacks access to the speech mechanisms of the left hemisphere (Kolb and
Whishaw, 2003).
The special capacities of the right hemisphere in facial recognition can also be
demonstrated in split-brain patients.
Levy et al. (1972) devised the chimerical figures test, which consists of pictures of
faces and other patterns that have been split down the centre and recombined in
improbable ways. When the recombined faces were presented selectively to each
hemisphere, the patients appear to be unaware of gross discordance between the two sides
of the pictures. When asked to pick out the picture that they had seen, they chose the face
1556
20. Corpus callosum
seen in the left visual field (that is, by their right hemisphere), demonstrating that the
right hemisphere has a special role in the recognition of face.
Thus, a surgical section of the corpus callosum cuts off direct interhemispheric
communication (Bogen, 1985; Seymour et al., 1984; Baynes and Gazzaniga, 2000). When
examined by special neuropsychological techniques (Zaidel et al., 1990), patients who
have undergone a section of commissural fibres (commissurotomy) exhibit profound
behavioral discontinuities between perception, comprehension, and response, which
reflect significant functional differences between the hemispheres.
Probably because direct communication between two cortical points occurs less
frequently than indirect communication relayed through lower brain centres, especially
the thalamus and the basal ganglia, these patients generally manage to perform everyday
activities quite well, including tasks involving interhemispheric information transfer
(Myers and Sperry, 1985; Zaidel et al., 1990; Sergent, 1990, 1991) and emotional and
conceptual information not dependent on language or complex visuospatial processes
(Cronin-Golomb, 1986). In noting that alertness remains unaffected by commissurotomy
and that emotional tone is consistent between the hemispheres, Sperry (1990) suggested
that both phenomena rely on bilateral projections through the intact brain stem.
In sum, the results of careful studies of patients with commissurotomies provide
clear evidence of the complementary specialization of the two cerebral hemispheres. It
must be recognized, however, that, as interesting as these patients are, they represent only
a very small population and their two hemispheres are by no means normal.
The right hand is superior in drawing fine, detailed featural information, and the left
for the overall gestaltic interrelationships and general outline, in a manner analogous to
the left - right dissociations noted in a constructional apraxia.
Similar hand differences appeared with respect to strategies adapted in tactually matching
a viewed, unfolded, three-dimensional object: this led to the general conclusion that the right
hemisphere has the synthetic ability to integrate unrelated parts into a meaningful whole,
whereas the left hemisphere specializes in the analysis of component features.
Levy and Trevarthen (1976) concluded that each hemisphere has its own cognitive
strategy, the right hemisphere synthesizing over space, the left hemisphere analyzing over time.
Callosal agenesis
Occasionally, individuals may be born with partial or complete absence of the corpus
callosum. More and more instances of such “experiments of nature” are emerging with
the development of new imaging techniques (Jeeves, 1990).
In large autopsy series their incidence is of 5.5% - 26 % (Jellinger et al., 1981).
However, its clinics and pathogenicity remain partially obscure. Rohmer et al. (1960)
claim that, although the agenesis of the corpus callosum had been described for the first
time by Reil in 1812, its pathogenicity is little known.
Callosal deficits in such cases vary in degree, depending on the time after conception
that the presumed causative insult occurred.
1557
Fig. 20.22. Sagittal MRI, shows the posterior half agenesia of the corpus callosum.
Andermann et al. (1994) and Wisniewski and Jeret (1994) support the importance of
the age-gestation factor, because the size of the malformation seems to be related to the
moment in which the damaging factors enter in the course of foetal development. Thus,
interrupting the development itself between the end of the first gestation month and the
beginning of the forth month lead to a total absence of all neocortical commissures.
Interrupting the development during the fourth month leads to the agenesis of the
corpus callosum with preservation of the anterior commissure. On the other hand, the
development anomalies that appear after the forth month determine a partial agenesis,
which especially affects the splenium (Fig. 20.22).
The splenium or rostrum are more likely to be absent, and the anterior commissure
is usually still present, and is often hypertrophied due to the enclosure of heterotopic
callosal fibres. The anterior commissure in fact is important in the extensive functional
reorganization that seems to occur in such cases (Bradshaw and Mattingley, 1995).
During the development, there can only occur an imperfect commissure and not a real
agenesis, as the fibres of the corpus callosum are present, but instead of having a
transversal projection they form the margins of the internal facets of the two hemispheres.
Therefore, from an anatomical point of view, the agenesis of the corpus callosum
may be partial or total associated or not to craniofacial, either tumoural or constitutional
(hydrocephalus, lack of septum pellucidum, microgyria etc.) (Lassonde, 1994).
Clinical manifestations. Ten percent of such cases are quite asymptomatic, coming
to light by chance at necropsy, and other being recognized because of other neurological
problems.
The symptoms in a callous agenesis may be discovered in a patient with normal
intelligence or may be included in a major polimalformation syndrome. Because of this
1558
20. Corpus callosum
reason, different psychic disorders, mental debility, epilepsy etc. are related to the
simultaneous presence of an extracallous pathology. Totally asymptomatic cases are
discovered only in autopsy and are debatable.
However, many scientists tried to check for the presence of a disconnection syndrome,
but the results were negative (Rohmer et al., 1960; Jeeves, 1979; Saul and Sperry, 1968;
Sauerwein and Lassonde, 1983; Lassonde et al., 1981, 1984; Lassonde, 1994).
The absence of disconnection deficits led to more interpretation based on the use of
some compensatory mechanisms (Jeeves, 1986, 1991, 1994) such as: (1) bilateralization
of cerebral functions; (2) the use of subtle behavioral strategies (cross-cueing), that allow
the non-stimulated hemisphere to use proprioceptive markers (a movement) derived from
the answer provided by the other hemisphere. This ensures a bilateral distribution of
information (Gazzaniga, 1970); (3) the overuse of ipsilateral sensitive and motor
projection tracts, which allow each hemisphere to have a bimanual representation; (4)
the maximum use of residual commissures (anterior and subcortical) in order to ensure
an interhemispheric transfer.
The philogenetic, morphologic and functional characteristics of the anterior
commissure show that it represents a single possible alternative for an interhemispheric
transfer in case of a callous agenesis. In all situations in which this commissure is present
it forms the main functional system capable of compensating the deficits induced by the
absence of the corpus callosum (Guénot, 1998).
Moreover, there is a degree of anomalies in tests of interhemispheric transfer which
correlates in case of a callous agenesis with the presence or absence of the anterior
commissure which can sometimes be hypertrophic. Whichever the nature of the
compensatory mechanisms used by subjects with an agenesis of the corpus callosum,
they do not pass certain limits because the interhemispheric communication for these
people has decreased (Lassonde et al., 1990, 1996).
According to Jeeves (1979), Sauerwein et al. (1994), Sylver and Jeeves (1994), and
Lassonde et al. (1996), this decrease of interhemispheric commutation includes the
following: slower motor tests, if bimanual coordination is needed; mostly severe difficulty
of grabbing, well observed at the beginning of school age; slowness in performing certain
visual tactile transfer tasks; difficulty in a crisscross localizing test for a tactile stimulus;
difficulty of unimanual transfer (Geffen et al., 1994); deficit of median fusion observed at
a discrimination test of two tactile stimulation points (Schiavetto et al., 1993); and deficit
in the evaluation of distance between visual stimuli (Lassonde et al., 1981; Jeeves, 1991);
and disorders of the ability to locate sound within the entire audio-field (Poirier et al., 1993).
Problems of phonologic analysis and video-constructive deficits have also been
observed in children with normal intelligence (Temple and Ilsley, 1994). These deficits
observed in persons with an agenesis of the corpus callosum are also seen in normal little
children, because of the myelinization processes in the corpus callosum, which for them
is not yet finished (Yakovlev and Lecours, 1967). As the growth process in the
commissural system is ending, these aptitudes improve progressively (Lassonde et al.,
1996).
1559
Failure of the corpus callosum to develop (agenesis of the corpus callosum) may be
accompanied by an absence of the anterior and hippocampal commissures.
Although some patients with this condition may experience focal seizures and have
mental retardation, others live for many years with few or no obvious neurologic deficits.
These individuals frequently have developmental abnormalities in other parts of the
nervous system.
Some persons with agenesis of the corpus callosum (a rare congenital condition in which
the corpus callosum is insufficiently developed or absent altogether) are identified only when
some other condition brings them to a neurologist’s attention, as they normally display no
neurological or neuropsychological defects (Harris, 1995; Zaidel et al., 2003) other than
slowed motor performances, particularly of bimanual tasks (Lassonde et al., 1991).
Thus, persons who are born without a corpus callosum can perform interhemispheric
comparisons of visual and tactile information. The interpretation of these results is that
the patients have enhanced conduction in the remaining commissures (for example, for
vision) and that they develop enhanced abilities to use their few uncrossed projections
(for example, for tactile information) (Kolb and Whishaw, 2003)
There are a number of reports of poor transfer of information if stimuli are complex.
Furthermore, nonspecific deficits in task performance have been reported in these
patients.
Lassonde (1986) and Lassonde et al. (1991) presented pairs of stimuli to six patients
with agenesis of the corpus callosum, asking them if the pairs were the same or different.
Letters, numbers, colours or forms were used, either the pair was presented one on top
of the other in one visual field (interahemispheric task) or one stimulus was presented in
one visual field and the other stimulus in the other visual field (interhemispheric task).
The acallosal group was equally accurate in identifying same - different pairs under
both conditions.
Their reactions, however, were very slow for both forms of presentation. Lassonde
(1986) suggested that the callosum participates in hemispheric activation as well as in
the transfer of information.
Thus, the acallosal group has alternative ways of obtaining the interhemispheric
transfer of information but not of activation.
According to Jeeves (1986, 1990), one explanation of why language is lateralized
to one hemisphere is that it gets a start there and then that hemisphere actively inhibits
its development in the other hemisphere. In people with callosal agenesis, the opportunity
for such an inhibitory process to work is much reduced. Yet the lateralization of language
and other functions in most of these people is similar to that in the general population.
Thus, the corpus callosum and other commissures are not necessary for the development
of asymmetries.
They are clearly not indispensable, but may play the following roles (Jeeves, 1990):
1. Interhemispheric integration, updating, and information transfer;
2. Inhibition of ipsilateral pathways to avoid unnecessary competition;
3. Inhibition during development so as to facilitate hemispheric specialization.
1560
20. Corpus callosum
4. Regulation and switching of attention and arousal levels;

5. Facilitation of information processing not only at an interhemispheric but even
at an intrahemispheric level (Lassonde et al., 1996). Indeed, commissurotomy does not
just stop seizure activity spreading to the other hemisphere, but also reduces it at the
initial focus.
Stroke of the corpus callosum

A stroke involving the anterior cerebral artery may affect the anterior corpus
callosum and result in apraxia (impairment of the capacity to execute various movements)
of the left arm as a consequence of the isolation / disconnection of the language-dominant
(left) hemisphere from the right motor cortex.
A stroke involving the posterior cerebral artery or a lesion involving the posterior
corpus callosum on the left side, may result in alexia (the inability to recognize words or
to read).
Visual input from the left visual field is relayed to the right, intact visual cortex,
which is isolated / disconnected from the language dominant (left) hemisphere. If the
basilar artery is affected, which gives rise to both the posterior cerebral arteries, the
infarction of the visual cortex will be bilateral and will cause cortical blindness; however,
the affected individual is unaware that he cannot see.
Tumors and degenerative diseases of corpus callosum

Open surgical approaches to lesions of the third and lateral ventricle are divided into
2 general categories: interhemispheric/transcallosal and transcortical. Each requires the
violation of normal neural tissue via either a corticotomy or a callosotomy. Reported
postoperative seizure rates after transcortical approaches, ranging from 26% to 70%
(Fornari et al., 1981; Desai et al., 2002) have led some to advocate transcallosal over
transcortical approaches when anatomic considerations would be conductive to either
approach (Anderson et al., 2003). According to Milligan and Meyer (2010), although the
2 traditional approaches to the ventricular system had similar major complication rates,
the transcallosal approach was associated with a significantly increased seizure risk.
The two main groups of tumors in the corpus callosum, lipomas and gliomas,
represent between 1 and 5% of the intracranial neoplasias.
The lipomas of the corpus callosum are congenital tumors, which frequently appear
in association to other callous malformations (hypoplasia or the agenesis of the corpus
callosum) and other cerebral anomalies (cortical atrophy, microgyria etc.). They lead to
few characteristic symptoms; therefore, the presence of these neoplastic processes is
frequently discovered during autopsy. A patient with a corpus callosum lipoma and
dysraphism was found to have trisomy 13 (Wainright et al., 1995).
The tendency for lipomas to occur in the midline and their frequent association with
dysraphic anomalies have led some authors to believe that they are caused by an
imperfection of neural tube closure, relating them to inclusion tumors (Gerber and
1561
Plotkin, 1982; Hori, 1986). However, Zettner and Netsky (1960) believe that their
pathogenesis lies in faulty differentiation of primitive meninx tissue in the
intrahemispheric fissure, which may later interfere with the development of midline
structures. More than 50% of patients with intracranial lipomas present with seizures.
Almost 20% of patients have mentation defects (Clarici and Heppner, 1979). The
symptoms are usually due to obstructive hydrocephalus.
The management of an intracranial lipoma should generally be conservative. Only
in unusual cases does the tumor require debulking or removal. The tenacious attachments
to surrounding structures may account for the poor results.
The gliomas of the corpus callosum (glioblastomas, oligodendrogliomas and
astrocytomas) have a different symptomatology, which can be expressed even during the
first days through headaches, epileptic seizures, neurologic disorders (lesions of cranial
nerve, hemiparesis, walking disorders, and dysfunctions of the autonomous nervous
system) and psychological changes (impulsivity, apathy, spatial or temporal disorien-
tation, memory disorders etc.).
In this context, when the assembly in the callous territory and its neighbouring
regions are invaded by the tumoural process, occurs a syndrome of callous disconnection.
When there is a partial invasion of the corpus callosum, we find only some components
of the disconnection syndrome (Fig. 20.23). Frontal lobe gliomas tend to invade the
frontal lobe, crossing through the corpus callosum. Gliomas arising in the regions below
the corpus callosum are largely confined and tend to invade the basal structures, such as
the thalamus and peduncles along the corticospinal tracts.
Fig. 20.23. Sagittal T1-weight gadolinium-enhanced magnetic resonance imaging scan

from a patient with anaplastic astrocytoma of the corpus callosum.
1562
20. Corpus callosum
T2-weight studies suggested that a larger proportion of tumors located close to the
corpus callosum invade this white matter tract.
The spread of malignant gliomas through all the white matter tracts (i.e., corpus
callosum, uncinate fasciculus, fasciculus longitudinalis and occipitofrontalis, auditive
and visual bundle, and corona radiata) has been documented (Matsukado et al., 1961).
The corpus callosum is the main white matter tract that leads to bilateral growth (Scherer,
1940; Salazar and Rubin, 1976). Grafted human glioma cells migrate along the glia
limitans, the basement membrane-lined blood vessels and Virchow-Robin space, the
subpial and subependymal space and the white matter fascicles of anatomic pathways,
including the corpus callosum, internal capsule, optic tract, and other parallel and
intersecting fibre tracts.
The intact vascular basement membrane is not penetrated by glioma cells (Bernstein
and Woodard, 1995).
Marchiafava-Bignami disease
In 1903, Marchiafava and Bignami described a curious syndrome of selective
demyelinisation of the corpus callosum in alcoholic Italians who indulged in large
quantities of red wine.
The disease seems to affect severe and chronic alcoholics in their middle or late life,
with a peak incidence between 40 and 60 years of age. A toxic cause, such as direct
toxicity of ethanol or other constituents, seems equally plausible. Clinical observations
of that three alcoholic patients were few and incomplete; in two of them, a chronic ill-
defined psychosis had been present, and, in all three, seizures and coma had occurred
terminally. In 1907, Bignami described a case in which the corpus callosum lesion was
accompanied by a similar lesion in the central portion of the anterior commissure.
These early reports were followed by a spate of articles that confirmed and amplified
the original clinical and pathological findings. About 40 cases of this disorder had been
described in the Italian literature (Mingazzini, 1922). A clinical diagnosis is often
difficult, because neurological presentation varies considerably. Many patients present
in terminal coma, which often preludes a premortem diagnosis. Mental and motor
slowing, other personality and behavior changes, incontinence, dysarthria, seizures, and
hemiparesis occur to a varying extent. The most common picture on neurological
evaluation is probably that of a frontal lobe or dementia syndrome.
Anterior corpus callosum vascular malformations

Anterior callosal arteriovenous malformations involve the corpus callosum, the
cingulate gyrus and ventricular ependyma.
The blood supply comes from the pericallosal and callosal marginal arteries. Venous
drainage occurs superiorly into the sagittal sinus and intraventricularly into the septal,
thalamostriate, and eventually internal cerebral veins.
Larger lesions can involve the medial aspect of the striatum and anterior
hypothalamus as well as the septal and preseptal regions. With lateral extension, the
recurrent feeders of these malformations come from the recurrant artery of Heubner and
1563
A B
C D
Fig. 20.24. Conventional anteroposterior and lateral angiographic view (A, B) show a large arteriovenous
malformation that involve the anterior part of the corpus callosum, the cingulate girus and the right ventricular
ependyma. Postoperative (C, D) carotid angiography demonstrates complete resection of that malformation
with very good results.
from medial lenticulostriate arteries (Fig. 20.24). Blood supply also comes from
perforators of the anterior cerebral arteries and anterior communicating artery (Dănăilă
et al., 2010).
The approach uses a unilateral frontal craniotomy extending to the midline. The
subfrontal approach allows identification and division of the feeding vessels from the
anterior communicating complex and the anterior cerebral arteries. This can be followed
by an anterior interhemispheric approach to follow A2 vessels distally.
Thus, these lesions can be resected by skeletonizing the pericallosal arteries as they
pass through the lesion and taking only the side branches to the malformation. The
dissection of the medial and intraventricular plane of the lesion is completed using an
approach through the corpus callosum (Fig. 20.25).
Fig. 20.25. Preoperative (A, B, C) carotid angiography of a large interhemispheric arteriovenous malformation. This
was approached through a large right frontoparietal craniotomy. Postoperative (D, E, F) carotid angiography
demonstrates complete resection of that arteriovenous malformation. Postoperative evolution was excellent. ►
1564
20. Corpus callosum
A B
E F
1565
The AVMs of the splenium are supplied primarily by pericallosal branches of the
posterior cerebral artery and distal pericallosal branches of the anterior cerebral artery as
well as by medial and lateral choroid branches of the posterior cerebral artery. Drainage
is usually into the internal cerebral vein and the vein of Galen (Fig. 20.26).
The surgical approach is parasagittal interhemispheric from the opposite side with
division of the falx to have a more direct access to the lateral aspect of the lesion.
The lateral extent of the lesion is defined by splitting the splenium in the direction
of the fibres.
A B
C D
1566
20. Corpus callosum
E F
Fig. 20.26. Preoperative (A, B, C) carotid angiography of a splenial arteriovenous malformation. These AVMs of the
splenium were supplied primarily by distal pericallosal branches of the anterior cerebral artery as well as by medial
and lateral choroidal branches of the posterior cerebral artery. Drainage is into the internal cerebral vein and vein of
Galen. The surgical approach was parasagittal interhemispheric from the right (opposite side with division of the falx
to have more direct access to the left aspect of the lesion. Postoperative (D, E, F), carotid angiography demonstrates
complete resection of the malformation. The evolution of the patient was excellent.
Summary
The loss of the ability to transfer information from the left hemisphere to the right
hemisphere and vice-versa seems to have no impact on their overall psychological state.
However the question of the perceived unity of the world continues to interest scientists.
The most spectacular finding in that respect has been the discovery that the corpus callosum
can be cut in humans without changing the perceived unity of the world and of the self.
According to Baars (2007), the role of the two hemispheres in human cognition and
mind-brain identity has been the subject of extensive studies, and we are still unfolding
the subtle and not so subtle differences in the roles that the mirror-image hemispheres
play in perception, language, thought, and consciousness.
For many years such callosotomies were performed to improve intractable epilepsy.
This surgical procedure has proved to be effective in preventing seizures from being
transferred from one cerebral hemisphere to the other (Fig. 20.27).
It was the introduction to lateralized procedures in early studies that led to that unique
research opportunity presented by split-brain patients. Thus, more careful studies have
provided evidence that a complete callosotomy does have subtle but long lasting effects.
Because of this, a partial resection (callosectomy) is preferred.
There are some hemispheric differences that are fairly well understood, such as
crossover wiring. Many aspects of sensory and motor processing entail the crossing over
of input (sensory) or output (motor) information from the left side to the right, and vice-
versa (Fig. 20.28).
1567
Fig. 20.27. The symptoms of callous disconnection and the location of the responsible lesions: 1. The fibres that pass
through the rostrum and through the ventral area of the genu come from the ventral and medial region of the
prefrontal cortex; 2. The arched fibres of the genu and the cingulate fibres that pass underneath the cortex of the
cingulate gyrus are connected in the posterior area with the septal nucleus; 3. The fibres of the anterior half of the
corpus callosum are destined to the fronto-frontal tracts; their lesion leads to the apraxia of the left hand without
agraphia; 4. Fibres that connect the somato-sensorial cortex; their lesions lead to the left tactile anomia; 5. Fibres that
connect the supramarginal gyrus; their lesions leads to the left ideomotor apraxia; 6. Fibres that connect the lateral
temporal cortex; their lesions leads to a dichotic extinction in the left ear; 7. Fibres that connect the superior parietal
lobe; their lesions leads to a diagnostic dyspraxia; 8. Fibres that connect the superior parietal lobe; their lesions leads
to constructive disorders of the right hand and tactile anomia of the left hand; 9. Fibres that connect the angular gyrus;
their lesions leads to agraphia of the left hand; 10. Fibres that connect the prestriate cortex; their lesions leads
to left visual anomia and left hemialexia.
Only the olfactory nerve, which is a very ancient sensory system, stays on the same
side of the brain on its way to the cortex.
The time lag between the two hemispheres working on the same task may be as short
as 10 ms, or one-hundredth of a second (Handy et al., 2003).
Therefore, when the great information highway of the corpus callosum is intact, the
differences between the hemispheres are not very obvious. But when it is cut, and the
proper experimental controls are used to separate the input of the right and left half of
each eye’s visual field, suddenly major hemispheric differences become observable
(Baars, 2007).
However, tactual testing of the right hand showed no significant impairment of the
dominant but disconnected left hemisphere. Similar testing of the left hand indicated
severe agnosia, anomia, and agraphia. Also, in tachistoscopic presentations, the results
showed no abnormality in response to stimuli presented to the right visual field, but the
patient was severely impaired with stimuli presented to the left visual field (Gazzaniga
and Miller, 2009).
Severing the entire callosum blocks, the interhemispheric transfer of sensory, motor,
perceptual, gnostic, and other forms of information in such a way that it allows us to
study hemispheric differences and the unique ways in which the hemispheres interact
with each other (Zaidel, 1990; Gazzaniga, 2000; 2005).
The most obvious hemispheric difference is the capacity to learn language. It had
been known prior to split-brain research that the left hemisphere is dominant for language
and, particularly, speech production (Broca, 1865; Wernicke, 1874).
1568
20. Corpus callosum
Fig. 20.28. Liepmann’s theory of apraxia resulting from

lesions of the corpus callosum. (A) Normal response to a
verbal command to move the left hand. The command is
processed through the posterior speech zone (areas 22,
39, and 40) from the motor cortex of the left hemisphere
through the corpus callosum to the motor cortex (area 4)
of the right hemisphere to move the left hand. (B) Apraxic
response. The jagged line through the callosal area
indicates sectioning of the callosum.
The verbal command has no way of informing the right-
hemisphere motor cortex to move the left hand.
Geschwind proposed that bilateral apraxia could result
from a lesion disconnecting the posterior speech zone
from the motor cortex of the left hemisphere because the
verbal command cannot gain access to either the left or
the right motor cortex.
(after Kolb and Whishaw, 2003)
The left hemisphere is also specialized in written language. And, while the right
hemisphere does have a limited capacity for reading and is able to read whole words
(ideographic lexical / semantic access), it is unable to convert graphemes to phonemes as
can the language-dominant left hemisphere (Zaidel and Peters, 1981; Zaidel et al., 1985).
Gazzaniga and Miller (2009) have a patient who generates spoken language
exclusively from the left hemisphere, and the written language exclusively from the right
hemisphere.
Previously, it had been assumed that spoken and written language shared the same
neural mechanism but this patient demonstrates that the output of these two functions
can be operated by independent modules (Baynes et al., 1998).
As much as cognitive styles and personal tastes and habits might seem to reflect the
processing characteristics of one or the other hemisphere, these qualities appear to be
integral to both hemispheres (Arndt and Berger, 1978; Sperry et al., 1979). “In the normal
intact state, the conscious activity is typically a unified and coherent bilateral process
that spans both hemispheres through the commissures“ (Sperry, 1976).
1569
However, very few tasks rely exclusively on one hemisphere. The interaction between
hemispheres has important mutually enhancing effects. Complex mental tasks such as
reading, arithmetic, and word and object learning are performing best when both hemispheres
can be actively engaged (Rey, 1959; Moscovitch, 1979; Huettner et al., 1989; Gaillard, 1990;
Belger and Banich, 1998; Weissman and Banich, 2000; Dănăilă and Golu, 2006).
Other mutually enhancing effects of bilateral processing show up in the superior
memorizing and retrieval of both verbal and configurational material when
simultaneously processed (encoded) by the verbal and configurational system (Milner,
1978; Moscovitch, 1979); in enhancing cognitive efficiency of normal subjects when
hemispheric activation is bilateral rather than unilateral (Berger and Perret, 1986; Berger
et al., 1987); and in better performances of visual tasks by commissurotomized patients
when both hemispheres participate than when vision is restricted to either hemisphere
(Zaidel, 1979; Sergent, 1991 a, b).
The cerebral processing of music illuminates the differences in how each hemisphere
contributes, the complexities of hemispheric interactions, and how experience can alter
hemispheric roles.
The left hemisphere tends to predominate in the processing of sequential and
discrete tonal components of music (Gaede et al., 1978; Breitling et al., 1987; Botez
and Botez, 1996).
The inability to use both hands to play a musical instrument (bimanual instrument
apraxia) has been reported with left hemisphere lesions that spare motor functions
(Benton, 1977).
The right hemisphere predominates in melody recognition and in melodic singing
(Gordon and Bogen, 1974; Yamadori et al., 1977; Samson and Zatorre, 1988; Kumkova,
1990; Dănăilă and Golu, 2006 ). Its involvement with chord analysis is generally greatest
in musically untrained persons (Gaede et al., 1978). Training can alter these hemispheric
biases so that, for musicians, the left hemisphere predominates for melody recognition
(Bever and Chiarello, 1974; Messerli et al., 1995), tone discrimination (Shanon, 1981;
Mazziota et al., 1982), and musical judgments (Shanon, 1980, 1984).
Moreover, intact, untrained persons tend most to show lateralised effects for tone
discrimination or musical judgments (Shanon, 1980, 1981, 1984). Taken altogether, these
findings suggest that while cerebral processing of different components of music is
lateralized with each hemisphere predominating in certain aspects, both hemispheres are
needed for musical appreciation and performance (Bauer and McDonald, 2003).
The bilateral integration of cerebral function is most clearly exhibited by creative
artists, who typically have intact brains. Excepting singing, harmonica playing, and the
small repertoire of piano pieces written for one hand, making music is a two-handed activity.
Moreover, for instruments such as guitars and the entire violin family, the right hand
performs those aspects of music that are mediated predominantly by the right hemisphere,
such as expression and tonality, while the left hand interprets the linear sequence of notes
best deciphered by the left hemisphere.
Thus, by its very nature, the artist’s performance involves the smoothly integrated
activity of both hemispheres (Lezak et al., 2004).
1570
20. Corpus callosum
Although each hemisphere appears to have redundant knowledge structures that

support basic functioning, the extent of the semantic systems in the right hemisphere is
clearly impoverished compared to the left (Gazzaniga et al., 1984; Gazzaniga and Miller,
1989; Baynes et al., 1992; Reuter-Lorenz and Baynes, 1992), including a limited lexical
organization in the right (Gazzaniga, 1983).
Kihlstrom and Klein (1997) have emphasized that the self is a knowledge structure,
not some mystical entity. Severing the corpus callosum raises an interesting issue about
whether a disconnected half brain will still have the same sense of self.
According to Turk et al. (2003), although it is very difficult to accurately assess the
extent of the right hemisphere’s knowledge (self and otherwise) given its limited language
ability, there does appear to be hemispheric differences in the knowledge system that
bias each hemisphere’s responses.
Although the left hemisphere is clearly dominant for language, many problem-
solving skills, and semantic knowledge (Gazzaniga, 2000), the right hemisphere does
have some specialization as well. Studies with split-brain patients have revealed right
hemisphere superiority for various tasks involving such components as part-whole
relations (Nebes, 1972), spatial relationship (Nebes, 1973), apparent motion detection
(Forster et al., 2000), mental rotation (Corballis and Sergent, 1988), spatial matching
(Corballis et al., 1999) and mirror image discrimination (Funnell et al., 1999).
The right hemisphere also appears to be more veridical in its memory recollections
(Phelps and Gazzaniga, 1992; Metcalfe et al., 1995) and to be better at illusory contour
perception and amodal boundary completion (Corballis et al., 1999). One of the more
compelling recent findings regarding the right hemisphere is its superiority in casual
perception, although the left hemisphere was found to be superior at causal inference
(Roser et al., 2005).
Understanding cause and effect is fundamental to making sense of the dynamic
physical world, and the perception of spatial and temporal contiguity of the movements
of colliding objects is a critical component of this basic understanding (Gazzaniga and
Miller, 2009).
A well-known specialization of the right hemisphere is the detection of upright faces.
The term prosopagnosia was introduced by Bodamer (1947) for a type of visual
defect in which the patient cannot identify a familiar face by looking at the person or a
picture, even though he knows that a face is a face and can point out features. They may
also be unable to interpret the meaning of facial expression or to judge the ages or
distinguish the gender of faces. As a rule, other agnosias are present in such cases (colour
agnosia, simultanagnosia), and there may be topographical disorientations, disturbances
of body schema, and constructional or dressing apraxia. Visual field defects are nearly
always present. The small number of cases that have been studied anatomically and by
CT scanning and MRI indicate that prosopagnosia is associated with bilateral lesions of
the ventromedian occipitotemporal regions (Damasio et al., 1982).
In their studies of split-brain patients Levy et al. (1972), Gazzaniga and Smylie
(1983) and Miller et al. (2002), showed that the left hemisphere can perceive and
1571
recognize faces and it can perform just as well as the right with familiar faces, but the
right hemisphere is superior in its ability to perceive and recognize unfamiliar faces.
However, while both hemispheres can generate spontaneous facial expression, only
the dominant left hemisphere can generate voluntary facial expression (Gazzaniga and
Smylie, 1990).
The expected right-hemispheric superiority in visuospatial functions has been
demonstrated in callosotomy patients. The use of tactile information to built spatial
representation of abstract shapes also appears to be better developed in the right
hemisphere (Milner and Taylor, 1972).
Although the right hemisphere demonstrates superior levels of performance on a
variety of perceptual and spatial tasks, the left hemisphere appears to have at least some
competence in most areas and in some cases is essential for the solution of complex visual
problems.
Verbal IQ appears to be stable following callosotomy, although performance IQ may
decline (Zaidel, 1990).
However, the cognitive functioning of each hemisphere is quite redundant.
Both hemispheres are quite capable of encoding and retrieving of past events, despite
a significant theory in the 1990s on the brain region underlying episodic memory function
based on neuroimaging works. The theory, called HERA (hemispheric encoding /
retrieval asymmetry), stipulated that episodic encoding was predominantly a left
hemisphere process while episodic retrieval was predominantly a right hemisphere
process (Tulving et al., 1994). The asymmetries observed in neuroimaging studies were
based on the fact that most studies at the time used verbal material. Miller et al. (2002)
found in split-brain patients that manipulating the encoding of words led to greater effects
in the left hemisphere than the right, and that manipulating the encoding of faces led to
greater effects in the right hemisphere than in the left.
Since that split-brain study, recent neuroimaging studies have confirmed that
encoding and retrieval asymmetries are primarily due to the type of stimuli used and not
the general hemispheric differences in processing (Wig et al., 2004).
Despite some unique specialization in the right hemisphere, breaking up the right
hemisphere is not hard to do for the left hemisphere.
Although some effects due to the callosotomy surgery have been observed (e.g.,
Phelps et al., 1991, found impairments in free recall but not in recognition performance
on some memory tasks that may be due to limitations in strategic and search processes
imposed by the severing of the corpus callosum), most functions remain intact after the
right hemisphere is disconnected from the left, including verbal IQ (Nass and Gazzaniga,
1987; Zaidel, 1990), and many problem-solving skills (LeDoux et al., 1977). However,
in some cases, problems with higher order cognitive processes such as concept formation,
reasoning, and problem solving with limited social insight have been observed (Brown
and Paul, 2000).
The disconnection does not seem to affect another critical component of our
conscious system, the “interpreter” (Gazzaniga and Miller, 2009).
1572
20. Corpus callosum
Conclusions
Some authors consider the activity of the corpus callosum to have an inhibitory role
(Eidelberg, 1969; Jeeves, 1986). It allows each hemisphere to apply an inhibiting action
on its homologous, with the purpose of controlling a given function. This reciprocal
inhibition avoids the duplication of functions (Dennenberg, 1981). The inhibiting model
was suggested in order to explain the development of a domination of the contralateral
tract over the ipsilateral fibres in motor and sensitive systems (Dennis, 1976).
However, the inhibiting role of the corpus callosum in the ontogenesis of hemi-
spheric specialization has not yet been confirmed (Lassonde et al., 1990; Jeeves, 1994).
In the context of epilepsy pathogenesis, it was common to mention that the callous
tract had a facilitating action (Bremer, 1966; Geoffroy et al., 1986). This affirmation
supports the fact that a section of the corpus callosum determines not only the abolishment
of bilateral propagation, but also a decrease or ceasing of epileptic discharge in the initial
focal (Bogen and Vogel, 1962; Geoffroy et al., 1986; Lassonde et al., 1996). This is due
to the fact that influxes from the intact hemisphere would moderate the activity of
abnormal cells and the propagation of epileptic discharge to the healthy hemisphere
through retroaction (Bremer, 1966, 1967; Lassonde, 1986).
On the other hand, clinical observations show that the corpus callosum is
significantly involved in a functional reorganizing after a cerebral aggression. Thus,
speech recovery, observed in patients with left hemispheric lesions is severely limited if
produced at the same time as a lesion of the corpus callosum (Goldstein, 1948; Russel,
1963). As an assembly, these data suggest that the intact hemisphere could facilitate a
better function of the damaged hemisphere through the effect of the corpus callosum
In the case of patients with unilateral lesions and bilateral symptoms, the reciprocal
transcallous facilitation may disrupt a well functioning intact hemisphere.
However, it is highly probable that the normal interhemispheric regulating process
depends both on the inhibiting influences and on the stimulating ones (Lassonde et al.,
1996). In this context, Berlucchi (1983) claims that the function of the corpus callosum
is to equilibrate the activity of the two hemispheres and to allow an optimal integration
of cortical activity.
The callous disconnection has an important role in the explanation of syndromes
such as apraxia of limbs, pure alexia and unilateral agraphia.
The consequences of a callous lesion in adults are at the same time complex but
relatively discrete. At first sight, they are not a major handicap and are compatible with
a normal life and daily activity, if not associated with hemispheric lesions (Habib, 1996),
ideomotor apraxia, left unilateral anomia and agraphia, right constructive apraxia,
hemialexia and other manifestations given by a deficit of informational transfer between
hemispheres that can pass unnoticed if not specifically searched for.
Consequently, even though after a callosotomy the behavior is almost unchanged,
investigations revealed the capacity of each hemisphere and confirmed the hypothesis
based on studies conducted on normal patients as well as those based on studies conducted
on patients with focal lesions.
1573
The most systematic investigations of hemispheric specialty and integration have

been performed in patients with callosotomies (split-brain patients) in order to remove
intractable epilepsy. Initial studies confirmed the affirmations of neurologists who claim
that the left hemisphere is dominant for speech while the right hemisphere cannot name
and “cannot describe objects presented visually or tactile”, although it is capable of
performing certain visual tasks. Experiments help with a better understanding of
perceptual, cognitive, mnemonic and linguistic processes and with a better integration of
these concepts in a coherent thinking and behavior.
The isolated right hemisphere cannot read, write or speak although it has an entire
variety of conscious behaviours. A dissociation of the left hand by tactile anomia and
agraphia indicates a minor linguistic capacity of the right hemisphere. The ability to
understand visual and audio language can contribute to selecting aphasic and alexic
patients.
Other observations show that the right hemisphere can participate in recovering
aphasia in a long term, but the highest interest is represented by studying patients with
callosotomies and investigating the basics of hemispheric cognition and integration of
diverse perceptual sensorial and emotional information in a single behavioral plan. The
independent function of hemispheres proved the important role played by the verbal left
hemisphere in observing and interpreting of self action and recognizing emotional
statuses.
It is worth noticing as far as the emotional functions, besides alexithymia, are
concerned, that the callous lesion does not lead to obvious changes in affection and
personality.
All in all, the callous syndrome remains a relatively homogenous entity, independent
of the nature of the callous lesion.
1574
20. Corpus callosum
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Zettner A, Netsky MC, Lipoma of the corpus callosum. J Neuropathol Exp Neurol 19; 305-319,
1960.
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CEREBRAL CORTEX
Introduction
Anatomists use the term cortex (from the Latin for “bark”, as in a tree’s bark) to
refer to any outer layer of cells. In neuroscience, the terms cortex and neocortex (new
cortex) are often used interchangeably to refer to the outer part of the forebrain, and so
by convention “cortex” refers to “neocortex” unless otherwise indicated. So, most of the
cortex that covers the cerebral hemispheres is neocortex, defined as the cortex that has
six cellular layers, or laminae. Each layer comprises more or less distinctive populations
of cells based on their different densities, sizes, shapes, inputs, and outputs. Despite an
overall uniformity, regional differences based on these laminar features have long been
apparent, allowing investigators to identify numerous subdivisions of the cerebral cortex.
The cortex is the part of the brain that has expanded the most in the course of evolution;
it comprises 80% by volume of the human brain (Kolb and Whishaw, 2003).
The human neocortex has an area as large as 2 500 cm2 but a thickness of only 1,5
to 3,0 mm. It consists of four to six layers of cells (gray matter) and is heavily wrinkled.
This wrinkling is nature’s solution to the problem of confining the huge neocortical
surface within a skull that is still small enough to pass through the birth canal. Just as
crumpling a sheet of paper enables it to fit into a smaller box than it could when flat, the
folding of the neocortex permits the human brain to fit comfortably within the relatively
fixed volume of the skull (Kolb and Whishaw, 2003).
According to Baars (2007), we usually see the brain from the outside, so that the
cortex is the most visible structure. But the brain grew and evolved from the inside out,
very much like a tree, beginning from a single seed, then turning into a thin shoot, and
then mushrooming in three directions: upward, forward and outward from the axis of
growth. That point applies both to phylogenesis – how species evolved – and ontogenesis
– how the human brain grows from the foetus onward.
The mature brain reveals that pattern of growth and evolution. It means, for example,
that lower regions like the brain stem are generally more ancient than higher regions,
such as the frontal cortex. Basic survival functions like breathing are controlled by neural
centres in the lower brain stem, while the large prefrontal cortex in humans is a late
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21. Cerebral cortex
addition to the basic mammallian brain plan. It is located the farthest upward and forward
in the neural axis. Thus, local damage to the prefrontal cortex has little impact on basic
survival functions, but it can impair sophisticated abilities like decision-making, self-
control and even personality (Baars, 2007).
The cerebral cortex of the cerebral hemispheres, the convoluted outer layer of gray
matter composed of tens of billions of neurons and their synaptic connections, (Fig. 21.1)
is the most highly organized correlation centre of the brain, but the specificity of cortical
structures in mediating behavior is neither clear-cut nor circumscribed (Collins, 1990;
Franckowiak et al., 1997). The bulk of the cerebral cortex is comprised of the neocortex.
The phylogenetically older parts of the cortex include the paleocortex (olfactory cortex,
entorhinal and periamygdaloid areas) and the archicortex (the hippocampal formation).
The tens of billions of neurons send, in all directions, a large number of axons, covered
by supportive myelin. These form the white matter of the cortex that fills the large
subcortical space.
Fig. 21.1. A schematic

representation
of information flow in neuron
(after Kolb and Whishaw, 2003).
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Because the brain involves hundreds of millions of years of evolutionary layering

on top of older layers, the more recent levels hide the older ones.
That is particularly true for the fast-ballooning neocortex in primates and humans,
called the “new cortex” because it is more recent, and has six layers rather than the four
or five layers of the reptilian and early mammallian brain (Baars, 2007).
Other large mammals have bigger muscles and greater speed, but humans have an
exceptionally big and flexible brain, specialized for excellent vision and hearing, language
and social relationships, and for manual control and flexible executive control. The human
brain makes culture and technology possible (Baars, 2007).
The cerebral cortex receives sensory information from the internal and external
environments of the organism, processes this information and then decides on and carries
out a response to them. To receive information regarding the external and internal milieu
and to generate commands to control the muscles and organs, the cerebral cortex has both
direct and indirect connections with all other regions of the brain and spinal cord.
Multiple cortical and subcortical areas are involved to some degree in the mediation
of complex behavior (Fuster, 1995; Mesulam, 2000), and specific regions are typically
multifunctional (Lloyd, 2000).
The boundaries of functionally definable cortical areas, or zones, are vague. Cells
subserving a specific function are highly concentrated in the primary area of a zone, thin
out, and overlap with other zones as the perimeter of the zone is approached (Polyakov,
1966; Goldberg, 1989, 1995).
While the cortex is vital for cognitive functions, it interacts constantly with major
satellite organs, notably the thalamus, basal ganglia, hypothalamus, cerebellum, brain
stem and limbic regions, among others.
Different regions of the cerebral cortex have modular specific functions (somatic
sensory and motor, visceral sensory and motor, integrative cognitive functions, speech
functions etc.) responsible for the high-order cognitive processing of the conscious mind.
These correspond to the Brodmann areas, as well as to each of the four cerebral lobes
(frontal, parietal, temporal and occipital).
Modules are dynamic structures which, in neural terms, roughly coincide with
neuronal assemblies and the connections between the neurons. Modular view of
functional neocortical organization is in favour of the distributed-emergent principle of
functional cortical organization.
The nature of cortical modules is distributed as well as localized. Modules can be
considered unitary in the sense that they are in charge of action, both external and internal,
and work to integrate such factors as time, novelty, complexity, and possibly ambiguity.
So, the term modular or functional localization is used to indicate that certain functions
can be localized in a particular area of the cerebral cortex. The mapping of cortical
functions began with the inference made from the deficits produced by cortical lesions
in humans.
Cognitive functions are represented by information exchange within and between
modules.
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21. Cerebral cortex
Partial or total lesions of same Brodmann specialized areas or one of the lobes leads
to a modular loss of consciousness. When all the cerebral cortex is destroyed as well as
the white matter, the patient becomes unconsciousness.
The majority of the human cerebral cortex is devoted to tasks that transcend encoding
primary sensations or commanding motor actions.
Collectively, the association cortices mediate these cognitive functions of the brain,
broadly defined as the ability to attend to, identify, and act meaningfully in response to
complex external or internal stimuli.
Descriptions of patients with cortical lesions, functional brain imaging of normal
subjects, and behavioral and electrophysiological studies of non-human primates have
established the general purpose of the major association areas.
Subsequently, techniques such as single-cell recording and electrical stimulation of
cells in the cerebral cortex have been used in animals, non-human primates, as well as
humans undergoing surgery for diseases such as epilepsy and Parkinson’s disease to map
out functional areas of the brain (Jones, 2000).
Functional neuroimaging techniques such as positron emission tomography (PET),
functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG)
have been used to confirm previous knowledge about the localization of functions within
the cerebral cortex as well as to conduct studies in healthy human subjects that were
previously not possible.
Even those functions that are subserved by cells located within relatively well-
defined cortical areas have a significant number of components distributed outside the
local cortical centre (Brodal, 1981; Paulescu et al., 1997).
In this way, effortful tasks show a wider spread of brain activity, even beyond the
executive regions of the frontal cortex. For example, in a classic study, Smith and Jonides
(1998) found dramatically expanded cortical activity as a function of memory load. The
difficulty level rises very quickly with the number of items to be kept in mind.
What we cannot see yet, even with advanced brain recording methods, is the strength
of connections between brain cells. Mental effort changes connection strengths, the neural
signalling density between cortical localizations. Cognitive efforts is one of the biggest
factors in brain functioning.
The neural firing or brain metabolism is not a direct measure of the complexity of
some mental processes. It seems to indicate the recruitment of neuronal resources that
are needed to work together to perform a task that is new or unpredictable. Once even
very complex processes are learned, they seem to require less cortical activity.
Automaticity also involves a loss of conscious access and voluntary control as assessed
by behavioral measures (Schneider, 1995; Baars, 2002).
Cortical involvement appears to be a prerequisite for awareness of experience
(Fuster, 1995; Kohler and Moscovitch, 1997; Roth, 2000).
Patterns of functional localization in the cerebral cortex are broadly organized along
two spatial planes. The lateral plane cuts through homologous areas of the right and left
hemispheres. The longitudinal plane runs from the front to the back of the cortex, with a
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relatively sharp demarcation between functions that are primarily localized in the forward
portion of the cortex and those whose primary localization is behind the central sulcus or
fissure of Rolando (Lezak et al., 2004).
In the newborn, the two cerebral hemispheres weigh approximately 402 g in the
male and 380 g in the female. By the end of the first year, the weight of the brain has
doubled, and by the end of the sixth year, it has tripled to at least 90% of its adult weigh
at that time. This increase in weight is due mainly to an increase in the number of blood
vessels, myelin layers, and supporting or glial elements (Schmitt et al., 1981; Roland and
Zilles, 1996; Steinmetz, 1996; Zilles, 2004).
The role of glia, in among other examples, synapse formation, synapse maturation
and plasticity, and rapid conduction of action potentials, as well as their immunological
functions in the nervous system, have by now been unequivocally established (Stern,
2010). The molecular mechanisms underlying astrocyte specifications and growth and
the interaction with other cell types to assemble the nervous system are still not
completely understood. Another type of glial cell, oligodendrocytes, is central to the
brain’s myelination, which ensures the efficiency and speed of action potentials (Emery,
2010). Microglia are another fascinating subpopulation of glial cells. They sense
pathological tissue alternation and they can develop into brain macrophages and perform
immunological functions (Graeber, 2010).
Lee at al. (2010) report that tonic inhibition in the cerebellum is due to GABA being
released from glial cells by permeation through the Bestrophin 1 anion channel. Ginhoux
et al. (2010) investigate the developmental origin of microglia and show that adult microglia
derive from primitive myeloid progenitor cells that arise before embryonic day 8.
In a perspective, Fields (2010) presents his hypothesis that white matter, which
consists mostly of myelinated axons, may play a role in brain plasticity and learning.
In adults, the cerebral hemispheres weight about 1 450 g in males with a normal
range of 1 200 to 1 600 g. In females, the cerebral hemispheres weight about 1 350 g,
with a normal range between 1 100 and 1 500 g. The brain of an elephant weighs about
5 000 g and that of the blue whale weighs about 6 800 g.
The surface of the brain is folded such that two-thirds of its surface area lies buried
and out of view in the depths of the cerebral fissures or sulci.
When one considers the surface area of the brain per lobe, about 41% of the human
brain consists of the frontal lobe, 17% consists of the occipital lobe, 21% consists of the
temporal lobe, and the parietal and insular lobes make up about 21% of the surface area
of the brain (Roland and Ziels, 1996; Steinmetz, 1996; Augustine, 2008).
The surface gray matter of the cerebral hemispheres, or cerebral cortex, average
about 2.5 mm in thickness, with variations from one brain region to another. The primary
visual cortex (area 17 of Brodmann) is about 1.5 mm in depth whereas the primary motor
cortex (area 4 of Brodmann) is about 4.5 mm. There is a variation in the thickness of the
cerebral cortex, with it being thinner in the depths of the fissures than at the upper margins
of the fissures. Some 1012 neurons may be present in both cerebral hemispheres (1012 =
= 1 trillion or 1 million ´ 1 million) (Augustine, 2008).
The total area of the cerebral cortex is about 2 500 cm2.
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21. Cerebral cortex
Fissures, sulci, and gyri

The wrinkled surface of a neocortex consists of clefts and ridges. A cleft is called a
fissure if it extends deeply enough into the brain to indent the ventricles, whereas it is a
sulcus (plural: sulci) if it is shallower.
A ridge is called a gyrus (plural: gyri).
There is some variation in the location of these features on the two sides of a single
individual’s brain, and substantial variation in the location, size, and shape of the gyri
and sulci in the brains of different individuals.
Adjacent gyri differ in the way that cells are organized within them; the shift from
one kind of arrangement to another is usually at the sulcus. There is some evidence that
gyri can be associated with specific functions.
There are four major gyri in the frontal lobe: the superior frontal, middle frontal,
inferior frontal and precentral (which lie in front of the central sulcus).
Lateral organization
The two mirror-image halves of the cortex have puzzled people for centuries. Why
are there two hemispheres? If we have but one mind, why do we have two hemispheres?
The two cerebral hemispheres are nearly symmetrical. The primary sensory and
motor centres are homologously pozitioned within the cerebral cortex of each hemisphere
in a mirror-image relationship. With certain exceptions, such as the visual and auditory
systems, the centres in each cerebral hemisphere predominate in mediating the activities
of the contralateral (other side) half of the body.
Thus, an injury to the primary somesthetic or somatosensory area of the right
hemisphere results in decreased or absent sensations in the corresponding left-sided body
part; an injury affecting the left motor cortex results in a right-sided weakness or paralysis
(Lezak et al., 2004).
The hemispheres are completely separate, divided by the longitudinal fissure that
runs between the two hemispheres from the anterior to the posterior part of the brain.
But, how do the two hemispheres “talk” to each other? The answer lies in the fibre
tract (corpus callosum), a large arch of white matter that runs from the front to the back
of the brain, linking the two hemispheres.
Although the two hemispheres are similar in appearance and structure, they are not
biologically identical and they have different information processing abilities and
propensities.
The corpus callosum, with at least 200 million nerve fibres, is the largest tract that
connects the two cerebral hemispheres. Although there are no cortical landmarks that
divide the corpus callosum, it is generally the cause that different regions of the corpus
callosum contain fibres originating in different cortical areas. That is, the anterior portion
of the corpus callosum contains primarily fibres that originate in promotor and frontal
regions of the cortex, middle portion contain fibres that originate in motor and
somatosensory regions and so forth. In addition, many callosal fibres are homotopic; that
is they connect homologous areas of the two hemispheres. The corpus callosum also
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contains fibres that originate in a specific region of one hemisphere and terminate in a
completely different region of the opposite hemisphere.
Comparisons of split-brain patients with intact individuals provide a clear indication
that the corpus callosum is critical to normal interhemispheric interactions, especially
interactions that require the transfer of information about the identity or name of a
stimulus.
The corpus callosum has been hypothesized to play two important but very different
roles: transferring information between the hemispheres and creating a kind of inhibitory
barrier that minimized maladaptive cross talk between the complementary processes for
which each hemisphere is dominant. Anyhow, same types of information can be
transferred subcortically, and subcortical structures can also play a role in producing
unified behavioral responses. Studies of perceptual processing in normal individuals
provide important insights about the factors that determine when it is more efficient for
the two hemispheres to operate collaboratively than to operate independently (Ivry and
Roberts, 1998).
A major difference in the sources of innervation of the association cortices is the
enrichment in direct projections from other cortical areas called corticocortical
connections. These connections form the majority of the input to the association cortices.
Ipsilateral corticocortical connections arise from primary and secondary sensory and
motor cortices, and from other association cortices within the same hemisphere.
Corticocortical connections also arise from both corresponding and noncorresponding
cortical regions in the opposite hemisphere via the corpus callosum and anterior and
posterior commissure, which together are referred to as interhemispheric connections.
In the association cortices of humans and other primates, corticocortical connections
often form segregates bands or columns in which interhemispheric projection bands are
interdigitated with bands of ipsilateral corticocortical projections (De Felipe and Jones,
1988; Garey, 1994; Posner and Raiche, 1994; Purves et al., 2004).
One general conclusion suggested by this research is that distributing information
across both hemispheres becomes more beneficial as the task becomes more demanding of
attentional resources. That is, when the processing demands are minimal, there is often a
within-hemisphere advantage. However, when the processing demands are increased (as
much as indicating whether two letters of different cases have the same name or whether
both are vowels), there is typically an across-hemisphere advantage (Gazzaniga, 2000).
Interhemispheric collaborations can have emergent properties that are impossible to
deduce from the sum of the parts provided by the two individual hemispheres.
Longitudinal organization
Although no two human brains are exactly alike in their structure, all normally
developed brains share the same major distinguishing features. The external surface of
each half of the cerebral cortex is wrinkled into a complex of ridges or convolutions
called gyri (sing.: gyrus), which are separated by two deep fissures and many shallow
clefts, the sulci (sing.: sulcus).
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21. Cerebral cortex
The two prominent fissures and certain of the major sulci divide each hemisphere
into four lobes, the occipital, parietal, temporal and frontal lobes (Brodal, 1981; Mesulam,
2000; Dănăilă and Golu, 2006).
Point-to-point representation on the cortex

A consistent theme in neuroanatomy throughout the past century is that cortical
regions can be categorized as primary sensory cortex, primary motor cortex, and
association cortex. The last of these categories, the association cortex, is usually also
categorized as secondary cortex, which elaborates information coming from primary
areas, and as higher-order areas, which may combine information from more than one
system. This idea can be traced to Flechsig (1920) and his studies of the development of
myelin in the cortex.
Flechsig (1920) divided cortical regions into: 1) an early-myelinating primordial
zone including the motor cortex and a region of visual, auditory, and somatosensory
cortex; 2) a field bordering the primordial zone that myelinates next; and 3) a late-
myelinating zone, which he called the “association zone”.
Flechsig hypothesized psychological functions for his hierarchy, with the general
idea being that the primary zones perform simple sensorimotor functions, whereas the
association areas conduct the highest mental analyses. Flechsig’s ideas greatly influenced
neurological thinking throughout the twentieth century.
According to Lezak et al. (2004), the organization of both the primary sensory and
primary motor areas of the cortex provides for a point-to-point representation of the body.
The amount of cortex identified with each body portion or organ is proportional to the
number of sensory or nerve endings in that part of the body rather than to its size. For
example, the areas connected with sensation and movement of the tongue or fingers are
much more extensive than the areas representing the elbow or back.
The visual system is also organized on a contralateral plan, but it is one-half of each
visual field that is projected onto the contralateral visual cortex. The precise point-to-point
arrangement of projection fibres from the retina to the visual cortex permits an especially
accurate localization of lesions within the primary visual system (Sterling, 1998). Visual
recognition is mediated by (at least) two different systems: one system processes
visuospatial analysis, and one is dedicated to pattern analysis and object recognition.
Movement perception may involve a third system (Zihl et al., 1983; Iwata, 1989).
An adult-onset lesion limited to the primary visual cortex produces loss of visual
awareness (cortical blindness, blind sight) while reasoning ability, emotional control, and
even the ability for visual conceptualization may remain intact (Farah and Weiskrantz,
1986; Guzeldere et al., 2000; Farah, 2003).
A majority of nerve fibres transmitting auditory stimulation from each ear are
projected to the primary auditory centres in the opposite hemisphere; the remaining fibres
go to the ipsilateral auditory cortex. Thus, the contralateral pattern is preserved to a large
degree in the auditory system, too. So, destruction of one of the primary auditory centres
does not result in loss of hearing in the contralateral ear. A point-to-point relationship
between sensory receptors and cortical cells is also laid out on the primary auditory
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cortex, with a cortical representation arranged according to pitch, from high tones to low
ones. So, these areas that receive projections from structures outside the neocortex or
send projections to it are called primary projection areas. Nevertheless, the primary
projection areas of the neocortex are small relative to the total size of the cortex.
Destruction of a primary cortical sensory or motor area results in specific sensory
or motor deficits but generally has little effect on the higher cortical functions. Some
mild decrements in movement speed and strength of the hand on the same side as the
lesions in the motor cortex have been reported (Smutok et al., 1989; Cramer et al., 1999).
Association areas of the cortex

When Penfield and Boldrey (1958) stimulated the motor and somatosensory strips
of their patients, they identified two regions of the parietal cortex that appeared to
represent localised body parts such as the leg, hand, and face. These regions called
homunculi were seen as the areas of the cortex responsible for basic tactile sensations
such as touch, pressure, and temperature.
Subsequent investigations of nonhuman subjects led to the identification of
analogous maps of the visual and auditory worlds as well.
Thus, the human cortex was generally believed to be occupied by complex mental
analyses that we might loosely call cognition.
Doubt about this simple view of cortical organisation arose in the late 1970s and the
1980s, however, as more refined physiological and anatomical research techniques began
to reveal literally dozens of maps in each sensory modality, rather than just one or two.
For example, between 25 and 32 regions in the monkey cortex have roles in visual
functioning, depending on the definition used (Kolb and Whishaw, 2003).
Although the somatosensory and auditory maps are less numerous, from about 10
to 15 cortical maps in each of these modalities, do not duplicate the original maps but
rather process different aspects of sensory experience. For example, visual areas are
specialised for analysing basic features such as form, colour, and movement. Furthermore,
many psychological processes, such as visual object memory and visually guided
movements, require visual information (Kolb and Whishaw, 2003).
Cortical representation of sensory or motor nerve ending in the body takes place on
a direct point-to-point basis, but stimulation of the primary cortical area gives rise only
to meaningless sensations or nonfunctional movements (Luria, 1966; Brodal, 1981).
Modified and complex functions involve the cortex adjacent to the primary sensory and
motor centres (Goldberg, 1990; Passingham, 1997; Paulescu et al., 1997).
According to Purves et al. (2004), the connectivity of the association cortices is
appreciably different from that of the primary and secondary sensory and motor cortices,
particularly with respect to inputs and outputs. For instance, two thalamic nuclei that are
not involved in relaying primary motor or sensory information provide much of the
subcortical input to the association cortices: the pulvinar projects to the parietal
association cortex, while the medial dorsal nuclei project to the frontal association cortex.
Several other thalamic nuclei, including the anterior and ventral anterior nuclei, innervate
the association cortices as well.
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21. Cerebral cortex
So, signals coming into the association cortices via the thalamus reflect sensory and
motor information that has already been processed in the primary sensory and motor
areas of the cerebral cortex.
Unlike the thalamic nuclei that receive peripheral sensory information and project
to primary sensory cortices, the input to these association cortex-projecting nuclei comes
from other regions of the cortex. The primary sensory cortices receive thalamic
information that is more directly related to peripheral sense organs and to the basal ganglia
and cerebellum.
In any case, the primary sensory areas send projections into the areas adjacent to
them, and the motor areas receive fibres from areas adjacent to them. These adjacent
areas, less connected with the sensory receptors and motor neurons, are referred to as
secondary areas. The secondary areas are thought to be more engaged in interpreting
perceptions or organising movements than are the primary areas.
Neurons in these secondary cortical areas integrate and refine raw percepts or simple
motor responses.
Tertiary association or overlap zones are areas peripheral to the functional centres
where the neuronal components of two or more different functions or modalities are
interspersed. The posterior association cortex, in which the supramodal integration of
perceptual functions takes place, has also been called the multimodal (Pandya and
Yeterian, 1990) or heteromodal (Strub and Black, 1988; Mesulam, 2000) cortex.
So, the areas that lie between the various secondary areas are referred to as tertiary
areas. Often referred to as association areas, tertiary areas serve to connect and coordinate
the functions of the secondary areas. Tertiary areas mediate complex activities such as
language, planning, memory, and attention. These processing areas are connected in a
“stepwise” manner so that information-bearing stimuli reach the cortex first in the primary
sensory centres. They then pass through the cortical association areas in order of
increasing complexity, interconnecting with other cortical subcortical structures along
the way to the frontal and limbic system association areas and finally comes the
expression through action, thought, and feelings (Pandya and Yeterian, 1998; Mesulam,
2000; Arciniegas and Beresford, 2001).
Another important source of innervation to the association areas is subcortical,
arising from the dopaminergic nuclei in the midbrain, the noradrenergic and serotonergic
nuclei in the brain stem reticular formation, and cholinergic nuclei in the brain stem and
basal forebrain.
This diffuse input projects to different cortical layers and, among other functions,
determines the mental state along a continuum that ranges from deep sleep to high alert
(Mc Cormick, 1992; Mc Carley, 1995; Provencio et al., 2000; Willie et al., 2003).
Generally, each association cortex is defined by a distinct subset of thalamic, cortico-
cortical, and subcortical connections. As a result, inferences about the function of human
association areas continue to depend critically on the observation of patients with cortical
lesions. Damage to the association cortices in the parietal, temporal, and frontal lobes,
respectively, results in specific cognitive deficits; this indicates much about the operations
and purposes of each of these regions (Purves et al., 2004).
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These projection systems have both forward and reciprocal connections at each step
in the progression to the frontal lobes; and each sensory association area makes specific
frontal lobe connections which, too, send their reciprocal connections back to the
association areas of the posterior cortex (Rolls, 1998).
Generally, there are identified areas that function in more than one modality (for
example, vision and touch). These areas, known as the multimodal or polymodal cortex,
presumably function to combine characteristics of stimuli across different modalities.
For example, we can visually identify objects that we have only touched, which implies
some common perceptual system linking the visual and somatic system (Kolb and
Whishaw, 2003). Insight into the function of these cortical regions has come primarily
from the observations of human patients with damage to one or another of these areas.
Noninvasive brain imaging of normal subjects, functional mapping during neurosurgery,
and electrophysiological analysis of comparable brain regions in non-human primates
have generally confirmed the clinical deduction. There are four distinct regions of
multimodal cortex, one in each of the occipital, parietal, temporal and frontal lobes. These
areas imply that more than one process requires polymodal information.
Different regions could take part in different memory processes, object perception,
emotion, movement control, and so on.
Anyhow, it is now clear that virtually the entire cortex behind the central fissure has
some kind of sensory function.
The multimodal cortex appears to be of two general types, one type related to the
recognition and related processing of information and the other type controlling
movement related to the information in some manner (Kolb and Whishaw, 2003). This
concept suggests that we have parallel cortical systems: one system functions to
understand the world, whereas the other system functions to move us around in the world
and allows us to manipulate our world. According to Kolb and Whishaw (2003), the
cortex is fundamentally an organ of sensory perception and related motor processes.
Jerison (1991) suggested that our knowledge of reality is related directly to the structure
and number of our cortical maps. As the number of maps possessed by an animal brain
increases, more of the external world is known to the animal and more behavioral options
are available to it. For instance, animals such as rats and dogs, whose brain does not have
a cortical region analysing colour, perceive the world in black and white. This lack must
limit their behavioral options, at least with respect to colour.
Jerison (1991) suggested that cortical maps determine reality for a given species.
Furthermore, he noted that, the more maps a species has, the more complex the internal
representation of the external world must be.
Thus, if humans have more maps than dogs, then our representation of reality must
be more complex than that of a dog. Similarly, if dogs have more maps than mice then a
dog’s understanding of the world is more complex than that of a mouse. This viewpoint
suggests that the relative intelligence of different mammallian species may be related to
the number of maps that the cortex uses to represent the world.
Dogs would have more olfactory maps than people and would thus be more
intelligent about smells, but the total number of maps in all sensory regions taken together
is far greater in humans than in dogs.
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21. Cerebral cortex
This referred to the cognition, which is the process by which we came to know the
world.
More specifically, cognition refers to the ability to attend to external stimuli or
internal motivation: to identify the significance of such stimuli and to make meaningful
responses. So, the association cortices receive and integrate information from a variety
of sources, and they influence a broad range of cortical and subcortical targets.
Unlike damage to primary cortical areas, a lesion involving association areas and
overlap zones typically does not results in specific sensory or motor defects; rather, the
behavioral effects of such damage will more likely appear as a pattern of deficits running
through related functions or as impairment of a general capacity (Goldberg et al., 1989;
Goldberg, 1995).
Thus, certain lesions that are implicated in drawing distortions also tend to affect
the ability to do computations on paper; lesions of the auditory association cortex do not
interfere with hearing acuity per se but with the appreciation of patterned sounds.
In sum, the association cortex includes most of the cerebral surface of the human
brain and is largely responsible for the complex processing that goes on between the
arrival of input in the primary sensory cortices and the generation of behavior.
The diverse functions of the association cortices are loosely referred to as cognition,
the process by which we came to know the world (Mountcastle et al., 1975; Platt and
Glimcher, 1999).
Inputs to the association cortices include projections from the primary and secondary
sensory and motor cortices, the thalamus, and the brain stem. Outputs from the association
cortices reach the hippocampus, the basal ganglia and cerebellum, the thalamus, and other
association cortices.
So, different regions of the neocortex have different functions. Some regions receive
information from sensory systems, other regions command movements, and yet other
regions are the sites of connections between the sensory and the motor areas, enabling them
to work in concert (Penfield and Boldrey, 1958; Truex and Cerpenter, 1969; Elliott, 1969).
Overall, the neocortex can be conceptualized as consisting of a number of fields:
visual, auditory, body senses, and motor. Because vision, audition and body senses are
functions of the posterior cortex, this region of the brain (parietal, temporal, and occipital
lobes) is considered to be largely sensory; and because the motor cortex is located in the
frontal neocortex, that lobe is considered to be largely motor.
Finally, because each lobe contains one of the primary projection areas, it can
roughly be associated with a function (Kolb and Whishaw, 2003).
Frontal lobes: motor
Parietal lobes: body senses
Temporal lobes: auditory function
Occipital lobes: visual functions
On the other hand, all studies indicate that, among other functions, the frontal
association cortex is especially important for the planning of appropriate behavioral
responses, the parietal association cortex is especially important for attending to stimuli
1603
in the external and internal environment, and the temporal association cortex is especially
important for identifying the nature of such stimuli.
Anyhow, these parts of the brain are responsible for encoding sensory information
(primary sensory cortices), and commanding movements (primary motor cortex). But
these regions account for only a fraction (perhaps a fifth) of the cerebral cortex. Much of
the remaining cortex is concerned with attending to complex stimuli, identifying the
relevant features of such stimuli, recognizing related objects, and planning appropriate
responses as well as storing aspects of this information. Collectively, these integrative
abilities are referred to as cognition, and it is evidently the association cortices in the
frontal, parietal and temporal lobes that make cognition possible.
The extrastriate cortex of the occipital lobe is equally important in cognition; its
functions, however, are largely concerned with vision. These other areas of the cerebral
cortex are referred to collectively as the association cortices (Tanji and Shima, 1994;
Garey, 1994; Glimcher, 2003).
Connections between cortical areas and binding problems

According to Kolb and Whishaw (2003), the various regions of the neocortex are
interconnected by three types of axon projections: (1) relatively short connections between
one part of a lobe and another, (2) longer connections between one lobe and another, and
(3) interhemispheric connections or commissures, between one hemisphere and another.
Most of the interhemispheric connections link homotopic points in the two
hemispheres – that is, contralateral points that correspond to one another in the brain’s
mirror-image structure. Thus, the commissures act as a zipper to link the two sides of the
neocortical representation of the world and of the body together.
The two main interhemispheric commissures are the corpus callosum and the anterior
commissure.
The cortex also makes other types of connections with itself. Cells in any area may
send axons to cells in a subcortical area such as the thalamus, and the cells there may
then send their axons to some other cortical area. These types of relations are more
difficult to establish anatomically than are those based on direct connections (Curtis,
1972; Passingham, 1979).
The various connections between regions of the cortex are of considerable functional
interest, because damage to a pathway can have consequences as severe as damage to
the functional areas connected by the pathway.
As we saw, the cortex has multiple anatomically segregated and functionally
specialised areas. But, according to Kolb and Whishaw (2003), how does brain organization
translate into our perception of the world as a gestalt – a unified and coherent whole?
When you look at the face of a person, why do shape, colour, and size combine into a
coherent, unchanging image? This question identifies the binding problem, which asks how
sensations in specific channels (touch, vision, hearing, and so forth) combine into per-
ceptions that translate as a unified experience that we call reality (Kolb and Whishaw, 2003).
Various researchers (Pandya and Yeterian, 1985, Fellemen and van Essen, 1991;
Zeki, 1993) have tried to determine the rules of connectivity, but they did not succeed.
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21. Cerebral cortex
In reality, only about 40% of the possible intercortical connections within a sensory
modality are actually found, which leads us to the flowing solution: intracortical networks
of connections among subsets of cortical regions. This idea has considerable appeal.
First, all cortical areas have internal connections among units with similar properties.
These connections link neurons that are neighbours and synchronise their activity.
Second, through a mechanism called re-entry, any cortical area can influence the
area from which it receives input. This remarkable, interactive aspect of cortical
connectivity means that, when area A sends information to area B, area B reciprocates
and sends a return message to area A (Kolb and Whishaw, 2003). Zeki suggested that an
area could actually modify its inputs from another area before it even receives them. An
important point is that the connections from area A and B do not originate from the same
layers, suggesting they play different roles in influencing each other’s activity. Computer
modelling suggests that the primary function of neural connections is to coordinate
activity within and between areas in order to produce a globally coherent pattern, known
as integration, over all areas of the perceptual system (Kolb and Whishaw, 2003). This
concept of cortical organisation is likely to be foreign to many readers.
Jerison (1991) related the binding problem to his analogy of multiple cortical maps.
The evolutionary expansion of the cortex in area has implications for the brain with
multiple neurosensory channels that are trying to integrate information into a single
reality. Because so many different kinds of sensory information reach the cortex, it is
necessary somehow discriminate equivalent features in the external world.
Suppose that the brain creates labels to designate objects and a coordinate system to
locate objects in the external world – that is, in space and time. Suppose also that sensory
information must be tagged to persist through time and must be categorized to be retrieved
(remembered) when needed.
Labels, coordinates, and categories are products of cognition (knowledge and
thought). Viewed in this way, jerison’s analogy of multiple cortical maps provides a basis
for thinking about how the information that is arriving to the cortex is integrated into
perception and organized as knowledge and thought.
It should not be a surprise that injuries to discrete cortical areas alter the way people
perceive the self and the environment and the way they think about them.
One form of sensory deficit is agnosia. It renders a partial or complete inability to
recognize sensory stimuli.
Histology of the cerebral cortex

The gray matter of the cerebral cortex is composed of neuron cell bodies of variable
sizes and shapes, intermixted with myelinated and unmyelinated fibres. These cell bodies
may be visualized with stains that bind to the rough endoplasmic reticulum (Nissl
substance). Such stains leave the axons and dendrites almost invisible.
Yet another way of looking at cortical cells is to immerse small blocks of tissue in
dilute silver salts, which precipitate on the membranes of the entire neuron. This reaction
causes the cell body, its dendrites, and portions of the axon to become visible; this
technique is called the Golgi method (Lunch, 2006).
1605
The pattern of distribution of neuron cell bodies, is, generally, called cyto-
architecture.
There are five neuronal types in the human cerebral cortex. These include the
characteristic neuron of the cerebral cortex, the pyramidal neuron which measures some
10 to 70 µm in diameter. The majority of neurons in the human cerebral cortex are
pyramidal neurons. These excitatory neurons project to other pyramidal neurons forming
networks among themselves. A single pyramidal cell may have up to 200 synapses from
other neurons on its cell body but upwards of 40,000 synapses on its axon and dendrites.
Pyramidal cells are found in all layers of the cortex with the exception of molecular
layer I, and they are the predominant cell type in layers II, III and V.
Pyramidal cells are characterized by a roughly triangular cell body, a single large
apical dendrite that arises from the apex of the cell body and usually extends towards the
molecular layers, giving off branches along the way, an array of basal dendrites that run
in a predominantly horizontal direction, and an axon that originates from the base of the
soma leaves the cortex, and passes through the white matter.
The largest pyramidal neurons, called the giant pyramidal cell of Betz, are found
almost exclusively in the primary motor cortex, which is located in the precentral and
anterior paracentral gyri. Betz cells are most common in the region of the motor cortex
that projects to the anterior horn of the lumbar spinal cord and hence are concerned with
the control of leg movement.
Apical and basal dendrites of pyramidal cells are characterized by membrane
specialization called dendritic spines that give the impression of thorns on a rose bush.
Pyramidal neurons represent virtually the only output pathway for the cerebral cortex.
Axons of pyramidal cells may terminate in another region of the cortex in the same
hemisphere (association fibres), decussate in the corpus callosum to terminate in the
cerebral cortex of the opposite hemispheres (callosal fibres), or course through the white
matter to any of the numerous subcortical targets in the forebrain, brain stem, or spinal
cord (projection fibres) (Lynch, 2006).
Pyramidal cells display a laminar organization, with the cell bodies in a given layer
projecting to specific neural targets (Fig 21.2). Generally, pyramidal neurons in layers II
and III give rise to association and callosal fibres. Pyramidal cell in layers V project to
many subcortical structures, including the spinal cord, as projection fibres. The neurons
in layer VI send their axons to a variety of locations, including the thalamic nuclei and
other regions of the cortex. Within the cortex, the axons of pyramidal cells send off an
extensive and relatively dense array of axon collaterals. These collaterals terminate in all
cortical layers and extend through a horizontal area covering several millimetres around
the cell body (Fig. 21.3). Pyramidal cells use an excitatory aminoacid, either glutamate
or aspartate, as their neurotransmitter.
The stellate or granule neuron is another neuronal type found in the cerebral cortex.
These cells are small, polygonal or triangular in shape and have dark-staining nuclei and
scanty cytoplasm. These neurons, ranging from 4 to 8 µm, have a number of dendrites passing
in all directions and a short axon which ramifies close to the cell body (Golgi type II).
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21. Cerebral cortex
Fig. 21.2. Representative cell types in the cerebral cortex and the layers in which their cell bodies and dendrites are
found. Dendrites of pyramidal cells (Py) of layers II, III, and V extended into layer I, whereas those of modified
pyramidal cells (mPy) in layer VI extend only to about layer IV. Chandelier cells (Ch) are restricted almost entirely to
layer III. The somata of aspiny and spiny stellate neurons (Asp, Sp) are in layer IV, although their processes extend
into other layers. Basket cells (Bas) have processes that collectively extend into all cortical layers from cell bodies
located mainly in layers III and V. (Adapted from Hendry SHC, Jones EG: Size and distributions of intrinsic neurons
incorporating tritiated GABA in monkey sensory motor cortex. J. Neurosci. 1; 390-408, 1981, and from Jones EG:
Laminar distribution of cortical efferent cells. In: Cerebral Cortex, vol. 1, New York, Plenum Press, 1984, pp. 521-553.
Other larger stellate cells have longer axons which may enter the medullary
substance. Some resemble the pyramidal cells in that they have an apical dendrite which
extends to the surface. These cells are known as stellate or star pyramidal cells (Lorente
de Nó, 1949). Stellate cells are found throughout all layers of the cortex but are especially
numerous in layer IV.
This neuronal type has a wide distribution and is probably correlative in function,
interrelating different cortical layers.
Spiny stellate cells are the second most numerous cell type in the neocortex. Several
primary dendrites, profusely covered in spines, radiate for a variable distance from the
cell body. Their axons ramify within the grey matter predominantly in the vertical plane.
Spiny stellate cells probably use glutamate as their neurotransmitter.
The smallest group comprises the heterogeneous non-spiny or sparsely spinous
stellate cells. All are interneurones and their axons are confined to the grey matter.
However, there is not a single class of cells, but a multitude of different forms, including
basket, chandelier, double bouquet, neurogliaform, bipolar / fusiform and horizontal cells.
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Fig. 21.3. Diagram showing some of the intracortical circuits. Sinaptic junction are indicated by loops; Afferent
thalamocortical fibres; efferent cortical neurons, intracortical neurons; G, granule cell; H, horizontal cell; M, Martinotti
cell; P, pyramidal cell; S, stellate cell; B, mode of termination of afferent cortical fibres.
(Based on data by Lorente de Nó, 1949).
These types may have horizontally, vertically or radially ramifying axons. The principal
recognisable neuronal type is the neurogliaform or spiderweb cell. These small spherical
cells, 10 to 12 µm in diameter, are found mainly in laminae II to IV, depending on cortical
area. Seven to ten dendrites typically radiate out from the cell soma, some branching
once or twice to form a spherical dendritic field of approximately 100 to 150 µm in
diameter. The slender axon arises from the cell body or a proximal dendrite. It branches
profusely within the vicinity of the dendritic field to give a spherical axonal arbour up to
350 µm in diameter (Crossman, 2008).
The horizontal cells of Cajal are located in the superficial cortical layers. These
small neurons correlate adjoining areas with each cerebral hemisphere and have axons
and dendrites that run parallel to the cortical surface.
The cells of Martinotti, present in practically all cortical layers, are small triangular
cells whose axons are directed towards the surface. Some fibres arborize in the same
layer; others send collaterals to a number of layers.
The fifth cortical neuronal type is the polymorph, multiform, or pleomorphic
neuron. These essentially modified pyramidal neurons are associative in function and
occur in the innermost cortical layers (Augustine, 2008).
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21. Cerebral cortex
The majority of non-spiny or sparsely spinous non-pyramidal cells probably use

GABA as their principal neurotransmitter. This is almost certain in case of basket,
chandelier, double bouquet, neurogliaform and bipolar cells. Some are characterised by
the coexistence of one or more neuropeptides, including neuropeptide Y, vasoactive
intestinal polypeptide, cholecystokinin, somatostatin and substance P.
Acetylcholine is present in a subpopulation of bipolar cells, which may additionally
be GABAergic and contain vasoactive intestinal polypeptide (Toga et al., 2006;
Crossman, 2008).
Inhibitory interneurons in the neocortex

The neocortex contains two major classes of neurons: glutamatergic excitatory
neurons and gamma-aminobutyric acid – (GABA)-ergic – inhibitory interneurons. Proper
functioning of the neocortex critically depends on the production of a correct number of
excitatory and inhibitory neurons, which largely occurs during the embryonic stages
(Brown et al., 2011).
Clones of neocortical excitatory neurons originating from the same progenitor cell
provided a comprehensive view of excitatory neuron neurogenesis in the developing of
the neocortex. These cells are spatially organized and contribute to the formation of
functional microcircuits.
In contrast, little is known about the production and organization of neocortical
interneurons (Brown et al., 2011) especially inhibitory interneurons (Brown et al., 2011).
Most, if not all, neocortical interneurons are generated in the developing ventral (i.e.,
subcortical) telencephalon, including the ganglionic eminence (GEs) and the preoptic
area (PoA), and migrate tangentially over long distances to reach their destination in the
neocortex (Wonders and Anderson, 2006; Batista-Brito and Fishell, 2009; Gelman and
Marin, 2010).
Different regions of the GEs generate distinct interneuron subgroups that differ in
morphology, expression of neurochemical markers, biophysical properties and synaptic
connectivity (Butt et al., 2005; Flames et al., 2007; Fogarty et al., 2007; Wonders et al.,
2008; Miyoshi et al., 2010; Xu et al., 2010).
Distinct temporal origin of physiologically defined interneuron subgroups have also
been reported (Butt et al., 2005; Miyoshi et al., 2007).
However, little is known about the cellular processes that produce neocortical
interneurons.
The neocortex is thought to be functionally organized into columns consisting of
excitatory neurons and inhibitory interneurons (Mountcastle, 1997). Clonal analysis of
neocortical excitatory neuron production and migration has revealed that individual radial
glial progenitor cells in the ventricular zone of the dorsal telencephalon undergo
consecutive rounds of asymmetric cell division, producing a number of lineage-related
sister excitatory neurons (Noctor et al., 2001). Despite some lateral dispersion during
migration (Walsh and Cepko, 1993; Reid et al., 1995; O’Rourke et al., 1995), clonal
related sister excitatory neurons are often spatially organized into vertical clusters and,
1609
to a lesser extent, horizontal arrays in the mature neocortex (Rakic, 1988; Price and
Thurlow, 1988; Kornack and Rakic, 1995; Yu et al., 2009). Moreover, specific chemical
synapses preferentially form between vertically aligned sister excitatory neurons,
suggesting that spatially organized ontogenetic clones of excitatory neurons contribute
to the formation of functional columnar microcircuits in the neocortex (Yu et al., 2009).
Whether inhibitory interneurons are spatially organized with respect to the formation
of repetitive functional columns in the neocortex remains an outstanding question (Brown
et al., 2011).
However, neocortical interneurons are remarkably diverse and often classified by
distinctive morphologies, expression of neurochemical markers, firing pattern, and
synaptic connectivity (Markram et al., 2004; Huang et al., 2007; Ascoli et al., 2008).
Proper production of a correct number of each of these different subgroups of neocortical
interneurons is essential for constructing a functional neocortex.
Brown et al. (2011) found that neocortical inhibitory interneurons were produced as
spatially organized clonal units in the developing ventral telencephalon.
Furthermore, clonally related interneurons did not randomly disperse but formed
spatially isolated clusters in the neocortex. Individual clonal clusters consisting of
interneurons expressing the same or distinct neurochemical markers exhibited clear
vertical or horizontal organization.
These results suggest that the lineage relationship plays a pivotal role in the
organization of inhibitory interneurons in the neocortex (Brown et al., 2011).
Proper production of each of these different subgroups of neocortical interneurons is
essential for constructing a functional neocortex. Radial migration of daughter cells along
the mother radial glial cell has been extensively characterized in the dorsal telencephalon
during excitatory neuron neurogenesis and migration. Brown et al. (2011) showed that before
tangential migration differentiating daughter cells in the medial GE (MGE) and the PoA,
which include neocortical interneurons, migrate radially along the mother radial glial
progenitor cell. The physiological importance of this initial radial migration is unclear (Brown
et al., 2011). It may allow proper neuronal differentiation of the daughter cells before they
begin migrating tangentially to reach the neocortex (Brown et al., 2011).
It has been suggested that direct contact with the radial glia promotes GABAergic
interneuron differentiation (Li et al., 2008). Consistent with this, Brown et al. (2011)
found that cells within individual clones with the most pronounced neuronal
characteristics are located furthest away from the ventricular zone. They possess the
typical bipolar morphology of a tangentially migrating interneuron, indicating that they
are poised for tangential migration. Cells with less pronounced neuronal characteristics
are located close to the ventricular zone (Brown et al., 2011).
Neocortical interneurons generated in the MGE and PoA undertake complex
migration routes to reach their final destination in the neocortex (Corbin et al., 2001;
Mariss and Rubenstein, 2003).
They migrate tangentially over long distances to enter the neocortex through the
marginal zone or the intermediate and subventricular zones before turning radially to
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21. Cerebral cortex
reach their ultimate location in the neocortex. Similar to excitatory neurons, inhibitory
interneurons generated in the MGE and PoA display a birth date-dependent laminar
distribution in the neocortex (Ang et al., 2003; Batista-Brito and Fishell, 2009; Miyoshi
and Fishell, 2011), thereby arguing for a regulated process of interneuron migration.
However, the long-distance tangential migration of interneurons has been considered to
be mostly random (Ang et al., 2003; Tanaka et al., 2009).
Brown et al. (2011) found that clonally related interneurons do not randomly disperse
but form spatially organized vertical and horizontal clusters in the neocortex.
Nearly all neocortical neuronal circuits are composed of excitatory neurons and
inhibitory interneurons.
Similar to excitatory neurons, inhibitory interneurons in the neocortex develop highly
specific synaptic connections for the assembly of functional circuits (Gupta et al., 2000;
Yoshimura and Callaway, 2005; Thomson and Lamy, 2007; Fino and Yuste, 2011).
The synaptic connections from local inhibitory interneurons to excitatory neurons
exhibit a stereotypic spatial pattern (Kätzel et al., 2011), suggesting a high degree of
spatial and functional organization of neocortical interneurons (Brown et al., 2011).
Cortical layers
Although the cerebral cortex contains an enormous number of cells, the number of
cell types is small (Colonnier, 1967).
Based on cell size and packing density (cytoarchitectonics) each cortical region is
divisible into six cellular layers, with three of these layers being subdivided based on
their architectural features.
This six-layered cellular arrangement is characteristic of the entire neopallial cortex,
which is referred to as neocortex, isocortex (Vogt and Vogt, 1919) or homogenetic cortex
(Brodmann, 1909).
Two regions of the cerebral cortex have fewer than six layers. The first contains
only three layers, is classified as archicortex, and includes the hippocampal formation.
The second contains from three to five layers, is classified as paleocortex, and includes
the olfactory sensory area and the nearby entorhinal and periamygdaloid cortices.
On the other hand, those cortical areas with six definite layers are termed homotypic
areas.
Homotypical variants, in which all six laminae are found, are called frontal, parietal
and polar.
Those cortical areas in which six layers are obscure, such as in the primary motor
cortex (where there appears to be only five layers) or where seven layers are identifiable,
such as in the primary visual cortex, are termed heterotypic areas.
The two types of cortex, granular and agranular, are regarded as virtually lacking
certain laminae, and are referred to as heterotypical.
The agranular type is considered to have diminished, or absent, granular laminae
(II and IV), but always contains scattered stellate somata. Large pyramidal neurones are
found in the greatest densities in the agranular cortex, which is typified by the numerous
1611
efferent projections of pyramidal cell axons. Agranular cortex occurs in areas 4, 6, 8, and
44 and parts of the limbic system.
In the granular type of cortex the granular layers are maximally developed, and it
contains densely packed stellate cells, among which small pyramidal neurons are
dispersed.
Layers III and IV are poorly developed or unidentifiable. This type of cortex is
particularly associated with afferent projections.
However, it does receive efferent fibres, derived from the scattered pyramidal cells,
although they are less numerous than elsewhere.
Granular cortex occurs in the postcentral gyrus (somatosensory area), striate area
(visual area) and superior temporal gyrus (acoustic area), and in small areas of the
parahippocampal gyrus. Despite its very high density of stellate cells, it is almost the
thinnest of the five main types.
The other three types of cortex are intermediate forms. In the frontal type, large
numbers of small- and medium-sized pyramidal neurons appear in laminae III and V,
and granular layers (II and IV) are less prominent.
The parietal type of cortex contains pyramidal cells, which are mostly smaller in
size than those found in the frontal type.
In marked contrast, the granular laminae are wider and contain more stellate cells:
this kind of cortex occupies large areas in the parietal and temporal lobes.
The polar type is classically identified with small areas near the frontal and occipital
poles and is the thinnest form of cortex. All six layers are represented, but the pyramidal
layers (III) are reduced in thickness and not as extensively invaded by stellate cells as is
the granular type of cortex. The multiform layers (VI) are more highly organised than
other types.
However, these six cortical layers include the: (I) molecular layer, (II) external
granular layer, (III) external pyramidal layer, (IV) internal granular layer, (V) internal
pyramidal layer, and (VI) multiform layer.
Layer (I) – the molecular layer contains very few neuron cell bodies and consists
primarily of axons running parallel (horizontal) to the surface of the cortex. Within it are
found the terminal dendritic ramifications of the pyramidal and fusiform cells from the
deeper layers, and the axonal endings of the Martinotti cells.
Layer (II) – the external granular layers are composed of a mixture of small neurons
called granule cells and slightly larger neurons, which are called pyramidal cells based
on the shape of their cell body.
The apical dendrites of these pyramidal cells extend into layer I and their axons
descend into, and through the deeper cortical layers. This layer is poor in myelinated
fibres. Myelin fibre stains show mainly vertically arranged processes traversing the layer.
Layer (III) – the external pyramidal layers are composed mainly of well formed
pyramidal neurons. The size of the pyramidal cells is smallest in the most superficial part
of the layer and greatest in the deepest part. Two sublayers are recognized: a superficial
layer of medium-sized pyramidal cells, along with some neurons of other types, and a
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21. Cerebral cortex
deeper layer of larger ones. Their apical dendrites go to the first layer, while most of their
axons enter the white matter, chiefly as association or commissural fibres. Intermingled
with the pyramidal neurons are granules and Martinotti cells. In the most superficial part
of the layer, a number of horizontal myelinated fibres constitute the band of Kaes-
Becherew.
Layer (IV) – the internal granular layer is usually the narrowest of the cellular
laminae and is composed almost exclusively of smooth (aspiny) stellate neurons and
spiny stellate neurons many of which have short axons ramifying within the layer. By
the 1950s it had become customary to refer to virtually all intrinsic cortical neurons as
stellate cells, even though many were not actually star shaped.
Now, a number of distinct morphologic types are recognized. Some of the more
important are the spiny and aspiny stellate cells, basket cells, and chandelier cells.
Three types of intrinsic neurons receive thalamocortical axon terminals in layer IV:
the small spiny cells, the aspiny stellate cells, and dendrites of the large basket cells. Of
these, the spiny cells are believed to be excitatory, whereas basket cells and aspiny stellate
cells use the neurotransmitter GABA and are thus considered to be inhibitory interneurons.
Most other intrinsic neurons are presumed to be inhibitory (Lynch and Tian, 2005).
This layer is free of pyramidal-shaped cells. It can be divided into an outer (IV a)
and inner (IV b) portion in many neocortical areas and into three portions (IV a, IV b, IV
c) in the primary visual cortex.
Layer IV is the primary target for ascending sensory information from the thalamus
(Lynch, 2006).
Layer (V) – the internal pyramidal (ganglionic) layer, consists of medium-sized and
large pyramidal neurons intermingled with granule and Martinotti cells. The apical
dendrites of the larger pyramids ascend to the molecular layer; dendrites of the smaller
pyramids ascend only to layer IV.
The large pyramidal cells of this layer are a major source of cortical efferent fibres
including axons to the basal nuclei, brain stem, and spinal cord. Some corticocortical
axons also originate in layer V. These are probably collateral branches of axons that are
projecting to some subcortical targets. A considerable number of callosal fibres is
furnished by the smaller pyramidal cells. The horizontal fibre plexus in the deeper portion
of this layer constitutes the internal band of Baillarger.
Layer VI – the multiform (or fusiform / pleomorphic) layer, contains an assortment
of neuron types including some with pyramidal, ovoid and fusiform cell bodies. These
spindle-shaped cells have their axes perpendicular to the cortical surface. Like the pyramidal
neurons of layer V, the spindle cells vary in size; the longer ones send a dendrite into the
molecular layer, while the dendrites of the smaller ones ascend to layer IV, or arborize
within the fusiform layer. Thus, the dendrites of many pyramidal and spindle cells from
layers V and VI come into direct relation with the endings of sensory thalamocortical fibres,
which ramify chiefly in the internal granular layer (Mountcastle, 1997).
The axons of the cells of this layer project to subcortical targets, such as the thalamus,
and to other cortical regions as corticocortical connections.
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Many of the short arcuate association fibres connecting adjacent convolutions are
furnished by the deep stellate cells of layer VI (Lorente de Nó, 1949).
Cortical connectivity
Different cortical areas have widely different afferent and efferent connections.
Afferent connections
The widely separated but functionally interconnected areas of cortex share common
patterns of connections with subcortical nuclei and within the neocortex. Thus, contiguous
zones of the striatum, thalamus, claustrum, cholinergic basal forebrain, superior colliculus
and pontine nuclei connect with anatomically wide areas of the prefrontal and parietal
cortex, which are themselves interconnected.
In contrast, other functionally distinct regions, e.g., areas in the temporal and parietal
cortex, do not share such contiguity in their subcortical connections.
All the various nonpyramidal neurons of the cerebral cortex function as cortical
interneurons, because their axons do not leave the immediate region of the cell body
(Jones 1975; Lynch and Tian 2005).
With the help of the Golgi technique, the distribution of dendritic and axonal
terminals has been worked out by a number of investigators, notably Cajal (1909-1911).
Lorente de Nó (1949) has given a detailed account for the elementary pattern of
cortical organization that is applicable to the parietal, temporal and occipital isocortex.
According to this investigator, the arrangement of the axonal and dendritic branchings
forms the most constant feature of cortical structure.
The afferent fibres to the cortex include projection fibres from the thalamus,
association fibres from other cortical areas of the same side and commissural fibres from
the opposite side.
The thalamocortical fibres, especially the specific afferent ones from the ventral
tier thalamic nuclei and the geniculate bodies, pass unbranched to layer IV. Here, the
axons form a dense terminal plexus (Colonnier, 1967); some of these fibres extend to
layer III where they arborize. Specific afferent fibres in layer IV establish both
axodendritic and axosomatic synapses upon stellate neurons which are fantastically
profuse on some cells (Colonnier, 1968).
Fibres of the so-called nonspecific thalamocortical system, related to the intralaminar
thalamic nuclei and indirectly to the ascending reticular activating system, also reach the
cerebral cortex. Histological data concerning the origin, course and termination of these
afferent fibres, have been meagre (Hanberry and Jasper, 1953; Nauta and Whitlock, 1954;
Bowsher, 1966).
Jones and Leavit (1974) and Jones (1984) have been shown that the intralaminar
thalamic nuclei, which project mainly to the striatum, project collateral fibres diffusely
to broad regions of the cerebral cortex.
Thus, the cerebral cortex receives inputs, called diffuse inputs, and it consists of
fibres that branch extensively and end diffusely over a wide area of cortex without respect
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21. Cerebral cortex
for the cytoarchitectural boundaries. These inputs arise from the nonspecific nuclei of
the thalamus (for example, the ventral anterior, central lateral, and midline nuclei), the
locus ceruleus, and the basal nucleus (of Meynert). These structures are generally
concerned with regulating overall levels of cortical excitability and the associated
phenomena of arousal, sleep, and wakefulness (Lynch, 2006).
According to Jasper (1960), the synaptic termination of fibres of this nonspecific
system in the cortex is chiefly axodendritic and widely distributed in all layers, but the
principal physiological effects appear to be within the superficial layers.
The association of callosal fibres give off some collaterals to layer V and VI and
ramify mainly in layer II and III, and to a lesser extent in layer IV (Carpenter, 1979).
Thus, thalamocortical axons terminate primarily in layer IV and to a lesser extent in layers
III and VI. In layer IV, they terminate on excitatory and inhibitory interneurons as well
as on dendrites from neurons in other layers. The axons of interneurons, in turn, may end
on dendrites of pyramidal cells or of other interneurons.
Generally, the details of intrinsic circuitry of the cerebral cortex are very complex.
A single neuron may also receive synaptic contacts from thousands of other neurons. The
basic framework of cortical circuitry consists of afferent fibres, local circuits for the
processing of this afferent information, and efferent fibres that convey the processed
information to another site.
The local processing of information culminates in connections to pyramidal cells,
which carry the information to other cortical and subcortical regions. A copy of the
information also goes to neurons in the immediate vicinity via axon collaterals. Generally,
the termination of corticocortical axons is quite different from that of thalamocortical
axons. Corticocortical axons branch repeatedly and make synaptic contacts on neurons
in all layers of the cortex (Lynch, 2006).
Thalamocortical relationship
According to Lynch (2006) the cortex of the frontal lobe encompasses Brodmann’s
areas 4, 6, 8 to 12, 32 and 44 to 47. The primary somatomotor cortex (area 4) and the
premotor and supplementary motor cortices (area 6) receive input mainly from the ventral
lateral nucleus of the thalamus and subserve important motor functions.
The lateral, medial, and orbital aspects of the frontal lobe receive thalamocortical
fibres mainly from the dorsomedial and anterior nuclei of the thalamus.
These latter cortical areas relate primarily to functions of the limbic system through
a variety of direct and indirect connections. Of particular note are the pars orbitalis and
pars triangularis of the inferior frontal gyrus, damage to which results in Broca aphasia.
Areas 3, 1, 2, 5, 7, 39, 40 and 43 are located in the parietal lobe. The primary
somatosensory cortex (areas 3, 1 and 2) receives inputs from the ventral posterolateral
and ventral posteromedial nuclei.
These thalamic nuclei receive a full range of somatosensory inputs through synaptic
relays in the spinal cord and brain stem and transmit this information to the cerebral
cortex. The inferior parietal lobule comprises, in general, areas 39 and 40. Along with
area 22, these areas are the cortical regions associated with Wernicke aphasia.
1615
The occipital and temporal lobe encompass areas 17 to 22, 36 to 38, and 41 and 42.
These areas of the cortex, plus portions of the parietal lobe, have extensive connections
with the pulvinar nucleus of the thalamus and are involved in the processing of visual
and auditory information at several different functional levels. In this area are the primary
sensory cortices for vision and hearing. Area 17, on the bank of the calcarine sulcus, is
the primary visual cortex; areas 41 and 42, in the depth of the lateral fissure in the
transverse temporal gyri, constitute the primary auditory cortex.
These cortical areas receive inputs from the lateral and medial geniculate nuclei of
the thalamus, respectively.
The limbic lobe, which forms the most medial edge of the hemisphere, contains
areas 23 to 31 and 33 to 35. The cingulate cortex receives fibres primarily from the
anterior nucleus of the thalamus but also from the lateral dorsal nucleus.
Other regions of the limbic lobe have some connections with the dorsomedial
nucleus. However, many of the subcortical targets of the parahippocampal and uncal
cortices are structures such as the hippocampal formation. These are, in turn, projects to
a variety of thalamic and basal forebrain targets (Lynch, 2006).
Major afferents to the cortical area tend to terminate in layers I, IV and VI.
Quantitatively lesser projections end either in the intervening laminae II / III and V, or
sparsely throughout the depth of the cortex. Numerically, the largest input to a cortical
area tends to terminate mainly in layer IV. This pattern of termination is seen in the major
thalamic inputs to visual and somatic sensory cortex.
Generally, non-thalamic subcortical afferents to the neocortex, which are shared by
wide spread areas, tend to terminate throughout all cortical layers, but the laminar pattern
of their endings still varies considerably from area to area (Crossman, 2008).
Generally, all cortical areas receive topographically organized cholinergic
projections from the basal forebrain, noradrenergic fibres from the locus ceruleus,
serotoninergic fibres from the midbrain raphe nuclei, dopaminergic fibres from the ventral
midbrain, and histaminergic fibres from the posterior hypothalamus.
Efferent connections
All neocortical areas have axonal connections with other cortical areas on the same
side (association fibres), the opposite side (commissural fibres), and with subcortical
structures (projection fibres). The pyramidal cells are the efferent neurons of the cerebral
cortex.
Thus, all neocortical areas are connected with subcortical regions although their
density varies between areas. First among these are connections with the thalamus. All
areas of the neocortex receive afferents from more than one thalamic nucleus, and all
such connections are reciprocal.
The vast majority, if not all, of the cortical areas project to the striatum, tectum, pons
and brain stem reticular formation. Additionally, all cortical areas are reciprocally
connected with the claustrum; the frontal cortex connects with the anterior part and the
occipital lobe with the posterior part (Crossman, 2008).
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21. Cerebral cortex
The primary somatosensory, visual and auditory cortices give rise to ipsilateral
corticocortical connections to the association areas of the parietal, occipital and temporal
lobes, respectively, which then progressively project towards the medial temporal limbic
areas, notably the parahippocampal gyrus, entorhinal cortex and hippocampus.
Thus, the first (primary) somatosensory area (SI) projects to the superior parietal
cortex (Brodmann’s area 5), which in turn projects to the inferior parietal cortex (area
7). From here, connections pass to the cortex in the walls of the superior temporal sulcus,
and so on to the posterior parahippocampal gyrus, and into the limbic cortex.
Similarly, for the visual system, the primary visual cortex (area 17) projects to the
parastriate cortex (area 18), which in turn projects to the peristriate region (area 19).
Information then flows to the inferotemporal cortex (area 20), to the cortex in the walls
of the superior temporal sulcus, then to the medial temporal cortex in the posterior
parahippocampal gyrus, and so to limbic areas. The auditory system shows a similar
progression from the primary auditory cortex to the temporal association cortex and so
to the medial temporal lobe (Crossman, 2008).
The primary somatosensory cortex (SI) in the postcentral gyrus is reciprocally
connected with the primary motor cortex (area 4) in the precentral gyrus.
The superior parietal lobule (area 5) is interconnected with the premotor cortex (area
6), that in turn is connected with area 7 in the inferior parietal lobule. This has reciprocal
connections with the prefrontal association cortex on the lateral surface of the hemisphere
(areas 9 and 46), and the temporal association areas, which connect with more anterior
prefrontal association areas, and, ultimately in the sequence, with the orbitofrontal cortex.
Similar stepwise links exist between areas on the visual and auditory association pathways
in the occipitotemporal lobe and areas of the frontal association cortex.
The connections between sensory and association areas are reciprocal (Crossman,
2008). Generally, short corticocortical fibres arise more superficially, and long
corticocortical (both association and commissural) axons come from cells in the deeper
parts of the layer III.
The internal pyramidal lamina, layer V, gives rise to cortical projection fibres, most
notably corticostriate, corticopontine, corticobulbar, and corticospinal axons. In addition,
a significant proportion of feedback corticocortical axons arise from cells in this layer,
as do some corticothalamic fibres. Layer VI, the multiform lamina, is the major source
of corticothalamic fibres.
Supragranular pyramidal cells, predominantly from layer III, but also lamina II, give
rise primarily to both association and commissural corticocortical pathways.
Myeloarchitectonics
Based on the types of fibres present (radial, oblique, and horizontal fibres), their
distribution, layering, and amount of myelin, collectively termed myeloarchitectonics,
six major cortical fibre layers are identifiable in the human cerebral cortex.
Related to layer II is the stria of the external granular layer. This layer of fibres
is associative in function with many association and commissural fibres. The stria of the
1617
internal granular layer in layer IV, receives inputs from various specific thalamic
nuclei.
Finally, the stria of the internal pyramidal layer is located in the deep part of layer
V (Fig. 21.4).
The infragranular cortical layers have their output through the stria in layer V (Jones,
1984; Braitenburg and Schüz, 1998; Zielles and Palomero-Gallagher, 2001; Augustine,
2008).
Thus, two features of the myelinated fibres in the neocortex are noteworthy. First,
there are prominent plexuses of horizontally running myelinated fibres in layers IV and
V. These are called the outer and inner bands of Baillarger, respectively. In the primary
visual cortex, bordering on the calcarine sulcus the outer band of Baillarger is greatly
expanded. This band can be seen with the naked eye in fresh and stained sections and is
called the stria (line) of Gennari.
Second, in most regions of the neocortex, there are many radially oriented bundles
of axons passing between the subcortical white matter and various parts of the cortex or
between the inner and outer cortical layers (Fig. 21.5).
Fig. 21.4. Layers of the human cerebral cortex (from Standring, 2005).
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21. Cerebral cortex
Fig. 21.5. Nissl (A) and myelin (B) stains of adjacent sections of the human cerebral cortex and a Golgi impregnation
(C) of a pyramidal neuron in the primate neocortex. (A and B by courtesy of Drs. Grazyna Rajkowska and Patricia
Goldman-Rakic, University of Mississippi Medical Center and Yale University; C by courtesy of Dr. José Rafols,
Wayne State University).
Cortical columns spots and stripes (microarchitecture)

Although the most striking feature of Nissl-stained sections of the cerebral cortex is
its horizontal lamination, physiological studies of the somatosensory and visual cortex
indicate that a vertical column of cells, extending across all cellular layers, constitutes
the elementary functional cortical units (Mountcastle, 1957; Powell and Mountcastel,
1957, 1959 a; Hubel and Wiesel, 1962, 1963).
This conclusion is supported by the following evidence: (1) neurons of a particular
vertical column are all related to the same, or nearly the same, peripheral receptive field,
(2) neurons of the same vertical column are activated by the same peripheral stimulus,
and (3) all cells of a vertical column discharge at more or less the same latency following
a brief peripheral stimulus.
Thus, the cell size and packing density of the cerebral cortex (cytoarchitectonics),
permits the identification of cortical layers and cortical parcellation into regions and areas.
In addition, there is also a columnar cortical organisation (microarchitecture).
The term “column” refers to the observation that all cells encountered by a
microelectrode penetrating and passing perpendicularly through the cortex respond to a
single peripheral stimulus, a phenomenon first identified in the somatosensory cortex.
The columns display variations in size and cross-sectional area, and the receptive
field axis of orientation varies in a continuous manner as the surface of the cortex is
traversed. Anatomically, an elementary functional unit of the cortex, represented by a
column of cells, must contain the afferent, efferent and internuncial fibre system necessary
for the formation of a complete cortical circuit. In the basic columnar unit, the internal
circuitry must vary with differences in cytoarchitecture.
1619
The convergence of specific afferents upon specific cells in the columnar units
appears to imprint a specific modality which is relayed by intracortical connections to
other cells in the column. The complex axonal branching suggests that intracortical
circuits involve cells in all parts of the column. These vertical circuits are interconnected
by short neuronal links represented primarily by the short axons of granule cells whose
processes arborize within a single layer.
Through these short links, cortical excitation may spread horizontally and involve a
progressively larger number of vertical units.
Thus, in one cortical region, all neurons might have receptive fields for a finger,
whereas, in a nearby region, the neurons might have receptive fields for the wrist. Within
a cortical region in which all neurons had about the same receptive field, the neurons
responded to different sensory submodalities. Some neurons are activated by light touch
on the skin, others by joint rotation, and still others by strong pressure on deep tissue
(Lynch, 2006).
So, neurons in the somatosensory cortex are located in vertical columns at right
angles to the surface and extend through all cortical layers; they often share similar
receptive fields and have specific functions. The width of these cortical columns has an
upper limit in primates of about 5 mm. Columns in SI are functionally interrelated by
intrinsic corticocortical connections and by direct horizontal connections between
columns. These intrinsic connections serve to connect parts of the cerebral cortex having
different response properties, yet lying in regions of similar regional representation
(Augustine, 2008). Thus, a specific afferent fibre may not only fire vertical columns of
cells in its immediate vicinity, but may reach other units through Golgi type II cell relays
(Lorente de Nó, 1949).
According to Cajal (1909, 1911) the unique morphological feature of the human
cortex is the enormous number of Golgi type II cells considered to interrelate vertical
cell columns.
The topographical pattern present on the cortical surface extends throughout its
depth. Studies of the visual (striate) cortex demonstrate similar discrete functional
columns extending from the pial surface to the white matter that are responsive to a
specific kind of retinal stimulation in the form of long narrow rectangles of light (“slits”),
dark bars against a light background, or straight-line borders, all of which must have a
particular axis of orientation (Hubel and Wiesel, 1962, 1963).
Thus, in the visual cortex, narrow (50 µm) vertical strips of neurons respond to a bar
stimulus of the same orientation (orientation columns) and wider strips (500 µm) respond
preferentially to stimuli detected by one eye (ocular dominance columns). Adjacent
orientation columns aggregate within an ocular dominance column to form a hypercolumn,
responding to all orientations of a stimulus for both eyes for one point in the visual field
(Lynch, 1980; Peters and Jones, 1999; Casanova Manuel, 2005; Crossman, 2008).
Thus, in the visual cortex, at least three types of regularly repeating features are
superimposed on the laminar patterns of neurons: the stimulus orientation columns, the
ocular dominance columns, and the cytochrome oxidaze-rich blobs.
1620
21. Cerebral cortex
The ocular dominance columns in the visual cortex provide a clear example of the
role of thalamic inputs in columnar organization.
Neurons in the layers of the lateral geniculate nucleus that receive inputs from the
right eye send their axons to layer IV of the right eye-dominant columns. Here, the axons
terminate predominantly on spiny and aspiny stellate cells, which, in turn, project to
pyramidal cells. Collaterals of pyramidal cell axons provide one pathway by which neural
signals can spread from one column to influence activity in adjacent columns.
This influence may be either excitatory via direct connections, or inhibitory via
interneurons.
The right eye has a direct and strong influence on neurons in right-eye-dominant
columns and an indirect and weaker influence on neurons in the adjacent left-eye-
dominant columns (Lynch, 2006).
When a microelectrode was inserted at right angles to the surface of the cortex, all of
the neurons encountered were activated by only one of these submodalities (Fig 21.6, B).
In contrast, when a microelectrode was moved parallel or obliquely relative to the
surface of the cortex, it encountered neurons of different submodalities as it moved from
one functionally related group of neurons to another (Fig. 21.6, A) (Lynch, 2006).
Fig. 21.6. Diagramatic section through

the precentral and postcentral gyri
showing the organization of columns in
the somatosensory cortex. The columns
are shown as compartments oriented,
generally, perpendicular to the surface
of the cortex. An electrode (at A)
passing parallel to the surface of the
cortex will pass through several
columns with resultant recordings of the
several modalities represented by the
types of afferent information arriving at
each column. An electrode passing
through one column (at B) passing
perpendicular to the surface of the
cortex penetrates only a single column.
Therefore, it records activity related to
the single submodality received by that
column (after Lynch, 2006).
1621
If all of the cells in one column respond to maintained pressure on the skin, the cells
in an adjacent column respond to joint position.
Similar columnar organization has been described in widespread areas of the
neocortex, including the motor cortex and association areas.
According to Kolb and Whishaw (2003), most interactions between the layers of
the cortex take place within the cells directly above or below the adjacent layers.
There have been many terms for the vertical organization of the cortex, two of the
most common being column and module. Although these terms are not always
interchangeable, the underlying idea is that groups of 150 to 300 neurons form little
circuits ranging from about 0.5 to 2.0 mm wide, depending on the cortical region.
Evidence for some kind of modular unit comes from two principal sources: staining and
probing (Purves et al., 1992).
If a radioactive aminoacid is injected into one eye of a monkey, the radioactivity is
transported across synapses to the primary visual cortex. The radioactivity is not evenly
distributed across the cortex, however, in that it travels only to places that connect with
the affected eye. Thus, the pattern of radioactivity seen in the primary visual cortex (area
17) is a series of stripes, much like those on a zebra (Purves et al., 1992).
A different pattern is seen in the same visual cortex when a different technique is used.
If the cortex is stained with cytochrome oxidaze, which shows areas of high metabolic
activity by staining mitochondria, the visual cortex appears spotted. These spots, known as
“blobs”, have a role in colour perception (Fig. 21.7, A and B) (Purves et al., 1992).
Curiously, if the same stain is applied to area 18, which is an adjacent visual region, the
staining pattern looks more like stripes (Fig. 21.7, C) than like spots (Purves et al., 1992).
Finally, if the primary somatosensory cortex of a rat is stained with succinic dehydro-
genaze, the cortex shows a pattern of spots that are known as “barrels” (Fig. 21.7, D). Each
barrel corresponds to one of the vibrissae on the face of the rat (Purves et al., 1992).
Fig. 21.7. Spots and stripes in the cortex, obtained by staining (after Purves et al., 1992).
1622
21. Cerebral cortex
As these examples illustrate, there appear to be many

types of modules, and even the same stain shows a
different modular organization in different regions.
A second way to demonstrate modular organization
is shown physiologically in the sensory cortex. According
to Kolb and Whishaw (2003), if a microelectrode is
moved vertically through the sensory cortex from layer I
to layer VI, all the neurons encountered appear to be
functionally similar. The functional similarity of cells
across all six layers at any point in the cortex suggests that
the simplest functional unit of the cortex is a vertically
orientated column of cells that composes a minicircuit.
Groups of these columns may be organized in somewhat
larger units as well. If an electrode samples the cells of
area 17 (visual cortex), all the cells in a column will
respond to a line of a given orientation (for example, 45º).
If the electrode is moved laterally across the cortex,
adjacent columns will respond to successively different
orientations (for example, 60º, 90º, and so on) until all
orientations over 360º are sampled. Thus, in the visual
cortex, columns are arranged in larger modules (Fig. 21.8).
One problem is that, although modules are apparent
in primary sensory regions, they are less apparent in the
association or motor areas of the cortex. The stripes and
spots are also a problem because they differ greatly in size.
Furthermore, closely related species often have very
Fig. 21.8. The six major layers of
different patterns of spots and stripes, which seem strange cortex in cross section. The figure
if they are fundamental units of cortical functions. shows three columns in Area 17,
Zeki (1993) suggested that the search for the basic also called V1, the first visual
module of cortical organization is akin to the physicist’s projection area to the cortex (source
Squire et al., 2003).
search for the basic unit of all matter.
The underlying assumption is that the cortical module might be performing the same
basic functions throughout the cortex. In this view, the evolutionary expansion of the
cortex corresponds to an increase in the number of basic units, much as one would add
chips to a computer to expand its memory or processing speed.
Anyhow, we are left wandering what the basic function and operation of the cortical
module might be.
Purves and his colleagues (1992) have offered a provocative answer. They noted
that the spots and stripes on the cortex resemble the markings on the fur of many animals.
They suggested that, even though these patterns may provide camouflage or broadcast
sexual signals, these functions are secondary to fur’s fundamental purpose of maintaining
body temperature. Pursuing this analogy, the researcher proposed that same modular
1623
patterns in the cortex may well correspond to secondary functions of cortical organization.
One suggested that the cortex forms its intrinsic connections to process information; one
efficient pattern of connectivity is the vertical module.
The module certainly conforms to an important aspect of cortical connectivity, but
it does not cause cortical connectivity. There must be an alternative way (or ways) of
organizing complex neural activity that does not require a constant module. Although a
cortical organization with columns is a useful arrangement, it is not the only way to
organize a brain (Kolb and Whishaw, 2003).
The organization of the cells of the cortex

Nerve cells can be easily distinguished in the cortex as spiny neurons or aspiny
neurons by the presence or absence, respectively, of dendritic spines.
Dendritic spines serve as functional comportments for chemicals as well as a location
for synaptic connections with other cells (Kolb and Whishaw, 2003).
About 95% of all excitatory synapses on spiny neurons occur on the spines (Peters
and Jones, 1984, 1999).
Spiny neurons include pyramidal cells, which have pyramid-shaped cell bodies and
generally send information from one region of the cortex to some other brain area, and
spiny stellate cells, which are smaller, star-shaped interneurons whose processes remain
within the region of the brain in which the cell body is located. Spiny neurons are
excitatory and are likely to use glutamate or aspartate as transmitters. The pyramidal
cells, which constitute the largest population of cortical neurons (70%-85%), are the
efferent projection neurons of the cortex (Peters and Jones, 1984, 1999).
They are found in layers II, III, V, and VI. Generally, the largest cells send their
axons the furthest.
The pyramidal cells of layer V are the largest, projecting to the brain stem and spinal
cord. Those in layer II and III are smaller and project to other cortical regions.
The neurons of the neocortex are arranged in about six layers. The six horizontal
layers of cortex are organized in cortical columns, vertical barrel-shaped slices. These
often contain closely related neurons, such as visual cells that respond to different
orientations of a single light edge in just one part of the visual field.
Columns may be clustered into hypercolumns, which may be part of an even larger
cluster. Thus, the cortex has both a horizontal organization into six layers, and a vertical
one, into columns, hypercolumns, and eventually entire specialized regions. These six
layers can be separated into three groups of functions (Everett, 1965; Elliot, 1969;
Passingham, 1979).
1. The output cell layers, layers V and VI, send axons to other areas. Both of these
layers and the cells of which they are composed are particularly large and distinctive in
the motor cortex, which sends projections to the spinal cord. Large size is typical for cells
that send information to long distances.
2. The input cell layer, layer IV, receives axons from the sensory system and other
cortical areas. This layer features large numbers of small, densely packed cells in the
1624
21. Cerebral cortex
primary areas of vision, somatosensation, audition, and taste-olfaction, which receive

large projections from their receptive sensory organs.
3. The association cell layers, layers I, II, and III, receive input mainly from layer
IV and are quite well developed in the secondary and tertiary areas of the cortex.
In short, sensory areas have many layer IV cells, motor areas have many layer V
and VI cells, and association areas have many layer I, II and III cells.
Some cortical neurons send their axons to the thalamus, while others receive input
from thalamic neurons. Millions of cortical nerve cells go to the opposite hemisphere,
while many others project their axons to the same hemisphere. However, the densest
connections are to neighbouring neurons. Cortical layer I consists largely of dendrites
(input fibres) that are so densely packed and interconnected that this layer is sometimes
called a “feltwork”, a woven sheet of dendrites. These connection patterns in the cortex
undergo major changes in human development and throughout the lifespan.
Aspiny neurons are interneurons with short axons and no dendritic spines. They are
diverse in appearance, with different types named largely on the basis of the
configurations of their axons and dendrites. One type of aspiny stellate cell is called a
basket cell because its axon projects horizontally, forming synapses that envelop the
postsynaptic cell like a basket.
Another, the double-bouquet type, has a proliferation of dendrites on either side of
the cell body, much as if bouquets of flowers were aligned stem to stem. Despite
differences in shape, all aspiny neurons are inhibitory and are likely to use GABA as a
transmitter.
Aspiny neurons also use many other transmitters; virtually every classical transmitter
and neuropeptide has been colocalized with GABA in aspiny cells. Thus, not only are
aspiny cells morphologically diverse, but they also show a remarkable chemical diversity
Cortical layers, afferents and efferents

According to Kolb and Whishaw (2003), each of the four to six layers of the cortex
has different functions, different afferents (inputs), and different efferents (outputs). The
cells from the middle layers of the cortex (especially in and around layer IV) constitute
a zone of sensory analysis in that they receive projections from other areas of the cortex
and other areas of the brain. The cells from layers V and VI constitute a zone of output
in that they send axons to other cortical areas or other brain areas (Fig. 21.9).
Therefore it is hardly surprising that the somatosensory cortex has a relatively large
layer IV and a small layer V, whereas the motor cortex has a relatively large layer V and
a small layer IV.
Anyhow, different cortical layers can be distinguished by the neuronal elements they
each contain, and by the thickness of the layers, which also corresponds to their function.
Afferents to the cortex are, specific and nonspecific:
1) Specific afferents bring information (sensory information, for example) to an area
of the cortex and terminate in relatively discrete cortical regions, usually in only one or
1625
Fig. 21.9. A schematic drawing of the six layers of cortex, the gray matter. Note that some cortical neurons
send axons to the thalamus, while other receive input from thalamic neurons. Ipsilateral = same side
of the cortex; Contralateral = opposite side.
two layers. Specific afferents include projections from the thalamus as well as from the
amygdala. Most of these projections terminate in layer IV, although projections from the
amygdala and certain thalamic nuclei may terminate in more superficial layers.
2) Nonspecific afferents presumably serve general functions, such as maintaining a
level of tone or arousal, so that the cortex can process information. They terminate
diffusely over large regions of the cortex – in some cases, over all of it. Nonspecific
afferents even release their transmitter substances into the extracellular space. The
norepinephrinergic projections from the brain stem, the cholinergic projections from the
basal forebrain, and the projections from certain thalamic nuclei are examples of
nonspecific afferents (Kolb and Whishaw, 2003).
Despite significant variations among different cytoarchitectonic areas, the circuitry
of all cortical regions has some common features. First, each cortical layer has a primary
source of inputs and a primary output target. Second, each area has connections in the
vertical axis (called columnar or radial connections) and connections in the horizontal
1626
21. Cerebral cortex
axis (called lateral or horizontal connections). Third, cells with similar functions tend to
be arrayed in radially aligned groups that span all of the cortical layers and receive inputs
that are often segregated into radial or columnar bands. Finally, interneurons within
specific cortical layers give rise to extensive local axons that extend horizontally in the
cortex, often linking functionally similar groups of cells. The particular circuitry of any
cortical region is a variation on this canonical pattern of inputs, outputs and vertical and
horizontal patterns of connectivity (Purves et al., 2004).
Mapping the human cortex

The cortex can be divided by topographic maps, which are based on various
cytoarchitectonic areas. These cytoarchitectonic areas are histologically defined
subdivisions, which a zealous band of neuroanatomists has painstakingly mapped over
the years in humans and in some of the more widely used laboratory animals. Early in
the twentieth century, cytoarchitectonically distinct regions were identified with little or
no knowledge of their functional significance. However, studies of patients in whom one
or more of these cortical areas had been damaged, supplemented by electrophysiological
mapping in both laboratory animals and neurosurgical patients, supplied this information.
This work showed that many of the regions neuroanatomists had distinguished on
histological grounds are also functionally distinct. Thus, cytoarchitectonic areas can
sometimes be identified by the physiological response properties of their constituent cells,
and often by their patterns of local and long-distance connections (Milner, 1963; Lezak,
1995). The first complete cortical map of the human brain was published in 1905 by
Campbell, and it was based on both cell structure and myelin distribution.
Soon after, several alternative versions emerged, the most notable belonging to
Brodmann.
In 1909, Korbinian Brodmann published a treatise “Localisation in the Cerebral
Cortex” on histological localization in the cerebral cortex. He described his work in the
introduction: “Localisation which uses exclusively anatomical features as the basis for
investigation, in contrast to physiological or clinical aspects” (Garey, 1994). The lasting
result of this work was a scheme for the parcellation of the cerebral cortex into 52 distinct
areas based on common anatomical features (Fig. 21.10).
About 100 Brodmann’s areas are now recognized, and it is therefore convenient to
take this as a rough estimate of the number of specialized regions of the cortex. The
Brodmann areas correspond well to different specialized functions of the cortex such as
the visual and auditory areas, motor cortex, and areas involved in language and cognition.
Brodmann’s map represents differences in the density of different kind of neocortical
neurons. In Brodmann’s map, the different areas are numbered, but the numbers
themselves have no special meaning. To do his analysis, Brodmann divided the brain at
the central sulcus and then examined the front and back halves of the brain separately,
numbering new conformations of cells as he found them but without following a
methodical path over the surface or through the layers. Thus, he found areas 1 and 2 in
the posterior section, then switched to the anterior section and found area 3 and 4, and
then switched back again, and then looked somewhere else.
1627
Fig. 21.10. Cerebral hemispheres of the human with Brodmann’s areas applied. From Vergleichende
Lokalisationsliehre der Grosshirnrinde in ihren Prinzipien dargestellt auf Grund der Zellenbaues.
1628
21. Cerebral cortex
Fig. 21.11. Cytoarchitectural map showing Brodmann areas on the lateral (A) and medial (B) surface of the
hemisphere. (Modified after Brodmann K from Carpenter MB, Sutin J: Human Neuroanatomy. Baltimore,
Williams and Wilkins, 1983.)
Brodmann’s map is very useful because the regions depicted in it correspond quite
closely with regions discovered with the use of noncytoarchitectonic techniques. Figure
21.11 summarises some of the relations between areas on Brodmann’s map and areas
that have been mapped according to their known functions (Brodmann, 1909; Everett
1965; Elliot, 1969). For example, area 17 corresponds to the primary visual projection
area, whereas areas 18 and 19 correspond to the secondary visual projection areas. Area
1629
4 is the primary motor cortex. Broca’s area related to the articulation of words is area 44,
areas 6 and 8 (eye movement) correspond to secondary areas. The motor territory
corresponds to areas 9, 10, 11, 45, 46 and 47.
Areas 1, 2 and 3 correspond to the primary body senses projection areas, areas 5 and
7 correspond to the secondary body senses projection areas, and areas 7, 22, 37, 39, and
40 correspond to the territory sensory projection areas.
One of the problems with Brodmann’s map is that new, more powerful analytical
techniques have shown that many Brodmann’s areas actually consist of two or more
architectonically distinct areas. For this reason, the map is continually being updated and now
consists of an unwieldy mixture of numbers, letters, and names (Kolb and Whishaw, 2003).
Anyhow, Brodmann’s areas (BA) are distinct areas of the cerebral cortex based on
the organization of cells or the cytoarchitecture of the human brain. A functional
distinction of brain regions correlates remarkably well with this neuroanatomic
differentiation.
Some of these are so important that we will call them modules (high functional areas).
These modules are widely used today when discussing the results of neuroimaging studies.
At a microscopic level of description, we have the Brodmann areas.
When the surface layers of the cortex are carefully studied under a microscope, small
regional differences can be seen in the appearance of cells in the layers and their
connections (Baars, 2007).
However, about 70% of the human cerebral cortex is buried in sulci which
complicate our ability to visualize its extent from a surface view or topographic map. A
surface view of the brain thus hides the source of the majority of activation in imaging
studies. This problem is solved by the flat map, which allows images to visualize the
entire surface area of a hemisphere in a single view.
Van Essen and Drury (1997) used the MRI analysis of the Visible Man, a digital
atlas of the human body, to generate flat maps of the human cortex. Figure 21.12, A
shows a surface view of the Visible Man’s two hemispheres with the lobes, identified by
different shadings. Flat maps display the sulci and gyri in an alternative format
(Fig. 21.12, B), in which buried cortex (not visible from the exterior of the hemisphere)
is shown in darker shades.
The location of brain areas in a whole brain can be calculated by using a three-
dimensional atlas. Sections are taken at regular intervals (typically 4 mm in the human
brain). So, van Essen and Drury were able to identify the coordinates for the regions in
their flat map. Their coordinate system makes it possible to identify the location of
activations in imaging studies with respect to cortical surface.
Neurotransmitters of the cerebral cortex

According to Lynch (2006), there are a variety of neuroactive substances associated
with neurons of the cerebral cortex.
Principal among these are glutamate, aspartate, and gamma-aminobutyric acid
(GABA). Pyramidal cells are the efferent neurons of the cerebral cortex. They are
predominantly glutaminergic and excitatory to their targets.
1630
21. Cerebral cortex
Fig. 21.12. Cortical maps. (A) A digital surface map. (B) The cortex has been “flattened” so that all tissues hidden in
sulci are visible. Flat maps provide a perspective on the relative size of various cortical regions and on the amount of
tissue dedicated to different functions, as detailed in the table (after van Essen and Drury, 1997).
The pyramidal cells of the cortex, and therefore the output of the cortex, are
modulated by a variety of cortical afferents. The influence of these afferent fibres is to
act on pyramidal cells either directly or via interneurons. Most interneurons within the
cortex are GABAergic and inhibitory.
A variety of neuropeptides (monoamines) are also found in the cerebral cortex; they
influence not only populations of neurons but also local metabolic activity and vascular
smooth muscle. The most important monoamines in the cortex are (1) norepinephrine,
which originates from the locus ceruleus of the pons and distributes sparsely to all cortical
layers, (2) dopamine, which arises from the substantia nigra – pars compacta and the
adjacent ventral tegmental area and is found in moderate amounts in layers I and VI and
sparsely in II-V, and (3) serotonin, which arises from the raphe nuclei and distributes heavily
to all cortical layers (Vogt et al., 1997; Mesulam, 2004; Lynch, 2006).
1631
Cortical areas
The cerebral cortex does not have a uniform structure. It has been mapped and
divided into a number of distinctive areas that differ from each other in total thickness,
in the thickness and density of individual layers and in the arrangement and number of
cells and fibres.
Fig. 21.13. A) The Brodmann classification

of the regions in the left hemisphere,
shown a lateral view. B) The Brodmann
B classification of the regions in the right
hemisphere, shown a medial view.
In 1905, Campbell defined some 20 cortical fields in the human cerebral cortex.
In 1909, Brodmann published a monograph that continues to guide the study of
neuroscience even today. The cerebral cortex was originally classified by Brodmann into
52 different cytoachitectural areas (Fig. 21.13), but he did not assign a function to each
area at that time. He numbered them 1 to 52, which reflects the order in which he
examined and mapped them. Additional studies have provided information correlating a
function to many of these areas.
The anatomical / functional correlation, however, is not as accurate as was thought
in the past.
Some of these areas are commonly referred to by both name and number, and should
be known by the student. These are: the primary somatosensory cortex (Brodmann’s areas
3, 1, and 2), motor cortex (Brodmann’s areas 4, 6, and 8), secondary sensory cortex
1632
21. Cerebral cortex
(Brodmann’s areas 5 and 7), visual cortex (Brodmann’s areas 17, 18 and 19), and auditory
cortex (Brodmann’s area 41 and 42). The functional areas of the cerebral cortex are shown
in figures 21.14 and 21.15.
Vogt and Vogt (1919) parcelled the human cerebral cortex into more than 200 areas
based on cellular patterns. The Vogts were leaders in this field, defining some 229 cortical
areas. Von Economo (1929) divided it into 109. Thus, according to von Economo (1929),
all cortical structure is reducible to five fundamental types (Fig. 21.16), based primarily
on the relative development of granule and pyramidal cells. Types 2, 3 and 4, known
respectively as the frontal, parietal, and polar types, are homotypical and constitute by
far the largest part of the cortex.
Type 1 (agranular) and 5 (granular) are heterotypical and limited to smaller
specialized regions (Fig. 21.17).
Even the last numbers are apparently insufficient, since other investigators have
found a number of distinctive cytoarchitectural fields in regions previously considered
homogeneous (Beck, 1929; Rose, 1935).
The brain map of Bailey and von Bonin (1951) utilizes various colours to distinguish
distinctive cytoarchitectural features. These authors felt that the concept of absolutely
sharp areal boundaries has been carried to absurd lengths and that most brain maps failed
to properly represent transitional areas.
Fig. 21.14. Lateral view of the cerebral hemisphere showing the functional areas of the cerebral cortex.
(Modified from Young PA, Young PH (1997), Basic Clinical Neuroanatomy. Williams and Wilkins, Baltimore.)
1633
Fig. 21.15. Coronal section through the

cerebral hemisphere showing homunculi of
the primary somatosensory cortex (left) and
the primary motor cortex (right) (after
Patestas and Gartner, 2008).▲
Fig. 21.16. The five fundamental types of

cortical structure. 1, agranular; 2, frontal; 3,
parietal; 4, polar; 5, granulous (koniocortex)
(von Economo, 1929).◄
However, such cortical fields or areas are a morphological expression of functional

differences between the various regions of the cerebral hemispheres. Cotemporary
methods of cortical parcellation have used a combination of anatomy, neurochemistry,
and function (Schüz and Miller, 2002).
Functional aspects of the cerebral cortex

Flechsig (1920) was the first to suggest that anatomical criteria could be used to
delineate a hierarchy of cortical areas, but Luria (1973) fully developed the idea in the
1960s. Luria divided the cortex into two functional units.
1634
21. Cerebral cortex
Fig. 21.17. Distribution of the

five fundamental types of
cortex over the convex (A)
and the medial (B) surface of
the hemisphere. 1, agranular;
2, frontal; 3, parietal; 4, polar;
5, granulous (koniocortex)
(von Economo, 1929).
The posterior part of the cortex is the sensory unit. It receives sensations, processes
them, and stores them as information.
The anterior cortex (the frontal lobe) is the motor unit. It formulates intentions,
organizes them into programs of action, and executes the programs. Both cortical units
have a hierarchical structure with three cortical zones arranged functionally one above
the other. The first zone corresponds to Flechsig’s primary cortex; the second corresponds
to the slower-developing cortex bordering the primary cortex, which Luria labelled
secondary cortex; and the third, the slowest-developing cortex, which Luria labelled
tertiary cortex.
Luria conceives of the cortical units as working in concert along zonal pathways.
Sensory input enters the primary sensory zones, is elaborated in the secondary zones,
and is integrated in the tertiary zones of the posterior unit. To execute an action, activation
is sent from the posterior tertiary sensory zones to the tertiary motor zone for formulation,
to the secondary motor zone for elaboration, and then to the primary frontal zone for
execution.
Information in the tertiary sensory zone activates the paralimbic cortex for memory
processing and the amygdala for emotional assessment. A lesion in the primary visual
1635
zone would produce a blind spot in some part of the visual field. A lesion in the secondary
visual zone might produce a perceptual deficit, making the person unable to recognize
the activity. A lesion in the tertiary sensory zone might make it impossible to recognize
the significance of the activity in its abstract form (somebody lost his money).
Damage to the paralimbic cortex would leave no memory of the event, and damage
to the amygdala would render the person unresponsive to the event’s emotional
significance. A lesion in the tertiary motor area might prevent the formation of the
intention. A lesion in the secondary motor zone might make it difficult to execute the
sequences of movements required in an activity. A lesion in the primary zone might make
it difficult to execute a discrete movement required in an action.
Luria (1973) based his theory on three assumptions:
1) The brain processes information is serially – that is, one step at a time. Thus,
information from sensory receptors goes to the thalamus, then to the primary cortex, then
to the secondary cortex, and finally to the tertiary sensory cortex. Similarly, the output
goes from tertiary sensory to tertiary motor, then to secondary motor, and finally to
primary motor.
2) Serial processing is hierarchical; that is, each level of processing adds complexity
that is qualitatively different from the processing in the preceding levels. The tertiary
cortex could be considered a “terminal station” in so far as it receives input from the
sensorimotor and perceptual areas and performs higher cognitive processes on that input.
3) Our perceptions of the world are unified and coherent entities. So, the same active
process creates each percept, and naturally the simplest way to do so is to form it in the
tertiary cortex.
According to Kolb and Whishaw (2003), a strictly hierarchical processing model
requires that all cortical areas be linked serially, but this serial linkage is not the case.
All critical areas have reciprocal (reentrant) connections with the regions to which they
connect, which means that there is no simple “feed forward” system. Only about 40% of
the possible connections among different areas in a sensory modality are actually found.
Then, Zeki (1993) made the interesting point that, because a zone of cortex has
connections with many cortical areas, it follows that each cortical zone is probably
undertaking more than one operation, which is subsequently relayed to different cortical
areas. In addition, the results of the same operation are likely to be of interest to more
than one cortical area, which would account for multiple connections.
These principles can be seen in the primary visual cortex, which appear to make
calculations related to colour, motion, and form. These calculations are relayed to specific
cortical regions for these processes. And the same calculation may be sent to cortical as
well as to subcortical regions. This implies that cortical processing can bypass Luria’s
motor hierarchy and go directly to subcortical motor structures.
So, an area such as the primary visual cortex, which is processing colour, form, and
movement, might be considered more complex than an area that processes only colour
Finally, Luria assumed that his introspection about perception being a unitary
phenomenon was correct.
1636
21. Cerebral cortex
There are two logical possibilities to put this knowledge together in a meaningful
way to see organization in the cortex. According to Kolb and Whishaw (2003), one
possibility is that there is no hierarchical organization but rather some sort of nonordered
neural network. As individual organisms gain experiences, this network becomes ordered
in some way and so produces perceptions, cognitions, and memories. The results of a
wealth of perceptual research suggest that the brain filters and orders sensory information
in a species-typical fashion.
Felleman and van Essen (1991) suggested that cortical areas are hierarchically
organized in some well-defined sense, with each area occupying a specific position
relative to other areas, but with more than one area being allowed to occupy a given
hierarchical level. Felleman and van Essen (1991) proposed that the pattern of forward
and backward connections could be used to determine hierarchical position.
Thus, ascending (or forward) connections terminate in layer IV whereas descending
(or feedback) connections do not enter layer IV, usually terminating in the superficial
and deep layers (Fig. 21.18).
Fig. 21.18. Inter- and intraareal connections. (A) The flow of information to and from the cortex. Information from the
thalamus goes to the primary cortex, which then projects to the association cortex. Note the reciprocal connections at
each level, representing feedback loops. (B) The principle of the reentry. When one cortical area sends information to
another, the projection arises from layers II and III and terminates in layer IV. The receiver returns a connection (reentry)
from layers V and VI to layers I and VI of the first area. In this way, a receiving cortical area can modify the inputs that it is
getting. This reentry principle holds for all levels of cortical connectivity (after Kolb and Whishaw, 2003).
1637
They also recognize a third type of connection, which is columnar in its distribution
and terminating in all layers. This type of connection is uncommon but provides a basis
for placing areas in the same location in the hierarchy.
By analysing the patterns of connectivity among the visual, auditory, and
somatosensory areas, Felleman and van Essen (1991) found evidence of what they call a
distributed hierarchical system.
The cerebral cortex is the organ of thought. More than any other part of the nervous
system, the cerebral cortex is the site of the intellectual functions that make us human
and that make each of us a unique individual. These intellectual functions include the
ability to use language and logic, and to exercise imagination and judgment (Lynch,
2006). Although other brain structures, including the thalamus, corpus striatum,
claustrum, and cerebellum contribute to these functions, the multimodal association
cortex is closely linked to the most complex intellectual functions, such as logical
analysis, judgment, language and imagination.
Neurons in the cortex receive input from many subcortical structures by way of the
thalamus and also from other regions of the cortex via association fibres.
Cortical neurons, in turn, project to a wide range of neural structures, including other
areas of the cerebral cortex, the thalamus, the basal nuclei, the cerebellum via the pontine
nuclei, many of the brain stem nuclei, and the spinal cord.
The cerebral cortex is divided into distinct functional areas, some of which are
devoted to the processing of incoming sensory information, others to the organization of
motor activity, and still others primarily to what are considered “higher intellectual
functions”.
These functions include memory, judgment, the planning of complex activities,
processing of language, mathematical calculations, and the construction of an internal
image of an individual’s surroundings. Thus, in discussing functions of the cortical areas
in humans, it is essential to understand that we are not dealing with properties inherent
in the cerebral cortex itself, but we are dealing with complete neuronal arcs or chains of
neurons that project their impulses from specific areas of the nervous system to their
terminations.
The functional features of any cortical area are dependent on the connections to and
from that area and the interrelations that exist between the various primary and secondary
sensory receptive areas, the motor projection areas and the primary, secondary, and
tertiary association areas (Augustine, 2008).
Cerebral dominance refers to the observation that one cerebral hemisphere of the
brain is more involved in certain functions such as language, handedness, musical talents,
visual-spatial abilities, attention, and emotion. (Amunts et al., 1996; Braitenburg and
Schuz, 1998; Augustine, 2008).
In some cases, there is a functional lateralization and, in other cases, there is an
accompanying structural asymmetry in the brain. The early studies of Broca and
Wernicke demonstrated the lateralization of language function to the left hemisphere.
1638
21. Cerebral cortex
Subsequent studies demonstrated a structural asymmetry in the temporal language

region termed the planum temporale which corresponds to the posterior superior surface
of the superior temporal gyrus.
This asymmetry in a region corresponding to the core of Wernicke’s region, an
auditory association area, was greater in right-handers than in left-handers.
Both macroscopic and microscopic structural asymmetry exists in the primary motor
area in humans with regard to handedness (Amunts et al., 1996).
In right-handers, MR morphometry reveals a deeper central sulcus on the left than
on the right and vice versa in left-handers (Moore et al., 2000; Schüz and Miller, 2002).
Correspondingly, at the microscopic level the neuropil volume is Brodmann’s area 4 is
larger on the left than on the right.
These anatomical asymmetries may reflect increased connectivity in area 4 along
with an increase in the intrasulcal length of the posterior bank of the precentral gyrus in
the left hemisphere of right-handers (Amunts et al., 1996; Geyer et al., 1996).
The functional areas of the cerebral cortex

There are different types of functional areas of the cerebral cortex including
receptive areas and projection areas. According to this view, the cerebral cortex can
be divided into four general functional categories: sensory, motor, unimodal association
cortex, and multimodal association cortex.
The receptive areas relate to specific sensory modalities and include the primary
somatosensory, primary visual, primary gustatory, primary olfactory, primary vestibular,
and primary auditory areas of cerebral cortex. The primary sensory areas, except that for
olfaction, receive thalamocortical fibres from diencephalic relay nuclei that are
functionally related to each modality.
In addition to primary and some well-defined secondary sensory receptive or motor
projection areas, there are also cortical association areas related to correlating,
interrelating, and interpreting information that reaches the cerebral cortex.
The association areas receive impulses from various cortical regions. In the
association areas are the ultimate functional capacities of the human brain. An association
area may be under the influence of only one type of impulse from a single neighbouring
projection (a primary association area) or receptive area, or it may correlate two different
types of sensory information (a secondary association area).
The remaining portion of the cerebral cortex that is classified as a tertiary or
multimodal association area in the human brain forms regions of integration, association,
and correlation. These areas receive information from several different sensory modalities
and create for us a complete experience of our surroundings.
Multimodal association areas are critical to our ability to communicate using language,
to use reason, to extrapolate future events on the basis of present experience, to make
complex and long-range plans, and to imagine and create things that have never existed.
Indeed, in terms of the associations that underlie the most complex of human
capabilities there may well be heteromodal and supramodal association areas that provide
the anatomical basis for our ability to read, write, speak, learn, think, reason, remember,
and ultimately create new concepts and ideas.
1639
Summary
Knowledge of the world is constructed by the brain. To Jerison, this knowledge is
mind. The levels of function in the brain are hierarchically organized and then focused
on the structure and functional organization of the cortex.
The cortex comprises spiny and aspiny neurons organized into about six layers
(sensory, motor and associational). The vertical organization of the cortex is referred to
as columns or modules. There are many cortical maps. As cortical maps develop, the
brain must also develop the mind to organize the maps in such a way as to produce
knowledge of the external world. The next step in mental development is language. After
all, language is the way of representing knowledge. Multiple representations of sensory
and motor functions exist in the cortex. One evolutionary change in mammals has been
an increase in the number of representations. The cortex processes information about the
world, in multiple representations, and these representations are not formally connected;
yet we perceive the world as a unified whole.
This conundrum is the “binding problem” (Kolb and Whishaw, 2003).
The connections among cortical areas in a sensory system constitute only a part of
all cortical connections. The four other principal connections in the cortical hierarchy are
with the frontal lobe, paralimbic cortex, (phylogenetically the older cortex), multimodal
cortex, and subcortical connections and loops.
Sensory regions do not connect directly with the motor cortex but may project to
either the premotor or prefrontal cortex. Connections to the premotor cortex participate
in ordering movements in time and controlling hand, limb, or eye movements with respect
to specific sensory stimuli. Projections to the prefrontal cortex take part in the control of
movements in time and short-term memories of sensory information.
The paralimbic cortex is adjacent and directly connected to the limbic structures and it
comprises roughly three layers. It can be seen in two places: 1) on the medial surface of the
temporal lobe, where it is known as the piriform cortex, entorhinal cortex, and para-
hippocampal cortex; and 2) just above the corpus callosum, were it is referred to as the
cingulate cortex. The paralimbic cortex plays a role in the formation of long-term memories.
Sensory inputs from subcortical structures are received by the cortex, from the
thalamus or indirectly through midbrain structures, such as the subcortical loops.
Each level interacts and is integrated with higher and lower levels by ascending and
descending connections. Subcortical loops connect the cortex, thalamus, amygdala, and
hippocampus; an indirect loop with the striatum connects with the thalamus (Kolb and
Whishaw, 2003).
Subcortical loops are presumed to play some role in amplifying or modulating
cortical activity. The amygdala adds affective tone to visual input. In absence of the
amygdala, laboratory animals display absolutely no fear of threatening objects.
Cortical areas controlling motor activity

Corticofugal fibres arise from all regions of the cerebral cortex. These projections
convey impulses concerned with motor functions, modifications of muscle tone and reflex
1640
21. Cerebral cortex
activity, modulation of sensory input and alterations of awareness and of the state of
consciousness (Carpenter, 1979).
Corticofugal fibres originating largely from the deeper layers of the cerebral cortex,
are projected to parts of the corpus striatum, the brain stem nuclei at all levels, and the
spinal cord.
Cortical efferent fibres projecting to other cortical areas of the same hemisphere are
designated as associational, while those projecting to cortical areas of the opposite
hemisphere are commissural. The frontal lobe is the rostral region of the hemisphere,
anterior to the central sulcus and above the lateral fissure. The precentral gyrus runs
parallel to the central sulcus on the superolateral surface, extends into the medial surface,
and is limited anteriorly by the precentral sulcus.
The motor activity of the entire opposite side of the body is controlled by the motor
areas of the cerebral cortex (area 4) that are located anterior to the central sulcus. Fibres
arise from the primary motor cortex (MI), the secondary motor cortex (MII), and the
primary somatosensory (somesthetic) cortex (SI) of the frontal and parietal lobes to
terminate in the motor nuclei of the brain stem and spinal cord. Cytoarchitecturally area
4 represents a modification of the typical six-layered isocortex in which the pyramidal
cells in layers III and V are increased in number and the internal granular layer is
obscured. For this reason this cortex is called agranular.
THE PRIMARY MOTOR AREA

The primary motor area is located superior to the lateral sulcus and in front of the
central sulcus in the frontal lobe. In this region are many significant functional areas.
This includes the primary motor cortex corresponding to Brodmann’s area 4, which
occupies the precentral gyrus on the lateral surface of the hemisphere.
It is broad at the superior border of the hemisphere, where it spreads over a
considerable part of the precentral gyrus, then it narrows inferiorly and, at the level of
the inferior frontal gyrus, it is practically limited to the anterior wall of the central sulcus.
On the medial surface of the hemisphere it comprises the anterior portion of the
paracentral lobule.
The unusually thick cortex of the motor area (3.5 to 4.5 mm) is agranular in structure,
and its ganglionic layer contains the giant pyramidal cells of Betz, whose cell bodies may
reach a height of 60 to 120 µm. These cells are the largest in the paracentral lobule and
the smallest in the inferior opercular region. The density of Betz cells also varies in
different parts of area 4 (Lassek, 1940). Approximate percentages of Betz cells in different
topographical subdivisions of area 4 are: 75% in the leg area, 18% in the arm area, and
7% in the face area. According to Lassek (1940, 1947), 34,000 giant pyramidal cells with
cross-sectional areas between 900 and 4100 µm2 have been counted in area 4 of the human
brain. Neurons in area 4 are responsive to peripheral stimulation, and have receptive
fields similar to those in the primary sensory cortex. Cells located posteriorly in the motor
cortex have cutaneous receptive fields, whereas more anteriorly situated neurons respond
to stimulation of deep tissues (Crossman, 2008).
1641
Thus, nerve cells in the primary motor cortex are organized into groups, each group
sending its axons to the cranial nerve motor nuclei, or the reticular formation, or the gray
matter of the spinal cord, where they control the motor activity of a single muscle.
The rostral border of area 4 has been distinguished physiologically as a distinct
subdivision, referred to as area 4S (Hines, 1936, 1937). Ablation of this narrow strip of
cortex along the rostral border of area 4 in monkeys was said to produce a transient spastic
paralysis, and stimulation of this area was reported to inhibit extensor muscle tone.
Subsequent studies indicated that area 4S was one of a number of cortical areas from
which suppressor effects could be obtained in response to stimulation (Dusser de Barenne
and Mc Culloch, 1939).
Thus, on the lateral surface of the brain, the precentral sulcus bounds the precentral
gyrus anteriorly and the central sulcus bounds it posteriorly. However, on the medial
surface of the brain there is no reliable anatomical landmark for the anterior border of
area 4.
The primary motor cortex (Brodmann’s area 4) plays an important role in the
execution of distinct, well defined, voluntary movements. The precentral gyrus of the
right cerebral hemisphere controls movement of the left side of the head and body,
whereas that of the left cerebral hemisphere controls the right side of the head and body
(Passingham, 1993).
Studies in primates have demonstrated two spatially separate motor representations
of the arm and hand in area 4 (Amunts et al., 1996; Augustine, 2008). The long axes of
these representations are oriented approximately parallel to the central sulcus. Stimulation
in both areas causes the same movements and activates the same muscles at similar
strengths. This phenomenon is termed the double representation hypothesis. These two
different areas or subareas of area 4 differ with regard to their somatosensory input. The
caudal area relates to movements that use tactile feedback for their execution whereas
the rostral area relates to movements that use proprioceptive feedback for their execution.
These findings along with cytoarchitectural observations and quantitative distri-
butions of transmitter-binding sites have led to the suggestion that area 4 in humans
includes area 4 anterior (4a) and area 4 posterior (4p) (Augustine, 2008).
In addition to the motor representation across area 4, tactile and proprioceptive maps
occur in 4a and 4p as well. Thus, the primary motor area in humans can be subdivided
based on anatomy, neurochemistry, and function.
The thumb, index, and middle fingers have a representation in both 4a and 4p
(Augustine, 2008).
The primary motor cortex (MI) corresponds to the precentral gyrus (area 4), and is
the area of cortex with the lowest threshold for eliciting contralateral muscle contraction
by electrical stimulation.
It contains a detailed topographically organized map (motor homunculus) of the
opposite body half, with the head represented most laterally, and the leg and foot
represented on the medial surface of the hemisphere in the paracentral lobule (Fig. 21.19)
(Penfield and Rasmussen, 1950).
1642
21. Cerebral cortex
Fig. 21.19. The motor

homunculus across the
precentral gyrus and
paracentral lobule
(after Penfield and
Rasmussen, 1950).
Electrical stimulation of the motor area evokes discrete isolated movements on the
opposite side of the body. Usually, the contraction involves the functional muscle groups
concerned with a specific movement, but individual muscles, even a single interosseous,
may be contracted separately.
Flexion or extension at a single finger joint, twitchings at the corners of the mouth,
elevation of the palate, protrusion of the tongue and even vocalization, expressed in
involuntary cries or exclamation, all may be evoked by careful stimulation of the proper
areas. Charts of motor representation, which are in substantial agreement, have been
furnished by a number of investigators (Foerster 1936 a, 1936 b; Penfield and Boldrey,
1937; Scarff, 1940; Penfield and Rasmussen, 1950; Penfield and Jasper, 1954).
The location of centre specific movements may vary from individual to individual,
but the sequence of motor representation appears constant. Ipsilateral movements have
not been observed in men, but bilateral responses occur in muscles of the eyes, face,
tongue, jaw, larynx and pharynx. According to Penfield and Boldrey (1937), the centre
for the pharynx (swallowing) lies in the most inferior opercular portion of the precentral
gyrus; it is followed, from below upward, by centres for the tongue, jaw, lips, larynx,
eyelid and brow, in the order named. Next come the extensive areas for finger
movements, the thumb being lowest and the little finger highest; these are followed by
areas for the hand, wrist, elbow and shoulder. Finally, in the most superior part, are the
centres for the hip, knee, ankle and toes. The last named are situated at the medial border
1643
of the hemisphere and extend into the paracentral lobule, which also contains the centres
for the anal and vesicle sphincters.
There has been considerable controversy regarding the location of representation of
the lower extremity, due mainly to difficulties in stimulating the medial surface.
According to Foerster (1936 a), the paracentral lobule contains foci related to the foot,
the toes, the bladder and the rectum. Penfield and Boldrey (1937) reported leg movements
in 23 cases produced by the stimulation of superior portions of the precentral gyrus, but
Scarff (1940) was unable to elicit any leg movements by stimulating the lateral surface
of the hemisphere. According to Scarff (1940), the leg, as a rule, is represented only on
the medial surface of the hemisphere (i.e., in the paracentral lobule). The threshold in
different topographical parts of area 4 varies. The region of the thumb appears to have
the lowest threshold, while the face area has the highest threshold.
Motor cortical neurons are active in relation to the force of contraction of agonist
muscles; their relation to amplitude of movement is less clear. Their activity precedes
the onset of electromyographic activity by 50 to 100 milliseconds, suggesting a role for
cortical activation in generating rather than monitoring movement (Passingham, 1993).
A striking feature is the disproportionate representation of body parts in relation to
their physical size: large areas represent the muscle of the face and hand, which are
capable of finely controlled or fractionated movements. The hand area is on the middle
third of the human precentral gyrus. The size of its representation reflects its extraordinary
capabilities to sense temperatures, to participate in the active sense of touch in exploring
the world around us, as well as carry out complex fine skilled movements including
communicating with our hands. In sum, the representation of the knee, leg, ankle, foot
and bladder begin on the edge of each cerebral hemisphere and pass over onto the anterior
paracentral lobule.
The bladder region is just anterior to the region representing the ankle and the toes.
The part of the precentral gyrus controlling movement of the toes is located near its
superior aspect, whereas the part of the precentral gyrus controlling movement of the
tongue, mouth, and larynx is located near its inferior aspect (bordering the lateral fissure).
Half of it is associated with motor activity of the hands, tongue, lips, and larynx –
reflecting the manual dexterity and ability for speech that humans possess.
Prior to the onset of movement, the primary motor cortex receives instructions and
information about the pattern of the intended movement from the other motor areas of
the cortex.
The ipsilateral somatosensory cortex (SI) projects in a topographically organized
way to area 4, and the connection is reciprocal. The projection to the motor cortex arises
in areas 1 and 2, with little or no contribution from area 3b. SI fibres terminate in layers
II and III of area 4, where they contact mainly pyramidal neurons. Evidence suggests
that neurons activated, monosynaptically, fibres from SI, as well as those activated
polysynaptically, make contact with layer V pyramidal cells, including Betz cells, which
give rise to corticospinal fibres (Passingham, 1993; Bodegard et al., 2000; Geyer et al.,
2000; Kaas, 2004). Movement-related neurons in the motor cortex which can be activated
1644
21. Cerebral cortex
from SI tend to have a late onset activity, mainly during the execution of movement. It
has been suggested that this pathway plays a role primarily in making motor adjustments
during a movement. Additional ipsilateral corticocortical fibres to area 4 from behind the
central sulcus come from the second somatic sensory area (S II) (Burton et al., 1995;
Amunts et al., 1996; Geyer et al., 1999; Disbrow et al., 2000; Bodegord et al., 2000;
Parsons et al., 2005).
The motor cortex receives major frontal lobe association fibres form the premotor
cortex and the supplementary motor area and also fibres from the insula (Augustine,
1985; 1996; Geyer et al., 1996; Kaas, 2004).
It is probable that these pathways modulate motor cortical activity in relation to the
preparation, guidance and temporal organization of movements. Area 4 sends fibres to,
and receives fibres from its contralateral counterpart, and also projects to the contralateral
supplementary motor cortex (Crossman, 2008).
Apart from its contribution to the corticospinal tract, the motor cortex has diverse
subcortical projections. The connections with the thalamus, striatum, pontine nuclei and
the subthalamic nucleus are strong.
Thus, the major thalamic connections of area 4 are with the ventral posterolateral
nucleus (VPL), which in turn receives afferents from the deep cerebellar nuclei. The VPL
nucleus also contains a topographic representation of the contralateral body, which is
preserved in its point-to-point projection to area 4, where it terminates largely in lamina IV.
Other thalamic connections of area 4 are with the centromedian and parafascicular
nuclei. These appear to provide the only route through which output from the basal
ganglia, routed via the thalamus, reaches the primary motor cortex, since the projection
of the internal segment of the globus pallidus to the ventrolateral nucleus of the thalamus
is confined to the anterior division, and there is no overlap with cerebellothalamic
territory.
The anterior part of the ventrolateral nucleus projects to the premotor and
supplementary motor areas of the cortex with no projection to area 4 (Crossman, 2008).
Corticospinal tract. The corticospinal tract, which is considered to transmit direct
impulses for highly skilled volitional movements to lower motor neurons, arises mainly
from area 4. The larger corticospinal fibres are probably the axons of giant pyramidal
cells, for these cells undergo chromatolysis following a section of the pyramid (Holmes
and May, 1909; Levin and Bradford, 1938).
Since the number of fibres in the human corticospinal tract at the level of the pyramid
is approximately 1,000,000, axons of the giant cells of Betz could account for only a little
over 3% of these fibres, assuming that each cell gives rise to a single corticospinal fibre
(Lassek, 1940). Studies of the fibre spectrum of the human corticospinal tract, indicating
about 30,000 fibres with diameters between 9 and 22 µm (Lassek and Rasmussen, 1939,
1940; Lassek, 1954), strongly support the view that these fibres are the parent axons of
the giant pyramidal cells.
Approximately 90% of the fibres of the corticospinal tract range from 1 to 4 µm in
diameter. Of the total number of fibres in the tract, about 40% are poorly myelinated.
1645
The more numerous small fibres of the corticospinal tract are considered to arise from
smaller cells in this and other cortical regions.
Interruption of the corticospinal tract also gives rise to chromatolytic cell changes
in small pyramidal cells in layers III and V, not only in area 4, but also in areas 3, 1, 2
and 5 (Levin and Bradford, 1938). Ablations of area 4 in monkeys cause degeneration of
27 to 40% of the corticospinal tract, including virtually all of the large myelinated fibres
(Lassek, 1942, 1954). Other authors have reported smaller percentages of degenerated
fibres after similar ablations (Häggqvist, 1937), but more reported complete degeneration
of the corticospinal tract (Mettler 1944 a; Welch and Kennard, 1944).
Ablations of the parietal cortex (areas 3, 1, 2, 5 and 7) also produce degeneration of
myelinated fibres in the corticospinal tract (Minkowski, 1923-1924; Peele, 1942).
Combined ablations of the precentral and postcentral gyri cause degeneration of 50
to 60% of the fibres in the corticospinal tract (Lassek, 1942, 1942 a; Russell and De
Myer, 1961).
A quantitative study of the origin of corticospinal fibres in monkeys based on silver
staining methods (Russell and De Myer, 1961) indicates that virtually all fibres of the
corticospinal tract arise from area 4, area 6 and parts of the parietal lobe.
Approximate percentages of corticospinal fibres arising from these areas are as follows:
(1) area 4, 31%; (2) area 6, 29%; and (3) parietal lobe, 40%. Complete decortication, or
hemispherectomy, causes all fibres of the corticospinal tract to degenerate in men (Lassek
and Evans, 1945) and in monkeys (Mattler, 1944 a; Russel and De Myer, 1961).
Thus, the corticospinal fibres arise from the pyramidal cells in layer V and give rise
to the largest corticospinal axons in diameter. There is also a widespread origin from
other parts of the frontal lobe, including the premotor cortex and the supplementary motor
area. Many axons from the frontal cortex, notably the motor cortex, terminate in the
ventral horn of the spinal cord. In cord segments mediating dexterous hand and finger
movements they terminate in the lateral part of the ventral horn, in close relationship to
the motor neuronal group. A small percentage establishes direct monosynaptic connec-
tions with alpha motor neurons.
Between 40 and 60% of pyramidal tract axons arise from parietal areas, including
area 3a, area 5 of the superior parietal lobe, and S II in the parietal operculum. The
majority of parietal fibres to the spinal cord terminate in the deeper layers of the dorsal
horn.
The motor cortex also projects to the subthalamic nucleus. The motor cortex sends
projections to all nuclei in the brain stem, which are themselves the origin of descending
pathways to the spinal cord, namely the reticular formation, the red nucleus, the superior
colliculus, the vestibular nuclei and the inferior olivary nucleus.
Ablation of the motor cortex in mammals produces increasingly greater
neurological deficits at progressively higher levels of the phylogenetic scale (Walker and
Fulton, 1938).
In cats, the removal of the motor cortex, or even hemidecortication, do not impair
the animal’s ability to walk upon recovery from anesthesia.
1646
21. Cerebral cortex
Ablations of area 4 in monkeys produce a contralateral flaccid paralysis, marked

hypotonia and areflexia. Within a relatively short time myotatic reflexes reappear, along
with withdrawal responses to nociceptive stimuli (Fulton and Keller, 1932). Recovery
of movement begins in the proximal musculature and progresses distally, but the digits
tend to remain permanently paralysed. Studies by Travis (1955) in monkeys confirm
these things, except that recovery of motor function in the distal parts of the extremity
was as rapid as that in proximal parts.
However, skilled movements were performed slowly and with some deliberation.
The atrophy present in the paretic limbs during the period of greatest disuse disappeared
after maximal functional recovery. No significant spasticity developed in these animals.
Other results (Denny-Brown and Botterell, 1948; Denny-Brown, 1960) differ from the
above in that some degree of spasticity accompanying by the paretic manifestations after
all lesions of the precentral gyrus in monkeys. Relatively mild spasticity developed first
in proximal muscle groups and was described as most enduring following total ablation
(Carpenter, 1979).
Because the precentral gyrus gives rise to a large number of nonpyramidal fibres,
and is the source of only a part of the corticospinal tract, it is instructive to compare the
motor deficits described above with those which follow a surgical section of the pyramids.
Selective pyramidotomy in monkeys and chimpanzees, accomplished by an anterior
approach, produces a contralateral paresis which is somewhat more severe in chim-
panzees than in monkeys (Tower, 1940, 1949). The usage which survives is stripped of
all the finer qualities which contribute to the skill, precision and versatility of motor
performance.
A pyramidotomy is associated with hypotonia and loss of superficial abdominal and
cremasteric reflexes.
The myotatic reflexes are increased in threshold and somewhat pendular. Tonic neck
reflexes are absent, and clonus does not occur. A forced grasp reflex is prominent and
may be so severe as to interfere with climbing.
Observation of monkeys with bilateral pyramidal lesions by Lawrence and Kuypers
(1968) also indicate that considerable recovery of independent limb movements occurs,
but recovery of individual finger movements never returns. All movements are slower
and the muscles fatigue more rapidly than in normal animals. These findings indicate
that the corticospinal pathway conducts impulses concerned with speed and agility of
movement, and fractionation of movements, as exemplified by individual finger
movements. Motor function remaining after bilateral pyramidotomy must be mediated
by brain stem pathway projections to spinal levels.
Lesions of the motor cortex in men produce neurological deficits similar to those
described in primates (Foerster, 1936 a; Bucy, 1949, 1959; Penfield and Rasmussen,
1950). Ablation limited to the “arm” or “leg” area of the precentral gyrus results in a
paralysis of a single limb. The ultimate loss of movement is always greatest in the distal
muscle groups, but motor recovery in the affected limb usually is more complete than
that associated with nearly total lesions of the motor area (Bucy, 1949).
1647
According to Bucy (1949), the spasticity is not severe and is less intense than that
commonly associated with hemiplegias resulting from large capsular lesions.
Although there is considerable restitution of function in proximal muscle groups,
relatively little recovery of skilled motor function occurs in the smaller distal muscles of
the extremities.
However, immediately after complete or partial lesions of the precentral gyrus, there
is a flaccid paralysis of the contralateral limbs or limb, marked hypotonia and loss of
superficial and myotatic reflexes. Within a relatively short time, the Babinski sign can
be elicited. The myotatic reflexes generally return early in an exaggerated form.
The total cortical area that mediates motor activity of a particular body region is
proportional to the complexity of the movements produced in that region.
Secondary motor cortex

The secondary motor cortex consists of four regions: the premotor cortex,
supplementary motor cortex, the frontal eye field, and the posterior parietal motor area
(Fig. 21.20).
The first three of these motor cortical areas reside in the frontal lobe (rostral to the
central sulcus); the posterior parietal motor area is located in the parietal lobe.
The principal function of the secondary motor cortex is the programming of complex
motor activity, which is then relayed to the primary motor cortex where the execution of
motor activity is initiated.
Fig. 21.20. Several Brodmann’s

areas in the frontal lobe of the
human brain: primary motor area
4, premotor area 6, Broca’s motor
speech region
(areas 44 and 45)
(from Paxinos and Mai, 2004).
1648
21. Cerebral cortex
The primary motor cortex then translates this information into execution of
movement, and relays it mainly to the brain stem or spinal cord. Most of the nerve signals
that arise in the secondary motor cortex mediate complex movements produced by groups
of muscles performing a particular task, unlike the discrete muscle contractions elicited
by the stimulation of the primary motor cortex (Patestas and Gartner, 2008).
PREMOTOR CORTEX
Immediately in front of the primary motor cortex lies Brodmann’s area 6. It extends
onto the medial surface, where it becomes contiguous with area 24 in the cingulate gyrus,
anterior and inferior to the paracentral lobule. Near the superior border it is quite broad
and includes the caudal portion of the superior frontal gyrus. The rostral border of area
6 on both medial and lateral surfaces of the human brain is unclear. On the medial surface
of the brain, area 6 extends inferiorly to the cingulate sulcus where its caudal border is
Brodmann’s area 24, part of the anterior cingulate cortex.
Inferiorly the premotor area narrows, and near the operculum, it is limited to the
precentral gyrus. Its histological structure resembles that of the motor area; it is composed
principally of large well formed pyramidal cells, but there are no giant cells of Betz. The
presence of pyramidal cells in layers III and V and the narrowness of layer V make it
difficult to distinguish an internal granular layer (Campbell, 1905).
For this reason, area 6, like area 4, is referred to as the agranular frontal cortex.
Area 6 has been subdivided into various portions (Fig. 21.21) (Foerster, 1936 b).
According to this parcellation, area 6aα lies immediately rostral to area 4 along the
convexity of the hemisphere, while area 6aβ occupies the region of the superior frontal
gyrus on both the lateral and medial surfaces of the hemisphere. A small area called 6b
lies in front of the face area.
Fig. 21.21. The areas of electrically excitable cortex on the lateral surface of the human brain.
The motor area is shown in black, and the so-called “extrapyramidal areas” are hatched except for the eye fields,
which are stippled (after Foerster, 1936 b).
1649
Electrical stimulation of area 6aα in men produces responses similar to those

obtained from area 4, although stronger stimuli are required (Foerster, 1931, 1936 a). It
is probably area 6aα that discharges via the corticospinal tract.
Stimulation of area 6aβ elicits more general movement patterns characterized by
rotation of the head, eyes and trunk to the opposite side, and synergic patterns of flexion
or extension in the contralateral extremities.
These general movements appear independent of area 4, since they can be obtained
after its removal.
Portions of area 6aβ on the medial aspect of the hemisphere are considered to
constitute part of the supplementary motor area. Stimulation of area 6b is reported to
produce rhythmic coordinated movements of a complex type involving facial,
masticatory, laryngeal and pharyngeal musculature (Foerster, 1931, 1936 a).
Unilateral ablations of area 6, including portions on the medial aspect of the
hemisphere, produce transient grasp reflexes in monkeys (Richter and Hines, 1932).
Bilateral removals of area 6 produce more enduring grasp reflexes (Kennard and
Fulton, 1933; Welch and Kennard, 1944).
The unilateral destruction of area 6aβ in men produces little or no motor deficits
(Foerster, 1936 a). Only lesions involving the supplementary motor areas produce
grasping phenomena (Erickson and Woolsey, 1951; Travis, 1955 a).
Combined ablations of areas 4 and 6 produce a contralateral spastic paralysis
(Kennard and Fulton, 1933; Fulton and Kennard, 1934; Kennard, 1949). Similar findings
were reported in men following ablations of area 6, which undoubtedly included parts of
area 4, as well as the so-called area 4 S (Kennard et al., 1934).
Ablations of the posterior part of area 4 result in a contralateral flaccid paresis.
Subsequent investigations (Travis, 1955 a) explain the spasticity resulting from combined
lesions of areas 4 and 6 on the basis of simultaneous destruction of precentral and supple-
mentary motor areas, which are known to produce a contralateral spastic paralysis.
According to Crossman (2008) the premotor cortex is divided into a dorsal and ventral area
on functional ground, and on the basis of ipsilateral corticortical association connections.
The premotor cortex receives axon terminals from the cerebellum via a relay in the
ventral lateral (VLp) nucleus of the thalamus, and fibres from the cortical association
areas. Input from the cerebellum assists the premotor cortex in its role in movement.
The major thalamic connections of the premotor cortex are with the anterior
division of the ventrolateral nucleus and with the centromedian, parafascicular and
contralateral components of the intralaminar nuclei. (Passingham, 1993; Toga et al.,
2006; Crossman, 2008).
Subcortical projections to the striatum and pontine nuclei are prominent, and this
area also projects to the superior colliculus and the reticular formation.
Area 6 contributes to the corticospinal tract. Commissural connections are with the
contralateral premotor, motor and superior parietal (area 5) cortex.
Ipsilateral corticocortical connections with area 5 in the superior parietal cortex, and
inferior parietal area 7b are common to both dorsal and ventral subdivisions of the
premotor cortex, and both send a major projection to the primary motor cortex.
1650
21. Cerebral cortex
The dorsal premotor area also receives fibres from the posterior temporal cortex and
projects to the supplementary motor cortex.
The frontal eye field (area 8) projects to the dorsal subdivision. Perhaps the greatest
functionally significant difference in connectivity between the two premotor area
subdivisions is that the dorsal premotor area receives fibres from the dorsolateral
prefrontal cortex, whereas the ventral subdivision receives fibres from the ventrolateral
cortex. All of these association connections are likely to be or are known to be, reciprocal
(Crossman, 2008).
The main function of this area is the motor control of axial and proximal limb
musculature. It also plays a role in orienting the body and upper limbs in the direction of
a target. Once a motor task has been initiated, activity in the premotor cortex diminishes,
reflecting its key function in the planning phase of motor activity.
A motor pattern exists across the premotor cortex with responses that are
contralateral, but not as discrete as the responses that follow stimulation of the primary
motor cortex.
Neuronal activity in the premotor cortex in relation to both preparation for movement
and movement itself has been extensively studied experimentally. Thus, according to
Crossman (2008) direction selectivity for movements is a common feature of many
premotor neurons. In behavioral tasks, neurons in the dorsal premotor cortex show
anticipatory activity and task-related discharge as well as direction selectivity, but little
or no stimulus-related changes.
The dorsal premotor cortex is probably important in establishing a motor set or
intention, contributing to motor preparation in relation to internally guided movements.
In contrast, the ventral premotor cortex is more related to the execution of externally
(especially visually) guided movements in relation to a specific external stimulus
(Crossman, 2008).
According to Roland and Zilles (1996), Zilles (2004), and Augustine (2008), the
premotor cortex is an extrapyramidal motor area in that it supplements the activity of the
primary motor cortex. The premotor cortex is also termed the frontal aversive field in
that stimulation of this area causes rotation of the head, eyes, and trunk to the opposite
side with complex synergistic movements of flexion and extension of the contralateral
arm and leg. In addition to the motor representation across area 6, a tactile map occurs
across this area as well.
Injury to the premotor cortex produces a motor apraxia. This purely cortical
concept refers to the inability to carry out a sequence of motor activities in the presence
of intact motor and sensory paths. Motor apraxia is evident through clumsiness in writing
or drawing (Augustine, 2008).
A grasp reflex is likely to appear as well. Following damage to the primary motor
cortex, the premotor cortex is able to substitute to some degree.
This region also participates in cortical automatic associated movements that
accompany fine skilled voluntary movements. The grasp reflex (grasping of the
examiner’s hand) is elicited by firmly stroking the palm fingers of the patient’s hand in
1651
an outward direction. The grasp tends to persist, and the more force exerted, the greater
the intensity of the grasp. Unlike a normal grasp, the thumb usually remains extended.
A grasp reflex appearing in newborns and disappearing at two to four months is
likely to be marked by suspending a child by his grasp. In older individuals, the primary
motor cortex inhibits this reflex.
Supplementary motor area (SMA)

Observations by early investigators indicated that responses in different parts of the
body could be elicited by electrical stimulation of the medial surface of the frontal lobe rostral
to the primary motor area (Carpenter, 1979). This motor area, identified in the human brain,
has been designed as the supplementary motor area (Penfield and Rasmussen, 1950).
The supplementary motor area lies medially to area 6, and extends from the most
superolateral part of the medial surface of the hemisphere. Area 24 in the cingulate gyrus
adjacent to area 6 contains several motor areas, which are termed cingulate motor areas.
An additional functional subdivision, the pre-SMA, lies anteriorly to the supplementary
motor area on the medial surface of the cortex. These additional medial motor areas are
included in the supplementary motor cortex (Crossman, 2008).
SMA is divisible into a rostral, pre-SMA and a caudal region (the SMA proper)
(Augustine, 2008).
Detailed descriptions of somatotopic representations within the supplementary motor
area of the monkey have been provided by Woolsey et al. (1951).
The threshold for stimulation of the supplementary motor area in men and monkeys
is slightly higher than for the precentral region, but the motor effects are not due to the
spreading of excitation across the cortex.
SMA receives axon terminals from the basal ganglia (the globus pallidus and the
pars reticulate of the substantia nigra) via a relay in the ventral lateral (VLa) nucleus of
the thalamus.
Subcortical connections, other than with the thalamus, pass to the striatum,
subthalamic nucleus and pontine nuclei, the brain stem reticular formation and the inferior
olivary nucleus. Additional thalamic afferents are form the ventral anterior nucleus, the
intralaminar nuclei, notably the centrolateral and centromedial nuclei, and also from the
mediodorsal nucleus. The connections with the thalamus are reciprocal. The supple-
mentary motor cortex receives connections from widespread regions of the ipsilateral
frontal lobe, including from the primary motor cortex, the dorsal premotor area, the
dorsolateral and ventrolateral prefrontal, medial prefrontal and orbitofrontal cortex and
the frontal eye field. These connections are reciprocal, but the major ipsilateral efferent
pathway is to the motor cortex (Crossman, 2008).
Parietal lobe connections of the SMA are with the superior parietal area 5 and
possibly inferior parietal area 7b. Contralateral connections are with the SMA, and motor
and premotor cortices of the contralateral hemisphere (Crossman, 2008).
The SMA makes a substantial contribution to the corticospinal tract, contributing as
much as 40% of the figures from the frontal lobe (Passingham, 1993; Toga et al., 2006;
Crossman, 2008).
1652
21. Cerebral cortex
The SMA contains a representation of the body in which the leg is posterior and the
face anterior, with the upper limb between them. According to Augustine (2008), SMA
is somatotopically organized in humans with index finger responses anterior and dorsal
to shoulder responses.
Unilateral ablations of the SMA in men produce no permanent deficit in the
maintenance of posture or the capacity of movement (Penfield and Rasmussen, 1950;
Penfield and Welch, 1951).
According to Travis (1955), unilateral ablations of the supplementary motor area in
monkeys produce weak transient grasp reflexes in the contralateral limbs, and moderate
bilateral hypertonia of the shoulder muscles, but no paresis.
Bilateral simultaneous ablations of this area result in disturbances of posture and
tonus, but produce no paresis. Gradually increasing hypertonia, resulting in muscle
contracture, develops in a period of 2 to 4 weeks.
The hypertonia is mainly in flexor muscles. Myotatic reflexes are hyperactive, and
clonus can be demonstrated. Ablations of the SMA and the precentral motor area on the
same side result in an immediate contralateral hypotonic paresis with impaired myotatic
reflexes. Within a period of 2 weeks, the hypotonus changes to hypertonus and the
myotatic reflexes become exaggerated.
All evidence indicates that the SMA is a bilaterally functioning entity concerned
primarily with mechanisms of posture and movement. Following bilateral simultaneous
ablations of the SMA in monkeys indicate that such lesions produce a milder increase in
muscle tone, inconsistent reflex changes and no evidence of joint contracture (Coxe and
Landau, 1965).
According to Bertrand (1956), ablations of the SMA do not produce degeneration
passing to the spinal cord, but electrical stimulation of the SMA in monkeys evokes
potentials bilaterally in the region of the corticospinal tracts at spinal cord levels. The
bilateral features of this system are striking and appear to explain why unilateral lesions
of the SMA cause only minor deficits.
Penfield and Jasper (1954) report that motor responses from the SMA can be elicited
after the removal of the precentral gyrus. Stimulation of this motor area in men, following
hemispherectomy, induces ipsilateral movements similar to those which can be produced
voluntarily (Bates, 1953).
According to Augustine (2008), complex motor tasks activate the rostral SMA
whereas simple motor tasks activate the caudal SMA proper. Pre-SMA is involved in the
acquisition of new motor sequences whereas SMA proper participates in the acquisition
of motor sequences that are essentially automatic.
Activation of SMA occurs during imagined movements whereas regional cerebral
blood flow increases in this area during complex sequential movements (Gelnar, 1998;
Bodegård et al., 2000; Fuster, 2001; Kaas, 2004).
According to Crossman (2008), the role of the SMA in the control of movement is
primarily in complex tasks which require temporal organization of sequential movements
and in the retrieval of motor memory. Input from the basal ganglia assists the SMA in its
1653
role in the programming phase of the patterns and sequences of complex movements,
and the coordination of bilateral movements. The SMA mediates muscle contractions of
the axial (trunk) and proximal limb (girdle) musculature (i.e., the muscle controlling
movements of the arm and thigh). Stimulation of the supplementary motor area in
conscious patients has been reported to elicit the sensation of an urge to move, or of
anticipation that a movement is about to occur. A region anterior to the SMA for face
representation (area 44, 45) is important in vocalization and speech production.
In sum, the traditionally defined supplementary motor area includes two separate
regions: a caudal region (SMA proper) that has reciprocal connections with the primary
motor area and project to the spinal cord, and a rostral region (presupplementary motor
area) that receives projections from the prefrontal and cingulate cortices. Basal ganglia
input reaches the caudal region, whereas cerebellar input reaches the rostral region.
Neuronal responses to visual stimuli prevail in the rostral region, whereas somatosensory
responses prevail in the caudal region. The urge to initiate movement in humans is elicited
only from the rostral region (Wise, 1985; Tanji and Kurata, 1989; Tanji, 1994; Gallese
et al., 1996).
Posterior parietal motor area

The posterior parietal motor area corresponds to Brodmann’s areas 5 and 7. Area 5
is involved in tactile discrimination (the ability to perceive a subtle distinction by the
sense of touch) and stereognosis (the recognition of the three-dimensional shape of an
object by the sense of touch), as well as statognosis in relation to reaching and guiding
movements.
Area 7 is involved with movements that require visual guidance. Thus, when one
reaches for a glass of cold water, visual guidance (turning the body and aiming the upper
limb in the direction of the glass) and tactile sensation (which in this case helps to realize
that the glass is slippery and must be grasped firmly), both play a role in accomplishing
a desired motor task (Patestas and Gartner, 2008).
Extrapyramidal cortical areas in the parietal and occipital lobes influence ocular
movements, particularly following of automatic movements of the eyes.
Frontal eye field

Because the direction of gaze often indicates the visual stimuli to which a subject
attends, the study of eye movement control is also producing important insights into the
mechanisms of visual attention and other higher-order cognitive processes (Corbetta et
al., 1998). Much of what is known about eye movement control has been learned from
combined eye movement and single-cell electrophysiological recordings from awake,
behaving monkeys.
Two types of eye movements are studied most often in human and nonhuman
primates: saccades and smooth pursuit. Saccades are shifts of gaze that serve to maintain
an image on the fovea, the area of the retina with the highest visual acuity. Saccades can
be reflexive, or voluntary.
1654
21. Cerebral cortex
Smooth pursuit allows for continuous, undistorted vision of objects moving across
the visual field by matching the velocity of eye movements with the velocity of a target.
Smooth pursuit likely requires a more complicated neural network, and more processing
in cortical, basal ganglia, brain stem, and cerebellar regions for proper functioning
(Krauzlis, 2004).
Because the generation of saccades can be largely automatic and independent of
cortical structures, study of “top-down” control of saccades can be used to model
cognitive aspects of motor control (Stuphorn and Schall, 2002).
Multiple regions within the frontal cortex and subcortical nuclei are involved in the
generation of eye movements. For saccades, it is believed that the frontal lobe oculomotor
regions are most important for voluntary saccades, whereas accurate reflexive saccades
can be generated with little input from the frontal lobes (Pierrot-Deseilligny et al., 2004).
Data from both monkeys and humans support the roles for the frontal lobes in both
movement perception and representation (Rizzolati and Luppino, 2001) as well as
planning and execution of movements.
The first intraoperative stimulation studies in humans resulted in a broad region for
the frontal eye fields because eye movements were elicited from various areas
encompassing Brodmann’s areas 6, 8, 9 and 46 (Foerster, 1936; Penfield and Boldrey,
1937; Smith, 1944). The latest studies, in which smaller current intensities have been
used, restricted the frontal eye fields to the anterior portion of the motor strip, in the upper
portion of the facial area (Woolsey et al., 1979; Lüders et al., 1988; Godoy et al., 1990).
However, the sulcal cortex could not be investigated with large subdural electrodes, and
the mediolateral position of frontal eye fields remains imprecise. Positron emission
tomography studies also have been utilised to improve our knowledge of the localization
and function of the frontal eye fields (Fox et al., 1985; Anderson et al., 1994; O’Sullivan
et al., 1995; Petit et al., 1996; Sweeney et al., 1996).
The results of these studies have indicated that human frontal eye fields are located
more posteriorly in the frontal lobe than expected by a comparison with monkey frontal
eye fields.
In humans, fMRI imaging, with its increased spatial resolution, has provided new
insights into the functional anatomy of frontal eye fields (Darby et al., 1996; Petit et al.,
1997; Luna et al., 1998; Corbetta et al., 1998).
Contrary to studies performed using subdural electrodes, intracerebral electrical
stimulation enables localized stimulation of almost any part of the cortex, including the
sulcal cortex (Munari et al., 1993, 1994).
Lobel et al. (2001) used intracerebral electrical stimulation in 38 patients with
epilepsy prior to surgery, and frontal regions where stimulation induced versive eye
movement were identified. These studies showed that two distinct oculomotor areas could
be individualized in the region classically corresponding to the frontal eye fields. One
oculomotor area was consistently at the intersection of the superior frontal sulcus with
the fundus of the superior portion of the precentral sulcus. The second oculomotor area
was located more laterally and close to the surface of the precentral gyrus. Lobel et al.
1655
(2001) compared results obtained from fMRI imaging with those obtained using
intracerebral electrical stimulation.
These two areas are anatomically distinct (mean distance from each other is 19 mm).
The deep oculomotor areas are the regions of the human frontal lobe where eye
movements can be most easily elicited by electrical stimulation. It is located more
posteriorly in the frontal lobe, apparently within Brodmann’s area 6. The most remarkable
feature is the specific anatomical link between the deep oculomotor areas and the
intersection of the superior frontal sulcus.
Anatomy. The frontal eye field in men occupies principally the caudal part of the
middle frontal gyrus (corresponding to parts of area 8) and extends into contiguous
portions of the inferior frontal gyrus (Carpenter, 1979).
According to Boxer (2007), in the frontal lobes, three regions are most involved in
eye movement control: the frontal eye field, the supplementary eye fields, and the
dorsolateral prefrontal cortex (Fig. 21.22). These frontal eye movement control regions
are strongly connected to regions in the dorsal parietal lobe involved in eye movement
control, particularly in the vicinity of the lateral intraparietal sulcus, the basal ganglia,
and brain stem structures.
Fig. 21.22. Brain regions involved in saccade control. In the frontal lobes, frontal eye field (FEF) is a critical node for
initiation of voluntary saccades. It receives input from the parietal eye fields (PEFs) and thalamus, which provide
visual information. The supplementary eye field (SEF) monitors and supervises FEF activity, and the dorsolateral
prefrontal cortex (DLPFC) likely exerts a direct modulatory influence on the FEF, as well as on downstream structures
in the brain stem. Other regions in the medial frontal lobes, including the pre-supplementary motor area (pSMA) and
anterior cingulate (cing), may also exert modulatory influences on the FEF via the SEF and DLPFC. There are three
main pathways from the FEF to the primary and secondary motor neurons in the brain stem nuclei that generate
saccades: (1) a direct connection between the FEF and the brain stem oculomotor nuclei; (2) a pathway through the
caudate eye field and substantia nigra pars reticulata (SNr), which helps to suppress saccades; and (3) a direct
connection between the FEF and superior colliculus (SC), which is finely tuned for saccade programming and can
generate reflexive saccades independently of the FEF (after Boxer, 2007).
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21. Cerebral cortex
Fig. 21.23. Lateral surface of the left cerebral hemisphere showing the frontal eye field (parts of areas 6, 8, 9), the motor
speech (Broca’s) area (areas 44, 45) and Wernicke’s area. The perimeter of these areas is delineated by an interrupted
line to indicate uncertainly as to their precise extent. Wernicke’s area is variously depicted by different authorities as
encompassing a large parietotemporal area which includes areas 39 and 40. Areas 22 and 37 are considered by some to
be respectively auditory and visuo-auditory areas associated with speech and language (after Crossman, 2008).
According to Augustine (2008) and Crossman (2008), there are primary and
secondary eye fields that occupy parts of Brodmann’s areas 6, 8 and 9 (Fig. 21.23). The
primary frontal eye field is in the posterior part of the middle frontal gyrus. The secondary
frontal eye field is in the dorsal part of the inferior frontal gyrus. Cytoarchitecturally,
area 8 is a typical six layered isocortex of the frontal type in which the granular layers
are distinct.
Processes of neurons in the eye fields project their fibres through the corticobulbar
path to nuclei of the ocular muscle. The primary eye fields project fibres to agonist
muscles, whereas neurons in the secondary eye fields project fibres to antagonist muscles.
Voluntary ocular movements obviously involve the cooperative action of eye field in
both cerebral hemispheres (Paus, 1996; Lebel et al., 2001).
Frontal eye field. The frontal eye field is located in the rostral bank of the arcuate
sulcus in macaque monkeys (Stuphorn and Schall, 2002). In humans, high-resolution
fMRI studies have localized the frontal eye field to the anterior wall of the precentral
sulcus, near the caudal end of the superior frontal sulcus, a region homologous to the
location of the frontal eye field in monkeys (Rosano et al., 2002).
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The frontal eye field can be further subdivided into two regions, one involved in the
generation of saccades, which is located in the upper portion of the anterior wall of the
precentral sulcus, and a smooth pursuit-related area, which is found deeper along the anterior
wall, extending in some subjects to the fundus or deep posterior wall. Using histopathological
markers from postmortem specimens, these regions have been demonstrated to be structurally
similar to other regions of the motor cortex (Rosano et al., 2003).
Electrical stimulation of the frontal eye field in men causes conjugate deviation of
the eyes, usually to the opposite side (Foerster, 1931; Penfield and Rasmussen, 1950).
Stimulation here causes occasionally upward movements, convergence, divergence of
the eyes and pupillary changes. Movements of the head and pupillary changes usually
accompany movements of the eyes.
Unilateral stimulation of the frontal eye fields in humans usually produces bilateral
opening or closing of the lids (Paus, 1996; Lobel et al., 2001; Milea et al., 2002).
Based on electrical stimulation studies of human subjects prior to brain surgery, the
saccade-generating portion of the frontal eye field is found 1-2 cm anterior to the primary
motor cortical regions involved in finger and hand movements, a region in close
agreement to that identified in fMRI studies (Yamamoto et al., 2004).
Similarly, cortical stimulation experiments in humans confirm that the smooth pursuit
region is located more posteriorly than the saccade region (Blanke and Seeck, 2003).
The frontal eye field receives connections that convey both visuosensory information
and motor information to its neurons. Importantly, regions within the frontal eye field
receive information from both the ventral visual stream (the “what” pathway) and the
dorsal visual stream (the “where” pathway; Schall et al., 1995). The neurons of the frontal
eye field that receive connections from the ventral stream generate shorter saccades than
those innervated by dorsal stream neurons. This is consistent with the expected size of
saccades necessary to explore visually a small object of the face (in detail) versus those
necessary to characterize distant aspects of a subject’s spatial environment.
The frontal eye field also receives information from the supplementary eye fields,
the dorsolateral prefrontal cortex, the thalamus, and the substantia nigra pars reticulata.
According to Crossman (2008), the frontal eye field receives its major thalamic projection
from the parvocellular mediodorsal nucleus, with additional afferents from the medial
pulvinar, the ventral anterior nucleus and the suprageniculate-limitans complex, and
connects with the paracentral nucleus of the intralaminar group.
The thalamocortical pathways to the frontal eye field form part of a pathway from
the superior colliculus, the substantia nigra and the dentate nucleus of the cerebellum.
Neurons in the cerebellum are critical for maintaining smooth pursuit eye movements
and may help to refine certain types of saccades.
The frontal eye field has extensive ipsilateral corticocortical connections, receiving
fibres from several visual areas in the occipital, parietal and temporal lobes, including
the medial temporal area (V5) and area 7a.
There are also projections from the superior temporal gyrus, which is auditory rather
than visual in function. From within the frontal lobe, the frontal eye field receives fibres
from the ventrolateral and dorsolateral prefrontal cortices.
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21. Cerebral cortex
These inputs can positively and negatively modulate the activity of neurons within
the frontal eye field.
From the frontal eye fields fibres descend in the corticobulbar path, enter the genu
of the internal capsule, the cerebral crus at the base of the midbrain, and descend into the
brain stem. Along the way, a few fibres turn off oculomotor nuclear levels to supply the
oculomotor nucleus as the remaining fibres descend and end in the abducens nucleus.
This area contains cell bodies whose axons join the corticonuclear tract and descend to
terminate in the eye movement control centres located in the midbrain reticular formation
and the paramedian pontine formation. In turn, they transmit information to the motor nuclei
of cranial nerves III, IV, and VI, which control voluntary eye movements.
The frontal eye field projects to the dorsal and ventral premotor cortices and to the
medial motor area, probably, to the supplementary eye field adjacent to the supplementary
motor area proper. It projects prominently to the deeper layer of the superior colliculus
via a transtegmental projection (Kuypers and Lawrence, 1967). However, the most
substantial and highly organized projections to the superior colliculus arise from the
visual cortex (Garey et al., 1968). These fibres mainly enter the stratum opticum via the
brachium of the superior colliculus. In the brain stem, the superior colliculus plays a
dominant role in organizing many aspects of eye movement control through its
connections with other nuclei in the dorsal midbrain (for vertical eye movements) and
the pons (for horizontal eye movements). Although the superior colliculus does not
project direct fibres to the nuclei of the extraocular muscles, it has projections to both
the reticular formation and the accessory oculomotor nuclei (Carpenter, 1971).
Thus, the frontal eye field projects to the pontine gaze centre within the pontine
reticular formation, and to other oculomotor related nuclei in the brain stem.
Studies in nonhuman primates suggest that in normal subjects most of the control
of saccades by the frontal eye movement regions is mediated by the superior colliculus
(Sparks, 2002).
Under conditions of superior colliculus damage, other cortical and brain stem regions
can partially compensate for the lost superior colliculus functions; however, saccades are
much less accurate in time and space.
Neurons that have saccade-related activity in the intermediate and deep layers of the
superior colliculus are arranged topographically and fire bursts of activity before an eye
movement, be it a saccade or smooth pursuit (Krauzlis and Dill, 2002).
Thus, the activation of rostral cells generates small-amplitude eye movements, and
the activation of caudal cells generates larger-amplitude saccades. Electrical stimulation
of the rostral pole of the superior colliculus inhibits saccades, consistent with an important
role for maintaining fixation on a target.
These neurons have monosynaptic excitatory inputs neurons in the brain stem that
inhibit eye movements (Leigh and Kennard, 2004). Upward saccades are represented
medially, and downward saccades, laterally, within the superior colliculus (Sparks, 2002).
Neurons that are located downstream of these signals in midbrain and pontine
oculomotor nuclei, have firing rates that directly correlate with the speed and amplitude
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of saccades. Via a basal ganglia circuit, which includes the oculomotor portions of the
caudate nucleus, with projections to the substantia nigra pars reticulata, the superior
colliculus integrates information regarding the reward value of saccades to specific
locations (Hikosaka et al., 2000).
Impairments in memory-guided and predictive saccades in neurodegenerative
disease with basal ganglia damage may in part arise from damage to this circuit (Leigh
and Kennard, 2004).
Nicotinic cholinergic inputs from the pedunculopontine nucleus to the superior
colliculus may also have important effects on attention and motivation for saccades
through a stimulatory effect on the superior colliculus (Kobayashi et al., 2001). Decreased
attention and visual search efficiency (Doffner et al., 1992; Mosimann et al., 2004) and
difficulties with saccade programming (Shafiq-Antonacci et al., 2003) in Alzheimer’s
disease may be in part explained by damage to this cholinergic circuit.
In addition to, and as part of, their roles in generating saccades, the neurons of the
frontal eye field represent the behavioral relevance of objects within the visual field; thus,
the activity over portions of the frontal eye field can be said to represent a visual saliency
map (Thompson and Bichot, 2005).
After the presentation of a visual stimulus, over time, activity within the frontal eye
field evolves to represent the behavioral significance of the stimulus. This behavioral
significance can be read out as a saccade to the novel stimulus, but it may be represented
as a covert shift of attention without an actual eye movement (Boxer, 2007).
However, this cortical field is believed to be a centre for voluntary eye movements
not dependent upon visual stimuli. The conjugate eye movements commonly are called
“movements of command”, since they can be elicited by instructing the patient to look
to the right or left (Cogan, 1956).
Some studies in men and primates suggest a double representation of specific eye
movements in each frontal eye field (Crosby, 1953; Lemmen et al., 1959; Crosby et al., 1962).
Unlike the frontal eye field, the occipital eye centre is not localized to a small area.
Eye responses can be obtained from a wide region of the occipital lobe in monkeys, but
the lowest threshold is found in area 17 (Walker and Weaver, 1940). The occipital eye
centres are presumed to subserve movements of eyes induced by visual stimuli, such as
following moving objects. These pursuit movements of the eyes are largely involuntary,
although they are not present in young infants.
Electrophysiological recordings in monkeys and lesion studies in humans have shown
that brain stem structures, the basal ganglia, thalamus, cerebellum, and within the cortex,
the parietal eye fields, supplementary eye field, and frontal eye fields are involved in the
execution and control of saccades (Leigh and Zee, 1991; Pierot-Deseiligny et al., 1995).
However, two regions of the cerebral cortex in humans influence ocular movements.
At the posterior end of the middle frontal gyrus and corresponding to Brodmann’s areas
8 and 9 is a region responsible for voluntary eye deviation called the primary eye field.
There is also a secondary motor eye field at the posterior end of the inferior frontal
gyrus on its dorsal part.
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21. Cerebral cortex
Stimulation of the human primary eye fields yields deviations of the eyes, including
divergence, horizontal conjugate deviation to the contralateral side, and deviation up and
to the contralateral side.
The pattern on the secondary eye field is a mirror image of that on the primary eye
field. The secondary eye fields permit relaxation of the antagonistic muscles during
voluntary eye deviations.
Thus, the frontal eye field plays a role in the coordination of eye movements,
particularly those mediating voluntary visual tracking of a moving object via conjugate
deviation of the eyes.
Supplementary eye fields. According to Boxer (2007), the supplementary eye field
is located on the medial surface of the superior frontal gyrus, in the dorsal aspect of the
paracentral sulcus. An oculomotor area in the frontal cortex, separated from the frontal eye
field, was defined by Schlag and Schlag-Rey in 1987. It is located rostrally to the
supplementary motor area (M II) on the medial surface of the hemisphere. The
supplementary eye fields receive connections form the frontal eye field, the dorsolateral
prefrontal cortex, the anterior cingulate cortex and the posterior part of the cerebral
hemisphere. The supplementary eye field projects to the frontal eye field and to the
subcortical nuclei involved in eye movements (superior colliculus and reticular formation).
The supplementary eye field is involved in programming sequences of saccades or
combined saccade-body movements and likely has important preparatory roles in more
complex eye movements (spatiotopic saccades), (Isoda and Tanji, 2003).
Functional imaging studies in humans suggest that the supplementary eye field is
activated prior to both simple and more complex saccade tasks (Gagnon et al., 2002),
suggesting that it may have a supervisory role over neurons in the frontal eye field (Schall
et al., 2002).
Dorsolateral prefrontal cortex. The dorsolateral prefrontal cortex is involved in
multiple aspects of saccade programming, including making decisions to initiate
voluntary saccades and maintaining spatial working memory for target locations
(Funahashi et al., 1993; Pierrot-Deseilligny et al., 2002, 2003; Cisek and Kalaska, 2004).
The regions of the dorsolateral prefrontal cortex that are most important for the control
of eye movements are located in the middle frontal gyrus in Brodmann’s areas 46 and 9.
The suppression of unwanted reflexive saccades likely involves a direct inhibitory
projection from dorsolateral prefrontal cortex neurons to the brain stem saccade-
generating circuitry, including the superior colliculus (Condy et al., 2004).
Experiments with monkeys suggest that there are neurons in the vicinity of the
dorsolateral prefrontal cortex whose activity signals the suppression of a reflexive saccade
or the command “Don’t look” (Hasegawa et al., 2004). Activity from these neurons may
be crucial for the ability of the dorsolateral prefrontal cortex ability to help select one
behaviorally relevant saccade over a range of other visually salient targets.
Nyffeler et al. (2002) confirmed the roles of the dorsolateral prefrontal cortex in
spatial memory, first identified in nonhuman primates by Constantinidis et al. (2001).
Thus, studies of the voluntary control of eye movements, particularly saccades, are
revealing important principles about the mechanisms of motor control by the frontal lobes.
1661
Thus, three cortical areas not involved directly in triggering of saccades play
important roles in planning, integration, and chronologic ordering of saccades.
The prefrontal cortex (Brodmann’s area 46) plays a role in planning saccades to
remembered target locations. The inferior parietal lobe is involved in visuospatial
integration. Bilateral lesions in this area result in Balint’s syndrome (optic ataxia, ocular
apraxia, psychic paralysis of the visual fixation).
The hippocampus appears to control the temporal working memory required for
chronologic order of saccade sequences (Afifi and Bergman, 2005).
Smooth-pursuit movements are slow eye movements initiated by a moving object.
Unlike saccades, smooth-pursuit movements cannot occur in darkness.
Cortical areas involved in smooth pursuit include the temporooccipital region and
the frontal eye field. Each of these areas has direct projections to brain stem neurons that
drive pursuit. The temporooccipital region is driven by input from the primary visual
cortex. The posterior parietal and the superior temporal cortices may also contribute to
smooth pursuit indirectly through visual attention.
Lesions in the temporooccipital cortex in humans associated with smooth-pursuit
deficits correspond to Brodmann’s areas 19, 37, and 39. Lesions in the frontal eye field
also have been associated with deficits in smooth pursuit.
A corticofugal pathway for smooth-pursuit courses from the temporooccipital cortex
through the posterior limb of the internal capsule to the dorsolateral pontine nucleus in
the mid-pons. The second courses from the frontal eye field to the dorsolateral pontine
nucleus and the nucleus reticularis tegmenti pontis (Afifi and Bergman 2005).
Cortical areas for smooth pursuit also project to the flocculus of the cerebellum after
relaying in the dorsolateral pontine nucleus. The flocculus, in turn, projects on the
vestibular nuclei, which project to the cranial nerve nuclei of extraocular movement (CN
III, IV, IV) (Leichnetz et al., 1981; Morrow and Sharpe, 1990; Tijsen et al., 1991;
Gaymard et al., 1993; Sharp et al., 1995; Lekwuuwa and Barnes, 1996; Deseilligny et
al., 1996; Morecraft and Yeterian, 2000; Pierrot-Deseilligny et al., 1995; Pryse-Phillip,
2003; Afifi and Bergman, 2005). Cerebral hemisphere lesions impair ocular pursuit
ipsilaterally, or laterally whereas posterior fossa lesions impair ocular pursuit either
contralaterally or ipsilaterally.
The antisaccade task. According to Boxer (2007), the antisaccade task has two
components: suppression of a reflexive saccade towards a target, and programming of a new
saccade in the opposite direction. Due to its ease of performance, this task has been used
extensively to investigate aspects of voluntary motor control. The ability to perform
antisaccades accurately develops in late childhood (Klein, 2001) and decline in normal elderly
subjects in parallel to other cognitive measures of frontal lobe function (Klein et al., 2000).
Early studies in patients with frontal lobe lesions showed that the antisaccade task
is exquisitely sensitive to frontal lobe damage (Guitton et al., 1985).
The anatomy of antisaccade dysfunction has been elicited in subjects with focal brain
lesions and shown to involve a dorsolateral prefrontal cortex internal capsule – the
superior colliculus brain stem circuit – in which damage to any component of the circuit
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21. Cerebral cortex
results in a difficulty of reflexive saccade suppression (Pierrot-Deseilligny et al., 2003;

Condy et al., 2004).
The antisaccade function is abnormal in attention-deficit / hyperactivity disorder in
both children (Mostofsky et al., 2001) and adults (Feifel et al., 2004). In contrast, subjects
with Tourette’s syndrome have enhanced ability to perform this task, possibly consistent
with the subjects’ necessity to suppress unwanted movements (Munoz et al., 2002).
A large number of studies have described the prominent antisaccade abnormalities
associated with schizophrenia (Huton and Kennard, 1998). The antisaccade task is
exquisitely sensitive to first-episode schizophrenia and correlates with disease severity and
working memory impairments (Nieman et al., 2000). Antisaccade impairments may serve
as a marker of an endophenotype or genetic risk factor for schizophrenia (Thaker et al.,
2000). More recently, antisaccade performance has been used as an outcome measure in
trials of therapeutic agents for this disease (Ettinger et al., 2003; Wonodi et al., 2004).
Impairment on the antisaccade task is a sensitive marker of human immuno-
deficiency virus (HIV) dementia (Johnston et al1996), and is present in subjects with
Alzheimer’s disease (Abel et al., 2002; Shafiq-Antonacci et al., 2003).
Antisaccade impairment is also associated with the presence of dementia in subjects
with Parkinson’s disease but not in cognitively normal patients with Parkinson’s disease
(Mosimann et al., 2005).
Injuries to the frontal eye fields in humans are either irritative or destructive.
Irritative injuries result in deviations of the eyes to the contralateral side, whereas
destructive injuries result in deviation of the eyes to the same side. Ablation of the frontal
eye field will result in deviation of the eyes to the side of ablation as a result of the
unopposed action of the intact frontal eye field. Such a condition is encountered in
patients with occlusion of the middle cerebral artery, which supplies the bulk of the lateral
surface of the hemisphere, including the frontal eye field. Such patients manifest paralysis
of the face and limbs (upper limbs more than lower) contralateral to the side of the arterial
occlusion and conjugate the deviation of the eyes towards the cortical lesion.
In humans, conjugate eye deviation occurs more frequently after lesions in the right
hemisphere than after lesions in the left hemisphere because it is related to the neglect
syndrome associated more frequently with right hemisphere lesions. Conjugate deviation
of the eyes with pupillary dilation of the abducting eye may appear with the onset of
seizures. Such cases localize the epileptogenic focus to the contralateral frontal lobe
(Augustine, 2008). Conjugate eye deviations have been observed with lesions that spare
the frontal eye field but that interrupt the connections between the posterior parietal and
frontal eye fields or their subcortical projections.
Subjects with brain lesions involving the dorsolateral prefrontal cortex have
difficulty in suppressing unwanted reflexive saccades and in generating predictive
saccades to targets presented in a predictable sequence in time and space (Pierrot-
Deseilligny et al., 2003).
There is evidence from studies in nonhuman primates and humans performing a
simple voluntary saccade paradigm, such as countermanding and antisaccade tasks, that
1663
the same brain region and patterns of activity are involved in deciding to initiate or cancel
an eye movement (Boxer, 2007). Data from human subjects with local brain lesions or
neurodegenerative syndromes suggest that the integrity of these circuits is necessary for
accurate voluntary saccade initiation (Boxer, 2007).
Motor speech region

The posterior parts of the frontal lobe have been more directly implicated in language
processing per se. In fact, the left posterior inferior frontal lobe (often referred to as
“Broca’s area”) likely has a role in all aspects of language – in comprehension and
production of both spoken and written language.
Broca’s region for motor speech occupies the triangular and opercular parts of the
posterior end of the inferior frontal gyrus of the left cerebral hemisphere in 95% of
humans. There exists a wealth of evidence about a great deal of individual variability in
the cytoarchitectural fields, as well as the shape and size of sulci and gyri, of the human
brain. Much of the evidence for this individual variability has in fact come from studies
of Broca’s area, which often (but not always) has been assumed to encompass
Brodmann’s areas 44 and 45 (pars opercularis and pars triangularis). Area 44 or the pars
opercularis (which is a dysgranular cortex) is separated from area 45 or pars triangularis
(which is a granular cortex) by the ascending or vertical ramus of the lateral sulcus
whereas the anterior ramus of the lateral sulcus divides the pars triangularis from pars
orbitalis (area 47).
This region, corresponding to Brodmann’s areas 44 and 45, has connections with
the primary motor cortex, especially with those parts of area 4 that supply muscles
concerned with speech (Grodzinsky and Amunts, 2006)
The left posterior inferior frontal cortex has diverse roles in both production and
comprehension of language. This area appears to be critical for phonological
discrimination and segmentation, processing of morphosyntactic structure, and / or
working memory functions needed for syntax processing, retrieval of modality-specific
lexical forms (especially in particular grammatical categories – such as verbs or particular
morphological forms – for spoken and written output), motor programming of speech
articulation, and selecting letter-specific motor programs for writing (Hillis, 2007).
Nearby regions are also engaged in various aspects of semantic tasks, including
controlled retrieval from semantic memory and response selection, although they are not
critical for decoding the meanings of individual words (Hillis, 2007).
In general, Broca’s area is involved in the planning of motor activity that is necessary
in order for words to be produced. Broca’s area projects this information to the premotor
cortex where activity is planned and relayed to the primary motor cortex, which initiates
the movements necessary to produce speech. A lesion in Broca’s area will disrupt Broca’s
area input to the premotor cortex.
Injury to the motor speech area causes an expressive or motor aphasia also described
as Broca’s aphasia or Broca’s loss of “articulated speech”. While there is no paralysis of
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21. Cerebral cortex
the muscles related to speech, there is a loss of coordination of those muscles leading to
a difficulty in expressing oneself.
Broca’s aphasia, also termed expressive aphasia or nonfluent aphasia, consists of
a loss of the ability to speak fluently.
Patients with the most severe form of Broca’s aphasia are unable to speak (mutism),
although they are able to swallow and breathe normally and make guttural sounds. Here
is a difficulty in turning a concept or thought into a sequence of meaningful sounds. In
less severe cases, or in patients during the recovery process, limited speech is possible.
In Broca’s aphasia, there is a low fluency associated with relatively well-preserved
comprehension.
The patient is likely to be unable to speak or continually repeats the last word said
before the injury occurred. There may be difficulty with certain sounds or letters.
However, speech is slow and laboured, enunciation is poor, and nonessential words are
commonly omitted (telegraphic speech).
Broca’s area is involved in the planning of motor activity that is necessary for words
to be produced. Broca’s aphasia also impairs an individual’s ability to express a thought
or concept by writing it down. So, affected persons typically have as much difficulty with
writing (agraphia) as with speaking. Although the patient is able to understand spoken
or written language and can communicate verbally to some degree, the extremely
laborious nature of the process of communication causes considerable frustration. Under
particular emotional stress, patients may use inappropriate or vulgar words or phrases to
express their distress.
Mild aphasia without other deficits indicates that the damage affects only cortical
areas. However, full-blown Broca’s aphasia indicates that the damage extends beyond
the Broca area of the cortex to include insular cortex and subjacent white matter.
Patients typically have contralateral motor signs and symptoms, such as weakness
(paresis of the lower part of the face, lateral deviation of the tongue when protruded, and
weakness of the arm (Lynch, 2006).
The resulting deficit depends on the size, depth, severity, timing, and whether the
cerebral hemisphere is dominant for language (the left cerebral hemisphere in
approximately 95% of humans).
Most patients with Broca’s aphasia are able to sing, although they do not speak well.
It is likely that the right cerebral hemisphere is dominant over the left for singing capacity.
If injury leading to aphasia takes place at an early age, it is possible to build up
speech patterns in the other cerebral hemisphere. This is an example of the plasticity of
the nervous system and its ability to compensate when injured (Grodzinsky and Amunts,
2006).
The most common causes of Broca’s aphasia are tumors and occlusions of frontal
M4 branches of the middle cerebral artery.
Aphasia plus motor problems suggest an occlusion of branches from the proximal
parts of the middle cerebral artery (M1), including the lenticulostriate arteries, which
serve the internal capsule.
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The mirror system: ventral premotor and parietal cortex

One of the most interesting findings in recent years related to the human cerebral
cortex is that some cortical motor areas that are active during the planning and execution
of movements are also active when viewing the motor actions of others. This phenomenon
is termed “mirror representation” of the actions of others.
Thus, a special class of neurons was discovered in the inferior frontal cortex of the
macaque brain. These neurons were found in area F5, the rostral sector of the ventral
premotor cortex (Matelli et al., 1985).
Area F5 is connected with the rostral part of the inferior parietal lobule (area PF).
Mirror neurons have also been observed in area PF (Fogassi et al., 2005; Shmuelof and
Zohary, 2006).
Thus, the mirror neurons system in macaques is composed of two major centres –
one in the posterior inferior frontal cortex and the other in the rostral inferior parietal
cortex, that are strongly interconnected. The anterior part of the human intraparietal sulcus
is involved in visually guided grasping as well as during the observation of other actions.
There is a complex network of cortical regions in the frontal, parietal and temporal lobes
forming this mirror system in the human brain.
The premotor neurons fire not only when the monkey performs goal-directed actions,
such as grasping objects, but also when holding, tearing, manipulating, and so forth.
These neurons also fire when the monkey is simply watching somebody else
performing goal-directed actions (di Pellegrino et al., 1992; Gallese et al., 1996).
Because of these properties, these neurons were dubbed “mirror” neurons (Gallese
et al., 1996). There is generally a good congruence between the action coded motorically
and the action coded visually by mirror neurons; that is, if a mirror neuron fires during a
monkey’s execution of a precision grip, it will likely fire when the monkey sees a
precision grip rather than a whole-hand prehension.
Mirror neurons fire even when the sight of the hand grasping the object is occluded,
as long as the monkey can see the initial movement of the hand towards the object (Umilta
et al., 2001). Moreover, they also fire when the monkey – in complete darkness – hears
the sound associated with an action, for instance, breaking a peanut (Kohler et al., 2002).
Mirror neurons also code for mouth actions, some of which are communicative
actions for monkeys, such as lip smacking (Ferrari et al., 2003).
Several brain-imaging techniques have addressed the properties of the human
homologue of the macaque mirror neuron system. In good accordance with the monkey data,
areas with mirror properties have been described in the posterior inferior frontal and rostral
inferior parietal cortex in humans (Iacoboni et al., 1999, 2005; Buccino et al., 2004).
These findings suggest that mirror neurons may implement very abstract
representations of actions, now that they can map actions of others into actions of the
self, a fundamental functional step for understanding other people (Geschwind and
Iacoboni, 2007).
In terms of their laterality, the single-unit data do not offer striking asymmetries.
However, with regard to the laterality of the human mirror neuron system, robust
lateralized responses have been observed in some cases.
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21. Cerebral cortex
In one of the original reports (Gallese et al., 1996), some interesting laterality patterns
were observed. About 40% of the mirror neurons tested demonstrated a discharge
influenced by the laterality of the observed hand.
The majority of these neurons responded more strongly when the observed hand
was ipsilateral to the recorded hemisphere (i.e., a left-hand action triggered stronger
discharge in mirror neurons in the left ventral premotor cortex, compared to a right-hand
action).
Another finding was related to the direction of the observed reach-and-grasp action.
About two-thirds of the mirror neurons tested demonstrated directional preference. More
than 80% of these neurons preferred the direction towards the recorded side, that is, from
right to left for mirror neurons in the left hemisphere (Gallese et al., 1996).
Iacoboni et al. (1996) described that the human left inferior frontal area responded to
action observation, action execution, and even more during action imitation. In light of the
evolutionary hypothesis of a link between mirror neurons and language (Rizzolatti and Arbib,
1998), the left lateralization report in this study has been often taken as suggesting that the
whole mirror neuron system in humans is left-lateralized (Corballis, 2003).
In that study, right-hand actions imitated left-hand observed actions. Even the
monkey data would have predicted a left-lateralized pattern in this case (Iacoboni et al.,
1999).
In fact, a reanalysis of seven fMRI studies of imitation adapting various forms of
hand imitation has shown a fairly bilateral activation pattern in the posterior inferior
frontal cortex (Molnar-Szakacs et al., 2005).
A highly reproducible effect that is likely due to the mirror neuron system is the
increase in the excitability of the motor corticospinal system during action observation.
When a transcranial magnetic stimulation (TMS) pulse is applied over the primary motor
hand area, a motor response is evoked in the contralateral hand. If subjects are also
watching somebody else’s actions, this motor evoked response is much stronger when
compared to watching some visual control stimuli (Fadiga et al., 1995; Aziz-Zadeh et
al., 2002; Fadiga et al., 2005).
This effect is likely due to the activation of mirror neurons in the premotor cortex
that feed directly onto primary motor regions (Cerri et al., 2003; Shimazu et al., 2004).
When subjects are listening to action sounds, their corticospinal excitability is
facilitated (Aziz-Zadeh et al., 2004).
This effect, likely mediated by mirror neurons that respond to the sound of an action
(Kohler et al., 2002), is completely lateralized to the left hemisphere in humans (Aziz-
Zadeh et al., 2004).
This strong left-hemisphere lateralization suggests that a fundamental step in the
hypothesized evolutionary progression from action recognition to language may be the
multimodal representation of action that only the left hemisphere appears to have in
humans (Geschwind and Iacoboni, 2007).
Right-hemisphere lateralization was observed during imitation and observation of
facial emotional expression (Carr et al., 2003).
1667
A strongly lateralized response in a mirror neuron area was observed in an action

observation task in which the context of the actions provided the observers information
to predict the intention of the actor, in other words, to predict the following (unseen)
action (Iacoboni et al., 2005). This suggests a link between the right hemisphere and the
capacity to “read the mind” of other people (Winner et al., 1998; Happe et al., 1999).
Thus, the laterality findings in the human mirror neuron system suggest that this
system is not lateralized to the left or right hemisphere, but that asymmetries may emerge
in the system on the basis of the function tapped by specific tasks (Geschwind and
Iacoboni, 2007).
PREFRONTAL CORTEX
The prefrontal cortex makes up about a third of the human neocortex and
corresponds to three major regions on the various surfaces of the frontal lobe. Collectively
these three regions forming the prefrontal cortex constitute a complex association area
that provides the structural basis for the most complex intellectual and moral functions
of which humans are capable (Markowitsch et al., 1979; Morecraft and Yeterian, 2000)
The lateral prefrontal cortex
The prefrontal cortex on the lateral surface of the hemisphere (the lateral prefrontal
cortex) which involves the superior, middle, and inferior frontal gyri anterior to the
premotor cortex, comprises Brodmann’s areas 8, 9, 10, 11, 45, 46, and 47 (Fuster, 2001).
Areas 44 and 45 are particularly notable in men since, in the dominant hemisphere, they
constitute the motor speech area (Broca’s area).
In nonhuman primates, two subdivisions of the lateral prefrontal cortex are
recognized, a dorsal area equivalent to area 9, and perhaps including the superior part of
area 46, and a ventral area, consisting of the inferior part of area 46 and area 45.
According to Crossman (2008), both the dorsolateral and ventrolateral prefrontal
areas receive their major thalamic afferents from the mediodorsal nucleus, and there are
additional contributions from the medial pulvinar nucleus, the ventral anterior nucleus,
and from the paracentral nucleus of the anterior intralaminar group.
The dorsolateral area receives long association fibres from the posterior and middle
superior temporal gyrus (including auditory association areas), from parietal area 7a, and
from much of the middle temporal cortex. From within the frontal lobe it also receives
projections from the frontal pole (area 10), the medial prefrontal cortex (area 32) and the
medial surface of the hemisphere. It projects to the supplementary motor area, the dorsal
premotor cortex and the frontal eye field. All these thalamic and corticocortical
connections are reciprocal. Commissural connections are with the homologous area, and
with the contralateral inferior parietal cortex (Crossman, 2008).
The ventrolateral prefrontal area receives long association fibres from both area
7a and area 7b of the parietal lobe, from auditory association areas of the temporal
operculum, from the insula and from the anterior part of the lower bank of the superior
temporal sulcus. From within the frontal lobe it receives fibres from the anterior
orbitofrontal cortex and projects to the frontal eye field and the ventral premotor cortex.
1668
21. Cerebral cortex
It connects with the contralateral homologous area via the corpus callosum. These
connections are probably all reciprocal (Crossman, 2008).
The cortex of the frontal pole (area 10) receives thalamic inputs from the
mediodorsal nucleus, the medial pulvinar nucleus and the paracentral nucleus. It is
reciprocally connected with the cortex of the temporal pole, the anterior orbitofrontal
cortex, and the dorsolateral prefrontal cortex.
The inferior or orbital prefrontal cortex

The inferior or orbital prefrontal cortex of the frontal lobe includes Brodmann’s
areas 10, 11, 13, and 47 (Fig. 21.24).
Fig. 21.24. Human prefrontal areas numbered according to Brodmann (from Fuster, 2001).
The orbitofrontal cortex connects with the mediodorsal, anteromedial, ventral

anterior, medial pulvinar, paracentral and midline nuclei of the thalamus.
Cortical association pathways come from the inferotemporal cortex, the anterior superior
temporal gyrus and the temporal pole. Within the frontal lobe it has connections with the
medial prefrontal cortex, the ventrolateral prefrontal cortex and medial motor areas.
Commissural and other connections follow the general pattern for all neocortical areas.
The medial prefrontal cortex

The medial surface of the frontal lobe involves in part the anterior cingulate gyrus
and includes Brodmann’s areas 8, 9, 10, 11, 12, 24 and 32 (Fuster, 2001).
The medial prefrontal cortex is connected with the mediodorsal, ventral anterior
medial pulvinar, paracentral, midline and suprageniculate-limitans nuclei of the thalamus.
1669
It receives fibres from the anterior cortex of the superior temporal gyrus. Within the
frontal lobe, it has connections with the orbitofrontal cortex, and the medial motor areas
of the dorsolateral prefrontal cortex (Crossman, 2008).
SENSORY AREAS OF THE CEREBRAL CORTEX
Primary sensory areas

The primary sensory areas are involved in distinguishing and integrating sensory
input relayed there primarily by the thalamic nuclei. Although certain aspects of sensation
probably enter consciousness at thalamic levels, the primary sensory areas are concerned
especially with the integration of sensory experience and with the discriminative qualities
of sensation. The organization of the thalamus is such that all of the specific sensory relay
nuclei are located caudally in the ventral tier. The cortical projections of the specific
sensory relay nuclei are localized in areas of the parietal, occipital and temporal lobes
(Carpenter, 1979).
Established primary sensory areas in the cerebral cortex are: (1) the somesthetic
area, consisting of the postcentral gyrus and its medial extension in the paracentral lobule
(areas 3, 1 and 2); (2) the visual or striate area, located along the lips of the calcarine
sulcus (area 17); and (3) the auditory area, located on the two transverse gyri (Heschl;
areas 41 and 42). The gustatory area appears to be localized to the most ventral part
(opercular) of the postcentral gyrus (area 43). The primary olfactory area consists of the
allocortex of the prepyriform and periamygdaloid regions and has not assigned numbers
under Brodmann’s parcellation. A vestibular projection to the human cerebral cortex has
not been established (Carpenter, 1979).
Primary somatosensory (somesthetic) cortex (S I)

A significant area in the parietal lobe is the primary somatosensory cortex, or S I,
that corresponds to Brodmann’s areas 3, 1 and 2 on the postcentral gyrus (Fig 21.25).
The primary somatosensory cortex also comprises the posterior part of the paracentral
lobule, which resides and is visible only on the medial surface of the cerebral hemisphere.
Fig. 21.25. Brodmann’s areas

in the human parietal lobe
(from Paxinos and Mai, 2004).
1670
21. Cerebral cortex
Area 1 is on the crown of the postcentral gyrus, area 2 intrasulcal in position forming
the anterior wall of the postcentral sulcus, area 3 is divisible into areas 3a and 3b in
nonhuman primates and humans, with area 3b being intrasulcal but forming the posterior
wall of the central sulcus. Area 3a, also intrasulcal, forms the floor of the central sulcus,
is a transition region between primary motor area 4 along the precentral gyrus and area
3b on the posterior bank of the central sulcus. Thus, there are four strep-like
somatosensory areas in the human primary somatosensory area of the postcentral gyrus
of the parietal lobe (Geyer et al., 1999, 2000; Augustine, 2008).
The primary somatosensory cortex contains within it a topographical map of the
contralateral half of the body. The face, tongue and lips are represented inferiorly, the
trunk and upper limb are represented on the superolateral aspect, and the lower limb on
the medial aspect of the hemisphere, giving rise to the familiar “homunculus” map
(Fig. 21.26). Thus, the body is represented on the somatosensory cortex by an upside-
down homunculus. The foot is represented on the superior medial surface of the
hemisphere, the leg, thigh, trunk, shoulder, arm, and forearm on the superior surface of
the postcentral gyrus, whereas the hand, head, teeth, tongue, larynx, and pharynx are on
the lateral surface of the postcentral gyrus. The total cortical area representing a body
part is proportional to the discriminative capability of the body part.
Fig. 21.26. The sensory homunculus across the postcentral gyrus and paracentral lobule
(after Penfield and Rasmussen, 1950).
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Cutaneous areas of the greatest sensitivity have corresponding larger cortical

representation. Hence, the size of the parts of the homunculus is a reflection of the cortical
area devoted to individual parts of the body. The sensory homunculus has the same order
as the motor homunculus in the frontal lobe.
Certain aspects of the human sensory homunculus are of special interest. The toes,
foot, ankle and leg have their representation in the posterior part of the paracentral lobule
on the medial surface of the brain.
The representation of the thigh or hip occurs at the medial to superolateral surface
junction followed in order by the trunk, neck, shoulder, arm, forearm, and hand across
the superolateral surface of the brain (Sutherling et al., 2002).
The genitalia and perineum likely have their representation on the medial surface of
the human brain just ventral to the representation of the toes.
Recent recording of cerebrocortical potentials evoked by stimulation of the dorsal
nerve of the penis in humans suggest a representation of the penis with the hip and upper
leg near the junction of the medial to superolateral surface (Bradley et al., 1998). The anal
and genital regions are represented in the most ventral portion of the medial surface just
above the cingulate gyrus. All five fingers have a separate medial to lateral representation
along the wall of the central sulcus not on the lateral surface (Gelnar et al., 1998; Overduin
and Servos, 2004). The anterior surfaces of the body face the central sulcus.
Experimental studies of the face area of S I in nonhuman primates demonstrate that
oral soft tissues (gingiva, inner aspect of the lips) have their representation near the
surface of the postcentral gyrus with the dental pulp along the floor of the central sulcus,
coinciding with area 3a (Urasaki et al., 1994).
Stimulation of dental pulp in humans causes painful sensations that are accurately
localized suggesting involvement of the primary somatosensory cortex for localization
of painful sensations (Geyer et al., 1996; Gelnar et al., 1998; Bodegård et al., 2000;
Disbrow et al., 2000; Overduin and Servos, 2004).
The face area, occupying most of the lower half of the postcentral gyrus, receives
trigeminal impulses including those from the face and mouth.
The back of the head has its representation caudal in the postcentral gyrus; the face
faces the central sulcus.
The primary sensory cortex also includes Brodmann’s area 3a, which is buried in
the central sulcus. This area receives sensory input from muscle receptors. Some of the
cells residing in the primary somatosensory cortex give rise to fibres that descend to
terminate in the brain stem and spinal cord gray matter. There they influence motor
activity, not by synapsing with motoneurons, but instead by modulating the transmission
of sensory inputs from peripheral structures into the brain stem and spinal cord.
In addition to the four cytoarchitectonic subdivisions of S I, there is also a columnar
cortical organization (microarchitecture) in the postcentral gyrus.
Neurons in S I are organized in vertical columns at right angles to the surface and
extend through all cortical layers; they often share similar receptive fields and have
specific functions. Columns in S I are functionally interrelated by intrinsic corticocortical
1672
21. Cerebral cortex
connections and by direct horizontal connections between columns. These intrinsic

connections serve to connect parts of the cerebral cortex having different response
properties yet lying in regions of similar regional representation. (Gelnar et al., 1998;
Geyer et al., 1999; Bodegård et al., 2000; Disbrow et al., 2000; Overduin and Servos,
2004; Augustine, 2008).
However, the somatosensory properties of S I depend on its thalamic input from the
ventral posterior nucleus of the thalamus, which in turn receives the medial lemniscal,
spinothalamic and trigeminothalamic pathways. Within, the ventral posterior nucleus,
neurons in the central core respond to cutaneous stimuli and those in the most dorsal
anterior and posterior parts, which arch as a “shell” over this central core, respond to
deep stimuli (Jones, 2007).
This is reflected in the differential projections to S I: the cutaneous central core
projects to 3b, the deep tissue-responsive neurons send fibres to areas 3a and 2, and an
intervening zone projects to area 1. Thus, ventral posterior nucleus is the principal
thalamic relay for the somatosensory pathways. It consist of two major divisions, the
ventral posterolateral and ventral posteromedial nuclei. The ventral posterolateral nucleus
receives the medial lemniscal and spinothalamic pathways (information from the trunk
and limb) and the ventral posteromedial nucleus receives the trigeminothalamic pathway
in which the head is represented. These fibres convey general sensory (touch, pain, and
temperature) as well as proprioceptive sensory modalities (position, vibration, and two-
point discrimination).
The laminar termination of thalamocortical axons from the ventral posterior nucleus
is different in the separate cytoarchitectonic subdivisions of S I in 3a and 3b; these axons
terminate mainly in layer IV and the adjacent deep part of layer III, whereas in area 1
and 2 they end in the deeper half of layer III avoiding lamina IV. Additional
thalamocortical fibres to S I arise from the intralaminar system, notably the centrolateral
nucleus (Jones, 2007; Crossman, 2008).
Corticospinal pyramidal cells are found in layer V of S I. The topographical
representation in the cortex is preserved in terms of the spinal segments to which different
parts of the postcentral gyrus project. Thus, the arm representation projects to the cervical
enlargement, the leg representation to the lumbosacral enlargement, and so on. Within
the grey matter of the spinal cord, fibres from S I terminate in the dorsal horn, in Rexed’s
laminae 3 to 5: fibres from 3b and 1 end more dorsally, and those from area 2 more
ventrally (Jones, 2007; Crossman, 2008).
S I has ipsilateral corticocortical association connections with a second soma-
tosensory area S II; area 5, in the superior parietal lobe; area 4, in the motor cortex, in
the precentral gyrus; and the supplementary motor cortex in the medial part of area 6 of
the frontal lobe.
So, although the primary somesthetic area is concerned basically with sensory
modalities, it is possible to elicit motor responses following its stimulation.
In addition to thalamic afferents, the primary somesthetic cortex receives commis-
sural fibres through the corpus callosum from the contralateral primary somesthetic cortex
1673
and short association fibres from the adjacent primary motor cortex. Callosal fibres in
S I arise mainly from the deep part of layer III and terminate in layer I to IV.
Thus, efferents from the primary somesthetic cortex project to the motor cortex, the
opposite primary somesthetic cortex, and the association somatosensory cortex (area 5
and 7) in the posterior parietal cortex (Fig. 21.27).
Fig. 21.27. The lateral (A) and medial (B) surfaces of the left cerebral hemisphere
depicting Brodmann’s areas (after Crossman, 2008).
The primary and secondary areas are reciprocally interconnected. In addition,

projection fibres descend within the internal capsule to the ventral posterior nuclei of the
thalamus, posterior column nuclei of the medulla oblongata, and dorsal horn of the spinal
cord. Thus, S I had reciprocal subcortical connections with the thalamus and claustrum,
and receives afferents from the basal nucleus of Meynert, the locus ceruleus and the
midbrain raphe. Corticostriatal fibres, arising in layer V, pass mainly to the putamen on
the same side. Corticopontine and corticotectal fibres from S I arise in layer V. S I projects
to the main pontine nuclei, and to the pontine tegmental reticular nucleus. In addition,
axons arising in S I pass to the dorsal column nuclei and the spinal cord (Ramansky et
al., 1979; Brodal, 1978; Brouwer and Ashby, 1991; Iwatsubo et al., 1990; Jones, 2007;
Crossman, 2008).
The ability to recognize, localize and assess pain and thermal sensation require
cortical participation. Although sensations of thermal extremes and superficial pain enter
consciousness at a thalamic level in humans, the primary somatosensory cortex is capable
of discriminating and comparing qualities of pain and slight variations in temperature,
accurately localizing these tactile and proprioceptive sensations (Augustine, 2008).
Although impulses for visceral pain likely reach consciousness at a thalamic level,
areas of the cerebral cortex are also involved in visceral sensation. The intralaminar
nuclei, part of the “diffuse thalamocortical projection system”, relay visceral impulses
to the cerebral cortex. Their diffuseness presumably accounts for the poor localization
1674
21. Cerebral cortex
of visceral pain. Electrical stimulation reveals that visceral sensory areas in the cerebral
cortex in humans include the lower end of the primary somatosensory cortex and part of
the insular lobe (Augustine, 2008).
In a study of the speed of moving stimuli across the skin of the hand, there was
primarily activation in area 1 and secondary in area 3b of the somatosensory cortex. In
another study, the discrimination of caricatures or objects rich in curvatures led to an
increase in regional cerebral blood flow outside of area 1 but perhaps in area 2 on the
posterior bank of the postcentral sulcus.
Positron emission tomography, cytoarchitectonic mapping, and a combination of
sensory stimuli (passive or active touch, brush velocity, edge length, curvature, and
roughness) reveal the probable hierarchical processing of tactile shape in sensory areas
of the human brain. This involves areas 3b and 1 as the first steps in the process, area 2
being the next step, and the anterior part of the cortex lining the intraparietal sulcus and
the adjacent part of the supramarginal gyrus being the final step. The anterior part of the
human intraparietal sulcus is involved in visually guided grasping (Augustine, 2008).
Lastly, in a fourth study, a pleasant and soft touch to the hand elicited by using velvet in
comparison to a neutral stimulus produces activation in the orbitofrontal cortex. This
suggest that the pleasant or rewarding aspects of touch (“that feels good”) as well as the
pleasant rewarding aspect of taste (“that tastes good”) or smell (“that smells good”) all
of which are represented in different parts of the orbitofrontal cortex, collectively
contribute to our state of emotion (Badegård et al., 2000 a, b, 2001; Augustine, 2008).
Functional imaging studies of the human S I show that multiple digit representations
occur in the four subdivisions (3a, 3b, 1 and 2) resembling a multiple representation
hypothesis that is present in nonhuman primates (Kaas et al., 1999, 2004).
Neurophysiologic studies of the somesthetic cortex have revealed the following
information: (1) the functional cortical unit appears to be associated with a vertical
column of cells that is modality specific. Neurons within a cortical unit are activated by
the same peripheral stimulus and are related to the same peripheral receptive field. (2)
Area 3b is activated by cutaneous stimuli and areas 2 and 3a by proprioceptive impulses,
whereas area 1 is activated by either cutaneous or proprioceptive impulses. Area 2 appears
to represent predominantly deep receptors, including those signalling the position of joints
and other deep body sensations, whereas area 3a represents sensory input from muscles
(Burton et al., 1995).
(3) Somatosensory neurons responding to joint movement show a marked degree of
specificity in that they respond to displacement in one direction. (4) Fast- and slow-
adapting neuronal pools have been identified in response to hair displacement or
cutaneous deformation. (5) Fibres mediating cutaneous sensations terminate rostrally,
whereas those mediating proprioceptive sensations terminate more caudally in the
somesthetic area (Afifi and Bergman, 2005).
The cortical representation along the postcentral gyrus reflects a composite of
somatotopically organized areas instead of a continuous homunculus.
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Stimulation of the primary somesthetic cortex in conscious patients elicits sensations

of numbness and tingling, a feeling of electricity, and a feeling of movement without actual
movement. These sensations are referred to the contralateral half of the body, except when
the face area is stimulated. The face and tongue are represented bilaterally (Penfield and
Boldrey, 1937; Penfield and Rasmussen, 1950; Urasaki et al., 1994).
Ablation of the postcentral gyrus will result, in the immediate postoperative period,
in loss of all modalities of sensation (touch, pressure, pain, and temperature). Soon,
however, pain and temperature sensation will return. It is believed that pain and
temperature sensation are determined at the thalamic level, whereas the source, severity,
and quality of such sensations are perceived in the postcentral gyrus.
Thus, the effects of postcentral gyrus lesions would be (1) complete loss of
discriminative touch and proprioception; and (2) crude awareness of pain, temperature,
and light touch (Penfield and Rasmussen, 1950; Afifi and Bergman, 2005).
Thermal and painful auras. Loss of discriminative pain or thermal sensation may
result from cortical injury. Thermal and painful sensations foreshadow the onset of an
epileptic seizure, a phenomenon known as an aura.
Sensory Jacksonian seizures. An analysis of seizure patterns involving subjective
sensory experiences without objective signs has shown that such episodes, or sensory
Jacksonian seizures, involve abnormal, localizable, cutaneous sensations without apparent
prior stimulation. Seizures arise from discharges in the cerebral cortex. The behavioral
manifestations of a seizure are determined by the normal functions of the region of cortex
in which neurons fire abnormally. A diversity of potential mechanisms exist by which a
small region or focus of cortex could become hyperexcitable after injury, and it seems
likely that different mechanisms may operate in different patients or even at different
stages of the disease in the same patient.
The sensation spreads or progresses to adjacent cutaneous areas, in the body or along
a limb, reflecting propagation of an epileptic discharge – an abnormal firing of neurons
in the postcentral gyrus. Thus, sensory disorder is usually described as numbness,
tingling, or a “pins-and-needles” feeling and occasionally as a sensation of crawling
(fornication), electricity, or movement of the part. Pain and thermal sensation may occur
but are infrequent. In the majority of cases, the onset of the sensory seizure is in the lips,
fingers, or toes, and the spread to adjacent parts of the body follows a pattern determined
by sensory arrangements in the postcentral (post-rolandic) convolution of the parietal
lobe. If the sensory symptoms are localized to the head, the focus is in, or adjacent to the
lowest part of the convolution, near the sylvian fissure. If the symptoms are in the leg or
foot, the upper part of the convolution, near the superior sagittal sinus or on the medial
surface of the hemisphere, is involved.
Secondary somatosensory cortex (S II)

Near each primary receptive area there are cortical zones which may receive sensory
inputs directly, or indirectly, from the thalamus. These cortical zones, adjacent to primary
sensory areas, but outside of the principal projection area, of the specific sensory relay
1676
21. Cerebral cortex
nuclei of the thalamus, are referred to as the secondary sensory areas (Carpenter, 1979).
These areas have been defined and mapped in experimental animals by recording evoked
potentials in response to peripheral stimulation (Adrian, 1940, 1941; Woolsey and Walzl,
1942; Woolsey and Fairman, 1946; Thompson et al., 1950). Studies of these secondary
sensory areas indicate that sequential representation of parts of the body, or of the
tonotopic pattern in the case of the auditory areas, is not the same as in the primary areas
(Woolsey, 1958; Rose and Woolsey, 1958).
Adjoining the primary somatosensory cortex or S I is a smaller region, the secondary
somatosensory cortex or S II, on the superior bank of the lateral sulcus, continuing onto
the parietal operculum of the human brain and corresponding to Brodmann’s area 43.
(Eickhoff et al., 2006 a, b). S II contains a somatotopic representation of the body, with
the head and face most anteriorly, adjacent to S I, and the sacral regions most posteriorly.
Thus, body representation in this area is bilateral, with contralateral predominance, and
is reverse of that in the primary area so that the two face areas are adjacent to each other.
The secondary somatosensory area in animals appears to coincide with the so-called
secondary motor area (Welker et al., 1957; Disbrow et al., 2000).
The secondary sensory area contains neurons with receptive fields that are large,
poorly demarcated, overlap extensively, and often have bilateral representation.
Representation of the body form in the secondary somatosensory area (II) is nearly
as detailed as that in the postcentral gyrus (Woolsey, 1958), and single unit analysis
(Carreras and Levitt, 1959) has revealed many cells in this area to both mode and place
specific. Although a detailed somatotopic organization exists in S II, with the exception
of parts of the digit representation, neighbouring neurons in S II do not form a precise
body map comparable to that in S II of nonhuman primates.
In S II, there is a split in the representation for the face, thumb, and foot causing a
dual presentation of the same body part in the composite map of S II (Krubitzer et al.,
1995; Kaas, 2004).
Within the cortex, S II is reciprocally connected with S I in a topographically
organized manner, and projects to the primary motor cortex. S II also projects in a
topographically organized way to the lateral part of area 7 (area 7b) in the superior parietal
lobe, and makes connections with the posterior cingulate gyrus. Both right and left S II
areas are interconnected across the corpus callosum, although distal limb representations
are probably excluded. There are projections to S II and area 7b (Crossman, 2008).
The secondary somesthetic area contains no cells sensitive to join movement or join
position.
The S II is reciprocally connected with the ventral posterior nucleus of the thalamus in
a topographically organized fashion. Some thalamic neurons probably project to both S I
and S II via collaterals. Other thalamic connections of the S II are with posterior groups of
nuclei and with the intralaminar central lateral nucleus. S II also projects to laminae IV to
VII of the dorsal horn of the cervical and thoracic spinal cord, the dorsal column nuclei, the
principal trigeminal nucleus, and the periaqueductal grey matter of the midbrain.
S II in nonhuman primates receives fibres from the ventral posterior medial nucleus
and the caudal part of the ventral posterior lateral nucleus. Reciprocal corticothalamic
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fibres occur from S II in nonhuman primates to the ventral posterior nucleus. Output from
S II is to S I, to the primary motor cortex (Brodmann’s area 4), and the premotor cortex
(Brodmann’s area 6).
Lesions interrupting connections between the secondary somesthetic area, posterior
parietal cortex, and ventral posteromedial and centrolateral thalamic nuclei have been
associated with pseudothalamic pain syndrome. The pain is spontaneous and
characterized as burning or icelike and is associated with impairment of pain, and
temperature appreciation (Déjérine 1900; Schmahmann and Leifer, 1992).
The unilateral or bilateral removal of area S II in monkeys causes a profound defect
of tasks requiring tactile learning and retention. Even in the face of injury to the primary
association cortex in the parietal lobe, patients are still able to recognize two points as
two points and to identify the position of the parts of their body.
However, the patient will be unable to name an object placed in the affected hand,
based on somatosensory information. There are disturbances mainly of the discriminative
sensory function of the opposite leg, arm, and side of face without impairment of the
primary modalities of sensation. The lack of recognition of shape and form is frequently
a manifestation of cortical disease. Thus, astereognosis, connotes an inability to identify
an object by palpation, even though the primary sense data (touch, pain, temperature, and
vibration) are intact. Astereognosis is either right-, or left-sided, and is the product of a
lesion in the opposite hemisphere, involving the sensory cortex, particularly S II, or
thalamoparietal projections. With this deficit, (cortical astereognosis) patients lose the
ability to use the somatosensory information.
Part of the parietal lobe including the primary (area 3, 1, and 2) and secondary
somatosensory cortex (area 43) is often termed the anterior parietal cortex. The entire
parietal cortex behind S I and S II is often termed the posterior parietal cortex. Posterior
parietal cortex, in turn, is divisible in the superior parietal lobule and the inferior parietal
lobule.
The superior parietal lobule lies superior to the intraparietal sulcus and includes
Brodmann’s areas 5 and 7a and 7b, whereas the inferior parietal lobule lies inferior to
the intraparietal sulcus and includes Brodmann’s areas 39 and 40.
Based on the serial processing of sensory information from secondary sensory areas,
the superior parietal lobule is likely to be a tertiary somatosensory association area in
terms of its higher order processing.
Area 5 receives a dense feedforward projection from all cytoarchitectonic areas of
S I in a topographically organized manner. The thalamic afferents to this area come from
the lateral posterior nucleus and from the central lateral nucleus of the intralaminar group.
Ipsilateral corticocortical fibres from area 5 go to area 7, the premotor and supplementary
motor cortices, the posterior cingulate gyrus, and the insular granular cortex.
Commissural connections between both sides of area 5 tend to avoid the areas of
representation of the distal limb. The response properties of cells in area 5 are more
complex than in S I, with larger receptive fields and evidence of submodality
convergence. Area 5 contributes to the corticospinal tract (Crossman, 2008).
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21. Cerebral cortex
Areas 5 and 7 receive their inputs mainly from the primary somatosensory areas but
also have reciprocal connections with the pulvinar and lateral posterior nucleus of the
thalamus. Such connections permit the reinforcement, correlation, and integration of
sensory information. The superior parietal lobule is involved in spatial orientation.
In monkeys area 7a is not related to the cortical pathway for somatosensory
processing but instead forms part of a dorsal cortical pathway for spatial vision. The
major ipsilateral corticortical connections to area 7a are derived from visual areas in the
occipital and temporal lobes. In the ipsilateral hemisphere, area 7a has connections with
the posterior cingulate cortex (area 24) and with area 8 and 46 of the frontal lobe.
Commissural connections are with its contralateral homologue. Area 7a is connected with
the medial pulvinar and intralaminar paracentral nuclei of the thalamus.
In experimental studies, neurons within area 7a are visually responsive: they relate
largely to the peripheral vision, respond to stimulus movement, and are modulated by
eye movement (Crossman, 2008).
In monkeys, area 7b receives somatosensory inputs from area 5 and S II. Connections
pass to the posterior cingulate gyrus (area 23), insula and temporal cortex. Area 7b is
reciprocally connected with area 46 in the prefrontal cortex and the lateral part of the
premotor cortex. Commissural connections of area 7b are with the contralateral
homologous area, and with area S II, the insular granular cortex and area 5. Thalamic
connections are with the medial pulvinar nucleus and the intralaminar paracentral nucleus
(Crossman, 2008).
Neuronal responses in the tertiary somatosensory association areas involve the
integration of a number of cortical and thalamic inputs. The processing of multisensory
somatosensory inputs in these areas allows for the perception of shape, size and texture,
and the identification of objects by contact (stereognosis).
The tertiary somatosensory association areas project to multimodal nonprimary
association areas (areas 39 and 40) in the inferior parietal lobule that receive inputs from
more than one sensory modality and serve intermodal integration and multisensory
perception.
Single-cell recording in area 5 in monkeys suggests that this area is essential for the
proper use of somatosensory information, for goal-directed voluntary movements, and
for the manipulation of objects (Lüders et al., 1985).
Single-cell recording in area 7 indicates that this area plays an important role in the
integration of visual and somatosensory stimuli, which is essential for the coordination
of the eyes and hands in visually guided movements (Godoy et al., 1990; Pierrot-
Deseilligny and Gaymard, 1990; Pierrot-Deseilligny et al., 1995).
Injuries to the parietal tertiary somatosensory association areas often lead to rare
visual illusions that are modifications of the normal position of objects. The world appears
upside down and the chair, table or other objects also appear upside down.
Such phenomena do not have any emotional component to them, as do such illusions
that occur after injury to the temporal lobe.
Loss of the body schema often results because such patients do not recognize a
body part as belonging to themselves. This agnosia can occur for a digit, hand, or half of
1679
the face. This condition, most frequently results from an extensive lesion in the superior
aspect of the nondominant parietal lobe (areas 5, 7, 40, and 39). The individual does not
recognize certain parts of the body as being his and show unilateral unawareness of denial
defects on one side of the body (anosognosia).
In milder cases, patients may show an inappropriate lack of concern for their deficits
(anosodiaphoria). Tests such as line bisection, drawing, copying, and visual search tasks
may provide useful clinical screening procedures (Robertson and Marshall, 1993).
Apraxia is a deficit in the voluntary use of the limbs to carry out a series of
movements in which each step depends on the preceding movement. Injuries to the
dominant parietal lobe often result in the phenomena of ideational apraxia. Ideational
apraxia is impairment of familiar and well-practiced movements (pick up a cup, pour
water in it, drink the water etc.).
Sensory extinction is a subtle symptom of parietal lobe injury due to perceptual
rivalry so that the injured area loses out, and the sensation coming from that side of the
body is extinguished.
The inferior parietal lobule includes the supramarginal gyrus and the angular gyrus
corresponding to Brodmann’s areas 40 and 39. The intraparietal sulcus forms the dorsal
border of the inferior parietal lobule. The supramarginal gyrus caps the posterior tip of
the lateral sulcus (Fig. 21.28), whereas the angular gyrus caps the posterior tip of the
superior temporal sulcus. The angular gyrus, corresponding to Brodmann’s area 39, is
functionally involved in language.
Fig. 21.28. Superolateral surface of the left cerebral hemisphere including the boundaries, major sulci,
and gyri of the parietal lobe (after Augustine, 2008).
A unilateral lesion involving Brodmann’s areas 39, 40, 22 and 37, results in
Wernicke’s (receptive) aphasia. Because this area plays a role in the comprehension and
formulation of language, an individual with a severe form of this condition has difficulty
in comprehending the spoken words. These patients cannot name an object they are able
1680
21. Cerebral cortex
to see, although they know how to use it, and have a condition termed alexia without
agraphia or the inability to read, although the ability to write remains.
Sentence comprehension impairments are usually observed in the context of tasks
requiring a precise understanding of the grammatical relationships among words in a
sentence. In 1906, Pierre Marie first noted that this type of test was very sensitive to mild
degrees of language deficit.
Injury to the supramarginal gyrus, particularly in the left hemisphere corresponding
to Brodmann’s area 40, causes the loss of the ability to express oneself in language, a
condition called conduction apraxia. Speech is broken but comprehension is good. In
classic conduction aphasia, phonemic errors are more common in repetition tasks than
in spontaneous speech. In transcortical motor aphasia, repetition may be spared, but
spontaneous speech is contaminated by phonemic errors.
The major association cortex is connected with all the sensory cortical areas and,
thus, functions in higher-order and complex multisensory perception. The major
association cortex refers to supramarginal and angular gyri in the inferior parietal lobule
which corresponds to areas 39 and 40 of Brodmann. Its relation to the speech areas in
the temporal and frontal lobes gives it an important role in communication skills. Patients
with lesions in the major association cortex of the dominant hemisphere present a
conglomerate of manifestations that include receptive and expressive aphasia, inability
to write (agraphia), inability to synthesize, correlate, and recognize multisensory
perceptions (agnosia), left - right confusion, difficulty in recognizing different fingers
(finger agnosia), and the inability to calculate (acalculia). These symptoms and signs are
grouped together under the term Gerstmann’s syndrome (Afifi and Bergman, 2005).
Involvement of the major association cortex in the nondominant hemisphere is
usually manifested by disturbances in drawing (constructional apraxia) and in the
awareness of body image. Such patients have difficulty in drawing a square or circle or
copying a complex figure. They often are unaware of a body part and thus neglect to
shave half of face or dress half the body (Afifi and Bergman, 2005).
Primary vestibular cortex

According to Brandt and Dieterich (1999) and Augustine (2008), the primary
vestibular cortex, along the upper lip of the intraparietal sulcus (Fig 21.29), has the
cytoarchitectural appearance of area 2 (Guldin and Grüsser, 1998). The cognitive
perception of motion and spatial orientation arise through the convergence of information
from the vestibular, visual, and somatosensory systems at the thalamocortical level.
Neurons in the superior, lateral, and inferior vestibular nuclei project bilaterally to two
thalamic areas. The first is located in the ventral posterolateral (VPL) nucleus and
includes adjacent cells in the ventral posteroinferior (VPI) nucleus. The second is the
posterior nuclear group, located near the medial geniculate body (Baloh and Honrubia,
1990; Goldberg, 1991; Highstein et al., 1996; Yates and Miller, 1996; Dickman et al.,
2000; Dickman, 2006).
1681
Fig. 21.29. Path for vestibular impulses from receptors in the peripheral vestibular apparatus to the primary vestibular
cortex of the parietal lobe. This path is presumably bilateral in that there is never any direction of movement of the head
that does not stimulate both sets of vestibular receptors. The thalamic termination of this path includes the oral part of the
ventral posterior lateral nucleus (VPLo), caudal part of the ventral lateral nucleus (vLc) and dorsal part of the ventral
posterior inferior nucleus (VPId). Some authors include VPI in the borders of the ventral posterior lateral nucleus (VPL) of
the dorsal thalamus. The few primary fibres that reach the cerebellum are not shown (after Augustine, 2008).
1682
21. Cerebral cortex
Thalamic VPL and posterior nucleus neurons constitute separate, parallel pathways
transmitting vestibular information from the brain stem to the cortex, because their
connections with cortical areas are distinct. In addition, vestibular signals indirectly
project to the anterior thalamic nuclei, where cells respond only when facing a preferred
heading direction. These neurons are thought to be involved in spatial navigation and
lose their directional selectivity through vestibular ablation (Baloh, 1990; Yates and
Miller, 1996; Guldin and Grusser, 1998).
According to Dickman (2006), two cortical areas respond to vestibular stimulation
(Fig. 21.30). One region, area 2v, lies at the base of the intraparietal sulcus just posterior
to the hand and mouth representation in the postcentral gyrus. This region functions in
vestibular consciousness – the awareness of position or movement of our body caused
by the effects of gravity and acceleration and deceleration. Other than vertigo (the
abnormal sensation of self-motion or of the motion of external objects often described as
“dizziness”), there is no easily definable, discrete vestibular sensation. Cells in area 2v
receive visual and proprioceptive inputs. Thus, area 2v is probably involved with motion
perception and spatial orientation, because it has reciprocal connections with other
parietal regions involved in similar functions (e.g.: area 5 and 7) (Kahane et al., 2003;
Dickman, 2006).
Fig. 21.30. The vestibulo-thalamo-cortical pathway. Vestibular input arises from the vestibular nuclei as
vestibulothalamic fibres and is relayed to the cortex as thalamocortical fibres. (A) Areas 3a and 2v (B) are the main
cortical regions that receive this input (after Dickman, 2006).
1683
It appears that vestibular stimuli integrate with visual and somatosensory modalities.
In the process of this integration, vestibular stimuli seem to lose their original, pure
character. This overlap of vestibular and visual with other somatosensory modalities often
allows each to compensate for a deficiency in the other (Leigh, 1994; Brand and
Dieterich, 1999; Augustine, 2008).
Electrical stimulation of area 2v in humans produces sensations of moving, spinning,
or dizziness. Area 2v neurons respond to head movements and receive projections from
the posterior thalamic nucleus.
Lesions of parietal cortical areas result in confusion in spatial awareness. Injuries
along the intraparietal sulcus lead to dizziness and a subjective feeling that the world is
whirling about the patient. There is the illusion of rotation or of flouting.
The second cortical area responding to vestibular stimulation, area 3a, lies at the
base of the central sulcus, adjacent to the motor cortex, and receives input from the VPL
or VPI thalamic nuclear neurons. In addition, area 3a cell receives inputs from the
somatosensory system. Because these cells project to areas of the motor cortex, it is
believed that one of their function is to integrate motor control of the head and body.
(Leigh, 1994; Kahane et al., 2003).
Visual disorientation and the disorder of spatial (topographic) localization is
another syndrome. Spatial orientation depends upon visual, tactile, and kinesthetic
perceptions. There are instances where the deficit in visual perception predominates.
Patients with this disorder, in distinction to those with environmental agnosia, are unable
to orient themselves in an abstract spatial setting (topographagnosia). Such patients cannot
draw the floor plan of their house or a map of their town, and cannot describe a familiar
route, from their home to their place of work, or find their way in familiar surroundings.
In brief, they have lost topographic memory. This disorder is almost invariably caused
by lesions in the dorsal convexity of the right parietal lobe, which is of interest, since it
suggests that there are two separate processes for spatial orientation – one for the actual
space (environmental) and one for the abstract topography of space.
Awareness of voluntary action and the parietal cortex

Voluntary action implies a subjective experience of the decision and the intention
to act, as well as neural control of motor execution. For willed action to be a functional
behavior, the brain must have a mechanism for matching the consequences of the motor
act against the prior intention (Sirigu et al., 2004).
It is widely thought that the brain uses internal anticipatory models for this purpose
(Wolpert et al., 1995; Kawato, 1999).
Estimating the time of a conscious intention presumably requires access to an
internal representation of the desired movement. Internal motor representation, or internal
models predict the future outcome of a given action (Wolpert and Ghahramani, 2000).
Several studies suggest that the parietal cortex is important in activating and
maintaining such internal models (Sirigu et al., 1996; Desmurget and Grafton, 2000).
For instance, when the parietal cortex is damaged, patients lose the ability to predict
through mental simulation the time necessary to perform various hand movements (Sirigu
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21. Cerebral cortex
et al., 1996, 2004), indicating that this region is involved in generating conscious motor
images. According to some reports (Wolpert et al., 1995; Kawato, 1999; Blakemore et
al., 2001), another brain region, the cerebellum, is also involved in predicting the future
state of a motor act.
For example, when lifting an object, subjects anticipate the increase in load force
and accordingly adapt their grip force to hold the object (Flanagan and Wing, 1997).
However, these processes may not be available to conscious awareness. Sirigu et al.
(2004) found that cerebellar patients, similar to normal control subjects, were able to
report when they first intended to move, whereas patients with parietal damage could
not. These results suggest that the parietal cortex is involved in monitoring awareness of
one’s movements.
Sirigu et al. (2004) show that patients with parietal lesions could report when they
started moving, but not when they first became aware of their intention to move. This
stands in contrast with the performance of cerebellar patients who behaved as normal
subjects. Thus, Sirigu et al. (2004) propose that when a movement is planned, activity in
the parietal cortex, as part of a corticocortical sensorymotor processing loop, generates a
predictive internal model of the upcoming movement. This model might form the neural
correlate of motor awareness.
Sirigu et al. (2004) suggest that the brain may contain several internal models used for
predictive control of voluntary action. An implicit module in the cerebellum would provide
fast processing for execution of action and predicting their sensory consequences (Blakemore
et al., 2001; Wolpert et al., 2001). A second system, in the parietal cortex, would monitor
intentions and motor plans at a higher level, detecting when actions match their desired goals.
These processes typically involve conscious experience (Sirigu et al., 2004).
Primary visual cortex (V1)

The occipital lobe comprises almost entirely Brodmann’s areas 17, 18 and 19. Area
17, the striate cortex, is the primary visual cortex (V1). A host of other distinct visual
areas resides in the occipital and temporal cortex. The functional subdivisions V2, V3
(dorsal and ventral) and V3A lie within Brodmann’s area 18. Other functional areas at
the junctions of the occipital cortex with the parietal or temporal lobes lie wholly or partly
in area 19.
The primary visual cortex is located mainly in the medial surface of the occipital
lobes on the banks of the calcarine fissure, although it extends into their posterolateral
surface.
The primary visual cortex is the thinnest cortex of the entire brain. Layer IV of this
cortex is prominent due to a thick layer of myelinated fibres, the external band of
Baillarger. This band is characteristically so thick in this cortex that it gives the primary
visual cortex a grossly visible striped appearance, and is referred to as the stripe of
Gennari. In sections of fresh cortex, area 17 of Brodmann is characterized by the
appearance of a prominent band of white matter that can be identified by the naked eye
and is named the band of Gennari, after the Italian medical student who described it in
1685
1782. This band of Gennari represents a thickened external band of Baillarger in layer
IV of the cortex.
In myelin preparations, the band of Gennari appears as a prominent dark band in the
visual cortex, also known as the striate cortex. The term striate refers to the presence in
unstained preparations of the thick white band of Gennari.
It occupies the upper and lower lips and depths of the posterior part of the calcarine
sulcus and extends into the cuneus and lingual gyrus.
The primary visual cortex receives afferent fibres from the lateral geniculate nucleus
via the optic radiation. The latter curves posteriorly and spreads through the white matter
of the occipital lobe. Its fibres terminate in strict point-to-point fashion in the striate area.
The superior lip of the calcarine sulcus receives fibres projecting from the superior
retinal quadrants whereas the inferior lip of the calcarine sulcus receives projections from
the inferior retinal quadrants.
Thus, the lateral geniculate nucleus projects visual information to the primary visual
cortex (V1) (Brodmann’s area 17). This cortical area receives input arising from the
contralateral visual field: the temporal half of the ipsilateral retina and the nasal half of
the contralateral retina. The cortex of each hemisphere receives impulses from two
hemiretinas, which represent the contralateral half of the binocular visual field.
The superior and inferior retinal quadrants are connected with corresponding areas
of the striate cortex. Thus, the superior retinal quadrants (representing the inferior half
of the visual field) are connected with the visual cortex above the calcarine sulcus, and
the inferior retinal quadrants (representing the upper half of the visual field) are connected
with the visual cortex below the calcarine sulcus. Thus, fibres originating from the
superior half of the retina terminate in the superior part of the visual cortex; those from
the inferior half of the retina terminate in the inferior part. The peripheral parts of the
retina activate most anterior parts of the visual cortex.
Geniculocalcarine fibres pass in the external sagittal stratum which is separated from
the wall of the inferior and posterior horns of the lateral ventricle by the internal sagittal
stratum and by fibres of the corpus callosum designed as the tapetum. Fibres of the
internal sagittal stratum are corticofugal fibres passing from the occipital lobe to the
superior colliculus and the lateral geniculate body (Altman, 1962; Garey et al., 1968).
The macular fibres project most posteriorly along the calcarine sulcus around the
occipital pole, followed by fibres from the paramacular areas. The macular representation
in the primary visual cortex is much larger than that of other areas of the retina, reflecting
the high visual acuity of the macula.
Unilateral injury to the calcarine sulcus will lead to a contralateral homonymous
hemianopsia in which there is blindness in the ipsilateral nasal field and the contralateral
temporal field.
Lesions involving portions of the visual cortex, such as the inferior calcarine cortex,
produce a homonymous quadrantanopsia, in which blindness results in the superior half
of the visual field contralaterally. Similarly, lesions limited to the upper calcarine cortex
produce a lower contralateral quadrantanopsia in which blindness is limited to the
contralateral lower quadrant of the visual field (Fig. 21.31).
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21. Cerebral cortex
Fig. 21.31. Visual field deficits caused by interruption or transection of fibres at certain points along the visual path.
A. Section of the optic chiasma with a resulting bitemporal hemianopia (loss of vision in the temporal parts of both right
and left visual fields). B. Section of the left optic nerve with blindness in the left visual field and a normal right visual field.
C. Section of the optic tract causing a contralateral homonymous hemianopia. D. Section of the optic radiations in the
temporal lobe with an incongruous visual field defect. The temporal part of the right visual field is affected, as is the
superior nasal quadrant of the left visual field – a superior quadrantanopia. E. Section of the optic radiations in the
parietal lobe with a resulting contralateral homonymous hemianopia (modified from Harrington, 1981).
A bilateral destruction of the striate areas causes total blindness in men, but other
mammals, such as dogs and monkeys, retain the ability to distinguish light intensities
after ablations of the visual cortex (Klüver, 1942; Glees, 1961; Snyder et al., 1966). If
the destructive lesion is of vascular origin as occurs in occlusions of the posterior cerebral
artery, central (macular) vision in the affected visual field is spared. This phenomenon is
known clinically as macular sparing and is attributed to the contralateral arterial supply
of the posterior visual cortex (macular area) from the patent middle cerebral artery.
The striate cortex is granular. Layer IV, bearing the stria of Gennari, is commonly
divided into three sublayers. Passing from superficial to deep, these are IV A, IV B (which
contains the stria) and IV C. The densely cellular IV C is further subdivided into a
superficial IV Cα and a deep IV Cβ. Layer IV B contains only sparse mainly non-
pyramidal neurons.
Thus, the primary visual cortex occupies about 21 cm2 in each cerebral hemisphere.
Area 17 in young adults has about 35,000 neurons per mm3.
The primary visual cortex (Area 17 / V1) is thin, averages 1,8 mm in thickness, and
sums up to about 3% (range 2-4%) of the entire cerebral cortex. Although it resembles
other cortical areas, being arranged in six layers (I to VI), extensive quantitative analyses
and correlation studies in humans have identified at least ten layers in the primary visual
1687
cortex: layer I, II, III, IVa, IVb, IVc, Va, Vb, VIa and VIb. Layer IVc, in turn, is divisible
into IVc-α and IVc-β. Neurons in each layer have a distinctive size, shape, density, and
response to visual stimuli (Zilles et al., 1986; Glickstein, 1988; Zeki et al., 1991; Zilles,
1995, 2004). The input to area 17 from the lateral geniculate nucleus terminates
predominantly in IV A and IV C (Paxinos, 1990; Lee et al., 2000).
Other thalamic afferents from the inferior pulvinar nucleus and the intralaminar
group pass to layers I and IV. Geniculocortical fibres terminate in alternating bands.
Axons from the geniculate lamina which receives information from the ipsilateral eye
(laminae 2, 3 and 5) are segregated from those of laminae which receive input from the
contralateral eye (laminae 1, 4 and 6).
Neurons within layer IV C are monocular, i.e., they respond to stimulation of either
the ipsilateral or contralateral eye, but not both.
This horizontal segregation forms the anatomical basis of the ocular dominance
column in that neurons encountered in a vertical strip from below the pia to the white
matter, although binocular outside layer IV, exhibit a preference for stimulation of one
or the other eye (Lee et al., 2000; Crossman, 2008).
Thus, the primary visual cortex is arranged into columns oriented perpendicularly
to the cortical surface, extending from the cortical surface (under the pia mater) to the
subcortical white matter. Nerve cells, in a particular cortical column, are functionally
similar. Columns in the primary visual cortex include the ocular dominance columns,
the site where fibres relaying information from the ipsilateral or the contralateral eye
terminate, and the orientation columns, where nerve cells are responsive to visual stimuli
that have a comparable spatial orientation.
Layers II and III of the primary visual cortex also contain vertically oriented
aggregates of nerve cells that are responsive to colour.
The striate cortex, anatomically far more complex than the retina or lateral geniculate
body, does not have cells with concentric receptive fields. Cells of the striate cortex show
marked specificity in their response to restricted retinal stimulation (Hubel and Wiesel,
1959, 1963). A given cell responds vigorously when an appropriate stimulus is shone on
its receptive field, or moves across it, provided the stimulus is presented in a specific
orientation.
Thus, all cells within each column have the same receptive field axis of orientation.
The receptive field axis of orientation differs from one cell column to the next, and may
be vertical, horizontal or oblique. Thus for each stimulated area of the retina, each line
and each orientation of the stimulus, there is a particular set of “simple” striate cortical
cells that respond.
Changing any of the stimulus arrangements will cause an entirely new and different
population of “simple” striate cells to respond (Hubel and Wiesel, 1962).
“Complex” type cells, like “simple” cells, respond best to “slits”, “bars”, or “edges”,
provided the orientation is suitable. Unlike “simple” cells, these cells respond with
sustained firing as the slits of light are moved across the retina, preserving the same
receptive field axis of orientation (Hubel and Wiesel, 1962). There is a relationship
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21. Cerebral cortex
between the complexity of response and the position of cells in relation to the cortical
laminae. Simple cells are mainly in layer IV and complex and hypercomplex cells
predominate in either layers II and III or layers V and VI.
Since columns of cells constitute the fundamental functional units of the cortex, each
small region of the visual field must be represented in the striate cortex many times, in
column after column of cells with different receptive field orientation.
The receptive fields of all binocularly influenced cortical cells occupy corresponding
sites in the two retinas. About 80% of the cells in the striate cortex are influenced
independently by the two eyes (Hubel and Wiesel, 1962).
Considerable evidence indicates that early visual experience can change the
distribution of the selective orientation of striate cortical units (Hirsch and Spinelli, 1970;
Blakemore and Cooper, 1970).
Cells of the striate cortex in kittens with controlled visual deprivation appear to adapt
functionally to the restricted visual orientations to which they have exposed during the
early critical period (Pettigrew et al., 1973).
Studies of controlled, visually deprived kittens, that permitted normal binocular
viewing after the critical period, show a dramatic increase in the number of striate cells
which are binocularly activated (Spinelli et al., 1972).
The other major functional basis for visual cortical columnar organization is the
orientation column. Thus, an electrode passing through the depth of the cortex at right
angles to the plane from below the pia to the white matter, encounters neurons that
respond preferentially to either a stationary or a moving straight line of a given orientation
within the visual field. Cells with simple, complex and hypercomplex receptive fields
occur in area 17. Simple cells respond optimally to lines in a narrowly defined position.
Complex cells respond to lines anywhere within a receptive field, but with a specific
orientation. Hypercomplex cells are similar to complex cells except that the length of
the line or bar stimulus is also critical for an optimal response. Thus, the visual cortex
units are of two varieties: simple and complex. Simple units respond only to stimuli in
corresponding fixed retinal receptive fields. Complex and hypercomplex units are
connected to several simple cortical units. It is presumed that the complex units represent
an advanced stage in cortical integration.
Thus, the visual cortex is organized into units, and, for each unit, a particular
orientation of the stimulus is most effective. Some units respond only to vertically
oriented stripes, while others respond only to horizontally oriented stripes. Some units
respond at onset of illumination, while others respond at cessation of illumination.
Units that respond to the same stimulus and orientation are grouped together in
repeating units referred to as columns. Two general varieties of functional columns have
been described: ocular dominance and orientation columns. Thus, the striate cortex is
organized into vertical and horizontal columns. The vertical columnar system is
concerned with retinal position, line orientation, and ocular dominance. The horizontal
system segregates cells of different orders of complexity. Simple cells located in layer
IV are driven monocularly, while complex and hypercomplex cells, located in other
layers, are driven by impulses from both eyes (Afifi and Bergman, 2005).
1689
Ocular dominance columns are parallel columns arranged perpendicularly to the

cortical surface and reflect eye preference (right versus left) of cortical neurons. Alternating
ocular dominance columns are dominated by inputs from the left and right eye. Orientation
columns comprise a sequence of cells that have the same receptive field axis orientation
(Hubel and Wiesel, 1962; Hirsch and Spinelli, 1970; Pettigrew et al., 1973; Spinelli et al.,
1972; Afifi and Bergman, 2005). Visual units respond optionally to moving stimuli. Most
cortical units receive fibres from corresponding receptive fields in both retinas, thus
allowing for single-image vision of corresponding points in the two retinas. Thus, units in
the primary visual secondary areas are of the complex and hypercomplex types.
The output from the primary visual cortex. Ipsilateral corticocortical fibres pass
from area 17 to a variety of functional areas in areas 18 and 19 and in the parietal and
temporal cortices. Fibres from area 17 pass to area 18 (which contains visual areas V2,
V3 and V3a), area 19 (which contains V4), the posterior intraparietal and the parieto-
occipito areas, and to parts of the posterior temporal lobe, the middle temporal area and
the medial superior temporal area (Livingstone and Huber, 1984; Crossman, 2008).
The main output from the primary visual cortex follows two pathways or streams: a
dorsal stream to the occipitoparietal cortex (the “where” pathway) and a ventral stream
to the occipitotemporal cortex (the “what” pathway). Bilateral lesions in the “where”
pathway, result in the inability to direct the eyes to a certain point in the visual field
despite intact eye movements (Balint syndrome).
Balint’s syndrome consists of (1) an inability to look voluntarily into and to scan
the peripheral field, despite the fact that the eye movements are complete (psychic
paralysis of fixation or gaze); (2) a failure to precisely grasp or touch an object under
visual guidance, as though hand and eye were not coordinated (inappropriately called
optic ataxia); and (3) visual inattention (disorientation) affecting mainly the periphery of
the visual field, attention to other sensory stimuli being intact.
Bilateral lesions in the “what” pathway result in the inability of patients, with normal
visual perception, to comprehend the meaning of nonverbal visual stimuli (visual
agnosia).
Subcortical efferents of the striate cortex pass to the superior colliculus, pretectum
and parts of the brain stem reticular formation.
Projections to the striatum (notably, the tail of the caudate nucleus), and to the
pontine nuclei, are sparse.
Geniculo- and claustrocortical projections are reciprocated by prominent descending
projections, which arise in layer IV (Crossman, 2008).
Secondary visual cortex (V2)

Adjoining the primary visual cortex is an extrastriate cortex which consists of the
secondary and tertiary visual cortical areas. They include areas 18 and 19 of Brodmann
on the lateral and medial aspects of the hemisphere. Areas 20, 21, and 37 in the inferior
temporal cortex are also dedicated to visual information processing. Area 18 corresponds
to the second (V2) and area 19 to the third (V3) visual areas. V4, in humans, is probably
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21. Cerebral cortex
located in the inferior occipitotemporal area, in the region of the lingual or fusiform gyrus.
V5 in humans is probably located in area 19 of Brodmann. V2 like V1 is retinotopically
organized. V3 is associated with form, V4 with color, and V5 with motion.
Area 18, also termed the parastriate area, has connections with the primary visual
cortex and with area 19 in the occipital lobe through short association fibres. Area 18 has
connections with areas 18 and 19 in the contralateral cerebral hemisphere by way of
commissural fibres. Long association fibres connect area 18 with the frontal lobe
permitting this region to receive sensory, motor, and auditory impulses as well as those
from the insular and temporal lobes (Augustine, 2008). The importance of the existence
of long association fibres, that interrelate the frontal lobe with the occipital lobe, is evident
in a patient who has an injury in the middle frontal gyrus and saw stars and flashes of
light. This suggests that the occipital lobe was being stimulated when in fact the lesion
irritated fibres in the frontal lobe that interrelate the frontal and the occipital lobes
(Augustine, 2008).
Thus, the primary visual cortex projects to the visual association area where
information is processed and subsequently relayed to the tertiary visual areas (areas V3,
V4, and the middle temporal area) of the cortex. So, the major ipsilateral corticocortical
feedforward projection to V2 comes from V1. Areas 18 and 19 do not have a visible
stripe of fibres in layer IV. Area 18, the secondary visual cortex or area V2, surrounds
V1, connects with it, and lacks a specialized layer IV. More than 30 extrastriate
association areas are identifiable in the temporal, parietal and occipital lobes of primates
(Huck et al., 2002; Zilles, 2004).
Feedforward projections from V2 pass to several other visual areas (and are
reciprocated by feedback connections) including the third visual area (V3) and its various
subdivisions (V3 / V3 d; VP / V3v; V3a), the fourth visual area (V4), areas in the temporal
and parietal association cortices, and the frontal eye field (Crossman, 2008).
Thus, primary visual area 17 sends many fibres to the extrastriate visual area 18 and
area 19 that have an especially well-differentiated system of intracortical and myelinated
fibres. Area 18, in turn, has reciprocal connections with other extrastriate areas.
Thalamic afferents to V2 come from the lateral geniculate nucleus, the inferior and
lateral pulvinar nuclei and parts of the intralaminar group of nuclei. Subcortical efferents
arise predominantly in layers V and VI. They pass to the thalamus, claustrum, superior
colliculus, pretectum, brain stem reticular formation, striatum and pons.
As for area 17, the callosal connections of V2 are restricted predominantly to the
cortex, which contains the representation of the vertical meridian (Crossman, 2008).
Area 18 interprets, associates, and facilitates the understanding of impulses that reach
area 17. Information from area 18 in the dominant cerebral hemisphere correlates with
that from area 18 in the nondominant cerebral hemisphere. Area 18 participates in colour
vision in humans (Hurlbert, 2003). Area 18 and 19 in the parietal lobe are involved with
following of automatic eye movements. Stimulation of area 18 in humans yields
unformed images, wheels, flashing lights, streaks, flickering light, and coloured spots
(Fox et al., 1987; Zeki et al., 1991; Huck et al., 2002; Goodale and Westwood, 2004).
1691
Injury to area 18 will result in the loss of following eye movements towards the
contralateral side. Although the patient is still able to see because the primary visual
cortex is intact, they often present with a visual agnosia – the loss of power to recognize
the import of visual stimuli in the absence of visual defects.
Connections of the secondary visual cortex to the angular gyrus (area 39) play a role
in recognition of visual stimuli. Lesions interrupting this connection result in visual
agnosia (De Renzi, 2000).
The third visual area (V3)

It is a narrow strip adjoining the anterior margin of V2, probably still within area 18
of Brodmann. V3 has been subdivided into dorsal (V3 / V3d) and ventral (VP / V3v)
regions on the basis of its afferents from area V1, myeloarchitecture, callosal and
association connections, and receptive field properties (Zilles, 2004).
The dorsal subdivision receives afferent from V1, whereas the ventral does not
(Burkhalter and Bernardo, 1989).
Functionally, the dorsal part shows less wavelength selectivity, greater direction
selectivity and smaller receptive fields than does the ventral subdivision.
Both areas receive a feedforward projections from V2 and are interconnected by
association fibres.
A further visual area, area V3a, lies anterior to the dorsal subdivision of V3. It
receives afferent association connections from V1, V2, V3 / V3d and VP / V3v and has
a complex and irregular topographic organization.
All subdivisions project to diverse visual areas in the parietal and temporal cortices,
including V4, and to the frontal eye fields (Zilles, 2004; Crossman, 2008).
Thus, extrastriate area 19 is the most rostral part of the visual cortex in the occipital
lobe. This latter area is not homogenous but is divisible into a number of visual areas. It
is likely a tertiary visual area.
Current concepts of visual processing in inferior temporal and temporoparietal
cortices suggest that two parallel pathways (dorsal and ventral) emanate from occipital
lobe. The dorsal pathway, concerned primarily with visuospatial discrimination, project
from V1 and V2 to the superior temporal and surrounding parietotemporal areas and
ultimately to area 7a of the parietal cortex.
The fourth visual area (V4)

This visual area lies within area 19 anterior to the V3 complex. Visual area V4 is in
the collateral sulcus or lingual gyrus of the occipital lobe. It receives input from the
parvicellular layers of the lateral geniculate in nonhuman primates, and a major ipsilateral
feedforward projection from V2. In humans, this extrastriate visual area is specialized
for different aspects of object recognition including colour and shape. Colour selectivity
as well as orientation selectivity may be transmitted to V4 and bilateral damage causes
achromatopsia (Hurlbert, 2003; Goodale and Westwood, 2004; Zilles, 2004).
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21. Cerebral cortex
V4 is more complex than a simple colour discrimination area because it is also

involved in the discrimination of orientation, form and movement (Goodale and Milner,
1992; Goodale and Westwood, 2004; Crossman, 2008).
It sends a feedforward projection to the inferior temporal cortex and receives a
feedback projection.
It also connects with other visual areas that lie more dorsally in the temporal lobe,
and the parietal lobe. Thalamocortical connections are with the lateral and inferior
pulvinar and the intralaminar nuclei.
Other subcortical connections conform to the general pattern for all cortical areas.
Callosal connections are with the contralateral V4 and other occipital visual areas
(Glickstein and Whitteridge, 1987; Fox et al., 1987; De Yoe et al., 1994; Zilles, 2004;
Crossman, 2008).
Thus, afferents to areas 18 and 19 are mainly from the primary visual area (area 17)
but include some direct thalamic projections from the lateral geniculate nucleus and
pulvinar nucleus. The primary visual area projects bilaterally and reciprocally to areas
18 and 19. The projections from the pulvinar nucleus constitute important extrageniculate
links to the visual cortex (Burkhalter and Bernardo, 1989).
Outputs from areas 18 and 19 project to the posterior parietal cortex (area 7) and to
the inferotemporal cortex (areas 20 and 21) (Livingstone and Hubel, 1984; Ishai et al.,
2000; Hurlbert, 2003; Lennie, 2003; Zilles, 2004).
The projection to area 7 is concerned with stereopsis (depth perception and
movement (Goodale and Milner, 1992; Goodale and Westwood, 2004). The infero-
temporal projection is concerned with the analysis of form and colours (Hurlbert, 2003).
The fourth visual area, V4, is a key relay station for the ventral pathway, which is related
to perception and object recognition. Its connections pass sequentially along the inferior
temporal gyrus in a feedforward manner, from V4 to the posterior, intermediate, and then
anterior, inferior temporal cortices. Ultimately they feed into the temporal polar and medial
temporal areas and so interface with the limbic system (Burkhalter and Bernardo, 1989; De
Yoe et al., 1994; Goodale and Westwood, 2004; Zilles, 2004; Crossman, 2008).
Thus, information travels first to the primary visual cortex and then relays in serial
fashion through a series of increasingly complex visual association areas (the extrastriate
visual area).
This “what” and “where” model of vision in nonhuman primates includes a ventral
stream (“what” path), the occipito-temporo-prefrontal path for perception, identification,
and recognition of visually presented objects (object vision, faces, and words) based on
features like colour, texture and contours. The occipitotemporal cortex includes
Brodmann’s areas 19 and 37. Area 37, behind area 21, at the occipitotemporal junction
contains modules devoted to recognition of faces.
Colour vision is localized inferiorly in the inferior occipitotemporal cortex (V4). No
colour representation is found in the superior association visual cortex. Thus, in unilateral
inferior association visual cortex lesions, the patient loses colour vision in the contralateral
half of field (central hemiachromatopsia).
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Cerebral achromatopsia results from bilateral damage to the V4/V4 α region of the
colour centre. If patients experience complete ablation of V4, they lose colour vision in
the entire visual field. Thus, cerebral achromatopsia arises following brain damage to
V4/V4 α located in the ventral medial region of the occipital lobe, typically caused by a
tumor, haemorrhage, or some sort of brain trauma. Because V4 is located in the vicinity
of the fusiform gyrus and the lingual gyrus, known to process faces, the comorbidity
between achromatopsia and prosopagnosia is extremely high (Kanwisher et al., 1997;
Bouvier and Engel, 2006).
In less extreme cases, known as dyschromatopsia, patients lose the ability to
perceive selective colour and / or colour constancy (Glickstein and Whitteridge, 1987;
Goodale and Milner, 1992; Bartels and Zeki, 2000; Bouvier and Engel, 2006).
The first cases of cerebral achromatopsia were reported by Verry in 1888. In
response to these patients, Verry introduced the concept of a “colour centre” in the brain.
Continued research confirmed the existence of a cortical region devoted to colour
processing. Thus, Meadows (1974) demonstrated a correlation between the cortical region
sensitive to colour and the damaged cortical regions in achromatopsic patients.
The dorsal stream (“where” path) or occipito-parieto-prefrontal path participates
in the appreciation of the spatial relations among objects (spatial vision) as well as for
the visual guidance of movements towards objects in visual space (Ungerleider and
Haxby, 1994).
The occipitoparietal cortex includes parts of Brodmann’s area 19 and area 7 from
the superior parietal lobule. The prefrontal part of these paths includes parts of the inferior
frontal gyrus corresponding to Brodmann’s areas 45 and 47 as well as the dorsal part of
premotor area 6.
There seems to be some left hemisphere specialization or dominance for visual form
in the ventral stream. Evidence from neuropsychology, electrophysiology, and
neuroimaging suggests that there are specialized processing regions for specific categories
of visual objects (i.e., faces).
Face recognition is a biological necessity and unique behavioral capacity that
requires a dedicated neuronal system that can be selectively damaged (Kanwisher and
Yovel, 2006).
Prosopagnosia is a deficit in the general capacity to discriminate between very
similar exemplars in a class of objects due to damage to neural representations of objects
that are widely distributed and overlapping (Haxby et al., 2001). Prosopagnosia is the
result of injury to a specialized neural system that develops with experience and is
required when distinguishing between subtle differences within a category of complex
visual material (Gauthier et al., 1999; Riesenhuber and Poggio, 2000; Serre et al., 2007).
Loss of face recognition and colour vision usually coexist because of the proximity of
the areas responsible for them (Gorno-Tempini et al., 2001; Hadjikhani and de Gelder,
2002; Hubel et al., 2003; Schiltz et al., 2006).
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21. Cerebral cortex
The fifth visual area (V5)

Another extrastriate visual area is visual area V5 in the ascending limb of the inferior
temporal sulcus. It is found in nonhuman primates towards the posterior end of the
superior temporal sulcus. It receives ipsilateral association connections from area V1,
V2, V3 and V4, in a topographically organized way.
Other lesser projections are received from widespread visual areas in the temporal
and parieto-occipital lobes and from the frontal eye field. This area in nonhuman primates
receives input from the magnocellular layers of the lateral geniculate nucleus by way of
the primary visual cortex. There may be direct projections from V1 to V5 or indirect to
V5 through V2 or V3.
V5 is primarily a movement detection or discrimination area, and contains a high
proportion of movement-sensitive, direction-selective cells. This motion pathway likely
extends beyond the middle temporal area to the medial superior temporal area, the parietal
lobe and the frontal eye fields (Goodale and Milner, 1992; Huck et al., 2002; Schneider
et al., 2004; Goodale and Westwood, 2004; Zilles, 2004;).
Feedforward projections of V5 go to surrounding temporal and parietal areas, and
to the frontal eye field. Thalamic connections are with the lateral and inferior pulvinar
and intralaminar group of nuclei. Other connections follow the general pattern of all
neocortical areas (Crossman, 2008).
Patients with lesions in this area may have a selective disturbance of movement
vision such as visual tracking. Bilateral lesions of the fifth visual area (V5) are associated
with a defect in visual motion perception (akinetopsia). This visual area in humans is
comparable in many ways to area MT in nonhuman primates.
Preoccipital areas involved in following ocular movements

The posterior parietal eye field corresponds to areas 39, 40, 19 and 18 of Brodmann.
This area triggers reflexive, visually guided saccades. It exerts its influence on saccadic
eye movements via its connections to the frontal eye field or directly to the superior
colliculus.
Thus, in the parietal lobe and in part of the occipital lobe, is an area involved in
following of the automatic ocular movements (Morrow and Sharpe, 1990; Pierrot-
Deseilligny and Gaymard, 1990; Pierrot-Deseilligny et al., 1995; Lekwuw and Barnes,
1996; Afifi and Bergman, 2005).
The posterior parietal cortex (the cortex in the posterior region of the intraparietal
sulcus and the adjacent superior parietal lobule) is activated by the primary visual cortex
during saccades for which there is a visual goal.
According to Augustine (2008), in the parietal lobe and in part of the occipital lobe,
is an area involved in the following of automatic ocular movements.
In the parietal lobe, this area corresponds to Brodmann’s area 19, while in the
occipital lobe it corresponds to Brodmann’s area 18. One is often not aware of these
movements as the eyes fix on a moving object. These ocular movements are
extrapyramidal in type and obviously significant as emphasized by the presence of two
1695
different cortical fields (the frontal eye fields for voluntary ocular movement and
preoccipital areas for following movements of the eyes) as well as two separate
extrapyramidal paths for their production. (Paus, 1996; Pandya and Yeterian, 1996; Milea
et al., 2002).
Cortical stimulation of parietal area 19 and occipital area 18 yields deviation of the
eyes upward, downward, or horizontal deviations. If the upper part of area 19, or the
lower part of area 18, is stimulated, upward deviation of the eyes will occur. Presumably,
there are connections from these two regions of the parietal and occipital lobes,
respectively, to the tegmentum of the midbrain by way of the internal corticotectal fibres.
In particular, these fibres pass the rostromedial part of the superior colliculus (Lobel
et al., 2001; Schüz and Miller, 2002; Zilles, 2004; Augustine, 2008).
From the rostromedial superior colliculus, tecto-oculomotor fibres pass to the
oculomotor and trochlear nuclear complexes of the midbrain. They end on neurons that
supply muscles that raise the lids and lift the eyes in an upward direction (Jampel, 1975;
King et al., 1976; Bortolami et al., 1977; Augustine et al., 1981; Leigh and Zee, 2006;
Augustine, 2008).
If the upper part of area 18, or the lower part of area 19, is stimulated, downward
deviation of the eyes will occur. The anatomic basis is by way of internal corticotectal
fibres that pass from the parietal and occipital lobes to the caudolateral part of the superior
colliculus. From this region, tecto-oculomotor fibres pass to the oculomotor nucleus,
particularly to these neurons that supply muscles that lower the eyes (Tijssen et al., 1991;
Augustine, 2008).
If the middle part of parietal area 18 and the middle part of occipital area 19 are
stimulated, horizontal deviation of the eyes will occur. In this situation, corticotegmental
paths pass from the cerebral cortex to the tegmentum of the midbrain. From there,
connection fibres project to the contralateral abducens nucleus and the abducens reticular
gray matter in order to initiate a horizontal deviation of the eyes (King et al., 1976;
Augustine et al., 1981; Leigh and Zee, 2006).
Thus, projections from area 18 and 19 also reach the frontal eye fields (area 8 of
Brodmann) in the frontal lobe, as well as the superior colliculus and motor nuclei of the
extraocular muscles. These projections play a key role in conjugate eye movement
induced by visual stimuli (visual pursuit). However, the connections and functional
aspects of ocular movements are exceedingly complex.
Patients with lesions in the posterior parietal eye field lose reflexive visually guided
saccades but are able to move their eyes in response to command (intentional saccades).
Saccadic movements are fast eye movements with rapid fixation of vision from
point to point with no interest in the points in between. Positron emission tomography
(PET) scans and lesion studies indicate that the cerebral areas most important for saccadic
control are: (1) the posterior parietal cortex; and (2) the frontal premotor cortex (Pierrot-
Deseilligny et al., 1995; Lekwuwa and Barnes, 1996).
Frontal eye field. Three areas in the frontal lobe participate in saccadic processing:
(1) the frontal eye field (area 8 of Brodmann); (2) the dorsolateral prefrontal cortex (area
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21. Cerebral cortex
46 of Brodmann); and (3) the supplementary eye field (anterior part of the supplementary
motor area). The frontal and supplementary eye fields are activated during all types of
saccadic movements. The dorsolateral prefrontal cortex is activated during fixation.
The frontal eye field located in the middle frontal gyrus, anterior to or in the anterior
portion of the motor strip, corresponds to area 8 of Brodmann and the immediately
adjacent cortex. This field triggers intentional (voluntary) saccades to visible targets in
the visual environment, and subserves intentional exploration of the visual environment
(Pierrot-Deseilligny et al., 1995; Lekwuwa and Barnes, 1996). The frontal eye field
receives multiple cortical inputs, from the parietooccipital cortex, supplementary eye
fields, and the prefrontal cortex (Brodmann’s area, 46). The frontal eye field elicits
intentional (voluntary) saccades through connections to the nuclei of the extraocular
muscles in the brain stem.
The pathway from the frontal eye field to the nuclei of extraocular movements is
not direct but involves multiple brain stem reticular nuclei, including the superior
colliculus, the interstitial nucleus of the longitudinal fasciculus, and the paramedian
pontine reticular formation.
This frontal eye field can be functionally subdivided into different sectors depending
on the direction of the eye movements that can be elicited from it.
Transcranial magnetic stimulation in humans has permitted the delimitation of the
frontal eye field within an area that comprises portions of the dorsolateral prefrontal and
premotor cortex (Chouinard et al., 2003; Pierrot-Deseiligny et al., 2004).
Auditory cortex
Primary auditory cortex

The temporal lobe has three parallel gyri on the lateral surface: superior
(Brodmann’s area 22), middle (Brodmann’s area 21), and inferior (Brodmann’s area
20). Thus, its lateral surface is divided into three parallel gyri by the superior temporal
and inferior temporal sulci (Fig. 21.32). The superior temporal sulcus begins near the
temporal pole and slopes slightly up and backwards parallel to the posterior ramus of the
lateral sulcus. Its end curves up into the parietal lobe.
The inferior temporal sulcus is subjacent and parallel to the superior one and is often
broken into two or three short sulci. Its posterior end also ascends into the parietal lobe,
posterior and parallel to the upturned end of the superior sulcus. The temporal lobe is
inferior to the lateral fissure.
The cortex of the medial temporal lobe includes major subdivisions of the limbic
system, such as the hippocampus and entorhinal cortex. Areas of neocortex adjacent to
these limbic regions are grouped together as the medial temporal association cortex.
Ferrier (1876; 1878; 1890), a British physician, is credited with localizing the primary
auditory cortex of monkeys to the superior temporal gyrus. This localization was not
accepted by his contemporaries.
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Fig. 21.32. Superolateral surface of the left cerebral hemisphere including the boundaries,
major sulci and gyri of the temporal and occipital lobes.
The primary auditory cortex (Brodmann’s areas 41 and 42) resides deep in the
lateral fissure of Sylvius, in the hidden superior surface of the superior temporal gyrus,
containing the transverse temporal gyri of Heschl, and in the floor of the lateral fissure.
Thus, two transversely-oriented gyri, the anterior and posterior transverse temporal
gyri are continuous with the superior temporal gyrus but folded and hidden from view
when one observes the lateral surface of the cerebral hemisphere. The anterior transverse
temporal gyrus (of Heschl), lying in depth of the lateral sulcus and corresponding to
Brodmann’s area 41 (Fig. 21.33) is the primary auditory cortex or A I. Recordings of
primary evoked responses to auditory stimuli during surgery for epilepsy provide
evidence for a restricted portion of Heschl’s gyrus as the primary auditory area (Heffner,
1987; Hocherman and Yirimiya, 1990; Liegeois-Chauvel et al., 1994).
However, the two transverse temporal gyri are buried in the lateral sylvian sulcus,
covered by parts of the frontal and parietal opercula, and continuous with the superior
temporal gyrus. Caudal to the transverse temporal gyri is a smooth area, the planum
temporale, which is usually larger on the left side than on the right (Fig. 21.34).
The temporal operculum houses the primary auditory cortex. This is coextensive
with the granular area 41 in the transverse temporal gyri. Surrounding areas constitute
the auditory association cortex (Fig. 21.35).
The length and surface area of the left primary auditory cortex is greater than the
right in newborns and adults.
The circular insular sulcus limits area 41 medially while laterally area 43 does not
reach the temporal operculum.
Thus, the primary auditory cortex (Brodmann’s area 41 or A I) is located in the first
(anterior) transverse temporal gyrus but many extend into the second (posterior) gyrus.
1698
21. Cerebral cortex
Fig. 21.33. Cytoarchitectural map showing Brodmann areas on the lateral surface of the hemisphere (modified after
Brodmann K, from Carpenter MB, Sutin J: Human Neuroanatomy. Baltimore, Williams and Wilkins, 1983).
Fig. 21.34. The organization of auditory cortical areas. Location and interconnections of auditory cortical areas
(A) and of the granular cortex in area 41 (B), and the orthogonal isofrequency and binaural responses columns in the
primary auditory cortex (detail from A) (after Henkel, 2006).
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Fig. 21.35. Modern rendition of the

cytoarchitectural map showing
Brodmann’s areas on the lateral
surface of the human brain (figure
provided by Mark Dubin, University
of Colorado, 2006).
Cytoarchitecturally, area 41 encompasses the granular cortex, with its well-

developed layer IV containing small granule cells and densely packed small pyramidal
cells in layer VI.
Adjacent to the granular cortex in the second transverse gyrus and planum temporale
is area 42, which constitutes the secondary auditory cortex (Yost, 1994).
Since studies of the somesthetic and visual cortex indicate that a vertical column of
cells constitutes the elementary functional unit, it might be expected that a similar
arrangement would exist in the auditory cortex. Thus, a study in anaesthetized cats has
indicated that: (1) units responsive to noise bursts are randomly distributed; (2) different
regions to a high or low proportion of click stimuli do not follow the direction of vertical
columns; and (3) narrowly tuned units aligned with vertical columns tend to occur in
clusters (Abeles and Goldstein, 1970).
Microelectrode studies of the auditory cortex in cats and monkeys have revealed a
rather precise tonotopic organization (Merzenich and Brugge, 1973; Merzenich et al.,
1973). Best frequencies in the full auditory range for monkeys were represented in an
orderly fashion in the primary auditory area in a cytoarchitectonic field coextensive with
the koniocortex. Lowest frequencies were represented rostrally and laterally, whereas
highest frequencies were found caudally and medially.
In monkeys, the primary auditory cortex is surrounded by a belt of auditory cortex
which cytoarchitectonically uniform and can be parcelled into several divisions. This
cortical belt, which appears to represent the secondary auditory area, has been divided
topographically into three main areas designated as the rostrolateral, lateral and
caudomedial fields.
Thus, column cells in the auditory cortex share the same functional properties.
Columnar organization is thus based on its frequency stripes, each stripe responding to a
particular tonal frequency.
The primary auditory cortex is arranged into two dimensional, alternating, vertically
oriented columns of neurons. One dimension of the auditory cortex is composed of
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21. Cerebral cortex
frequency columns. The cells in each frequency column respond to an auditory stimulus
of a particular frequency. So, cells responding to low frequencies reside in the frequency
columns located in the rostral extent of the transverse temporal gyri of Heschl, whereas
frequency columns containing cells responding to gradually higher frequencies are lined
up in sequence towards the caudal extent of the primary auditory cortex.
The other dimension of the auditory cortex is composed of alternating binaural
columns. There are two types of binaural columns: summation columns and suppression
columns. The neurons residing in the summation columns respond to an auditory stimulus
that stimulates both ears simultaneously.
In contrast, the neurons in the suppression columns respond maximally to an auditory
stimulus that stimulates only one ear, but respond minimally when the auditory stimulus
stimulates both ears (Patestas and Gartner, 2008).
The primary auditory cortex of each side receives information from both ears by way
of the medial geniculate body of the thalamus, and then sends projections to the contralateral
side via the corpus callosum. Area 41 is also reciprocally connected with the anterior division,
and area 42 with the posterior division of the medial geniculate body.
The primary auditory cortex receives fibres predominantly from the contralateral side.
Orderly projections from neurons of the medial geniculate body to the primary
auditory cortex are termed thalamotemporal projections or acoustic radiations that
reach the temporal lobe through the sublenticular part of the internal capsule. Auditory
fibres originate in the peripheral organ of Corti (Fig. 21.36) and establish neural synapses
in the neuraxis, both homolateral and contralateral to their side of origin before reaching
the medial geniculate nucleus of the thalamus (Altschuler et al., 1986, 1991; Pickles,
1988; Webster et al., 1992).
Physiologic studies of the primary auditory cortex have revealed that it does not
play a major role in sound frequency discrimination but rather in the temporal pattern of
acoustic stimuli. Sounds are heard in the primary auditory cortex and pattern for tones of
different pitch exist here in nonhuman primates and, presumably, also in human.
Frequency discrimination of sound is a function of subcortical acoustic structures.
The optimal stimulus that fires auditory cortical units seems to be a changing frequency
of sound stimuli rather than a steady-frequency stimulus (Webster et al., 1992; Yost,
1994).
One of the characteristic features of the auditory system is its tonotopic localization.
The tonotopic localization present in the cochlea appears to be preserved through all of
the relay nuclei of the auditory system to levels of the inferior colliculus (Neff, 1961;
Rose et al., 1963; Whitfield, 1977). At higher levels of the auditory system there is an
increasing proportion of neural elements not directly concerned with the parameter of
stimulus frequency, even though they respond to complex sounds (i.e., noise click)
covering broad bands of the audible spectrum (Ades, 1959).
The tonotopic organization of constituent cells of the cortical layers and incoming
afferent fibres from a series of orderly isofrequency columns extend through the primary
auditory cortex as long stripes. High frequencies are represented medially and low
frequencies laterally.
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Fig. 21.36. Ascending central auditory pathways. Monoaural pathways , binaural pathways, and other connections. A I
and A II, primary and secondary auditory cortices; H, high frequencies; L, low frequencies (after Henkel, 2006).
Single-cell responses are to single tones of a narrow frequency band. Cells in single
vertical electrode penetrations share an optimum frequency response.
The series of stripes so formed have one subcomponent composed of cells excited
by stimulation of both ears alternating with a subcomponent composed of cells excited
by the contralateral ear and inhibited by the ipsilateral ear (Webster et al., 1992; Yost,
1994; Henkel, 2006).
In the cerebral cortex two areas showing tonotopic localization have been defined
in cats by determining the loci of potentials evoked in response to stimulation of nerve
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21. Cerebral cortex
fibres in the cochlea, or different sound frequencies (Woolsey and Walzl, 1942; Ades,
1943, 1959). In the more dorsal area, referred to as auditory area I (A I), the basal coils
of the cochlea (high frequencies) are represented rostrally, and the apical region of the
cochlea (low frequencies) caudally. In the more ventral auditory area (A II) the tonotopic
localization is reversed. A third cortical zone designated PE (i.e., posterior ectosylvian
area) lies posterior to auditory areas I and II and appears to be related functionally to
auditory area I.
Anatomical studies of ablations of these auditory areas have provided information
concerning the origin of afferent fibres from the medial geniculate body (Rose and
Woolsey, 1949, 1958).
Auditory areas I and II have also been identified in monkeys (Ades and Felder, 1942;
Pribram et al., 1954). In chimpanzees, tones of low frequency are represented
anterolaterally, while tones of high frequency are represented posteromedially (Bailey et
al., 1943).
Stimulation of the cortical areas in the temporal lobe near the primary auditory area
(i.e., areas 42 and 22), in men, produces sounds described as the noise of a cricket, a bell
or a whistle. These sounds are elementary tones which may be high or low pitched,
continuous or interrupted, but are always devoid of complicated or changing qualities
(Penfiled and Rasmussen, 1950). Most of these auditory responses are referred to the
contralateral ear. The largest and most important fibre crossing is in the trapezoid body
at the level of the cochlear nuclei, but others also are present, including fibres from
auditory cortical areas that cross in the corpus callosum (Mettler, 1932).
Stimulation of the primary auditory cortex produces crude auditory sensations such
as buzzing, humming, or knocking. Such sensations are clinically referred to as tinnitus.
Physiological studies (Woolsey and Walzl, 1942; Ades and Brookhart, 1950;
Rosenzweig, 1954) indicate that each cochlea is represented bilaterally in the auditory
cortex, although some slight differences exist between the two sides. Thus, when the
sound is presented on one side, the cortical response is greatest in the contralateral
hemisphere. If the sound is presented in a median plane, the cortical activity in the two
hemispheres is equal.
Because audition is represented bilaterally at a cortical level, unilateral lesions of
the auditory cortex cause impairment in sound localization in space and diminution of
hearing bilaterally, but more often contralaterally.
According to Penfield and Evans (1934), the removal of one temporal lobe impairs
sound localization on the opposite side, especially judgment of distance of sound.
Clinically, unilateral lesions of the auditory cortex are difficult to recognize.
Experimental studies indicate that bilateral ablations of auditory areas I, II and PE
in cats do not abolish auditory localization of sound in space, although discriminations
of this kind are impaired (Neff et al., 1956; Neff and Diamond, 1958). Sound localization
in space is most critically impaired by bilateral ablations of A I (Strominger, 1969).
Bilateral ablations of the auditory cortical areas have little or no effect on the ability
of cats to discriminate changes in frequency (Meyer and Woolsey, 1952; Butler et al.,
1957; Neff and Diamond, 1958).
1703
Meyer and Woolsey (1952) reported that following bilateral ablations of auditory
areas I, II and PE, and somatic area II, cats could not relearn to discriminate changes in
frequency, but could discriminate changes in sound intensity. The ability to localize sound
in space is not affected by a section of the corpus callosum, is affected very little by a
section of the commissure of the inferior colliculus and is severely affected by a section
of the trapezoid body (Neff and Diamond, 1958; Jerger, 1960).
Neurons in each medial geniculate body project fibres to layers IIIb and IV of the
auditory cortex. Area 41 in sensorial area of the koniocortex with layers II-IV of densely
arranged small neurons surrounded by fields with large and medium-sized IIIc pyramidal
neurons.
The primary auditory cortex is connected with the primary (unimodal) association
auditory cortex. Other important connections include the auditory cortex of the
contralateral hemisphere, the primary somesthetic cortex, frontal eye fields, Broca’s area
of speech in the frontal lobe, and the medial geniculate nucleus. Thus, the auditory cortex
interconnects with the prefrontal cortex, though the projections from A I are small.
Generally, posterior parts of the operculum project to areas 8 and 9. Central parts project
to areas 8, 9 and 46. More anterior regions project to areas 9 and 46, to area 12 on the
orbital surface of the hemisphere, and to the anterior cingulate gyrus on the medial
surface. Contralateral corticocortical connections are with the same and adjacent regions
in the other hemisphere.
Onward connections of the auditory association pathway converge with those of the
other sensory association pathways in cortical regions within the superior temporal sulcus
(Pickles, 1988; Webster et al., 1992; Yost, 1994; Crossman, 2008).
Via its projection to the medial geniculate body in the thalamus, the primary auditory
cortex controls its own input by changing the excitability of medial geniculate neurons.
Auditory association cortex

Adjacent to the primary auditory cortex is the auditory association cortex
(Brodmann’s area 22). It is located mainly in the posterior portion of the superior temporal
gyrus and is unimodal. It comprises the area adjacent to Heschl’s gyri in the superior
temporal gyrus, including the posterior portion of the floor of the sylvian fissure (the
planum temporale). It is connected to the primary auditory cortex by the arcuate
fascicules. Area 22 includes a part of the planum temporale and the posterior portion of
the superior temporal gyrus. It receives connections from the primary auditory cortex, as
well as visual and somesthetic information. This speech receptive area, known as
Wernicke’s area, may be as much as seven times larger on the left side then on the right.
Thus, the auditory association cortex is connected via the anterior commissure with
the prefrontal cortex and via the corpus callosum with the prefrontal, premotor, parietal,
and cingulate cortices. This area is concerned with the comprehension of spoken sound.
Area 22 in the dominant hemisphere is known as Wernicke’s area. Lesions in this area
are associated with a receptive type of aphasia, a disorder of communication characterized
by the inability of the patient to comprehend spoken words. In such cases, comprehension
1704
21. Cerebral cortex
of speech sound is impaired but discrimination of nonverbal sound is largely unaffected.

The higher association area of the auditory cortex also extends into the inferior parietal
lobule. This lobule is made up of the angular gyrus (area 39) and supramarginal gyrus (area
40). These two areas are important in reading and writing and are sometimes included in
the Wernicke area (Webster et al., 1992; Yost, 1994; Afifi and Bergman, 2005).
The auditory association cortex in the nondominant (right) hemisphere is specialised
for nonspeech auditory information, such as environmental sounds, musical melodies,
and tonal qualities of sound (prosody).
Bilateral lesions in the auditory association cortices result in the inability to recognize
sounds (auditory agnosia) in the presence of normal hearing alertness and intelligence
(Altschuler et al., 1991; Yost, 1994; Afifi and Bergman, 2005).
Brodmann’s areas 44 and 45 are known as the Broca area for expressive speech and
language. They are located in the pars opercularis and pars triangularis of the inferior
frontal gyrus. The major pathway connecting these areas with the primary and association
auditory cortex is the arcuate fasciculus.
If areas 44 and 45 are damaged along with other motor cortices on the left side by a
stroke involving branches of the middle cerebral artery, the result is Broca’s aphasia. In
this disorder, speech is nonfluent, but comprehension of verbal and nonverbal sounds is
largely unimpaired (Henkel, 2006).
Disconnection of the auditory association cortex (area 22) from the primary auditory
cortex (areas 41 and 42) results in a condition known as pure word deafness,
characterized by poor comprehension of spoken language and poor repetition with intact
comprehension of written language. Thus, Brodmann’s area 22, bordering the primary
auditory area and presenting typical six-layered isocortex, receives fibres from areas 41
and 42 and has connections with areas of the parietal, occipital, and insular cortex (Bailey
et al., 1943; Sugar et al., 1948, 1950).
Lesions of area 22 in the dominant hemisphere, or bilateral lesions, produce word
deafness or sensory aphasia. This form of sensory aphasia usually is associated with
lesions in the posterior part of area 22. Although patients with these lesions can hear,
they cannot interpret the meaning of sounds, especially speech.
Area 21, the middle temporal cortex, is polysensory in men, and it connects with
auditory, somatosensory and visual cortical association pathways. The auditory
association areas of the superior temporal gyrus project in a complex ordered fashion to
the middle temporal gyrus, as does the parietal cortex.
The middle temporal gyrus connects with the frontal lobe: the most posterior parts
project to the posterior prefrontal cortex, areas 8 and 9, while intermediate regions connect
more interiorly with areas 9 and 46.
The middle temporal region has also connections with the anterior prefrontal areas
10, 11, 12, 14, 46, and with the medial surface of the frontal pole. Further forwards the
middle temporal region projects to the temporal pole and the entorhinal cortex.
Thalamic connections are with the pulvinar nuclei and intralaminar group.
Physiological convergence of different sensory modalities and many neurons respond to
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faces (Altschuler et al., 1991; Webster et al., 1992; Yost, 1994; Crossman, 2008). Lesions
of area 22 and part of area 21 of Brodmann have no effect on the perception of sound
and pure tone.
Area 20 is the higher visual association area. The posterior inferior temporal cortex
receives major ipsilateral corticocortical fibres from occipitotemporal visual areas,
notably V4.
The anterior inferior temporal cortex projects onto the temporal pole and to
paralimbic areas on the medial surface of the temporal pole.
Additional ipsilateral connections of the inferior temporal cortex are with the anterior
middle temporal cortex in the walls of the superior temporal gyrus, and with visual areas
of the parietotemporal cortex.
Unlike this, these are frontal lobe connections with area 46, with the orbitofrontal
cortex, and with the frontal eye field. Reciprocal thalamic connections are with the
pulvinar nuclei. Intralaminar connections are with the paracentral and central medial
nuclei. Callosal connections are between corresponding areas and the adjacent visual
association areas of each hemisphere.
The cortex of the temporal pole receives feedforward projections from widespread
areas of the temporal association cortex which are immediately posterior to it. The dorsal
part receives predominantly auditory inputs from the anterior part of the superior temporal
gyrus. The inferior part receives visual inputs from the anterior area of the inferior
temporal cortex (Crossman, 2008).
Other ipsilateral connections are with the anterior insular, the posterior and medial
orbitofrontal, and the medial prefrontal cortices.
The temporal pole projects onwards into limbic and paralimbic areas.
Thalamic connections are mainly with the medial pulvinar nucleus, and with
intralaminar and midline nuclei.
Physiological responses of cells in this and more medial temporal cortices
correspond particularly to behavioral performance and to other recognition of high-level
aspects of social stimuli (Crossman, 2008).
Descending auditory pathways. Descending projections make reciprocal con-
nections throughout the auditory pathway. They form feedback loops that provide circuits
to modulate information processing from the peripheral level to the cortex (Yost, 1994;
Henkel, 2006). Thus, the auditory cortex projects to the medial geniculate nucleus and
nuclei of the inferior colliculus. The inferior colliculus projects to the periolivary nuclei,
which, in turn, send olivocochlear efferents to the cochlea. There are also descending
projections from the periolivary nuclei to the cochlear nuclei (Fig. 21.37).
Acoustic startle reflex, orientation, and attention. Reflexive and learned responses
to sound require sensory-motor integration. In addition to corticocortical interconnections
for the dissemination of auditory information, there is also an integration of auditory sensory
inputs with motor pathways in the brain stem (Henkel, 2006). Reticulospinal neurons in the
region of the lateral lemniscus have dendrites that sample lemniscal activity and are involved
in rapid acoustic startle reflex pathways (Webster et al., 1992; Henkel, 2006).
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21. Cerebral cortex
Fig. 21.37. Descending auditory

pathways that modulate sensory
processing at central and peripheral
auditory sites. The lateral
olivocochlear efferents and the
medial olivocochlear efferents A I
and A II primary and secondary
auditory (cortices) (after Henkel,
2006).
In addition, the deep layers of the superior colliculus receive auditory information
from the inferior colliculus and auditory areas (Fig. 21.38). The deep layer of the superior
colliculus integrate auditory, visual and somesthetic information and project to the brain
stem and cervical spinal cord nuclei via tectobulbospinal fibres, which are involved in
controlling the orientation of the head, eyes, and body to sound (Altschuler et al., 1986,
1991; Yost, 1994; Henkel, 2006).
In sum, bilateral destructions of the primary auditory cortex, the bordering area 22,
or both will result in cortical deafness (bilateral loss of hearing caused by bilateral cerebral
injuries).
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Fig. 21.38. The pathways that subserve auditory-motor integration involved in simple orientation to a novel auditory
stimulus. RF, reticular formation; PPRF, paramedian pontine reticular formation (after Henkel, 2006).
Although such patients have bilateral cerebral injury, others often have a reasonably
normal audiogram because tones of different pitch came to consciousness at a thalamic
level. Destruction of only one primary auditory cortex will lead to subtle auditory deficits.
Such patients have difficulty in localizing sounds in the contralateral auditory field and
perhaps a loss of discrimination of distorted, interrupted, or accelerated speech
(Augustine, 2008).
Destruction of the auditory association cortex (Wernicke’s region) in the left cerebral
hemisphere often fields a handicapping auditory receptive aphasia. Such patients have
normal hearing and a normal production of words (fluent). Yet they are unable to interpret
spoken sounds related to language or use words appropriately. Patients with injuries
limited to the parietal operculum are often indifferent to loud and unpleasant noise
(Eickhoff et al., 2006; Augustine, 2008).
The medial geniculate nucleus forms a small protuberance on the lower caudal
surface of the thalamus between the lateral geniculate body and the pulvinar. Low
frequencies are represented laterally and higher frequencies are represented medially.
Thus, the anterior division of the medial geniculate nucleus receives afferents from the
central nucleus of the inferior colliculus and projects to the primary auditory cortex.
The posterior division receives inputs from the pericentral nucleus of the inferior
colliculus and projects to secondary auditory cortex. This pathway may convey
information about moving or novel stimuli that direct auditory attention.
The medial (magnocellular) division receives afferents from the external nucleus
of the inferior colliculus and projects to association areas of the auditory cortex. The
1708
21. Cerebral cortex
medial division projects to temporal and parietal association areas and to the amygdala,
putamen and pallidum. So, this pathway may be a part of the reticular activating system
(Pickles, 1988; Webster et al., 1992; Henkel, 2006).
INSULA
Vicq d’Azyr was the first, in 1781, to express interest in the insula. He referred to it
as the „convolutions” situated between the sylvian fissure and the corpus callosum. In
1809 (a, b), Reil was the first to describe the insula.
In order to view the insula, a highly developed structure in the depth of the sylvian
fissure, the frontal, temporal, and parietal opercula have to be pulled apart, since this lobe
is submerged within and forms the floor of the lateral sulcus (Eickhoff et al., 2006).
The sulcus separating the insula from the operculae is referred to by different authors
as the periinsular sulcus, limiting sulcus, circuminsular sulcus, insular sulcus, or circular
sulcus.
The frontal operculum is between the anterior and ascending rami of the lateral
fissure, forming a triangular division of the inferior frontal gyrus.
The frontoparietal operculum, between the ascending and posterior rami of the lateral
fissure, consists of the posterior part of the inferior frontal gyrus, the lower ends of the
precentral and postcentral gyri, and the lower end of the anterior part of the inferior
parietal lobule (Varnavas and Grand, 1999).
The temporal operculum (Fig 21.39), below the posterior ramus of the lateral fissure,
is formed by the superior temporal and transverse temporal gyri.
Fig. 21.39 Coronal representation showing the somatotopy of the body in the primary motor cortex, which is located in
the precentral and anterior paracentral gyri (adapted from Penfield and Rasmussen, 1968).
1709
Fig. 21.40. Lateral view of the left cerebral hemisphere. The frontal and parietal opercula are removed, and the
temporal operculum is retracted to expose the insula and transverse temporal gyri (after Hains and Mihailoff, 2006).
The term “operculum” (Latin: lid, or covering) refers to the fact that these parts of
the respective lobes form a lid or cover for the insular lobe that forms the floor of the
lateral sulcus. Anteriorly, the inferior region of the insula adjoins the orbital part of the
inferior frontal gyrus. The insula is shaped like a pyramid. The summit of the pyramid is
in the insular apex. Its apex is beneath and near the anterior perforated substance where
the circular sulcus is deficient. The medial part of the apex is termed the limen insulae
(gyrus ambiens). The limen insulae (threshold to the insula) is the area in which the
inferior surface of the hemisphere is continuous with the insular cortex.
The insula is traversed by an obliquely directed central insular sulcus which divides
the insular surface into a large anterior and a small posterior part. The anterior part
exhibits transverse and accessory insular gyri and three or four short gyri (anterior,
middle, and posterior). The transverse and accessory insular gyri form the insular pole
located at the most anterior inferior aspect of the insula (Fig. 21.40).
The posterior part, located caudally to the central insular sulcus, is composed of the
anterior and posterior long gyri, separated by the postcentral insular sulcus (Ture et al.,
1999). The cortex of the insula is continuous with that of its opercula in the circular
sulcus. The insula is approximately coextensive with the subjacent claustrum and
putamen.
The insula is surrounded by the arcuate fasciculus which interconnects the frontal
and temporal lobes. The superior longitudinal fasciculus, located in the core of the
hemisphere, interconnects the frontal, parietal and occipital cortices. In the white matter
of the temporal lobe, fibres passing between the frontal and occipital areas make up the
inferior fronto-occipital fasciculus.
1710
21. Cerebral cortex
The insular cortex of the primates shows a sequential transition from allo- to meso-
and finally to isocortex (Brackhaus, 1940; Stephan, 1975; Jones and Burton, 1976 b;
Mesulam and Mufson, 1982 a, 1985). Its most retro-ventro-mesial portion located right
at the limen insulae is allocortical and forms the insular segment of the prepyriform
olfactory cortex. Around this allocortical core are arranged three concentric, approxi-
mately semicircular belts. The first, the agranular insula, bordering rostroventrally on the
allocortical central segment of the prepyriform cortex, is part of the lateral mesocortical
belt that runs along the lateral edge of the prepyriform-periamygdaloid allocortex; it is
bordered along its dorsal and caudal periphery by the dysgranular insular proisocortex,
which at its periphery dorsally and caudally is followed by the isocortical granular insula.
Thus, cytoarchitectonically, three zones are recognized within the insula. Anteriorly, and
extending caudally into the central insula, the cortex is agranular. It is surrounded by a
belt of dysgranular cortex, in which the laminae II and III can be recognized, and this, in
turn, is surrounded by an outer zone of homotypical granular cortex which extends to the
caudal limit of the insula.
Although the function of the insula is still somewhat unclear, it is known that the
insular cortex receives nociceptive and viscerosensory inputs.
Connections. The insula of primates is reciprocally connected to many surrounding
and to some more distal cortical areas and to the amygdala (Mesulam and Mufson, 1982
b, 1985; Mufson and Mesulam, 1982; Seleman and Goldman-Rakic, 1988; Cavada and
Goldman-Rakic, 1989 a). The connections of the postero-dorsal granular and adjacent
portion of the dysagranular insula are part of the transinsular somatosensory association
path (Mufson and Mesulam, 1982; Mesulam and Mufson, 1985; Friedman et al., 1986).
This region also seems to receive inputs from the auditory association cortex
(Mufson and Mesulam, 1982; Mesulam and Mufson, 1985). It is also connected to a
segment of the premotor cortex in area 6 representing the face, to the prefrontal cortex
below the principal sulcus (areas 45 and 46), the isocortical portion of the orbitofrontal
cortex, the cingulate cortex, and the precentral nucleus of the amygdala (Mesulam and
Mufson, 1982 b, 1985; Mufson and Mesulam, 1982).
Rostral to this somatosensory association area in the posterior insula there may be
in the dysagranular insula an area of multimodal convergence between gustatory and
other afferents emanating from the somatosensory and premotor areas concerned with
the representation of the face and mouth region (Sudakov et al., 1871; Mesulam and
Mufson, 1971). In monkeys, this dysgranular and agranular area receives afferents from
the parvocelullar portion of the ventroposterior medial thalamic nucleus, the thalamic
gustatory relay nucleus (Mufson and Mesulam, 1984; Mesulam and Mufson, 1985;
Pritchard et al., 1986), and its neurons respond to gustatory stimuli (Sudakov et al., 1971;
Yaxley et al., 1990).
The parvocelullar portion of the ventroposterior thalamic nucleus, also receives
viscerosensory afferents that, as they ascend from the brain stem through the ventromedial
thalamus, are difficult to disentangle from ascending taste pathways (Beckstead et al., 1980).
1711
In rodents, the insula receives afferents from the same thalamic relay nucleus as well
as more diverse gustatory and viscerosensory inputs from gustatory-viscerosensory relay
nuclei in the brain stem, the parabrachial nuclei (Saper, 1982 a, b; Shipley and Saunders,
1982; Cechetto and Saper, 1987; Krushel and van der Kooy, 1988; Allen et al., 1991).
The rostro-ventral dysgranular-agranular insular cortex of primates is reciprocally
connected with the gustatory opercular cortex, the mesocortical orbitofrontal cortex
(especially its caudolateral portion), the cingulate cortex, the olfactory prepyriform
allcortex, the temporopolar cortex, most of the amygdaloid nuclei, and the peri- and
entorhinal cortices (Mesulam and Mufson, 1982 b, 1985; Mufson and Mesulam, 1982;
Rolls, 1989 a).
In primates the postero-dorsal granular-dysgranular sector may predominantly
function as a unimodal somatosensory association area. This is supported by the fact that
this region is reciprocally connected with the somatosensory subdivision (area 7 b) of
the parietal association cortex (Cavada and Goldman-Rakic, 1989 a; Neal et al., 1990 b).
Conversely, the anteroventral dysgranular-agranular sector is likely to be multimodal
with emphasis on gustatory, viscerosensory, and olfactory modalities together with some
visceromotor representations.
Thus, the insular lobe in primates including humans has connection with the cerebral
cortex of the frontal lobe (orbital cortex, frontal operculum, lateral premotor cortex,
ventral granular cortex and medial area 6) and the parietal lobe (second somatosensory
area and retroinsular area of the parietal lobe). Ipsilateral cortical connections of the insula
are diverse. Somatosensory connections are with S I, S II and surrounding areas, area 5
of the superior parietal lobe and area 7b of the inferior parietal lobe.
There are also insular connections with the temporal lobe (temporal pole and superior
temporal sulcus) and the insular lobe (an abundance of local intra-insular connections)
(Augustine, 1985, 1996, 2008).
There are insular projections to subdivisions of the cingulate gyrus and to the lateral,
lateral basal, central, cortical and medial amygdaloid nuclei. There are also insular
connections with nonamygdaloid areas such as the perirhinal cortex, entorhinal cortex,
and the periamygdaloid cortex. The thalamic taste area projects fibres to the ipsilateral
insular-opercular cortex (Augustine, 1996; Ture et al., 1999; Augustine, 2008).
The insular cortex projects to almost all the nuclei of the amygdala (Amaral and
Insausti, 1992; Carmichael and Price, 1995; Stefanacci and Amaral, 2002).
Most of these projections originate in the rostral insular cortices, specifically the
agranular (Ia) and rostral aspects of the dysgranular (Id) division (Amaral and Insausti,
1992; Carmichael and Price, 1995; Mufson et al., 1997; Stefanacci and Amaral, 2000,
2002).
Projections from more caudal division of the insular cortex (caudal divisions of Id
and the granular insular cortex Ig) are less dense and less widespread (Amaral and
Insausti, 1992; Stefanacci and Amaral, 2000, 2002).
The parainsular cortex sends projections to the lateral nucleus, the basal nucleus, and
the accessory basal nucleus (Amaral and Insausti, 1992; Stefanacci and Amaral, 2000).
1712
21. Cerebral cortex
Most of the insular projections are directed towards the middle to caudal aspects of
the amygdala and originate predominantly in layer II and III, with a lesser contribution
from layer V (Stefanacci and Amaral, 2002).
The amygdaloidal complex returns projections throughout the insular cortex and to
the superficial and deep layers (Carmichael and Price, 1995). These connections are
generated by the lateral nucleus, the basal nucleus, the accessory basal nucleus, the medial
nucleus, the anterior cortical nucleus, the periamygdaloid cortex, and the anterior
amygdaloid area (Amaral and Price, 1984; Carmichael and Price, 1995).
Caudal regions of area Id and area Ig receive fewer projections from the amygdaloid
complex (Amaral and Price, 1984).
Thalamic afferents to the insula come from subdivisions of the ventral posterior
nucleus and of the medial geniculate body, from the oral and medial parts of the pulvinar,
the suprageniculate / nucleus limitans complex, the mediodorsal nucleus and the nuclei
of the intralaminar and midline groups. It appears that the anterior (agranular) cortex is
connected predominantly with the mediodorsal and ventroposterior nuclei, while the
posterior (granular) cortex is connected predominantly with the pulvinar and the ventral
posterior nuclei.
The other nuclear groups appear to connect with all areas (Crossman, 2008).
Thus, the anterior insular part connects with the frontal lobe, and the posterior part
connects with the parietal and temporal lobes. Lesion-based analysis has shown that
distructions of the left anterior part impair coordination of articulation and speech
production.
Functional aspects
In rats, single-cell recording in the insular cortex reveals a „viscerotopic”
organization. Thus, the taste and gastric representation lies next to the somatosensory
representation of the tongue and that for cardiopulmonary receptors next to that of the
trunk (Cechetto and Saper, 1987).
In primates and rodents, the anteroventral portion of the insula is concerned with
alimentary and related visceral functions (Hoffman and Rasmussen, 1953; Penfield and
Faulk, 1955).
There is also a visceromotor representation in the insula. In various animal species
including primates, stimulation of the insula affects a number of autonomic functions
such as gastric peristalsis, salivation, blood pressure, and heart rate as well as respiration
(Kwada, 1951; Hoffman and Rasmussen, 1953; Oppenheimer and Cechetto, 1990).
In humans, insular stimulation affects gastric peristalsis (Penfield and Faulk, 1955), as
well as heart rate and blood pressure. Bradycardia and falls in diastolic blood pressure was
more often elicited from left insular stimulations whereas tachycardic and pressure responses
occured more commonly with stimulation of the right insula (Oppenheimer et al., 1992).
Thus, the insular cortex has been implicated in the mediation of heart rate, in taste,
and in gustatory processing. Given the role of the amygdaloid complex in identifying
danger in the environment, connections with insular cortex may be a route for gustatory
and autonomic information to be processed by the amygdala.
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The insular cortex receives nociceptive and viscerosensory inputs. Thus, it has
visceral sensory and somatic sensory roles as well as visceral motor and somatic motor
roles.
According to Mufson et al. (1997) and Augustine (1996, 2008), the insula partici-
pates in the autonomic regulation of the gastrointestinal tract and the heart and is as well
functioning as a motor association area. This motor function includes a role in the
recovery of motor functions after stroke and in ocular movements.
The insular lobe also serves as a vestibular area and as a language area including
memory tasks related to language and auditory processing underlying speech. Other
insular functions include a possible role in the verbal component of memory and its role
in selective visual attention.
CORTICAL LANGUAGE AREAS
Wernicke’s area
Language is an arbitrary and abstract way to represent thought processes by means
of sentences and to present concepts or ideas by means of words.
Most components of the language system are located in the left hemisphere, which
is the dominant hemisphere for language in approximately 95% of humans.
Nearly all right-handers and about two-thirds of left-handers have such dominance.
Wernicke’s area, comprises an extensive region that includes the posterior part of
the superior temporal gyrus (Brodmann’s area 22) including planum temporale in the
floor of the sylvian fissure, and the parietooccipitotemporal junction area including the
angular gyrus (Brodmann’s area 39).
According to Augustine (2008), those parts of the superior temporal gyrus cor-
responding to Brodmann’s areas 42 and 22 constitute Wernicke’s region, an auditory
association region.
The upper surface of area 22, the planum temporale, is distinctly longer on the left
side (dominant hemisphere for language) in most people. Together, Heschl’s gyrus
(primary auditory cortex) and the anterior and posterior temporal planes are sometimes
referred to as the planum temporale.
Brodmann’s areas 42 and 22 constitute Wernicke’s region, an auditory association
region. In this region, sounds are appreciated, they become meaningful for understanding
language, and are interpreted as words. Thus, Wernicke’s area is concerned with the
comprehension of language. The superior temporal gyrus component of Wernicke’s area
(area 22) is concerned with comprehension of spoken language, whereas the angular
gyrus (area 39) and adjacent regions are concerned with comprehension of written
language. According to Afifi and Bergman (2005), spoken language is perceived in the
primary auditory area (Heschl’s gyrus, area 41 and 42) in the superior temporal gyrus
and transmitted to the adjacent located Wernicke’s area, where it is comprehended.
According to Haines and Mihailoff (2006), the gyri that are part of the Wernicke’s
area are the supramarginal gyrus – Brodmann’s area 40 – and the angular gyrus –
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21. Cerebral cortex
Brodmann’s area 39. Clinically, the Wernicke area is regarded as extending into the
temporal lobe and encompasses portions of Brodmann’s area 22 and some of area 21.
According to Patestas and Gartner (2008), Wernicke’s area consists of auditory
association cortex (part of Brodmann’s area 22), as well as parts of the supramarginal
and angular gyri (Brodmann’s areas 37, 39, and 40, usually in the left, dominant
hemisphere). Wernicke’s area is also referred to as the receptive (sensory, language area,
general interpretative area, or the gnostic area. It plays an important role in the
comprehension and formulation of language. When an individual reads and says the
words, the visual pathway relays the sensory visual input to the primary visual cortex
where the words are “seen”. The primary visual cortex transmits this input to the
association visual cortex where the significance of the words is determined. The visual
information is then relayed to Wernicke’s area where the words are comprehended, and
the creation of the words takes place. Wernicke’s area then projects to Broca’s area,
which dictates the motor activity necessary to produce the words.
Reading requires the perception of visual language stimuli by the occipital cortex,
followed by correlation with auditory language information, via the intermodal
association cortex of the angular gyrus. Writing involves the activation of motor neurons
projecting to the arm and hand.
In the right cerebral hemisphere this cortical area is an auditory association area
that serves to determine the emotional undertones of language. When we hear someone
speak, the person’s voice often reveals if he / she is happy, upset, angry, etc.
Although several areas in the left hemisphere are dominant in the reception,
programming and production of language function, corresponding areas in the right
hemisphere are metabolically active during speech. These areas are believed to be
concerned with the melodic function of speech (prosody). Lesions in such areas of the
right hemisphere render speech amelodic (aprosodic). Lesions in area 44 on the right
side result in a dull monotonic speech. Lesions in area 22 on the right side, on the other
hand, may lead to an inability of the patient to detect inflection of speech. Such patients
may be unable to differentiate whether a particular remark is intended as a statement or
as a question (Afifi and Bergman, 2005).
In right-handed people and in a majority of left-handers as well, clinical syndromes
of aphasia result from left hemisphere lesions. Rarely, aphasia may result from a right
hemisphere lesion in a right-handed patient, a phenomenon called crossed aphasia
(Bakar et al., 1996).
Broca’s area
Gall and Spurzheim (1809), based on their observations of skull shape, placed the
ability to speech and recall words in the inferior aspect of the frontal lobes. Bouillaud
(1825) hypothesized that the anterior lobes of the brain contained a centre for speech
production. Bouillaud even offered a prize to the first individual who reported a case with
loss of speech without lesion to the frontal lobes.
However, there were a number of studies that were real contributions to the
knowledge of the clinical phenomenology of aphasia. One is the description by Osborne,
1715
in 1833, of a highly educated patient with severe jargon aphasia who understood spoken
speech quite well and could read with understanding. His writing was only mildly
affected.
Lordat’s case, reported in 1843, is of a priest who after a stroke showed an almost
complete motor aphasia but steadily improved.
There is also Marcé’s paper, in 1856, dealing specifically with impairment in writing.
Marcé described a number of cases of agraphia within the setting of oral language
disturbances of varying severity and different types, and he postulated the existence of a
cerebral centre for writing distinct from the coordinating centre for oral speech.
There is, also, an important reference to receptive aphasia in the 1843 monograph
of Lordat.
The association of aphasia with right hemiplegia is usually ascribed by Broca (1861,
1863), but this distinction is often dimmed by the accompanying mention of Marc Dax’s
earlier contribution in 1836 (1865), a quarter of a century before Broca’s first observation.
In 1836, Marc Dax presented a work indicating that disturbances in language production
were due to lesions of the left hemisphere. Dax’s work remained largely unknown until
his son, Gustav Dax (1865, 1877), presented and published his deceased father’s work
in the years after 1863 (see Benton, 2000 and Buckingham, 2006).
Dax’s memoir is not only interesting in that it is the first mention of the role of the
left hemisphere in the function of speech but also because it raises once again the problem
of “priority” in scientific observations (Benton, 2000).
Broca called the inability to produce language in the context of intact comprehension,
“aphenie”. Trousseau subsequently renamed such disturbances “aphasia” in 1864.
However, in 1863, Broca published a series of eight cases showing primarily left-frontal
lesions with language production deficit. In an 1865 and 1869 manuscript, Broca firmly
asserted that the left hemisphere is the dominant seat for language production.
Broca’s area is equivalent to areas 45 and 44 located in the opercular and triangular
portions of the left inferior frontal gyrus. This area of the cortex not only “programs” the
neurons in the adjacent motor cortex subserving the mouth and larynx from which
descending axons travel to the brain stem cranial nerve nuclei in the imitation of a
sequence of complex movements, but also has expressive language capacities (e.g.,
grammar).
Within Broca’s area, a coordination program for vocalization is formulated. The
elements of the program are transmitted to the face, tongue, vocal cords, and pharynx
area of the motor cortex for execution of speech.
The supplementary motor area is also necessary in the production of language for
the initiation of speech. Broca’s area receives input from Wernicke’s area via the arcuate
fasciculus (Wise et al., 1999; Sherwood et al., 2003).
Broca’s area is involved in planning the motor activity that is necessary for the word
to be produced. Broca’s area projects this information to the premotor cortex where motor
activity is planned and relayed to the primary motor cortex, which initiated the
movements necessary to produce speech. Thus, when a word is heard, the output from
1716
21. Cerebral cortex
the primary auditory area (Heschl’s gyrus) is conveyed to the adjacent Wernicke’s area,
where the word is comprehended. If the word is to be spoken, the comprehended pattern
is transmitted via the arcuate fasciculus from Wernicke’s area to Broca’s area in the
inferior frontal gyrus. The arcuate fasciculus is a long associated fibre bundle that links
Wernicke’s and Broca’s areas of speech. Damage to the arcuate fasciculus is associated
with impairment of repetition of spoken language. If the word is to be read,
representations visualized as words or images are conveyed from the visual cortex (areas
17, 18 and 19) to the angular gyrus (area 39), which in turn arouses the corresponding
auditory form of the word in Wernicke’s area. From Wernicke’s area, the information is
relayed via the arcuate fasciculus to Broca’s area (Afifi and Bergman, 2005).
These pathways, and doubtless others, constitute the cortical circuitry for language
comprehension and expression. In addition, other cortical centres involved in cognitive
processes project into the primary language cortex, influencing the content of language.
Finally, subcortical structures play increasingly recognized roles in language function
(the thalamus, the reticular activating system, the nuclei of the basal ganglia etc.).
Lesions in Broca’s area are associated with a type of aphasia (motor, anterior,
expressive, nonfluent) characterized by the inability of a patient to express himself by
speech. Such patients are able to comprehend language when Wernicke’s area is intact.
Autopsy data and neuroimaging studies have shown both the absence of Broca’s aphasia
in individuals with lesions in this area and also the reverse (Yang et al., 2008).
Depression is a common psychological consequence of aphasia, and is significantly
more common after anterior left-hemisphere lesions (including those associated with
nonfluent aphasia) than lesions in other areas (Carson et al., 2000).
Cortical localization of music

One should separate musical perception from musical execution by the naive, casual
listener and the music professional. Whereas a naive listener perceives music in its overall
melodic contour, the professional perceives music as a relation between musical elements
and symbols (language).
Thus, a naive listener perceives music in the right hemisphere, whereas the
professional perceives music in the left hemisphere.
Musical execution (singing), on the other hand, seems to be a function of the right
hemisphere irrespective of musical knowledge and training. The primary auditory cortex
of the right temporal lobe appears to make periodicity pitch discrimination (Zatorre, 1984,
2001; Zatorre and Belin, 2001; Zatorre et al., 2002).
Liégeois-Chauval et al. (1998) point out that distinct musical processes may depend
on specific cortical sites in the superior temporal gyrus.
Zatorre (2001) suggested that the right temporal lobe has a special function in
extracting pitch form sound, regardless of whether the sound is speech of music. In regard
to speech, the pitch will contribute to “tone” of voice, which is known as prosody.
The fact that the brain appears to have neural networks dedicated to the processing
of language and music leads to the conclusion that both language and music have
1717
biological roots. Although this conclusion seems obvious for language, it is less obvious
for music, which has often been perceived as an artefact of culture.
Ventral surface and midtemporal cortical areas

The ventral surface of the temporal lobe shows the continuation of the inferior
temporal gyrus from the lateral surface. Medial to the inferior temporal gyrus is the
occipitotemporal (fusiform) gyrus. The collateral sulcus separates the occipitotemporal
gyrus from the more medial parahippocampal gyrus and uncus, which constitute parts of
the limbic lobe.
In the middle part of the inferior temporal gyrus, on the lateral and ventral surface,
and in the region dorsal to the secondary auditory cortex, are visual and auditory
association areas (Schmitt et al., 1981; Schüz and Miller, 2002). These secondary
association areas are richly interrelated with occipital, frontal, parietal and insular cortices.
Penfield and Evans (1934) and Penfield and Mathieson (1974) suggested these
midtemporal areas participate in the recall of past events or so-called remote memory.
This appears to be the case especially with events that have visual and auditory
components visualized and heard at the same time in the past, and those events
accompanied by some emotional stress or intellectual conflict. These areas have
connections with the frontal lobe and limbic system including the amygdaloid body and
hippocampal formation (Augustine, 2008).
Slight irritation of these midtemporal areas often causes the vague feeling of
familiarity that falls under the term déjà vu. These seizures usually occur with impairment
of consciousness. A distorted memory experience such as the distortion of time sense, a
dreamy state, a flashback, or a sensation as if a naïve experience had been experienced
before, known as déjà vu, or as if a previously experienced sensation had not been
experienced, known as jamais-vu, may occur. When this refers to auditory experiences,
these are known as déjà-entendu or jamais-entendu. Occasionally, seizures manifest as
a form of forced thinking, in which the patient may experience a rapid recollection of
episodes from his past life, know as panoramic vision.
Cognitive disturbances include the dreamy state, distortions of time sense, sensations
of unreality, detachment or depersonalization.
Affective symptomatology includes sensations of extreme pleasure or displeasure,
as well as fear and intense depression with feelings of unworthiness and rejection.
Anger or rage is occasionally experienced. Fear or terror is the most frequent
symptom.
Epileptic or gelastic seizure laughter should not be classified as an affective symptom
because the laughter is usually without affect and hollow.
Illusions take the form of distorted perceptions in which objects may appear
deformed.
Hallucinations may occur as manifestations or perceptions without corresponding
external stimulus and may affect somatosensory, visual, auditory, olfactory, or gustatory
sense. Irritation of auditory association areas in these midtemporal regions is likely to
1718
21. Cerebral cortex
produce reminiscent speech or sounds, particularly a piece of music or a sound of

someone’s voice from our previous experience. The temporal lobe probably plays a vital
role in processing olfactory and gustatory information. The human temporal lobe is
probably involved in odour detection and is involved in olfactory memory functions,
particularly the right temporal lobe. Odour experiences often cause a retrieval of images,
an unfolding of past memories, and the imitation of a complex feeling state (Gibbs, 1951;
Gastaut, 1970; Geschwind, 1979; Bear, 1979; Mungus, 1982).
Automatisms may occur in both partial and generalized seizures. According to
Gastaut (1973), automatisms are described as more or less coordinated adapted (eupractic
or dyspractic) involuntary motor activity occurring during the state of clouding of
consciousness either in the course of, or after an epileptic seizure, and usually followed
by amnesia for the event. They may occur in complex partial seizures as well as in
absence of seizures.
Thus, the irritation of the medial or lateral temporal lobe causes temporal lobe
epilepsy. Temporal lobe epilepsy is a form of partial epilepsy characterized by recurrent
seizures that originate from these regions.
Temporal lobe epilepsy is most commonly associated with complex partial seizures,
although a large number of individuals also experience simple partial and / or secondary
generalized tonic-clonic seizures.
However, in recent years, most epileptologists distinguish between mesial
(amygdalo-hippocampal) and neocortical forms of temporal lobe epilepsy (Williamson
et al., 1993; Pacia et al., 1996; Engel and Weiser, 1997; Engel, 2001).
In mesial temporal lobe epilepsy, seizures arise most often in the hippocampus and
spread through adjacent cortical region. These seizures begin with an aura consisting of
a rising epigastric sensation and progress to an altered state of consciousness with variable
types of automatism (French et al., 1993; Williamson et al., 1993; Engel and Weiser,
1997; Engel, 2001). Motor automatism often occurs ipsilateral to the side of seizure, and
dystonia of the hand may occur contralateral. The combination of these findings in a
simple seizure is very suggestive of mesial temporal lobe epilepsy.
Seizures resulting from neocortical temporal lobe epilepsy can involve the inferior
temporal neocortex (excluding the parahippocampal gyrus), the temporal polar region,
and the superior plane of the temporal lobe (Pacia et al., 1996). These seizures
characteristically begin with an aura, which can include auditory hallucinations,
experiential auras, visual misperceptions, or dysphasia when the seizure focus is on the
language-dominant hemisphere. Complex partial seizures are evoked if the focus spreads
to medial temporal or extratemporal lobe structures (Barr and Karantzoulis, 2011).
The inferior occipital region of the temporal cortex is part of the “what” visual
pathway and contributes to the analysis of form.
Specific areas within the occipital temporal cortex are involved in recognition or
identification of colour, faces, letters, numbers, or objects. Thus, in the posterior temporal
and bordering occipital regions are complex association areas.
Damage can lead to visual agnosia, or the inability to recognize familiar objects,
faces, or words. For example, bilateral damage to occipital-temporal regions can result
1719
in prosopagnosia, the inability to recognize faces (Hadjikhani and Gelder, 2002; Schiltz
et al., 2006).
Thus, a severe deficit in discriminating and identifying faces with the inability to
recognize one’s own pictures or mirror images is likely to occur with injury to both
fusiform and lingual gyri. The visual association properties of these regions include the
synthesis of specific faces, which requires the complex synthesis of visual input, memory,
and other sensory phenomena. Individuals with prosopagnosia or face blindness may
learn to recognize people by their clothes, mannerisms, gait, hairstyle or voice. While
they connot recognize a person by their face, they are able to recognize facially expressed
emotions like happy, sad, and angry (Bodamer, 1947; Damasio et al., 1982; Landis et
al., 1986; Schiltz et al., 2006).
Medial regions of the temporal lobe are essential for learning and memory. Bilateral
damage results in the inability to learn new information or make new memories
(anterograde amnesia). These patients are unable to make new memories, learn new facts,
or recall new experiences. Their memory leading up to the surgery is largely intact and
general intelligence is also unaffected (French et al., 1993; Engel and Weiser, 1997;
Blumer et al., 1998; Engel, 2001).
Anomic aphasia
Anomia can occur in healthy individuals who occasionally experience difficulty in
thinking of an intended word during conversation, also known as the tip-of-the-tongue
state (Biedermann et al., 2008). It is a frequent occurence in individuals with left
hemisphere brain damage and aphasia (Raymer, 2005). Typically associated with
difficulties for nouns, anomia also can affect the ability to retrieve other classes of words,
such as verbs and adjectives. It is important to note that anomia and the anomic aphasia
are not synonymous. Anomia is the primary symptom of anomic aphasia and can also
be observed in virtually all other forms of aphasia, both as initial and residual signs when
other signs and symptoms of aphasia have revolved (Raymer and Rothy, 2008).
Anomia leads to a complete inability to retrieve a word and other times an
inappropriate word is retrieved known as a paraphasia. In severe forms of anomia,
neologisms may occur in which the uttered word may not be recognizable at all.
Anomic aphasia is the language impairment that involves only word finding
difficulties or pure anomia in contrast to other forms of aphasia (Goodglass et al., 2001).
In the left temporal / occipital region, particularly in parts of the fusiform and
probably the lingual gyrus corresponding to Brodmann’s areas 37 and 29, is a region
connected by the inferior occipitofrontal fasciculus with the inferior and perhaps
midtemporal regions and with other cortical areas along its course.
This region connects with the inferolateral and part of the lateral of the frontal lobe.
Acutely, anomic aphasia has been described following left temporal / occipital
lesions (e.g., area 37) and left thalamic lesion (Raymer et al., 1997 a, b).
The grammatical characteristics of the sentence remain intact. Common in anomic
aphasia is circumlocution, in which the speaker cannot think of the intended word and instead
describes or provides associated information about the word (Laine and Martin, 2006).
1720
21. Cerebral cortex
Primary gustatory cortex

Clinical and experimental evidence indicates that the cortical area for taste is located
in the parietal operculum, ventral to the primary somesthetic area in close proximity to
the cortical areas receiving sensory afferents from the tongue and pharynx.
It is represented to Brodmann’s area 43 in the parietal operculum and in the adjacent
parainsular cortex (Börnstein, 1940; 1940 a; Patton and Ruch, 1946; Penfield and
Rasmussen, 1959; Bagshow and Pribram, 1953).
Electrophysiological studies in rats, cats, and squirrel monkeys indicate that afferent
taste impulses conveyed by the chorda tympani and glossopharyngeal nerves are projected
to the most medial and caudal part of the posteroventral medial nucleus of the thalamus
(Landgren, 1961; Emmers et al., 1962; Blomquist et al., 1962; Emmers, 1964). Direct
lesions destroying this thalamic region produce gustatory deficits in monkeys (Blum et
al., 1943; Patton et al., 1944) and goats (Andersson and Jewell, 1957).
Anatomical studies (Benjamin and Akert, 1959) in rats indicate that unilateral
ablations of the cortical area in which potentials could be evoked by stimulating the
chorda tympani and glossopharyngeal nerves (i.e., the parietal operculum) did not impair
normal taste discrimination.
Bilateral ablation of this area produced a partial loss of taste. Ablation of this cortical
taste area produced retrograde degeneration of thalamic neurons confined to the most
medial, parvocellular subdivision of the posteroventral medial nucleus.
Ablations of the precentral and postcentral opercula in monkeys and chimpanzees
cause a loss of taste.
Similar lesions involving the anterior insular cortex, the postcentral operculum and
the anterior supratemporal cortex in monkeys impair taste sensibility (Bagshow and
Pribram, 1953). In humans, the gustatory cortex receives fibres from the posteroventral
medial nucleus of the thalamus, upon which converge sensory fibres from the face and
mouth, including taste fibres. Although crude taste sensation can be perceived at the
thalamic level, discrimination among different taste sensations is a cortical function.
Stimulation of the parietal operculum (Penfield and Boldrey, 1937) and adjacent
insular cortex (Penfield and Rasmussen, 1950) in conscious patients produce gustatory
sensations.
A report of an epileptic patient who experienced a gustatory aura characterized by
a sour or bitter taste is cited as providing information concerning localization of taste in
the cerebral cortex (Shenkin and Lewey, 1944).
Although this patient could recognize bitter and salty substances bilaterally, he was
unable to perceive sweet substances on one side of his tongue. A vascular anomaly was
found in the parietal opercular region contralateral to the taste deficit.
In an extensive study of thalamic projections to the insular and opercular cortex in
monkeys, it was established that the parvocellular subdivision of the posteroventral
medial nucleus projects to the parietal operculum and the insular cortex (Roberts and
Akert, 1963).
1721
The gustatory representation in the cerebral cortex is adjacent to the somesthetic

area for the tongue (Cohen et al., 1957), suggesting that taste may not have an exclusive
primary receiving area.
Different observations in squirrel monkeys suggest cortical areas concerned with
taste may be separated from somesthetic areas (Benjamin, 1963).
Irritative lesions in this area in humans have been shown to give rise to hallucinations
of taste, usually preceding the onset of an epileptic attack. Such a prodromal symptom
preceding an epileptic fit focuses attention on the site of the irritative lesion.
In sum, taste receptors relay gustatory information to the solitary nucleus in the
brain stem.
The solitary nucleus then transmits the information via the ipsilateral central
tegmental tract to the posteroventral medial nucleus of the thalamus.
The thalamus then projects these inputs to the inferior extent of the postcentral gyrus
(Brodmann’s area 43).
The cortical area where taste information is relayed resides next to the area where
the general sensory input from the tongue is transmitted.
The complete loss of taste (ageusia) is rarely encountered, in part because of the
large numbers of nerves that relay taste information to the central nervous system.
More frequently a patient suffers from hypogeusia or parageusia (dysgeusia),
distorsion in the perception of taste. Foci of seizure activity in central taste processing
areas can trigger unpleasant taste sensation (cacogeusia).
1722
21. Cerebral cortex
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1747
VENTRICULAR SYSTEM
AND MENINGES
Introduction
The cerebral ventricular system which consists of the four ventricles and the central
canal of the spinal cord are the remnants of the lumen of the embryonic neuronal tube.
The cells of the nervous system, both neurons and glia, originated from germinal
matrix adjacent to the lining of this tube. The cells multiply and migrate away from the
walls of the neural tube, forming the nuclei and cortex. As the nervous system develops,
the mass of tissue grows and the size of the tube diminishes, leaving various spaces in
different parts of the nervous system.
The parts of the tube that remain in the hemispheres are called the cerebral ventricles,
or the lateral ventricles. The ventricles are described in the order in which they are
numbered from rostral to caudal.
Thus, each cerebral hemisphere contains a large lateral ventricle that communicates
near its rostral end with the third ventricle via the interventricular foramen (foramen of
Monro) on either side of the median plane.
The third ventricle communicates with the forth ventricle by way of the aqueduct of
the midbrain, a wide tent-shaped cavity lying between the brain stem and cerebellum.
The fourth ventricle becomes continuous with the central canal of the medulla
oblongata and spinal cord and open by means of apertures into the subarachnoid space.
The ventricular system contains cerebrospinal fluid (CSF), which is mostly secreted
by the choroid plexuses located within the lateral, third and fourth ventricle. The total
volume of the fluid is about 100 to 140 ml and its pressure is about 150 mm of saline
(normal range: 70-180 mm) in the lateral recumbent position. The pressure is several
times higher in the lumbar region when sitting, but is about atmospheric at the foramen
magnum and is negative in the ventricles.
CSF flows from the lateral to the third ventricle, then through the cerebral aqueduct
into the fourth ventricle. It leaves the fourth ventricle through the foramen of Magendie
and the foramina of Luschka to reach the subarachnoid space surrounding the brain.
1748
22. Ventricular system and meninges
The neuroglial cells that line the ventricles of the brain and the central canal of the
spinal cord are termed ependymal cells. The ependyma is nonciliated in adult.
Lateral ventricle
The largest ventricles, the paired ventricles, separated from one another by the
septum pellucidum, are located in the right and left cerebral hemispheres. Thus, each
of the paired lateral ventricle is a C-shaped profile cavity that wraps around the thalamus
and is situated deep within the cerebrum. Thus, each lateral ventricle wraps around the
superior, inferior, and posterior surface of the thalamus. The superior surface of the
thalamus forms the floor of the body, the posterior surface of the thalamus forms the
anterior wall of the atrium, and the inferior surface of the thalamus forms the medial part
of the roof of the temporal horn.
The caudate nucleus is an arched, C-shaped cellular mass that wraps around the
thalamus and constitutes an important part of the wall of the lateral ventricle (Rhoton, 1987).
Each lateral ventricle possesses a body and three horns, the anterior, posterior, and
inferior horns. Thus, its various parts are the anterior horn, which lies deep to the frontal
lobes; the central portion or body, which lies deep to the parietal lobes; the atrium or
trigone where the ventricle widens and curves into the inferior horn, which goes into the
temporal lobes. In addition, there may be an extension into the occipital lobes, called the
occipital or posterior horn.
The frontal horn of the lateral ventricle has as its inferior boundary the rostrum, its
rostral boundary the genu, and its superior boundary the trunk, of the corpus callosum.
The anterior horns of the two ventricles are separated by the septum pellucidum.
Laterally the frontal horn of the lateral ventricle is limited by the bulging head of
the caudate nucleus. The anterior horn extends back as far as the interventricular foramen.
The narrow interventricular foramen is located immediately posterior to the column of
the fornix and separates the fornix from the anterior nucleus of the thalamus.
The body or the central portion of the lateral ventricle lies within the frontal and
parietal lobes and extends from the interventricular foramen to the splenium of the corpus
callosum. It is inferior to the trunk of the corpus callosum. The body is also on the medial
aspect of the thalamus (inferiorly) and body of the caudate nucleus (superiorly). The
bodies of the lateral ventricles are separated by the septum pellucidum, which contains
the columns of the fornices in its lower edge (Born et al., 2004). The inferior limit of the
body of the ventricle and its medial wall are formed by the body of the fornix. In the
central part of the lateral ventricle is the choroid plexus. The body of the lateral ventricle
widens posteriorly to become continuous with the posterior and inferior horn at the
collateral trigone or atrium (Rhoton, 2002; Born et al., 2004; Kawashima et al., 2006).
The posterior (occipital) horn of the lateral ventricle tapers into the occipital
lobe of each cerebral hemispheres. It is usually diamond-shaped or square in outline,
and the two sides are often asymmetrical. Fibres of the tapetum of the corpus callosum
separate the ventricle from the optic radiation and form the roof and lateral wall of the
posterior horn.
1749
Forceps major pass medially as they sweep back into the occipital lobe, and produce
a rounded elevation in the upper medial wall of the posterior horn. Lower down, a second
elevation, the calcar avis, corresponds to the deeply infolded cortex of the anterior part
of the calcarine sulcus (Mc Lone, 2004; Crossman, 2008). The occipital horns are usually
asymmetrical – the back part of one horn may appear as a separate entity.
The inferior (temporal) horn of the lateral ventricle extends into the temporal lobe
from the fourth part of the central part of the lateral ventricle. This is the largest
compartment of the lateral ventricle. It curves round the posterior aspect of the thalamus
(pulvinar), passes downwards and posterolaterally and then curves anteriorly to end
within 2.5 cm of the temporal pole, near the uncus (Switka et al., 1999; Crossman, 2008).
It corresponds to the superior temporal sulcus. The floor of the ventricle consists of
the hippocampus medially and the collateral eminence, formed by the infolding of the
collateral sulcus, laterally.
Superiorly, the inferior horn is formed mainly by the tapetum of the corpus callosum,
the tail of the caudate nucleus, and the stria terminalis which runs forward to end in the
amygdaloid body (Switkaetal, 1999; Mc Lone, 2004).
The temporal extension of the choroid plexus fills this fissure and covers the outer
surface of the hippocampus.
The choroid plexus of each lateral ventricle is invaginated along a curve line known
as the choroid fissure.
The fissure extends from the interventricular foramen in front and arches over the
posterior end of the dorsal thalamus, as far as the end of the temporal horn. The choroid
plexus of the lateral ventricle is only in the central part of the lateral ventricle and the
temporal horn (Strazielle and Ghersi-Egea, 2000).
At the junction of the central part with the temporal horn it is best developed and is
there known as the glomus choroideum.
Calcified areas (corpora amylacea) are frequent in the glomus.
The vessels of the plexus originate from the internal carotid (anterior choroidal
artery) and from the posterior cerebral (posterior choroidal arteries).
At the interventricular foramina, the choroid plexuses of both lateral ventricles
become continuous and then join that of the third ventricle.
Third ventricle
The third ventricle is a narrow cleft unilocular, located in the center of head, below
the corpus callosum and the body of the lateral ventricle; above the sella turcica, pituitary
gland, and midbrain; and between the cerebral hemispheres, thalami, and the walls of the
hypothalamus (Rhoton, 1987). Over a variable area, the thalami are frequently adherent
to each other at the interthalamic adhesion (massa intermedia). This interthalamic
adhesion varies in size, and the thalamus and hypothalamus create minor differences in
the lateral walls of the third ventricle.
It communicates at its anterosuperior margin with each lateral ventricle through the
foramen of Monro and posteriorly with the forth ventricle through the aqueduct of
Sylvius. It has an anterior, a roof, a floor, a posterior, and two lateral walls.
1750
Anterior wall
The anterior part of the third ventricle extends from the foramina of Monro, above,
to the optic chiasma below, which crosses its floor.
The part of the anterior wall visible on the surface is formed by the optic chiasma
and the lamina terminalis. The optic chiasma is a major modifier of the floor of the third
ventricle because its size and location affect the size and configuration of the optic and
infundibular recesses. The optic recess seems to be a residual space on the floor of the
third ventricle of which formation, shape, and size are the result of the varying indentation
of the ventricular floor by the chiasma (Yamamoto et al., 1981).
The lamina terminalis is a thin sheet of gray matter and pia mater that attaches to
the upper surface of the chiasma, to the anterior commissure and to the rostrum of the
corpus callosum.
The lamina terminalis forms the roof of the small virtual cavity lying immediately
below the ventricle called the cistern of the lamina terminalis.
Above this, the anterior wall is formed by the diverging columns of the fornices and
the anterior commissure.
When viewed from within, the boundaries of the anterior wall from superiorly to
inferiorly are formed by the columns of the fornix, foramina of Monro, anterior com-
missure, lamina terminalis, optic recess, and optic chiasma. The anterior commissure is
a compact bundle of myelinated nerve fibres that cross the midline in front of the columns
of the fornix. The diameter of the anterior commissure varies from 1.5 to 6.0 mm. The
distance from posterior end of the anterior commissure to the anterior border of the
foramen of Monro range from 1.0 to 3.5 mm (Yamamoto et al., 1981). The foramen of
Monro on each side is located at the junction of the roof and the anterior wall of the third
ventricle. The foramen is a ductlike canal that opens between the fornix and the thalamus
into the lateral ventricle and extends inferiorly below the fornix into the third ventricle
as a single channel. The foramen of Monro is bounded anteriorly by the junction of the
body and the columns of the fornix and posteriorly by the anterior pole of the thalamus
(Rhoton, 1987). The structures that pass through the foramen are the choroid plexus, the
distal branches of the medial posterior choroidal arteries, and the internal cerebral,
thalamostriate, superior choroidal, and septal vein.
Roof. A thin layer of ependyma covered by pia mater forms the thin roof of the third
ventricle. Above the roof is the body of the fornix. The body forms a gentle arch located
between the roof of the third ventricle and the floor of the body of each lateral ventricle.
The upper layer of the anterior part of the roof of the third ventricle is formed by the
body of the fornix, and the posterior part of the roof is formed by the crura and the
hippocampal commissure. The septum pellucidum is attached to the upper surface of the
body of the fornix.
According to Yamamoto et al. (1981), anteroposterior length of the septum
pellucidum varied from 28 to 50 mm. The tela choroidea forms two of the three layers in
the roof below the layer that is formed by the fornix.
1751
The roof has four layers: one neural layer formed by the fornix, two thin
membranous layers of tela choroidea, and a layer of blood vessels between the sheets of
the tela choroidea (Rhoton, 1987; Rhoton, 2002).
The final layer in the roof is a vascular layer located between the two layers of tela
choroidea. The vascular layer consists of the medial posterior choroidal arteries and their
branches and the internal cerebral veins. The internal cerebral veins arise in the anterior
part of the velum interpositum, just behind the foramen of Monro, and they exit the velum
interpositum above the pineal body to enter the quadrigeminal cistern and join the great
vein (Rhoton, 1987).
The velum interpositum is the space between the two layers of the tela choroidea.
The cleft between the lateral edge of the fornix and the superomedial surface of the
thalamus is called the choroidal fissure. The choroid plexus of the lateral ventricle is
attached along this fissure.
Floor. The floor of the third ventricle extends from the optic chiasma anteriorly, to
the orifice of the aqueduct of Sylvius posteriorly.
When viewed from inferiorly, the structures forming the floor from anterior to
posterior include the optic chiasma, the infundibulum of the hypothalamus, the tuber
cinereum, the mammillary bodies, the posterior perforated substance, and (most
posteriorly) the part of the tegmentum of the midbrain located above the medial aspect
of the cerebral peduncle (Rhoton, 1987; Rhoton, 2002).
There is a small angular, optic recess at the base of the lamina terminalis, just dorsal
to and extending into the optic chiasma. Behind it, the anterior part of the floor of the
third ventricle is formed mainly by hypothalamic structures. Immediately behind the optic
chiasma lies a thin infundibular recess, which extends into the pituitary stalk. The
posterior part of the floor extends posterior and superior to the medial part of the cerebral
peduncles and superior to the tegmentum of the midbrain.
Posterior wall. The posterior wall of the third ventricle extends from the suprapineal
recess above, to the aqueduct of Sylvius below. Thus, the posterior boundary of the third
ventricle is marked by a suprapineal recess above the pineal gland, which extends into
the pineal stalk, by the habenular commissure, by the pineal gland, by the posterior
commissure, and by the aqueduct of Sylvius. The habenulae are small eminences on the
dorsomedial surfaces of the thalamus just in front of the pineal gland. The habenulae are
connected across the midline in the rostral half of the stalk of the pineal gland by the
habenular commissure (Rhoton, 2002).
The suprapineal recess projects posteriorly between the upper surface of the pineal
gland and the lower layer of tela choroidea in the roof.
The shape and size of the suprapineal recess are related to the size of the corpus
callosum. The increasing size of the splenium, as seen from the cat and monkey, is
associated with a concomitant reduction of the suprapineal recess. The habenular
commissure, which interconnects the habenulae, crosses the midline in the cranial lamina,
and the posterior commissure crosses in the caudal lamina.
Because of the development of the neocortex and the relative unimportance of
olfaction, the habenulae are the smallest.
1752
The position of the anterior and posterior commissures are used as the basic reference
points for stereotaxic surgical procedures.
Lateral wall. The walls of the third ventricle are hidden between the cerebral
hemispheres. The upper part of the lateral wall is formed by the medial surface of the
anterior two-third of the thalamus, and the lower part is formed by the hypothalamus
anteriorly and the subthalamus posteriorly.
Hypothalamic sulcus between the interventricular foramen and the cerebral aqueduct
marks the boundary between the thalamus and hypothalamus. The superior limit of the
thalamic surfaces of the third ventricle is marked by narrow, raised ridges, known as the
striae medullaris thalami.
The massa intermedia projects into the upper one-half of the third ventricle and often
connects the opposing surfaces of the thalamus. It was present in 76% of the brains
examined and was located 2.5 to 6.0 mm posterior to the foramen of Monro (Yamamoto
et al., 1981; Rhoton 1987, 2002).
The columns of the fornix form distinct prominences in the lateral walls of the third
ventricle just below the foramen of Monro, but inferiorly they sink below the surface.
The third ventricle presents several recesses: (1) the optic recess superior to the
chiasma; (2) the infundibular recess in the infundibulum of the neurohypophysis; (3) a
less well-defined recess rostral to the mammillary bodies; (4) the pineal recess in the
stalk of the pineal body; (5) the suprapineal recess (Augustine, 2008).
Aqueduct of Sylvius
The aqueduct of Sylvius is a small tube in the midbrain, 1-2 mm in diameter and
about 1 cm in length. It extends throughout the dorsal quarter of the midbrain in the
midline, is widest in its central part, is surrounded by the gray matter and connects the
third and fourth ventricle. The superior and inferior colliculi are dorsal to aqueduct and
the midbrain tegmentum is ventral. Rostrally it commences immediately behind and
below the posterior commissure.
Caudally, it is continuous with the lumen of the fourth ventricle at the junction of
the midbrain and pons.
Fourth ventricle
The fourth ventricle is a romboid shaped space in the hindbrain who lies between the
brain stem and the cerebellum. Rostrally (superiorly) it is narrow becoming continuous
with the cerebral aqueduct (of Sylvius), and caudally (inferiorly), it narrows into the central
canal of the medulla oblongata (obex), which, in turn, is continuous with the central canal
of the spinal cord (Fig. 22.1). The ventricle is, at its widest, at the level of the
pontomedullary junction, where a lateral recess on both sides extends to the lateral border
of the brain stem. In the widest part of the ventricle, on either side, it has two openings, the
right and left foramina of Luschka and a single median foramen of Magendie.
1753
Fig. 21.1. Hemisected skull demonstrating the flow of cerebrospinal fluid in the ventricle of the brain
and the subarachnoid spaces (after Patestas and Gartner, 2008).
All three foramina permits cerebrospinal fluid to leave the ventricular system and
enter the subarachnoid space. The foramina of Luscha lead to the interpeduncular cistern,
whereas the foramen of Magendie delivers the CSF into the cerebellomedullary cistern.
Floor of the fourth ventricle. The floor of the fourth ventricle is a romboid cavity
on the dorsal surfaces of the pons and the rostral half of the medulla. It consists largely
of grey matter and contains important cranial nerve nuclei.
The superior part of the ventricular floor is triangular in shape and is limited laterally
by the superior cerebellar peduncles as they converge toward the cerebral aqueduct.
The inferior part of the ventricular floor is also triangular in shape and is bounded
caudally by the gracile and cuneate tubercles, which contain the dorsal column nuclei,
and more rostrally, by the diverging inferior cerebellar peduncles (Rhoton, 2010;
Crossman, 2008).
A dorsal median sulcus divides the floor into right and left halves. Each half is it-
self divided, by an often indistinct sulcus limitans, into a medial region known as the
medial eminence and a lateral region known as the vestibular area. The vestibular nuclei
lie beneath the vestibular area.
1754
The medial eminence, an elevation on the floor of the fourth ventricle, extends the
length of the pons and into the open medulla. In the caudal part of the pons, the medial
eminence presents a swelling called the facial colliculus, a small elevation produced by
an underlying loop of efferent fibres from the facial nucleus which covers the abducens
nucleus. Between the facial colliculus and the vestibular area the sulcus limitans widens
into a small depression, the superior fovea. In its upper part, a small region of bluish-
grey pigmentation denotes the presence of the subjacent locus ceruleus.
Inferior to the facial colliculus, at the level of the lateral recess of the ventricle is the
striae medullaris, which runs transversely across the ventricular floor (Rhoton, 2000).
The hypoglossal and vagal trigone are caudal to the facial colliculus and form the
caudal part of the medial eminence at medullary levels.
Thus, in the inferior area of the floor of the fourth ventricle, the medial eminence is
represented by the hypoglossal triangle (trigone), which lies over the hypoglossal nucleus.
Laterally, the sulcus limitans widens to produce an indistinct inferior fovea. Caudal to it,
between the hypoglossal triangle and the vestibular area, is the vagal triangle, which
covers the dorsal motor nucleus of the vagus. The triangle is crossed below by a narrow
translucent ridge, the funiculus separans, which is separated from the gracile tubercle by
the small area postrema. They are both covered by ependyma, containing tanycytes and
neurons (only area postrema) (Rhoton, 2000; Crossman, 2008).
The lowermost part of the floor of the fourth ventricle has the shape of the point of
a pen (calamus scriptorius). Here are nuclei related to respiration, cardiovascular activity
and the act of swallowing (deglutition) (Matsushima et al., 1982; Augustine, 2008).
Roof of the fourth ventricle. Sheets of white matter (the superior and inferior
medullary vela) which are lined by ependyma and which stretch between both superior
and inferior cerebellar peduncles form the roof of the fourth ventricle. The superior
medullary velum is continuous with the cerebelar white matter and is covered dorsally
by the lingula of the superior vernis (Rhoton, 2000).
The inferior medullary velum formed by ventricular ependyma and the pia mater of
the tela choroidea, presents a deficiency, the median aperture (foramen Magendie), just
inferior to the nodule of the cerebellum.
CSF flows through this foramen into the cisterna magna (Matsushima et al., 1982;
Barshes et al., 2005). The ends of the lateral recesses have similar openings, the lateral
apertures. These, are not well-defined openings but rather gaps between the cerebellum
and medulla oblongata with choroid plexus protruding through them. By turning fila of
the glossopharyngeal and vagal nerves medially, one is able to see the choroid plexus
projecting through the lateral aperture immediately inferior to the flocculus (Barshes et
al., 2005; Augustine, 2008). The choroid plexus of the fourth ventricle invaginates into
the roof of the ventricle on either side of the median plane. A prolongation of each plexus
protrudes through the corresponding lateral aperture.
The vessels to the plexus arise from cerebellar branches of the vertebral and basilar
arteries. The choroid plexus of the fourth ventricle is T-shaped, with vertical and
horizontal limbs but the precise form varies widely. The vertical (longitudinal) limb is
double, flanks the midline and is adherent to the roof of the ventricle.
1755
The horizontal limbs of the plexus project into the lateral recesses of the ventricle.
Small tufts of plexus pass through the foramina of Luschka and emerge, still covered by
the ependyma, in the subarachnoid space of the cerebellopontine angle (Rhoton, 2000;
Mc Lone, 2004; Crossman, 2008). The blood supply of the fourth ventricular choroid
plexus is from the inferior cerebellar arteries.
Capillaries drain into a rich venous plexus served by a single choroidal vein.
The vascular pia mater in the roofs of the third and fourth ventricles and in the medial
wall of the lateral ventricle along the line of the choroid fissure, is closely opposed to the
ependymal lining of the ventricles, without any intervening brain tissue.
It forms the tela choroidea, which gives rise to the highly vascularized choroid
plexuses from which CSF is secreted into the lateral, third and fourth ventricles.
The body or stroma of the choroid plexus consists of many capillaries, separated
from the subarachnoid space by the pia mater and choroid ependymal cells (Strazielle
and Ghersi-Egea, 2000; Crossman, 2008).
Production of the cerebrospinal fluid (CSF)

A major advance in localizing the site of CSF was made by Dandy in 1918 when he
made extirpation of the choroid plexus of the lateral ventricle in communicating
hydrocephalus and in 1919 when he completed a crucial experiment by stenosing both
foramina of Monroe and performing a unilateral choroid plexectomy in a single dog.
After the observing that the ventricle without choroid plexus collapsed, while the opposite
ventricle expanded greatly, it was initially thought that the sole source of CSF was
localized to the choroid plexus (Du Boulay et al., 1972).
Currently it is believed that while the choroid plexus is an important site of CSF
production, other significant sources exist. They include the ependyma and the brain
parenchyma (Fishman, 1992). Indeed, it has been estimated that approximately 30% of
CSF is produced by the ependyma (Milhorat, 1975).
CSF is secreted at a rate of 0.35-0.40 ml per minute, which means that normally
about 50% of the total volume of CSF is replaced every five to six hours (Zakharov et
al., 2004).
The total CSF volume is approximately 150 ml, of which 125 ml is intracranial. The
ventricles contain about 25 ml, most lying within the lateral ventricles, and the remaining
100 ml is located in the cranial subarachnoid space (Greitz, 2004).
Until Cushing’s paper The Third Circulation, in 1925, most had ascribed the idea that
CSF moved with an “ebb and flow” movement, an idea begun by Magendie, 100 years
before (Milhorat, 1975). Modern radiological technique confirmed the notion that CSF does
indeed circulate (Du Boulay et al., 1972; Ohara et al., 1988; Stoodley et al., 1997).
CSF flows from the lateral ventricles to the third ventricle via the paired
interventricular foramina of Monroe, and then through the cerebral aqueduct to the fourth
ventricle. CSF leaves the fourth ventricle through the medial and lateral apertures
(foramina of Luschka) to enter the subarachnoid space of the cisterna magna and the
subarachnoid cisterns over the front of the pons respectively (Notle, 1993).
1756
Many different routes are possible once the CSF has reached the cisterna magna.
The fluid may travel: superiorly toward the cerebellar hemispheres to the ambient cistern;
anterosuperiorly toward the interpenduncular and interchiasmatic cistern; anteriorly
toward the premedullary, prepontine, and cerebellopontine cistern; or inferiorly toward
the spinal subarachnoid space. CSF in the spinal subarachnoid space posterior to the
spinal cord and dentate ligaments is directed in the caudal direction. The overall direction
of fluid ventral to the spinal cord is in the cephalad direction; therefore, returning the
CSF to the basilar cisterns (Milhorat, 1975).
The movement of CSF in the subarachnoid space is complex and is characterized
by a fast flow component and a much slower bulk flow component. During systole, the
major arteries lying in the basal cisterns and other subarachnoid spaces dilate significantly
and exert pressure effects on the CSF, causing rapid CSF flow around the brain and out
of the cranial cavity into the upper cervical vertebral canal.
The flow of CSF is propagated by the cardiac cycle. The pulsation of the arterial
system transmits pulsation to the brain parenchyma, the choroid plexus, and the large
arteries at the skull base (Ohara et al., 1988). The volumetric displacement of the CSF
increases with low diastolic pressure and low systolic pressure (Barshes et al., 2005).
Perhaps the smallest contribution is from the outpouring of new CSF and the ciliary
beating of the ventricular ependyma. The pressure gradient across the arachnoid villi also
contributes to the bulk flow of CSF via the creation of a pressure gradient. The mean
CSF pressure in the brain is 150 mm saline while the pressure in the superior sagittal
sinus in 90 mm saline (Milhorat, 1975).
The amplitude of the CSF pulsations is also affected by the respiratory cycle, the
resistance of outflow created by the arachnoid villi, the mean intracranial pressure, and the
compliance of the cranial and spinal cord cavities (Fujii et al., 1980; Ohara et al., 1988).
Pulsations of 10-30 mm H2O and 20-30 mm H2O in amplitude are seen at particular
points in the respiratory and cardiac cycles, respectively, with isovolumetric measure-
ments in the lumbar CSF (Fujii et al., 1980).
The amplitude of pulsations in the cisterna magna is 50 mm H2O while that of the
lumbar fluid is 30 mm H2O) (Fishman, 1992).
According to Duboulay et al. (1972), an average of 0.1 mL CSF was displaced from
the third ventricle during each systole; in comparison to 1.0 mL in the basal cisterns and
0.64 mL in the cisterna magna.
Thus, radiographic studies in humans have shown that pulsations throughout the
neuraxis lead to the “pumping” of CSF and that various areas of the brain and spinal
cord provide varying contribution to the pumping activity (Ohara et al., 1988; Stoodley
et al., 1997).
CSF absorption. CSF is absorbed into the venous system by active diffusion into
cerebral capillaries which occurs as a result of the interstitial pressure differential.
Other routes of absorption exist, including the ependyma, the leptomeninges, and
the lymphatics of the spine (Milhorat, 1975). The driving forces for absorption of CSF
have been attributed to the gradient in both hydrostatic and colloid osmotic pressures
1757
between the protein-free CSF in the arachnoid villi and the venous spaces (Barshes et
al., 2005).
CSF function. The CSF does act to support as cushion elements in the central
nervous system. The CSF acts to lessen the apparent weight of the brain to approximately
4% of this mass (Burt, 1993).
The CSF appears to have a function at least partially analogous to that of lymphatics
in other organs – namely, removing fat-soluble and toxic substances from the brain’s
extracellular fluid. Many fat-insoluble molecules are also removed from the brain
extracellular fluid by the circulation of CSF including urea, albumin, homovanillic acid,
and norepinephrine (Milhorat, 1975).
The “internal milieu” of the brain may be regulated by exclusion of large and polar
molecules from the CSF and also by modification of the CSF by capillary-glial com-
plexes, epithelia, and neurons themselves (Fishman, 1992).
The CSF may also function as a mechanism of intracerebral transport for biogenic
amines which initiate the secretion of pituitary hormone release factors. Tanycytes appear
to have a role in this function (Milhorat, 1975).
Tanycites are found in clusters in the walls of the third ventricle and cerebral aqueduct,
in floor of the fourth ventricle, and in the cervical spinal canal. Clusters of tanycytes are
often associated with circumventricular organs, namely the median eminence, the area
postrema, the subcommissural organ, and the pineal gland (Peters et al., 1991).
In contrast to the ependymal cells, tanycytes have many microvilli and few cilia.
These cells have three portions: a somatic portion, a neck portion, and a tail portion with
end-feet which course through the hypothalamus to contact fenestrated blood vessels or
pial surfaces (Fishman, 1992).
Fixed macrophages are also present in the arachnoid border layer. These cells are
sometimes referred to as Kolmer or epiplexus cells when associated with the choroid
plexus. They contain many membrane-bound inclusions and variable vacuoles; they lack
cytoplasmic processes (Peters et al., 1991).
Composition of CSF. The fact that the CSF is isosmotic in comparison to the plasma
suggests that water freely equilibrates between the two fluid compartments (Fishman,
1992). The composition of CSF compared to that of plasma is presented in Table 22.1.
Thus, CSF is not simply a protein-free dialysate of the plasma but rather a true
secretion requiring energy for its production.
According to Barshes et al. (2005), the secretion of CSF is dependent upon the active
transport of sodium which is performed by a choroid epithelial sodium-potassium
activated ATPase. The in vivo inhibition of choroid plexus fluid formation by ouabain,
an inhibitor of this ATPase, support the idea that CSF is a secretion. This ATPase and
other transport enzymes are responsible for the transport of other ions and micronutrients
into the CSF. Small amounts of protein are transported into CSF mainly by pinocytosis
(Barshes et al., 2005).
1758
Table 22.1
Normal Composition of Cerebrospinal Fluid and Serum
(adapted from Fishman, 1992)
CSF Serum
(arterial)
Osmolarity (mOsm/L) 295 295

Water content (%) 99 93
Sodium (mEq/L) 138 138
Potassium (mEq/L) 2.8 4.5
Chloride (mEq/L) 119 102
Bicarbonate 22.0 24.0
Phosphorus (mg/dL) 1.6 4.0
Calcium (mEq/L) 2.1 4.8
Magnesium (mEq/L) 2.3 1.7
Iron (g/dL) 1.5 15.0
Urea (mmol/dL) 4.7 5.4
Creatinine (mg/dL) 1.2 1.8
Uric acid (mg/dL) 0.25 5.50
CO2 tension (mmHg) 47.0 41.0
pH 7.33 7.41
Oxygen (mmHg) 43.0 104.0
Glucose (mg/dL) 60.0 90.0
Lactate (mEq/L) 1.6 1.0
Pyruvate (mEq/L) 0.08 0.11
Lactate: pyruvate ratio 26.0 17.6
Proteins (mg/dL) 0.035 7.0
Meninges
Three connective membranes that envelop the central nervous system are collectively
known as the meninges. They provide support and protection for the delicate tissue they
surround. Although the dura mater surrounding the brain is continuous with the dura
mater surrounding the spinal cord at the level of the foramen magnum, it is customary to
discuss the two separately.
Thus, separating the brain and spinal cord from the calcified tissue are three more
or less concentric membranes. The outermost, dense, irregular collagenous connective
tissue is the dura mater or pachimeninx.
The innermost connective tissue membrane is the pia mater, the thin translucent
membrane, adherent to the surface of the brain and spinal cord, which accurately follows
every contour. The middle spiderweb-like is a delicate layer of reticular fibres, the
arachnoid.
The pia mater and arachnoid collectively are called the leptomeninges and are
separated from one another by the subarachnoid space.
1759
Cranial dura mater

The cranial dura mater is a thick, dense, opaque, fibrous coat which incompletely divides
the cranial cavity into compartments and accommodates the dural venous sinuses. It is
predominantly acellular, and consists mainly of densely packed fascicle of collagen fibres
arranged in laminae which run in different directions, producing a lattice-like appearance.
The cranial dura mater has two layers, on outer periosteal dura mater (endosteal
layer) that is attached to the internal table of the diploe and acts as a true periosteum, and
an internal meningeal dura mater that is in intimate contact with the arachnoid.
There is little histological difference between endosteal and meningeal layers. Both
contain fibroblasts, and the endosteal layer also contains osteoblasts. Focal calcification
may occur in the falx cerebri.
The periosteal dura mater firmly adheres to the inner aspect of the cranial bones,
especially at the sutures and along the base of the skull. The meningeal and periosteal
layers serve both meningeal and periosteal function.
Thus, the space external to the cranial dura, the epidural space, is a potential space.
Studies of the fine structure of the dura-arachnoid interface layer in humans reveal
that the innermost part of the cranial dura and the outermost part of the arachnoid are
intimately fused. However, there is a potential space between the meningeal layer of the
cranial dura mater and the cranial arachnoid, known as the subdural space, that, according
to some neuroanatomists, is occupied by an extremely thin film of fluid.
The periosteal and meningeal layers of the dura mater are tightly attached to each
other throughout much of their extent. The dura mater forms reflections upon itself, some
of which contain dural venous sinuses.
The periosteal dura mater is a coarse type of connective tissue composed of dense
irregular collagenous connective tissue interlaced with some elastic fibres.
It is especially firmly attached at the sutures, cranial base, and around the foramen
magnum.
At the foramina of the skull the periosteal dura mater forms a connective tissue
sheath around the cranial nerves as they leave the skull and this dural layer is quickly
replaced by the epineurium derived from the extracranial connective tissue. The endosteal
layer is continuous with the pericranium through the cranial sutures and foramina and
with the orbital periosteum through the superior orbital fissure. The dural sheath of the
optic nerve is continuous with the ocular sclera. The dura fuses with adventitia of major
vessels, such as the internal carotid and vertebral arteries, at sites where they pierce it to
enter the cranial cavity (Standring, 2008).
The innermost aspect of the meningeal layer of the dura mater, composed of dense
irregular collagenous connective tissue, is lined by a single layer of flattened fibroblasts
that form epithelioid sheet that is in direct contact with and separates the arachnoid from,
the collagenous connective tissue component of the meningeal dura.
Reflections of the meningeal layer of the dura mater

The meningeal layer of the dura mater give rise to several folds that divide the cranial
cavity into compartments, or to separate parts of the brain from one another.
1760
Thus, the meningeal layer of the dura is reflected inwards to form three folds, namely
the falx cerebri, falx cerebelli, and tentorium cerebelli that partially divide the cranial
cavity into compartments.
Additionally, this meningeal layer forms a diaphragm over the hypophysial fossa,
known as the diaphragm sella and Meckel’s cave (cavum trigeminale).
Falx cerebri. The largest of these folds is the sickle-shaped fax cerebri which
extends in the midline from the crista galli to the internal occipital protuberance. Falx
cerebri occupies the longitudinal fissure between the two cerebral hemispheres. The
crescent is narrow in front, and broad behind where it is attached to the superiors surface
of the tentorium cerebelli. The superior, convex surface of the falx cerebri is attached to
the periosteal layer of the dura, leaving only a narrow, endothelial lined channel, the
superior sagittal sinus. The inferior border that is free but concave in shape follows the
shape of the corpus callosum.
The layers of the falx along the convex border divide to accommodate the superior
sagittal sinus whereas those along the concave border divide to accommodate the inferior
sagittal sinus.
The superior sagittal sinus begins just behind the crista galli, at the foramen cecum,
and terminates posteriorly at the confluence of sinuses. At the junction where the falx
cerebri joins and fuses with the tentorium cerebelli is another endothelial lined space, the
straight sinus, that receives blood from the inferior sagittal sinus and the great cerebral
vein. Blood from the straight sinus also enters the confluence of sinuses.
Tentorium cerebelli. The tentorium cerebelli, a horizontal reflection of the menin-
geal layer of the dura mater, is interposed between the cerebellum and the occipital lobes
of the cerebrum. It divides the cranial cavity into supratentorial and infratentorial
compartments, which contain the forebrain and hindbrain respectively. Anteriorly, the
lateral aspect of the tentorium is attached to the superior surface of the petrous portion of
the temporal bone and forms endothelially lined spaces, the right and left superior petrosal
sinuses, and continues anteriorly to attach to the posterior clinoid processes of the
sphenoid bone. The tentorium forms a large part of the floor of the middle cranial fossa,
and fills much of the gap between the ridges of the petrous temporal bones. On both sides,
the rim of the tentorial incisures is attached to the apex of the petrous temporal bone and
continues forward as a ridge of dura mater to attach to the anterior clinoid process.
This ridge marks the junction of the roof and the lateral part of the cavernous sinus.
The periphery of the tentorium cerebelli (attached to the superior border of the
petrous temporal bone), crosses under the free border of the tentorial incisures at the apex
of the petrous temporal bone, and continues forward to the posterior clinoid processes as
a rounded, indefinite ridge of the dura mater.
The angular depression between the anterior parts of the peripheral attachment of
the tentorium and the free border of the tentorial incisure is part of the roof of the
cavernous sinus (Standring, 2008).
The free and concave anterior edge of the tentorium forms the tentorial incisure,
the only opening between the supratentorial and infratentorial components. This tentorial
1761
incisure or match is filled by the midbrain and the anterior part of the superior aspect of
the cerebellar vermis and permits the ascent of the posterior cerebral arteries to reach the
cerebral hemisphere. The convex outer limit of the tentorium is attached posteriorly to
the lips of the transverse sulci of the occipital bone and to the posterior-inferior angles of
the parietal bones, where it encloses the transverse sinuses.
Laterally, it is attached to the superior borders of the petrous parts of the temporal
bones, where it contains the superior petrosal sinuses.
The lateral borders of the tentorium cerebelli extend much further anteriorly than
does its midline.
The superior surface of the central region is convex. The layers of the tentorium
along the convex border divide to accommodate the transverse sinus.
The compartment inferior to the tentorium contains not only the cerebellum but also
the pons and medulla oblongata.
Falx cerebelli. The falx cerebelli, a relatively small reflection of the meningeal layer
of the dura lies below the tentorium and attaches to the inferior aspect of the tentorium
in the median plane and to the internal occipital crest. This small midsagittal septum
partially separates the cerebellar hemispheres.
The posterior margin of the falx cerebelli contains the occipital sinus and is attached
to the internal occipital crest. The apex of the falx cerebelli frequently divides into two
small folds, which disappear at the sides of the foramen magnum.
Diaphragma sella. The diaphragma sella is a thin reflection of the meningeal layer
of the dura mater over the pituitary fossa, which is perforated by the infundibulum
(Rhoton, 2002).
This fourth dural projection is circular in shape, forming a roof over the sella turcica
and covering its content.
The lateral aspect is attached to the clinoid processes. The anterior and posterior
edges of the diaphragma sella house the anterior and posterior intercavernous sinuses.
The infundibulum and pituitary stalk pass into the pituitary fossa through a central
opening in the diaphragma.
Cavum trigeminale (Meckel’s cave). The cavum trigeminale is a narrow, slit-like
region interposed between the periosteal and meningeal layers of the dura mater
positioned on the trigeminal impression of the petrous portion of the temporal bone. It is
occupied by the trigeminal ganglion as well as by the sensory and motor roots of the
trigeminal nerve (Patestas and Gartner, 2008).
Vascular and nerve supply. The periosteal layer of the dura mater is richly supplied
by blood vessel, whereas the meningeal layer has no vascular supply. The blood vessels
of the periosteal layer include the middle meningeal and accessory meningeal arteries of
the middle cranial fossa, as well as the meningeal branches of the anterior and posterior
etmoidal arteries and meningeal branches of the internal carotid artery of the anterior
cranial fossa. Meningeal branches of the vertebral, occipital, middle meningeal, and
ascending pharyngeal arteries serve the periosteal dura of the posterior cranial fossa.
Blood is drained from the dura by meningeal veins that empty their blood into several of
the sinuses as well as into nearby emissary veins and diploic veins. The diploic veins are
1762
large, thin-walled vessels that occupy chanels in the diploe of the cranial bones. Four
main trunks are usually described; these are the frontal, anterior or posterior temporal,
and occipital diploic veins.
Sinus pericranii is a rare condition involving congenital or acquired anomalous
connections between an extracranial blood-filled nodule and an intracranial dural venous
sinus via dilated diploic and / or emissary veins of the skull (Sheu et al., 2002).
Emissary veins traverse cranial apertures and make connections between intra-
cranial venous sinuses and extracranial veins. These connections are of clinical
significance in determing the spread of injection from extracranial foci to venous sinuses,
for example, the spread of infection from the mastoid to the venous sinuses or from the
paranasal sinuses to the cavernous sinus (Browder and Kaplan, 1976; Kaplan and
Browder, 1976; Ozveren et al., 2002).
Innervation of the cranial dura mater

Sensory nerve supply of the cranial dura mater derived mostly form cranial nerve V
(trigeminal nerve) but also from the first three cervical spinal nerves, and the cervical
sympathic trunk.
Less well-established meningeal branches have been described arising from the
vagus and hypoglossal nerves and possibly from the facial and glossopharyngeal nerves.
In the anterior cranial fossa, the dura is innervated by meningeal branches of the
anterior and posterior ethmoidal nerves and anterior filaments of the meningeal rami of
the maxillary (nervus meningus medius) and mandibular (nervus spinosus) divisions of
the trigeminal nerve. The nervus spinosus re-enters the cranium through the foramen
spinosum with the middle meningeal artery. The nervus spinosus contains sympathic
postganglionic fibres from the middle meningeal plexus.
Intraoperative mechanical stimulation of the falx may trigger the trigeminocardic
reflex (Bauer et al., 2005).
The dura in the posterior cranial fossa is innervated by ascending meningeal branches
of the upper cervical nerves which enter through the anterior part of the foramen magnum
(second and third cervical nerves) and through the hypoglossal canal and jugular foramen
(first and second nerves).
Meningeal branches from the vagus apparently start from the superior vagal ganglion
and are distributed to the dura mater in the posterior cranial fossa. Those from the
hypoglossal leave the nerve in its canal and supply the diploe of the occipital bone, the
dural walls of the occipital and inferior petrosal sinuses, and much of the floor and
anterior wall of the posterior cranial fossa. Sensory nerve endings are restricted tot the
dura mater and cerebral blood vessels, and are not found in either the brain itself, or in
the arachnoid or pia mater. Stimulation of these nerve endings causes pain and is the
basis of certain forms of headache (Standring, 2008).
Leptomeninges and CSF space

The term leptomeninges refers to the inner two of the three membranous layers
which envelop the brain: the arachnoid membrane and the pia mater.
1763
The prefix lepto-, denoting “fine” or “thin” in Greek, contrast of the pachymeningeal
layer called the dura mater (Nolte, 1993).
Whereas the dura mater and pia mater have been described since the time of the
Egyptians some 3000 years ago, the arachnoid mater was not clearly distinguished as a
separate layer until the work of the Dutch anatomist Gerardus Blaes in 1666 (Bakay, 1991).
The term arachnoid was applied by the Dutch anatomist Frederick Ruysch (1638-
1731), the name roughly meaning “spider-like” and referring to the web-like structure of
these layers (Sanan, van Loveren, 1999).
Key and Retzius (1875) made a landmark contribution to the anatomy of these layers.
Cranial arachnoid
The arachnoid is a delicate nonvascular membrane between the dura and pia mater
which passes over the sulci without following their contours. Ultramicroscopic exami-
nation of the arachnoid has revealed two components making up this layer: an outer layer,
often referred to as the arachnoid barrier cell layer; and an inner layer, often referred
to as the arachnoid trabeculae.
The arachnoid barrier cell layer is a layer of two to three tiers of flattened cells. These
cells have a large, oval- to spindle-shaped nucleus, multiple cytoplasmic processes, scant
mitochondria, small rough endoplasmic reticulum and a poorly developed Golgi apparatus
(Nabeshima et al., 1975; Oba and Nakanishi, 1984; Haines and Frederickson, 1991).
A basement membrane underlies the arachnoid barrier cell layer and separated this
layer from the underlying subarachnoid space (Haines and Frederikson, 1991). Numerous
zonulae occludens (tight junctions), zonulae adherens and macula adherens (desmosomes)
are found interconnecting cells of this layers. These connections function as the meningeal
barrier, which excludes proteins and other large molecules from diffusing from the blood
to the CSF in the subarachnoid space (Nabeshima et al., 1975; Haines and Frederikson,
1991, Peters et al., 1991).
Thus, the intravascular introduction of dyes will stain the dura but not the underlying
meningeal layers, the CSF or the brain parenchyma (Nabeshima et al., 1975).
Occasional intercellular connections (viz. desmosomes) also exist between the cell
of the arachnoid barrier cell layer in the cranium and the overlying dura.
From the arachnoid surface trabeculae, known as arachnoid trabeculae, extends
toward and attach to the external surface of the pia mater.
Trabeculae, traverse the subarachnoid space from the deep layer of the arachnoid
mater to the pia mater, as thin, web-like chordae. Each trabecula has a core of collagen
which is coated by leptomeningeal cells. In the meshes of the arachnoid trabeculae
(subarachnoid space), cerebrospinal fluid circulates. The cells of the trabecular layer have
smaller nuclei, abundant mitochondria, and well-developed Golgi apparatuses and rough
endoplasmatic reticulum (Oba and Nakanishi, 1984). Extracellular collagen fibrils are
found outside of the cells in this layer (Nabeshima et al., 1975). Gap junctions often
connect cells within the arachnoid trabecular layer. The extensive gap junction allow the
arachnoid cells to function together to allow the passage of small molecules from cell to
cell (Peters et al., 1991).
1764
The trabeculae that cross the subarachnoid space may form compartments,
particularly in the perivascular region, which may facilitate directional flow of CSF
throughout the subarachnoid space.
The subarachnoid space therefore contains CSF, the larger arteries and veins which
traverse the surface of the brain. These arteries and veins in the subarachnoid space are
coated by a thin layer of leptomeninges, often one cell thick.
Cranial and spinal nerves that traverse the subarachnoid space, to pass out of cranial
or intervertebral foramina, are coated by a thin layer of leptomeninges which fuses with
the arachnoid at the exit foramina. Blood vessels from the vascular meninges perforate the
arachnoid to reach the pia mater. However, each vessel is completely surrounded by
arachnoid fibroblasts and, therefore, the vessels never actually enter the subarachnoid space.
Scanning electron microscopy, however, has revealed that the pia actually surrounds
the vessels as it travels through the subarachnoid space but does not accompany the vessel
as it descends into the brain parenchima. Instead, the pia surrounding the vessel spreads
out over the pia which is covering the surface of the brain, effectively occluding the
perivascular space from the subarachnoid space (Hutchings and Weller, 1985). Thus, the
Virchow-Robin space communicates with the brain extracellular space rather than the
subarachnoid space.
The subarachnoid space who lies between the arachnoid and pia mater is connected
with the fourth ventricle of the brain by the median aperture (foramen of Magendie), and
by the paired lateral apertures (foramina of Luschka). Foramen of Magendie provides
communication with the cisterna magna, and foramina of Luschka open into the
subarachnoid space at the cerebellopontine angle, behind the upper roots of the
glossopharyngeal nerves.
Structurally and functionally, arachnoid barrier layer prevents cerebrospinal fluid in
the subarachnoid space from reaching the dura.
Arachnoid cisternae
In certain areas of the brain, the arachnoid completely diverges from the pia mater,
forming expanded subarachnoid spaces known as subarachnoid cistern. These more
expansive spaces identified as subarachnoid cisterns, are continuous with each other
through the general subarachnoid space.
As CSF percolates through the subarachnoid spaces it also enters the subarachnoid
cisterns, filling them.
The largest cistern, the cisterna magna is formed between the caudal aspect of the
cerebellum and the dorsal surface of the medulla oblongata, as the arachnoid stretches
across these two structures rather than following the contour of the brain. The cistern is
continuous above with the lumen of the fourth ventricle through its median aperture, the
foramen of Magendie, and below with the subarachnoid space of the spinal cord.
The pontine cistern is a much smaller space than the cisterna magna. It is located
along the ventral surface of the pons and communicates with the subarachnoid space of
the spinal cord caudally, and rostral to the pons, with the interpeduncular cistern.
1765
The basilar artery runs through the pontine cistern into the interpeduncular cistern.
The interpeduncular cistern is located between the right and left cerebral peduncles
and receives CSF by way of the two lateral foramina of Luschka, from fourth ventricle.
Anteriorly, the interpeduncular cistern extends to the chiasmatic cistern, frequently, the
two are considered to be a single cistern, the cisterna basalis, even though the optic
chiasma is interjected between them.
The cistern of the lateral fossa is formed by the arachnoid as it bridges the lateral
sulcus between the frontal, parietal, and temporal opercula. It contains the middle cerebral
artery.
The cisterna ambiens (superior cistern) or the cistern of the great cerebral vein is
located in the vicinity of the superior aspect of the cerebellum, the corpora quadrigemina,
and the pineal body. This superior cistern lies posterior to the brain stem and third
ventricle, and occupies the interval between the splenium of the corpus callosum and the
superior cerebellar surface.
The great cerebral vein traverse the superior cistern, and the pineal gland protrudes
into it.
Several smaller cisterns have been described, including the prechiasmatic and
postchiasmatic cistern, which are related to the optic chiasma, and the cistern of the
lamina terminalis and the supracallosal cistern, all of which are extension of the
interpeduncular cistern and contain the anterior cerebral arteries.
The subarachnoid space also extends through the optic foramen into orbit where it
is bounded by the optic nerve sheath. The latter is formed by fusion of the arachnoid and
dura mater, and surrounds the orbital position of each optic nerve as far as the back of
the globe, where the dura fuses with the sclera of the eye.
For the carotid bifurcation aneurysms, the entire carotid-ophthalmic and carotid
cisterns must be opened, as well as the cisterns surrounding the proximal A1 and M1
arteries.
Arachnoid granulations and villi

Arachnoid granulations were first illustrated by Vesalius in 1543 who observed their
imprint on the inner surface of the skull. In 1705, Pacchioni described the structures, but
mistakenly thought that they were lymph nodes which irrigated the meninges.
In 1853, Faivre is accredited with correctly proposing that the granulations serve to
drain CSF.
Arachnoid granulations are small, but visible mushroom-shaped evagination of the
arachnoid protruding into the lumen of the dural sinuses (Fig. 22.2).
Arachnoid villi and arachnoid granulations differ in term of size and complexity.
Villi are macroscopic structures that are present in the superior sagittal sinus of the fetus
and newborn infant. Granulations are visible to the naked eye by the age of 18 months in
the parieto-occipital region of the superior sagittal sinus, and by age of 3 years in the
laterally located sinuses of the posterior fossa. They increase in number and size with
increasing age, and become more lobulated and complex, and may become calcified,
1766
when they are known as Pacchionian bodies. The name Pacchionian granulations has
been used to refer to large, elaborate arachnoid granulations in horses and in man
(Wolpow and Schaumburg, 1972).
These outpushing of the arachnoid mater and subarachnoid space through the wall
of dural venous sinuses, very often are located close to points where veins enter the sinus.
Thus, most of the arachnoid granulations are associated with lacunae lateralis,
diverticula of the superior sagittal sinus, although some just into the lumen of the sinus.
At the base of each arachnoid granulation a thin neck of arachnoid mater projects
through an aperture in the dural lining of the venous sinus and expands to form a core of
collagenous trabeculae and interwoven channels.
Fig. 22.2. An arachnoid granulation (Modified). Morphology of CSF drainage pathways in man
(Raimond, ed, Kida and Weller, 1994).
1767
Fig. 22.3. Coronal section through the vertex of the skull to show the relationships between the superior
sagittal sinus, meninges and arachnoid granulations (adapted from Drake, Vogl and Mitchell, 2005).
The core of an arachnoid granulation, composed of arachnoid trabeculae, is

continuous with the subarachnoid space and is surrounded by the epithelioid layer of the
arachnoid and of the dura, forming a membrane that is two cell layer thick.
As the arachnoid granulation evaginates into the lacuna lateralis, it is invested by
some cellular and collagenous elements of the meningeal dura mater, which in turn is
surrounded by the endothelial lining of the blood vessel (Patestas and Gartner, 2008).
The core is surmounted by an apical cap of arachnoid cells, some 150 µm thick
(Fig 22.2). Channels extend through the cap to reach the subendothelial regions of
granulation. The cap region of each granulation is attached to the endothelium of the
sinus over an area some 300 µm diameter, whereas the rest of the core of the granulation
is separated from the endothelium by a fibrous dural cupola (Kida and Weller, 1994).
The arachnoid granulation are most prominent along the margins of the great
longitudinal fissure, commonly in the lateral lacunae of the superior sagittal sinus, and
also protruding directly into the lumen of the sinus (Fig. 22.3).
These leptomeningeal structures are often thought of as one-way valves from the
CSF compartment to the venous compartment. They are commonly called arachnoid villi,
when microscopic, or arachnoid granulation, when macroscopic.
According to Yamashima (1988), the functional ultrastructure of the human
arachnoid villi was studied to clarify drainage channels of cerebrospinal fluid. The apical
portion of each villus was usually covered by the arachnoid cell layer alone with no
endothelial investment, whereas most of the stromal central core was further encompassed
by a fibrous capsule with an endothelial investment. According, the CSF-blood interface
was assumed to be in both the endothelial cells and the arachnoid cell layer. The former
1768
were characterized by abundant micropinocytotic vesicles and occasional intracyto-

plasmatic vacuolis, whereas the latter was characterized by numerous extracellular
cisterns measuring 10 micron in maximal diameter. There were no free communications
such as endothelial open junctions or endothelium-lined tubules. In the villi affected by
subarachnoid hemorrhage, endothelial cells were intact and continuous despite the
erythrocyte packed subendothelial space, which appeared to be on the verge of rupturing.
Intracytoplasmic vacuoles, measuring less than 1 micron diameter, sometimes contained
serum protein-like substance. It is conceivable that, in human arachnoid villi, the
extracellular cisterns of the arachnoid cell layer contribute to the passive transport of
CSF, whereas micropinocytosis and vacuolization mechanisms of the endothelial cells
are availed for active transport (Yamashima, 1988).
The function of arachnoid granulation remains controversial. It has long been
thought that CSF from the subarachnoid space enters into the core of the arachnoid
granulation and from there penetrates, probably by osmosis, the epithelioid layers of the
arachnoid granulation and the endothelial lining, to escape into the lacuna lateralis.
Fig. 22.4. The superior

sagittal sinus opened up
after removal of the cranial
vault. Note the fibrous
bands that cross the sinus
from two of the
venous lacunae
(after Standing, 2008).
1769
Studies of Kida and Weller (1994), Greitz (2004) and Zakharov et al. (2004), have
shown that CSF may also be resorbed throughout the ventricles and subarachnoid space,
through the walls of pial and subarachnoid vessels. Moreover, there is a growing body
of experimental evidence that significant volumes of CSF may be absorbed into
extracranial lymphatics in animals. It has been suggested that extracranial lymphatics
play a major role in CSF reabsorption at relatively low pressures, but that other routes,
including arachnoid granulations, become increasingly important as CSF pressure rises.
A connection between parenchymal interstitial fluid and extracranial lymphatics in
humans has yet to be convincingly demonstrated (Crossman, 2008).
Therefore, the function of the arachnoid granulations is transporting CSF manu-
factured by the choroid plexuses of the ventricles of the brain into the vascular system.
Cerebrospinal fluid acts as a fluid buffer for the protection of the central nervous
system. Cerebrospinal fluid also compensate for changes in blood volume in the cranium,
allowing the cranial contents to remain at a constant volume.
No one element of the cranial contents (brain, blood or cerebrospinal fluid) can
increase, except at the expense of the other (Monroe-Kellie doctrine).
It is important to note that although the arachnoid granulations protrude into the
venous sinuses, they are always separated from the blood by the endothelial lining of the
dural sinus / lacuna lateralis (Kida and Weller, 1994) (Fig. 22.4).
Pia mater
This vascular membrane is composed of: (1) an inner membranous layer, the intima
pia (Key and Retzius, 1875), and (2) a more superficial epipial layer. The intima pia,
adherent to underlying nervous tissue, follows its contours closely and is composed of
fine reticular and elastic fibres. Where blood vessels enter and leave the central nervous
system, the intima pia is invaginated forming a perivascular space.
The intima pia, like the arachnoid, is avascular and derives its nutrients by diffusion
from the cerebrospinal fluid and the underlying nervous tissue (Millen and Woollam,
1961, 1962). The epipial layer is formed by a meshwork of collagenous fibre bundles
continuous the arachnoid trabeculae. Cerebral vessels lie on the surface of the intima pia
within the subarachnoid space.
However, the cranial pia mater is the most delicate layer of the cranial meninges,
which closely invests the surface of the brain, from which it is separated by a microscopic
subpial space. It follows the contours of the brain into concavities and the depths of
fissures and sulci. The cranial pia also lines the basal cistern.
The cranial pia mater is composed of a single layer (or, occasionally, two layers) of
attenuated fibroblasts that form a transparent epithelioid membrane that closely invests
the contours of the brain (Patestas and Gartner, 2008).
Since the pia mater is vascular, it has numerous blood vessels associated with it;
however, because this is so, thin vessels are in part surrounded by cells derived from the
arachnoid trabecular and, in part, by cells of the pia mater. Deep to the epithelioid sheath
is a thin, discontinuous layer of collagen and elastic fibres. The end-feet of the astrocytes
1770
form a protective layer that underlies this subpial extracellular matrix, separating it from
the neural tissue (Kida and Weller, 1994; Patestas and Gartner, 2008). The cell of the pia
mater are modified fibroblasts similar to the cells of arachnoid membrane. Their
morphology is often undistinguishable from that of the arachnoid cells (Cloyd and Low,
1974; Peters et al., 1991).
According to Kida and Weller (1994) and Crossman (2008), pia mater is formed
from a layer of leptomeningeal cells, often only 1 to 2 cells thick, in which the cells are
joined by desmosomes and gap junctions but few, if any, tight junctions. The cells are
continuous with the coating of the subarachnoid trabeculae and separated from the basal
lamina of the glia limitans by bundles of collagen and fibroblasts-like cells, and the
arteries and vein that lie in the subpial space (Fig. 22.5).
The intimal layer of pia is an avascular layer. In contrast to the overlying epipial
layer, it is adherent to the brain throughout all its contours. It has been proposed that the
vascular epipial layer represents the contribution of mesenchyme to the pia, while the
avascular intimal layer represents the contribution of the neural crest (Millen and
Woollam, 1961).
Fig. 22.5 The relationships between the dura, the leptomeninges and the blood vessels that enter and leave
the cerebral cortex. The subarachnoid space is divided by trabeculae (after Crossman, 2008).
1771
The cranial arachnoid trabeculae join the pia to the arachnoid mater. Although very
thin and apparently fragile, cranial pia nonetheless exhibits a high level of stiffness, thus
influencing the mechanical properties of the brain. The cerebral vessels that are in the
subarachnoid space have a superficial covering of the cranial pia. Smaller vessels ramify
on the pia before penetrating the brain (Barshes et al., 2005). Thus, pia mater is reflected
from the surface of the brain onto the surface of the blood vessels in the subarachnoid
space, which means that the subarachnoid space is separated by a layer of pia from the
subpial and perivascular space of the brain (Nicholas and Weller, 1988).
Interrelationships of the pia mater and the perivascular (Virchow-Robin) spaces in
the human cerebrum was studied by Zhang et al. (1990).
In addition to separating the subarachnoid space from the brain tissue, the pia mater
also serves to degrade neurotransmitter substances and to prevent material in the
subarachnoid space from entering the nervous tissue, as evidenced by the inability of
erythrocytes to cross the pia mater in case of subarachnoid hemorrhage (Barshes et al.,
2005; Patestas and Gartner, 2008).
Thus, despite its delicate nature, the pia mater appears to form a regulatory interface
between the subarachnoid space and the brain. Pial cells contain enzymes such as catechol
-O- methyltransferaze and glutamine synthetaze (which degrade neurotransmitters), they
also exhibit pinocytotic activity and ingest particles up to 1 in diameter.
A subpial space of variable thickness exists between the pia and the basement
membrane of the glial limitans (outer glial layer of the brain and spinal cord). This space
contains collagen fibrils (Cloyd and Low, 1974). Pial cells are often joined to arachnoid
trabecular cells with desmosomes (Haines and Frederikson, 1991).
1772
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1775
CEREBRAL ASYMMETRY
in nonhumans
Introduction
For many years it has been generally believed that lateralization of cerebral function
was uniquely human characteristic and in fact arose on response to specifically human
selective processes (Levy, 1969).
However, evidence of lateralization of functions has been documented in the brain
of several animal species (Le May, 1977; Webster and Thurber, 1978; Nottebohm, 1981;
Glick et al., 1982), and some studies (Denenberg, 1981; Glick et al., 1982) have brought
into question the view (Warren, 1977) that the human pattern of cerebral laterality is
“species unique”.
In 1885, Ernest Mach postulated a mechanism of spatial behavior that applied to
both man and beast. He recounted: “The idea that the distinction between right and left
depends upon an asymmetry, and possibly in the last resort upon a chemical difference,
is one which has been present to me from my earliest years”. It was not until about nine
decades later that the implications of Mach’s idea were investigated. In 1873, Nothnagel
found that injections of chromic acid into the striatum caused a bending of the trunk to
the side of lesion (Wilson, 1914).
Ferrier (1876) stated that “irritation of the corpus striatum causes general muscular
contraction on the opposite side of the body. The head and body are strongly flexed to
the opposite side, so that the head and tail become approximated.
In 1921, Lashley described a rotation syndrome after combined unilateral destruction
of caudate nucleus and the motor cortex above it.
“Circus” movements after “parietal and unsymmetrical injuries to the striatum” in
rats were reported by Herrick in 1926.
Thus, when subjected to repeated testing with the same dose of a given drug, some
animals rotate consistently to the left whereas others rotate to the right. It was further
shown that nonlesioned, untreated rats also rotate at night (the more active half of their
circadian cycle) and that this rotation is in the same direction as that induced by
amphetamine (Glick and Cox, 1978).
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23. Cerebral asymmetry in nonhumans
Mach (1885) noted that “human being and animals that have lost their direction
move, almost without exception, nearly in circle”.
Behavioral and biological laterality is also ubiquitous in many nonhuman species,
with many instances of asymmetry being at least analogous to asymmetries found in
humans. At least some may also be homologous, in the sense of sharing common
structures and developmental origins.
Motor asymmetries have been discovered for a number of species, with individuals
sometimes showing very strong left-right preference. Furthermore, preference seems to
depend on variables such as age and sex and on specific task demands. Despite these
caveats, in several species of primates there tends to be left-hand preference for reaching
and maintaining postural control but a right hand preference for manipulation and other
skilled activities (Hellige, 2002).
According to Corballis (1997), in freely moving animals, there is strong evolutionary
pressure for bilateral symmetry, in the placement of sense organs and limbs and those
parts of the brain that are associated to them. This is so because such animals must be
equally attentive to both sides of space and be able to move in a straight line.
For other systems, asymmetry may be favored in such cases as a way of packaging
organs more efficiently into the body cavity or of packaging cognitive functions more
efficiently into a brain whose size is limited.
Once an organism’s brain becomes functionally asymmetric, additional asymmetries
are likely to arise via the same kind of snow ball mechanism (Christman, 1997; Banich
and Heller, 1998).
That is, some of the additional evolutionary adaptations are favored by the
environment, with the result that those adaptations also become asymmetric.
This would occur regardless of whether the environment favored hemispheric
asymmetry for a new adaptation. As this process is repeated, the extent of functional
brain asymmetry increases (Hellige, 1993, 2002).
One of the most fundamental divisions of the human brain is that of the left and right
cerebral hemispheres.
Numerous studies have revealed the consistent presence of both behavioral and
anatomical asymmetries that reflect the specialized capacities of each hemisphere
(Gazzaniga, 1970; Geschwind and Galaburda, 1985; Annett, 1985; Galaburda, 1991;
Bogen, 1993). Apparently, the left and right hemisphere appear to be anatomically and
biologically identical, leading one to wonder why there are so many functional
asymmetries.
However, postmortem studies of anatomy and structural imaging studies of the living
brain have documented a number of consistent physical asymmetries.
The ability to measure structure within the normal, living brain has made it possible
to search for relationships between structural asymmetry and a variety of other
nonmotoric behavioral and perceptual asymmetries, but no clear-cut picture has emerged.
Perhaps those structural characteristics revealed by contemporary imaging
techniques are still relatively gross.
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However, it should be noted that attempts to relate structural asymmetries to other

dimensions, such as sex, psychopathology, and cognitive deficit, have produced mixed
results.
Among other things, laterality in other species indicates that the emergence of
language is not a prerequisite for the emergence of other behavioral and biological
asymmetries. However, the various functional aspects of asymmetry correlate with each
other weakly or not at all. The relative independence of different manifestations of
asymmetry indicates that there are probably several different environmental influences
to determine an individual’s pattern of asymmetry. Thus, the asymmetry patterns that are
characteristic of mature individuals are likely to be rooted in early stage of ontogenetic
development.
Rogers (1997) has shown that it is possible to eliminate these population-level
asymmetries by including the eggs in darkness and to reverse them by experimentally
manipulating the embryo. Similar developmental scenarios might exist for humans.
Various possibilities have been suggested in humans, in which certain functional
asymmetries could arise from the interaction of maturational asymmetries and changes
in the nature of environmental stimulation.
By being more responsive to early environmental influences, the right hemisphere
may become dominant for perceiving various nonphonetic sounds, for processing global
properties of visual stimuli and for maintaining postural control.
In contrast, by being on a later developmental trajectory, the left hemisphere may
be saved for complementary specialization that involves processing of more detailed or
finer-grained information and sensorimotor feedback and control. In addition, other
asymmetric growth spurts during childhood may provide a mechanism for the continuing
unfolding of functional hemispheric asymmetry (Hellige, 2002).
Thus, there are indications that even in newborns there is a kind of left hemisphere
dominance for speech perception and that activation of the left and right hemispheres is
associated with positive and negative emotions, respectively.
According to Heilman (1997), the existence of hemispheric asymmetry for emotion
has led to consideration of the possible relationship of laterality to psychopathology.
Among the more promising hypotheses is the idea that schizophrenia is related to
dysfunction of an anterior region within the left hemisphere, an area that is believed to
be important for language and for controlling parietal areas involved in attention. In a
complementary way, depression has been linked to disturbances of the right hemisphere.
At the other end of the life span, it has been hypothesized that performance of the
right hemisphere declines more rapidly in old age than does performance of the left
hemisphere (Corballis, 1997; Christman, 1997; Beeman and Chiarello, 1998; Banich and
Heller, 1998).
The seeds of laterality may be related to asymmetry in the molecules and particles
of which all living things are constructed.
The existence of the left hand preference for visual guided reaching in present-day
prosimians suggests that at least some type of motor asymmetry was present in our
ancestral line by the time of our line branched from the prosimian line, nearly 60 million
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years ago (mya). This left-hand advantage extends to some species of Old World
monkeys. In addition, some species of Old World monkeys show right hemisphere
dominance for processing monkey faces and left hemisphere dominance for processing
communicatively relevant vocalizations (Corballis, 1997; Christman, 1997; Banich and
Heller, 1998; Hellige, 2002).
The similarity of these asymmetries to those of humans suggests that their precursors
were present in our last common ancestors, approximately 40 mya (Corballis, 1997).
Asymmetry in rats
The phenomenon of rotation in normal rats was one of the first indications that
normal animals may have an intrinsic asymmetry in nigrostriatal function that is
accentuated by some drugs. Several experiments have been concerned with the general
functional significance of nigrostriatal asymmetry revealed by the rotation studies. All
results suggested that rotation is a stereotyped form of spatial behavior and that spatial
tendencies are derived, at least in part, from a nigrostriatal asymmetry.
Comparison of rats having stronger or weaker directional biases showed that the
strength of the biases was related generally to overall learning ability, as well as
specifically to the ability to discriminate between left and right (Zimmerberg et al., 1978).
Rats lacking clear spatial biases were hyperactive, had difficulty in learning a variety of
tasks, and were unable to distinguish left from right.
Cerebral lateralization in the rat is clearly present at birth, changes during
development, and is sexually dimorphic.
However, it is apparent that left- and right-sided rats differ behaviorally as well as
neurochemically (Valdes et al., 1981). Behavioral and cerebral differences between left-
and right-handed human beings are well documented. Whereas right-handed individuals
almost always have left cerebral dominance, left-handed individuals have either right
cerebral dominance, left cerebral dominance, or ambivalent dominance (Kolb et al., 1982).
It was generally observed that approximately 50% of rats rotated to the right and
50% to the left.
Because left frontal cortex was usually more active than right frontal cortex, the
implication was that, in a large population, more rats should have right side preferences
than left side preferences and right preferences should be greater than left preferences
(Glick and Ross, 1981). These scientists reexamined the data accumulated for the past
several years and determined that, in a group of 602 rats, there was small (54.8%) but
significant (p < 0.025) right population bias; right-sided rats were also found to be both
more active and have greater side preferences than left-sided rats (Glick and Ross, 1981).
Research with rats and chicks has also demonstrated asymmetry for emotional
behaviors. For example, in both handled rats and chicks the right hemisphere tends to
produce emotional activity, whereas the left hemisphere tends to inhibit emotional
activity. In addition to providing interesting instances of laterality, effects such as these
also illustrate the importance of reciprocal activity between the left and right sides of the
brain (Rogers, 1997; Vallortigara, 2000).
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Ross and Glick (1981) speculated that the increase in population bias in human being
as compared with rodents is perhaps related to the evolution and growth of the cortex in
relation to subcortical structures. The population bias would be expected to increase in
parallel with phylogeny if the left - right asymmetry in cortex increased as the cortex
became more convoluted in conjunction with an enhanced modulation of subcortical
structures (e.g., striatum).
Differences in the neurotransmitters found in each hemisphere have also been
associated with differences in hemisphere function (Glick et al., 1982; Direnfeld et al.,
1984; Robinson and Starkstein, 2002; Berridge et al., 2003) and sex (Arato et al., 1991).
It has been hypothesized that the distribution of two important neurotransmitters is
asymmetric in the human brain, with dopamine being more prevalent in the left
hemisphere and norepinephrine being more prevalent in the right hemisphere.
These differences may have an evolutionary foundation, for they have been found
in primates and other animals (Nottebohm, 1979; Geschwind and Galaburda, 1985;
Corballis, 1991).
The lateralized size differential in primates is paralleled in some species by left
lateralization for vocal communication (Mac Neilage, 1987).
Rossor et al. (1980) investigated directly the possibility of neurochemical symmetry
in postmortem human brain. They measured concentration of three to five neuro-
transmitters in nine structures, both left and right sides, of normal brain; their primary
goal was to learn whether left - right differences need consideration in comparisons of
abnormal and normal brain. Because only one substance (GABA-gamma-aminobutyric
acid) in one structure (substantia nigra) showed a left - right difference by a t test, it was
concluded that neurochemical laterality, although still possibly a substrate for functional
asymmetry, was unlikely to be an important consideration in such comparisons. After-
wards, data were eventually subjected to correlational analysis.
The results showed that human brain indeed has lateral asymmetries in several
structures and transmitter systems (Glick et al., 1982).
There were several similarities between the human data and those previously
reported in rats.
Thus, even though information on cerebral dominance was lacking in human beings
it was clearly demonstrated that levels of ChAT (choline acetyltransferaze) and DA
(dopamine) were higher in the left globus pallidus than in the right globus pallidus. Since
most of the patients (N = 14) should have been right-handed pallidal ChAT and DA levels
were obviously higher on the side contralateral to hand preference (Glick et al., 1982).
Similarly, in rats striatal DA levels were higher on the side contralateral to side
preferences (Zimmerberg et al., 1974).
The similarities between rat and human brains demonstrated that studies in the rat
may reveal mechanisms and functions of brain asymmetry that are relevant to human
beings.
In sum, studies in rats and mice focus on two rather different types of asymmetry.
1780
The first emphasizes postural and motor asymmetries such as paw preference and
direction of movement. Unlike handedness in humans, most postural asymmetries in
rodents are random across the population.
The second type of lateralization in rodents is more interesting in the current context
because it is seen in the population, much as we saw in birds.
As in humans, there is an asymmetry in the anatomy of the two cerebral hemispheres,
with the right hemisphere being larger. In addition, the cortex of the right hemisphere is
thicker, especially in the visual and posterior parietal regions, and this difference is
modulated by hormones.
Male rodents have a greater difference than females.
Both prenatal stress and postnatal castration were shown to abolish the anatomical
asymmetry in males, presumably owing to alterations in the normal hormonal
environment (Stewart and Kolb, 1988, 1994).
Evidence is accumulating to support the conclusion that the hemisphere is
specialized for the processing of species-specific calls.
The auditory asymmetry may represent a left-hemisphere advantage in the
processing of rapidly changing acoustic stimuli. Claims that the right hemisphere is
specialized for controlling emotional and spatial behavior remain speculative (Kolb and
Whishaw, 2003).
The results of studies on nonhuman primates and rodents show that the increased
aggression in males is probably a result of the male hormone testosterone both pre- and
postnatally. Castrating infant male rats or monkeys decreases aggression and treating
female with testosterone increases aggression (Kolb and Whishaw, 2003). Generally,
men are physically more aggressive than women.
An intriguing asymmetry in rodents is an apparent lateralization of immune
responses. So, lesions in the left hemisphere of mice, but not in the right, suppress T-cell
function. The T-cell suppression may be due to lateralized control of the secretion of the
specific hormones, such as prolactin. Whether similar asymmetries exist in the control
of immune functions in humans is not yet known, although such asymmetry has been
hypothesized by Kang et al. (1991).
Stress may alter anatomical asymmetries in the rat cortex, and many researchers
have suggested that stress may also alter functional asymmetries.
Thus, Denenberg (1981) hypothesized that specific experiences might alter the two
hemispheres differentially during development. So, Denenberg’s results could be
explained by the lateralized responses to various stress-related hormones, such as
glucocorticoids.
Asymmetry in birds
In 1981, Nottebohm severed the hypoglossal nerve in canaries and found a severe
disruption in the bird’s song after left lesions but not after right ones. Subsequent work
showed anatomical differences in the structure controlling birdsong in the two avian
hemispheres and identified many song-related regions as sexually dimorphic.
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Although a left hemisphere dominance for song has been shown in many species of
songbirds (and even in chickens), it is not characteristic of all songbirds. Apparently, the
zebra finch has little anatomical and functional asymmetry, even though it sings. It may
be that the lateralization is not for singing itself but for some other still-unrecognized
feature of bird vocalizations (Kolb and Whishaw, 2003).
Nottebohm’s discovery led to interest in the possibility of asymmetry in the visual
system of birds because the optic nerve of the most birds cross over almost completely
at the optic chiasma. Thus, each hemisphere receives most input from a single eye.
Furthermore, birds have no corpus callosum and, although other small commissures
connect the hemisphere, there is less interhemispheric transfer in birds than in mammals.
According to Bradshaw and Rogers (1993), the right-eye system is specialized for
categorizing objects, such as food versus nonfood items, whereas the left-eye system is
specialized for responding to the unique properties of each stimulus (color, size, shape,
and so forth), including topographical information. Thus, the left hemisphere of birds
appears to be specialized for categorizing objects and the right for processing
topographical information.
The result of research by Horn (1990) showed an asymmetry for memory formation
in the chicken brain.
One curious asymmetry is in sleep. Birds spend much of their sleep time with only
one hemisphere asleep, which presumably allows them to monitor the environment. On
the other hand, it also means that there is a transient asymmetry in sensory processing,
which might have significant implications for the animals. Kolb and Whishaw (2003)
note parenthetically that unilateral sleep is also characteristic of cetaceans (whales,
dolphins) and seals, a sensible adaptation in mammals that can drown.
In sum, lateralization takes many forms in the brain and is not a unique property of
mammals.
Asymmetry in nonhuman primates

A trend in primate brain evolution is the shift of the Sylvian fissure from an almost
vertical orientation to a more horizontal orientation. This shift implies an expansion of
the parietal lobe, which pushes the Sylvian fissure low, usually in the left hemisphere.
Thus, there is a greater upward slope in the Sylvian fissure in the right hemisphere in
apes and Old-World monkeys. In addition, the right frontal lobe and left occipital lobe
extend farther in the same species, again as in humans. So, there is an asymmetry in the
Sylvian fissure (Mac Neilage et al., 1988; Kolb and Whishaw, 2003).
Bradshaw and Rogers (1993) concluded that the asymmetries in the language-related
parietal and temporal lobe structure were not fully developed until the arrival of hominids.
Contemporary chimpanzees show right-hand dominance for certain high-level tasks as
well as left and right hemisphere dominance for processing communicatively relevant
symbols and certain visuospatial tasks, respectively. Thus, it is possible that these
asymmetries were present in the last common ancestors we shared with chimpanzees,
appropriately 5 mya (Corballis, 1997). So, it is sufficiently plausible to suggest that some
1782
forms of hemispheric asymmetry were already present in our ancestral line before the
first hominids emerged approximately 4 mya (Hellige, 2002).
Tool making and language are both forms of praxis and involve properties such as
recursion, embeddedness, and generativity. Both gestural communication and vocali-
zation also require sequences of precisely time movements. So, there may have been
pressure for the same brain hemisphere to become dominant for those aspects of
vocalization and language that are shared with tool making and gestural communication.
Thus, the increased development of language-related structures in the posterior part of
the brain is suggested to have occurred after the advent of hominids.
Studies in the 1977 by Warren unequivocally failed to find any systematic hand
preference in rhesus monkeys, and he concluded that observed preferences are task
dependent and are strongly affected by learning.
Afterwards, Mac Neilage et al. (1987) argued that, because earlier studies
concentrated on particular types of movements, a hand preference in monkeys has been
overlooked. Their basic premise is that primates evolved a preference for reaching with
one limb (the left) while supporting the body with the other (the right). As the prehensile
hand developed and primates began to adopt a more upright posture, the need for a hand
used primarily for postural support diminished and, because this hand was free, it became
specialized for manipulating objects. They later proposed that the hand specialization
was accompanied by hemispheric specializations: a right-hemisphere (left-hand)
perceptuomotor specialization for unimanual predation (grasping fast-moving insects or
small animals) and a left-hemisphere specialization for whole-body movements.
A significant difficulty of this hypothesis is that studies of limb use in primates are
hampered by poor control of myriad confounding factors including species, age, sex, task
difficulty, learning, and sample size (Kolb and Whishaw, 2003). One objection to the
theory is that cerebral asymmetry must precede handedness, and whether this asymmetry
did indeed precede handedness and why it might have done so is not clear.
Hoster and Ettlinger (1985) trained 155 rhesus monkeys to make a tactile response
in a task in which the subjects had to discriminate a cylinder from a sphere. The results
showed that the 78 monkeys spontaneously using the left hand outperformed the 77 using
the right hand. Thus, as in the humans, the right hemisphere outperformed the left one,
suggesting an asymmetry.
Hamilton and Vermeire (1988) took a different approach. They taught 25 split-brain
monkeys to discriminate two types of visual stimuli that have shown lateralization in
humans. In one task, the animals had to discriminate between pairs of lines differing in
slope by 15º (15º versus 30º, for example, or 105º versus 120º). For each pair, the more
vertical line was designated as positive, and the monkey received a food reward for
choosing it.
Most monkeys learned the line-orientation discriminations faster with the left
hemisphere.
The second task required the animals to discriminate different monkey faces. The
right hemisphere of most animals showed better discrimination and memory of the faces.
1783
There was no hemispheric difference in making a simple discrimination of black-and-

white patterns.
However, the line-orientation task appears to be one in which humans would show
a right-hemisphere bias, rather than the left-hemisphere bias shown by the monkeys. At
any rate, it is safe to conclude that there appears to be evidence in nonhuman primates of
hemispheric specialization for the processing of different types of visual information.
There is also evidence from primates that the two hemispheres may differ in their
production of facial expressions. The number of facial expressions elicited from the right
hemisphere was greater than the number made when using the left hemisphere, which is
what one would predict from studies of humans.
In another study, Hauser (1993) found that the left side of the monkey’s face began
to display facial expression before the right, and it was more expressive. A similar result
was reported for humans. Many studies look asymmetries in auditory perception.
Thus, Dewson (1977) removed the superior temporal gyrus (roughly equivalent to
Wernicke’s area in humans) in four rhesus monkeys, producing a lasting deficit on an
auditory-visual task if the lesion was in the left hemisphere but not if it was in the right.
The monkeys were required to press a panel that activated one of two acoustical stimuli,
either a 1-kilohertz (kHz) tone or white noise. They were then presented with two panels,
one green and one red. If the tone was heard, the monkeys pressed the red panel; if the
white noise was heard, they pressed the green panel to receive the reward. Lesions on
the left impaired performance of this task, but lesions on the analogous area on the right
did not.
Petersen et al. (1978) compared the ability of Japanese macaques to discriminate
between communicatively relevant sounds and irrelevant sounds. The animals could
discriminate relevant sounds presented to the right ear better than those presented to the
left. The researchers suggested that the Japanese macaques engage in the left-hemisphere
processing in a way that is analogous to that in humans.
The results of a further study by Heffner and Heffner (1984) support this conclusion.
However, with training, the animals with left temporal lesions were able to relearn the
task. When the remaining side was later removed, the animal had a permanent deficit in
the task and were unable to relearn it.
There are certain parallels between left hemisphere language dominance in human
and asymmetries in other species for the production and perception of vocalization.
In Japanese macaque, the left hemisphere is dominant for the discrimination of
species-specific vocalization that is relevant for communication but not for discrimination
of other vocalization (Petersen et al., 1978; Rogers, 1997; Springer and Deutsch, 1998;
Vallortigara, 2000). Also, chimpanzees that have been trained to use certain visual
symbols to communicate, there is evidence of left hemisphere dominance for processing
those symbols but not for processing other nonmeaningful symbols. There is evidence
that the ultrasonic calls emitted by rat pups are processed preferentially by the left
hemisphere of their mother and it is well-known that there is left-brain dominance for
the control of song in some species of song birds (Hellige, 2000, 2002).
1784
In language-trained chimpanzees, there is a right hemisphere advantage for

processing the location of a line within a geometric figure and for identifying complex
visual patterns that are not relevant for communication. In addition, rhesus monkeys have
been reported to have right hemisphere superiority for recognizing monkey faces.
In rats, there is evidence that the right hemisphere may be more involved than the
left hemisphere in spatial exploration, although the asymmetry emerges only in rats that
have been handled during the course of their early development.
Pigeons and newly hatched chicks exhibit left hemisphere dominance for visual
pattern discrimination. In chicks, this population-level bias occurs because light strikes
only the right eye during a critical period of incubation during which the visual system
is developing rapidly (Hellige, 1993; Provins, 1997; Rogers, 1997; Springer and Deutsch,
1998; Ivry and Robertson, 1998; Hellige, 2002).
Some biological asymmetries found in the human brain characterize the brain of
certain primates, although the nonhuman asymmetries are smaller and less frequent than
those of humans. For example, the brain of both humans and apes shows the kind of
counterclockwise torque described earlier, and in chimpanzees as well as in humans, the
Sylvian fissure tends to be longer on the left side than on the right side (Kosslyn, 1996;
Hellige, 2002).
However, it is difficult to know which laterality effects in other species are truly
homologous to the effects found in humans. Nevertheless, the presence of so many
asymmetries in other species provides a useful range of animal models that can be used
to learn about the development of laterality across the life span of an individual and
across evolutionary time (Corballis, 1997; Provins, 1997; Rogers, 1997; Vallortigara,
2000; Hellige, 2002).
Handedness and functional asymmetry

People use the word sinister as a synonym for wicked or evil.
Originally a Latin word, meaning “left-hand side”, the contemporary English meaning
implies that left-handedness has been historically viewed at best as strange or unusual.
Thus, handedness refers to the fact that most people consistently use the same hand
for task in which skill and dexterity are required and only one hand can be used.
Thus, a person who almost always uses his or her right hand when writing,
throwing a ball, cutting with a knife, or using a hammer would be defined as being
right-handed. Estimates of number of right-handers in the population are between 88
and 92% (Coren, 2002).
However, the handedness is only one aspect of a group of lateral biases.
In footedness, humans also show a right-sided bias, with approximately 80-82% of
the population being right footed (Bishop, 1990; Springer and Deutsch, 1995).
Coren (1990, 2002) demonstrates eyedness by consistently choosing the same eye
to right down a telescope or to peep through a small hole. They would be showing
earedness by usually choosing the same ear to listen to the faint ticking of a clock or to
press against a door to hear noises on the other side.
1785
Thus, approximately 66-71% of the population is right-eyed, and 58-60% are right-
eared.
Today, terms such as southpaw in baseball suggest an evolution of tolerance toward
left-handers and in professional sports, even admiration (Kolb and Whishaw, 2003).
The most common cited statistics for left handedness in the general population is
10%, referring to the percentage of people who write with the left hand. But, when
broader criteria are used, estimates range from 10% to 30%. The problem is that
handedness is not absolute; some people are nearly totally left- or right-handed, whereas
others are ambidextrous (that is, they use either hand with equal facility) (Annett, 1970).
The evidence of left handedness on Annett’s task varies from a low of about 6% when
cutting with scissors to a high of about 17% when dealing cards.
The evolution of handedness

Some animals must manipulate something with only one paw, but the nature of
human handedness is unique among mammallian species. Thus, most cats, rats, and
monkeys are right- or left-pawed. Although individual animals show behaviors analogous
to handedness, there is one major difference between these animals and humans. Whereas
9 of 10 humans are right-handed, in other species the proportion of right- and left-sided
individuals is approximately 50%. In other words, there is no right-sided bias to the
animal population (Coren, 1990, 2002).
It is possible to estimate the handedness of humans over history to determine if we
were always right-handed.
Coren’s study shows that examined paintings and drawings, reasoning that if artists
were drawing from life, then they would draw the tools and weapons held by their models
in the hand that they saw the person using (Coren, 2002). Analysis of more than
50 centuries of such drawings found that the proportion of right-handedness remained at
approximately 90% from the Paleolithic Era (the Old Stone Age) until the present
(Corballis, 1991; Coren, 2002). The date when right-handedness became dominant in
our species can be pushed further back in time.
Language and tool use are among the critical milestones that set us apart from other
species, and along with other milestone, such as walking upright, they are likely to have
played an important role in the continued evolution of brain laterality (Corballis, 1991).
An upright stance freed the hands from the need to provide postural support and
minimized their use in locomotion. As a result, the hands were under less environmental
pressure to be controlled in a symmetrical fashion.
The precursors of handedness in other primate species suggest that sufficient
asymmetry already existed to produce a bias toward right-handedness for the more skilled
aspects of movement. In fact, an analysis of the flaking patterns on stone tools
manufactured by Homo habilis suggests that the majority of the population was already
right-handed as far back as 1.5-2 mya.
Certain structural asymmetries, as longer left hemisphere Sylvian fissure, were also
characteristic of the brains of H. habilis (Corballis, 1997; Hellige, 2002).
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Thus, tool use and language seem to have interacted in a synergistic fashion to
produce dramatic changes in human skull in the period from 10,000 to 30,000 years ago
(Hellige, 2002).
Paleontologists have examined the wear patterns on stone tools and the grinding
marks on devices used to grind grains.
These tools and implements date back between 8 000 and 35 000 BC and involve
the early humanoid Homo habilis, one of the earliest tool makers. The wear patterns of
these artefacts confirm that, even at that early date, there appeared to be a consistent
predominance of right-handers. Perhaps the most astounding evidence derives from more
than 1.5 million years ago, involving one of our very early hominid ancestors, Australo-
pithecus (Corballis, 1991; Coren, 2002).
Although Australopitheciens were not tool makers, they were tool users and would
pick up an appropriately sized and shaped rock or stick and use it for a weapon.
Examination of the skulls of baboons hunted by this early precursor to humans shows
that the vast majority of these hominids were already right-handed (Corballis, 1991;
Iacoboni and Zaidel, 2002; Coren, 2002).
Theories of hand preference

Environmental theories
Behavioral utility. Sometimes called the theory of the Peloponnesian Wars, or the
sword-and-shield hypothesis, the behavioral theory proposes that a soldier who held his
shield in his left hand better protected his heart and improved his chances of survival.
Because the left hand was holding the shield, the right hand became more skilled at
various offensive and defensive movements, and it was eventually used for most tasks.
The mother, like soldier, used the free right hand for executing skilled movements (Kolb
and Whishaw, 2003).
Environmental reinforcement. The child’s world is right-handed in many ways,
which reinforces the use of that hand. In addition, children in many countries, including
the United Sates, have been forced to write with their right hands (Kolb and Whishaw,
2003). However, reinforcement theory also seems to be contradicted by what happened
when children were given their choice of hand in learning to write: the incidence of left-
hand writing rose to only 10%, which is the norm in most societies that have been studied
It should not be surprising that a technological and constructed environment created
by a species in which 9 of 10 individuals are right-handed should have a bias toward use
of the right hand.
Most tools, equipment, furniture and everyday implements such as scissors, gear
shifts, in cream scoops, pencil, sharpeners, are biased toward right-handed usage.
Given this right bias to the environment, it is apparent that left-handers are forced
to learn to do many things with their right hand that a right-hander would never be
expected to do with his or her left hand. If there is a learned component to handedness,
this should serve to greatly reduce the number of left-handers in the world (Coren, 2002).
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The presence of approximately 10% of left-handers among humans is even more

surprising due to direct cultural pressures to make the whole world right-handed. At some
level, our society seems to intensely dislike left-handers and for proof one need go no
further than our own language (Coren, 2002).
The very word “left” in English comes from the Anglo-Saxon word “lyft”, which
means “weak” or “broken”.
Many common phrases in the English language demonstrate their culture’s negative
view of left-handedness.
For instance, a left handed compliment is actually an insult. In general, there is not one
positive phrase to be found in the language regarding “left” or “left-handed” (Coren, 2002).
In French, the word for left is gauche, which also conveys the meanings “crooked”,
“ugly”, “clumsy”, “awkward”, “uncouth”, and “bashful”. The German word for left-hand
is links. The dictionary definition of the term linkisch is “akward, clumsy, and maladroit”.
Even in early Latin, in which the word for left was sinister, it had already taken on its
alternate contemporary meaning of evil (Coren, 2002).
Culture and language

In many societies, use of the left hand for activities as eating or writing is considered
impolite, insulting, or the sign of ill breeding. It is therefore not surprising that perhaps
between 70% and 80% of the population of left-handers report that parents or teachers made
over attempts to change them to right-handers. Some of these attempts could be quite brutal,
involving punishment for using the left hand or even strapping or tying the left hand down
to force right hand use (Coren, 1993; Springer and Deutsch, 1995; Coren, 2002).
What is most surprising about cultural pressure on handedness is that it has such a
poor success rate. For female, 4 of 10 left-handers fail to change their handedness,
whereas 3 of 4 males do not shift their handedness. Even for those who do change, the
change appears to be only for selected actions, which society puts direct pressure on.
Thus, a left-handed child may learn to eat or write with his or her right hand, but he or
she will still throw a ball or brush his or her teeth with the left hand (Coren, 2002). Thus,
handedness is not a causal learned set of behaviors. Handedness is determined early and
is quite intractable to change.
Those who speak two or more languages may develop a different pattern of language
organization from that of those who speak only one.
Uyehara and Cooper (1980) and Obler et al. (1982) support the idea that Asian and
Native American languages may be represented more bilaterally in the brain than, for
example, Spanish. Thus, inferring cultural differences in brain organization from the
results of these studies should be done with caution.
Rapport et al. (1983) evaluate the language function of seven Chinese-English
polyglots whose mother tongue was Malay, Cantonese or Hokkien. Their methods
included the use of carotid sodium amobarbital, cortical stimulation, and clinical
examination. They found that all these patients were left-hemisphere dominant for both
Chinese and English languages: this was no consistent evidence of increased participation
by the right hemisphere for language functions.
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All language is probably located in the left hemisphere of bilingual people, but the
possibility that their left-hemisphere language zones are enlarged or slightly different in
microorganization from those who speak only a single language cannot be ruled out (Kolb
and Whishaw, 2003).
However, the major effects of language and environment on the brain heavily depend
on culture rather than on changes in cerebral asymmetry.
Exposure to multiple languages does not change the normal pattern of brain
organization.
The results of PET studies by Klein et al. (1995, 1999) showed that no difference
appears in the cerebral activation for various language tasks performed in English and
French or English and Chinese by bilingual subjects. In particular, no activation of the
right hemisphere was recorded for any task in either language. There may, however, be
subtle differences in the cerebral representation of different languages within the left
hemisphere.
Using fMRI, Kim et al. (1997) showed that languages acquired later in life may
activate different, although adjacent, frontal regions from those activated by first
languages or second languages acquired early in life.
Sensory or environmental deficits

Brain organization in nonhearing people. Educational and congenital deafness are
alleged to alter hemispheric specialization. As for hearing people, left hemisphere damage
produces aphasia in people who converse by using American Sign Language, possibly
because of the praxic requirements. However, the congenitally deaf may have atypical
patterns of cerebral organization (Kolb and Whishaw, 2003).
Several laboratories report independently that congenitally deaf persons fail to show
the usual right-visual-field superiority in tasks of linguistic processing. These data could
result from strategy differences due to absence of auditory experience (Kolb and
Whishaw, 2003).
Neville (1977) reported that, during the perception of line drawing, visual evoked
potential was significantly larger on the right in children with normal hearing and
significantly larger on the left in deaf children who used American Sign Language to
communicate.
There was no asymmetry at all in deaf children who could not sign but merely used
pantomime to communicate. Neville (1977) inferred that the deaf signers acquire their
visual signing symbols, much as hearing children acquire auditory verbal symbols, with
the left hemisphere.
Thus, visuospatial functions may have developed in the left hemisphere of people
who sign, producing an unexpected left-hemisphere effect.
So, absence of language experience somehow abolished certain aspects on cerebral
asymmetry or that the expression of cerebral asymmetry depends on language experience.
Although congenital deafness may be suspected to affect the development of certain
aspects of cerebral lateralization, the results of studies of brain-injured patients show little
difference between hearing and nonhearing subjects.
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Hickock et al. (2001) studied 34 congenitally deaf patients who had unilateral brain
injury. Left-hemisphere patients performed poorly on all measures of language use,
whereas right-hemisphere patients performed poorly on visuospatial tasks, exactly what
would be expected in hearing people.
Environmental deprivation. According to Kolb and Whishaw (2003), an adolescent
girl endured nearly 12 years of extreme social and experimental deprivation and
malnutrition. She was discovered at the age of 13½ , after having spent most of her life
isolated in a small closed room during which time she was punished for making any
noise. After her rescue, Genie’s cognitive development was rapid, although her language
lagged behind other abilities.
Results of her dichotic listening tests showed a strong left-ear (hence right-
hemisphere) effect for both verbal and nonverbal environmental sounds. The right ear
was nearly totally suppressed. Genie’s right hemisphere appeared to be processing both
verbal and nonverbal acoustical stimuli, as would be the case in people with a left
hemispherectomy in childhood (Kolb and Whishaw, 2003).
Probably, in the absence of appropriate auditory stimulation, the left hemisphere lost
the ability to process linguistic stimuli. Another explanation is that Genie’s left
hemisphere was either being inhibited by the right hemisphere or by some other structure
or it was performing other functions (Kolb and Whishaw, 2003).
Environmental accident. This theory postulates a genetically determinated bias
toward being right handed.
Left-handedness develops through a cerebral deficit caused by accident. This idea
comes from correlating statistics on the incidence of the left-handedness and neurological
disorders in twins. About 18% of twins are left handed, close to twice the occurrence in
the population at large. Twins also show a higher incidence of neurological disorders,
which are suspected to result overwhelmingly from intrauterine crowding during fetal
development and stress during delivery (Kolb and Whishaw, 2003).
Bakan et al. (1973) argued for a high probability of stressful birth among left-
handers, which increases the risk of brain damage to the infant and so maintains the
statistical incidence of left handedness.
So, most deviation from the expected pattern of fetal development occurs because
something has gone wrong during pregnancy or the birth process. For this reason,
researchers began to focus on the handedness and birth stressors or pregnancy
complications. Such pathological factors are associated with an increased likelihood of
left-handedness.
These factors are premature birth, prolonged labor, Rh incompatibility, breech delivery,
multiple birth, anoxia, cesarian delivery, and forceps or other instruments to assist the
delivery. Thus, it is not surprising that older mothers (aged 40 and older), who are prime
candidates for pregnancy and birth complications, are more than twice as likely to produce
left-handed children (Bishop, 1990; Corballis, 1991; Springer and Deutsch, 1995).
Functional cerebral organization of left-handers

Left-handers can be subdivided into two genetic populations differing in cerebral
organization: familial left-handers, who have a family history of left-handedness, and
1790
nonfamilial left-handers, who have no such family history. According to Hécaen and
Sauguet (1971), the performance of nonfamilial left-handed patients with unilateral
lesions is like that of right-handed patients on neuropsychological tests. In contrast,
familial left-handers perform much differently, suggesting to Hécaen and Sauguet that
they have a different pattern of cerebral organization.
Rasmussen and Milner (1977) found that, in left-handers, language is represented
in the left hemisphere in 70%, in the right hemisphere in 15%, and bilaterally in 15%.
Kimura (1999) reported the incidence of aphasia and apraxia in a constitutive series of
520 patients selected for unilateral brain damage only. The frequency of left-handedness
in this population was within the expected range, and these patients did not have a higher
incidence of either aphasia or apraxia than right-handers did. In fact, the incidence of
aphasia in left-handed patients was approximately 70% of the incidence in right-handers,
exactly what would be predicted from the sodium amobarbital studies. Thus, although a
small proportion of left-handers have bilateral speech or right-hemisphere speech, the
majority of left-handers do not (Kolb and Whishaw, 2003).
However, there is larger incidence of left-handedness among mentally defective
children and children with various neurological disorders than it is found in the general
population. Thus, it can be excepted by probability alone that right-handed children with
left-hemisphere damage would switch to right-hemisphere dominance than in the reverse
direction.
Anatomical theories
One anatomical theory attributes right-handedness to enhanced maturation and
ultimately greater development of the left hemisphere.
Generalizing from assumption, the theory predicts that nonfamilial left-handers will
show an asymmetry mirroring the right-handers, whereas familial left-handers will show
no anatomical asymmetry (Kolb et al., 1982; Kolb and Whishaw, 2003).
However, no study has specifically considered anatomical asymmetry with respect
to handedness or to familial history and handedness (Kolb and Whishaw, 2003).
Another theory have emphasized that many animals have a left-sided developmental
advantage that is not genetically coded (Morgan, 1977).
For example, there is a left-sided bias for location of the heart, the size of the ovaries
in birds, the control of birdsong, the size of left temporal cortex in humans, the size of
the left side of the skull in the great apes, and so on (Morgan, 1977; Moscovitch, 1977).
This predominance of left-favoring asymmetries puts the celebrated left-hemisphere
speech dominance in the more general, structural perspective of all anatomical asym-
metries (Moscovitch, 1977).
Because neither genetic evidence nor genetic theory accurately predicts these human
asymmetries, Morgan (1977) assumes that they all result from some fundamental
asymmetries in human body chemistry. Thus, Morgan’s theory fails to explain left-
handedness in the presence of other normal asymmetries such as the location of the heart
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Hormonal theories
Geschwind and Galaburda (1987) proposed that brain plasticity can modify cerebral
asymmetry significantly during early life, leading to anomalous patterns of hemispheric
organization. A central factor in their theory is the action of the sex linked male hormone
testosterone in altering cerebral organization during development.
Testosterone does affect cerebral organization; so it is reasonable to suggest that
differences in testosterone level might influence cerebral asymmetry (Mc Glone, 1977, 1980).
Thus, while in the uterus, if the fetus is exposed to an elevated concentration of the
hormone testosterone, this fact could produce left-handedness by altering the relative
rate at which the two hemispheres of the brain develop. Since testosterone is also the
male hormone, this could also explain the observation that men are more likely to
become left-handed than are women (approximately 12% left-handedness for men versus
8% for women).
Geschwind and Galaburda (1987) suggested that testosterone’s effect is largely
inhibitory, meaning that higher-than-normal levels of testosterone will slow development,
possibly acting directly on the brain or indirectly through an action on genes. Thus,
testosterone’s inhibitory action is largely in the left hemisphere, allowing the right
hemisphere to grow more rapidly, which leads to altered cerebral organization and, in
some people, to left-handedness.
Testosterone also affects the immune system, leading to more diseases related to a
malfunctioning immune system (Gualtieri and Hicks, 1985).
Unfortunately, the bulk of available evidence does not support the model of
Geschwind-Galaburda theory (Grimshaw et al., 1993; Bryden et al., 1994).
Although there is sufficient homogeneity there is also sufficiently reliable heterogeneity
to warrant consideration of individual variation. Of particular interest has been the possible
relationship of functional hemispheric asymmetry to a number of other between-subject
factors including handedness, sex, intellectual ability and psychopathology.
Thus, hand dominance is determined by a variety of genetic and environmental
factors, both before and after birth.
Environmental influences include pre- and postnatal trauma, prenatal levels of
testosterone and other hormones (higher prenatal levels of testosterone are associated
with greater incidence of left-handedness), asymmetric positioning of the fetus in the
utero, as well as the biases of the postnatal world.
There are many effects of fetal hormone levels on brain development in other species
and in humans there are clear relationships between biological sex and cognitive ability.
For example, women tend to outscore men on tests of verbal fluency, and men tend to
outscore women on tests of spatial ability. Thus, the incidence of left-handedness is
slightly higher in men than in women, consistent with the hypothesis that higher levels
of fetal testosterone promote development of the right hemisphere relative to the left
hemisphere (Corballis, 1997; Halpen, 2000), so, deficits in patients with unilateral brain
damage, finding evidence of greater functional hemispheric asymmetry in men than in
women.
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Behavioral laterality studies using neurologically intact men and women provide, at
best, weak support for the hypothesis of greater functional laterality in men because the
results have been quite variable.
There are indications that individual variations in brain laterality may be related to
individual differences in cognitive ability. Relative performance on tests of verbal and
visuospatial ability are related to handedness. There is also evidence that extreme
intellectual precocity, especially for mathematical reasoning, is related to advanced
development of the right hemisphere relative to the left, perhaps as a result of increased
levels during fetal development (Hellige, 2000, 2002).
Genetic theories
Given the evidence that handedness pattern in humans extends far back into
evolutionary history it is not surprising that the vast majority of theories of handedness
have included the suggestion of a genetic factor.
Most genetic models for handedness postulate a dominant gene or genes for right-
handedness and a recessive gene or genes for left-handedness (Hardyck and Petrovich
1977). Annett (1970) rejects this idea in favor of a dominant gene (rs+) responsible for
the development of speech in the left hemisphere.
Annett (1970) hypothesizes further that the processes necessary for left-hemisphere
speech also confer advantage on motor control in the right hand. The recessive form of
the gene (rs– ) result in no systematic bias either for speech or for handedness. If both
alleles occurred equally often statistically, then 50% of the population would be (rs+– )
and the rest would be equally divided, 25% (rs++) and 25% (rs– –). People in the rs+– and
rs++ groups, constituting 75% of the population, would show a left-for-speech and right-
handedness shift. The remaining 25%, people in the rs– – group, would show no bias; so
half would, by chance, be left-handed (Annett, 1970).
Thus, Annett’s model predicts about 12.5% left-handers, which is pretty close to
what we see in the population. Unfortunately, her theory neither predicts the number of
left-handers with right-hemisphere speech nor attempts to differentiate between familial
and nonfamilial left-handers (Kolb and Whishaw, 2003).
Unfortunately, the empirical evidence on handedness does not strongly support
genetic theories. Some theorists are still trying to work out more sophisticated
mathematical descriptions that might show that handedness is inherited; however, there
still is a strong element of doubt in the data (Coren, 2002).
One way to investigate the contributions of genes and experience to cerebral
organization is to analyze MRIs from normal brain and to vary the genetic relationships
among the subjects.
Thompson et al. (2001) varied genetic relatedness by comparing the MRIs of unrelated
people, dizygotic twins, and monozygotic twins. The results were striking, because the
quantity of gray matter, especially in frontal, sensorimotor, and posterior language cortex
was dissimilar in unrelated people but almost identical in monozygotic twins.
Because monozygotic twins are genetically identical, we can presume that any
differences must be attributable to environmental effects. Curiously, there was an
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asymmetry in the degree of similarity, the left-hemisphere language zones being

significantly more similar than the right in the monozygotic twins. The high similarities
among monozygotic twins likely accounts for their highly similar cognitive abilities.
Thus, perhaps the most compelling evidence against a simple, strong genetic
determinant for handedness comes from the results of studies that compared the
handedness of monozygotic or identical twins with those of dizygotic or fraternal twins.
Twin studies are usually considered as providing the clearest indication of the presence
or absence of inherited components for most behavioral traits. Monozygotic twins have
an identical set of genes they come from a single egg fertilized by a single sperm, that
later split into two individuals in the early stages of cell division.
Dizygotic twins come from two eggs cells fertilized by different sperm; hence, they
share only the level of genetic similarity that we would find between any pair of brothers
or sisters. This means that, at a minimum, if there is a genetic component in handedness,
one would at least expect that pairs of monozygotic twin would be more likely to have
same handedness than dizygotic twins.
According to Coren (2002), there is no difference between monozygotic twins and
dizygotic twins with regard to the likelihood that they will share the same handedness.
Even more striking is that the likelihood that any form of twins will have the same
handedness is no greater than if we randomly chose pairs of unrelated individuals and
determined whether or not they had the same handedness (Coren, 2002).
Although there is a genetically fixed bias toward right-handedness, and this implies
some set of genes that determine handedness, in specific situations there might be partial
penetrance (which simply means that the gene does not express its full set of
characteristics). If the right-handed gene does not express itself, then handedness becomes
a matter of chance, and a left-hander could be the result.
Natural left-handedness could occur due to nonpathological differences in the uterus
during pregnancy, such as the position in which the fetus lies. If the fetus comes out with
the head directed to the back of the mother’s right side (right occiput anterior position),
the child is more likely to be left-handed than if it were born from the more common left
occiput anterior position (with the head directed toward the back of the mother’s left side)
(Coren, 2002).
More recently, social analysis of gene expression was performed by Sun et al. (2005).
They were able to show clear asymmetric gene expression in human brain for the first
time. The asymmetry was variable between individuals, and quite regional, being most
marked in perisylvian regions for the genes studied in most details.
Striking, the pattern of asymmetry in mouse was random for the cause of one gene,
LM04, whereas it was clearly enriched in right perisylvian cortex in majority of humans.
They have yet to identify any genes with a predominantly frontal asymmetry, although
several genes they identified using microarrays in their such screen have frontal lobe
enrichment. Such genes are candidates for patterning of frontal lobe structures and can
be used to probe evolutionary conservation of frontal lobe regions across primate species
and lower mammals (Preuss et al., 2004).
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This raises one very important issue – the relevance of animal models to human
development and function. Thus, what happens in the mouse is relevant to humans, but
many human diseases have proven hard to model in the mouse.
According to Abu-Khalil et al. (2003), there are few human studies of important
patterning molecules or signaling centers involved in mouse brain patterning.
Similarly, given those various diseases, such as schizophrenia and some dementias,
witch affect the integrity of the cortex, the high correlation between the brain structures
of identical twins could account for the strong genetic component of these diseases
(Thompson et al., 2001; Kolb and Whishaw, 2003).
Sex differences in cerebral organization

Generally, men and women behave differently. On average, women tend to be more
fluent than men in using language, and men tend to perform better than women in spatial
analysis. But sex, like handedness, is not absolute (Kolb and Whishaw, 2003).
Sex differences in behavior

In her book, Sex and Cognition, Kimura (1999) examines five cognitive behaviors
and finds compelling sex differences in all – namely, motor skills, spatial analysis,
mathematical aptitude, perception, and verbal abilities. Table 23.1 summarizing her major
conclusion, shows that the verbal-spatial dichotomy is a gross oversimplification.
Table 23.1
Summary of sex differences in cognitive behavior (after Kimura, 1999)
Behavior Sex difference Basic reference
Motor Skills
Target throwing and catching M>F Hall and Kimura, 1995
Fine motor skills F>M Nicholson and Kimura, 1996
Spatial Analysis
Mental rotation M>F Collins and Kimura, 1997
Spatial navigation M>F Astur et al., 2002
Geographical knowledge M>F Beatty and Troster, 1987
Spatial memory F>M McBurney et al., 1997
Mathematical Aptitude
Computation F>M Hyde et al., 1990
Mathematical reasoning M>F Benbow, 1988
Perception
Sensitivity to sensory stimuli F>M Velle, 1987
Perceptual speed F>M Majeres, 1983
Sensitivity to facial and
body expression F>M Hall, 1984
Visual recognition memory F>M McGivern et al., 1998
Verbal Abilities
Fluency F>M Hyde and Linn, 1988
Verbal memory F>M McGuinness et al., 1990
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Motor skills
One obvious difference in motor skills is that, on average, men are superior in
throwing objects, such as balls or darts at targets, and are superior at intercepting objects
thrown toward them. These differences are present in children as young as 3 years of age
(Kimura, 1999). In contrast, women have superior fine motor control and surpass men in
executing sequential and intricate hand movement. However, young girls are superior to
young boys at each of these skills (Mc Coby and Jacklin, 1974; Majeres, 1983; Hall,
1984; Hall and Kimura, 1995).
Spatial analysis
According to Kimura (1999), although men are generally believed to be superior to
women at spatial analysis, this belief applies to only some types of spatial behaviors.
Men are superior at tasks requiring the mental rotation of objects, and they are superior
at spatial navigation tasks (Collins and Kimura, 1997).
Subjects are given a tabletop map on which they must learn a designated route. On
average, men learn such tasks faster and with fewer errors than women do (Kimura,
1999). Although this map test is not a real-world test of spatial navigation, the findings
are consistent with those of studies showing that the men have better overall map
knowledge than women (Corsi-Cabrera et al., 1997).
Male superiority in spatial-navigation tasks contrasts with female superiority on test
of spatial memory. Women are better than men at identifying which objects have been
moved. In the map test women have better recall for landmarks along the route. Thus,
the spatial information itself is not the critical factor in this sex difference; rather the
critical factor is required behavior, that is the way in which the spatial information is to
be used (Kimura, 1999; Kolb and Whishaw, 2003).
In accounting for findings that the spatial performance of right hemisphere damaged
patients is adversely affected by lesions occurring anywhere in a fairly wide area while
only those left hemisphere damaged patients with relatively severe damage to a well
defined area show impaired performance on spatial tasks, De Renzi and Faglioni (1967),
too, hypothesized more diffuse representation of functions in the right hemisphere and
more focal representation in the left.
Mathematical aptitude
Stanley founded The Study of Mathematically Precocious Youth (SMPY) in
1971. The project primarily included holding talent search with the intent of identifying
gifted youth, particularly in the area of mathematics.
Within a 15-year period, thousands of 12-year-old children were given the Scholastic
Aptitude Test Mathematics exam. Stanley was particularly interested in the children with
the highest scores because they might be assumed to be least affected by extraneous
environmental factors such as social pressures. Benbow and Stanley (1980) and Benbow
(1988) have shown that the sex difference increased as the scores increased: 12 times as
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many “gifted” boys than girls at the top. Furthermore, this ratio was found worldwise
across different cultures, although the absolute scores varied with the educational system.
Benbow and Stanley (1980) have searched for support for a primarily environmental
explanation of their data but they have not found it.
On average, men get better scores on tests of mathematical reasoning, whereas
women do better at tests of computation.
Perception
According to Kimura (1999), perception refers to the recognition and interpretation of
the sensory information that we take in from the external world (Kolb and Whishaw, 2003).
There would appear to be no a priory reason to expect a sex difference, but the
evidence suggests that women are more sensitive to all forms of sensory stimulation,
except for vision. However, women are more sensitive than men to facial expressions
and body postures. They also detect sensory stimuli faster.
Males may have one perceptual advantage, however, in that their drawing of
mechanical things such as bicycles are superior (Kolb and Whishaw, 2003).
Verbal ability
According to Kimura (1999), women are superior to men on tests of verbal fluency,
on average, and they have superior verbal memory. The sex differences in verbal ability
have long been known, in part because girls begin talking before boys and appear to be
more fluent throughout life.
For example, the Chicago Word-Fluency Test asks subjects to write as many words
beginning with “s” as possible in 5 minutes and as many four-letter words beginning with
“c” as possible in 4 minutes. Girls performed better – at some ages, by as many as 10
words – in a broad study that Kolb and Whishaw (2003) did with children.
It is often argued that sex-related differences are related to life experience, but
Kimura (1999) argues compellingly that this relation is unlikely for the cognitive
behaviors. In particular, most if not all these differences, as well as differences in
aggression are found in both children and adults, and the differences are largely
unaffected by training. There are certainly training effects on most tests, but the effects
tend to be of similar magnitude in both sexes (Kolb and Whishaw, 2003).
The same sex differences seem unrelated to life experience.
Sex differences in the brain structure

In one study, Ankney (1992) compared the brain of men and women of the same
body size and found that men’s brains are about 100 g heavier than women’s throughout
the range of body sizes.
In another study, Pakkenberg and Gundersen (1997) found that the male brains in
their sample had about 4 billion more neurons than female brains, and body size did not
more account for this difference.
1797
Lynn (1994) and Alexopoulos (1996) have concluded that men have small (4 point)
advantage in IQ scores, on average.
When different cerebral regions are examined separately, with results being
correlated for relative size of the cerebrum of different brains, the findings of many studies
show areal-dependent sex differences, as summarized in Table 23.2.
Table 23.2
Summary of sex differences in gross brain anatomy
Sex difference Basic reference

Differences Favoring Female Brains
Larger language areas Harasty et al., 1997
Larger medial paralimbic areas Filipek et al., 1994
Larger lateral frontal areas Schlaepfer et al., 1995
Greater relative amount of gray matter Gur et al., 1999
More densely packed neurons in Witelson et al., 1995
temporal lobe
Differences Favoring Male Brains
Larger medial frontal areas Goldstein et al., 2001
Larger cingulate areas Paus et al., 1996
Larger amygdala and hypothalamus Swaab et al., 1985
Larger overall white matter volume Gur et al., 1999
Larger cerebral ventricles Murphy et al., 1996
Larger right planum parietale Jänke et al., 1994
More neurons overall Pakkenberg and Guderson, 1997
Sex-related differences in brain volume are not diffusely spread across the cerebral
hemispheres. Generally, female brain appear to have larger volumes in region associated
with language functions, in medial paralimbic regions, and in lateral frontal areas (Filipek
et al., 1994; Schlaepfer et al., 1995; Harasty et al., 1997). In addition, women have a
greater relative amount of matter and in the temporal lobe, they have more densely packed
neurons (Witelson et al., 1995; Gur et al., 1999).
Conversely, men have a larger medial frontal (Goldstein et al., 2001), and cingulate
areas (Paus et al., 1996), a larger amygdala and hypothalamus (Swaab and Fliers, 1995),
a larger overall white matter volume (Gur et al., 1999), a large cerebral ventricle (Murphy
et al., 1996), and a larger right planum parietale (Jäncke et al., 1994).
However, male brains tend to have more neurons (Pakkenberg and Gundersen, 1997)
and female brain more neuropils (that is dendrites and axons) per neuron (Kolb and
Whishaw, 2003).
The influence of sex hormones

Goldstein et al. (2001) did a large MRI study of sexual dimorphism in the male and
female brain, and have documented that sex differences were largest in regions of the
human brain in which the results of studies of nonhumans have shown that there are sex
1798
differences in the developmental expression of estrogen or androgen receptors. Thus,

Goldstein team proposed that a large part of the observed sex differences in cerebral
organization is related to differences in the distribution of receptors for gonadal hormones
during development.
However, their conclusions have limitations, because they do not consider
differences in cerebral organization that might be related to circulating hormones in
adulthood. Furthermore, the findings in many studies suggest that the rate of cell death
during aging may be higher in men than in women, especially in the frontal lobe (Kolb
and Whishaw, 2003).
The presence of sex differences in overall size and in relative size of different regions
does not speak directly to the question of whether there are sex differences in the degree
of cerebral asymmetry (Kolb and Whishaw, 2003).
However, there are several reliable sex differences in anatomical asymmetry:
Left larger than right in the planum temporale is seen more often in men than in
women. An MRI study by Kulynych et al. (1994) found a large asymmetry in males (left,
38% larger) but no asymmetry in females. Because Aboitiz et al. (1992) obtained different
results, this result must be interpreted with caution.
Witelson and Kigar (1992) quantified the slope of the Sylvian fissure with reference
to various cortical landmarks. This quantification led to separate measure of the horizontal
and vertical components of the Sylvian fissure. They found that, although the horizontal
component was larger in the left hemisphere of both sexes, men had a larger horizontal
component in the left hemisphere than women had.
Thus, male brain has a larger asymmetry in the Sylvian fissure than had female brain.
These sex differences are important in the organization of language-related functions.
Jäncke et al. (1994) found that the planum parietale, which favor right hemisphere,
is about twice as large in men as in women.
The callosal studies have proved controversial, but consensus appears to be that the
posterior part of the callosum (the splenium) is significantly larger in women than in men
(Witelson, 1985).
Allen and Gorski (1991) found that women have a larger anterior commissure than
men have. This difference is likely due to a difference in the number of neural fibres in
the two sexes, a difference presumably due to some difference in the way in which the
two hemispheres interact.
Kimura (1983) found that the ridges in our fingerprints, which are established early in
fetal life, are asymmetrical, with the finger on the right hand having more ridges. Given that
this pattern is visible in utero, it could not be influenced by environmental factors such as
differences in limb use. Kimura (1983) found that most people have the asymmetry, but
women are far more likely to show an optical pattern, much as we saw for brain asymmetries.
The cortical part of Kimura studies and others is that the pattern of ridges is correlated with
performance on certain cognitive tests (Kolb and Whishaw, 2003).
Generally, EEG (Corsi-Cabrera et al., 1997), MEG (Reite et al., 1995), blood flow
(Gur et al., 1982; Esposito et al., 1996), PET (Haverkort et al., 1999), and fMRI (Pugh
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et al., 1996; Frost et al., 1999) studies show more asymmetrical activity in men than in
women, particularly in language-related activities (Table 23.3).
Table 23.3
Sex differences in imaging studies
Measure Result Representative references

EEG Males more asymmetrical Corsi-Cabrera et al., 1997
MEG Males more asymmetrical Reite et al., 1995
Blood flow Females > males Gur et al., 1982
Females > males Esposito et al., 1996
in frontal lobe tests
PET Males > females Haverkort et al., 1999
in anterior blood flow
Females > males
in posterior blood flow
fMRI More left-hemisphere activity in Pugh et al., 1996
language-related tasks
(but see Frost et al., 1999)
in males
Measures of the blood flow, including those obtained with the use of PET, show
that women have more rapid overall blood exchange than men have, possibly due to the
difference in the density of neurons or the distribution of gray matter and white matter
From these results there are differences in anatomical organization and functional
activity of the male and female brain. Presumably, the anatomical differences correspond
to the functional differences that researchers have found (Kolb and Whishaw, 2003).
Because of these anatomical and functional differences, two types of lesion-related
differences are possible in the neurological patients.
Such difference might exist if the two hemispheres were more similar functionally
in one sex than in the other sex. Indeed, the greater asymmetry observed in EEG (Corsi-
Cabrera et al., 1997), MEG (Reite et al., 1995) and fMRI (Pugh et al., 1996, Frost et al.,
1999) studies in men suggests that men might show more asymmetry effects of unilateral
lesions than women.
Injury to the frontal lobe might have greater effects in one sex than in the other, a
difference that would be consistent with a greater relative volume of much of the frontal
lobes in women (Kolb and Whishaw, 2003).
One way to assess the asymmetry of left- or right-hemisphere lesions is to look at
the effects of lesions on general tests of verbal and nonverbal abilities.
So, Inglis and Lawson (1982) showed that, although left- and right-hemisphere
lesions in men affected the verbal and performance subscales of the WAIS (Wechsler
Adult Intelligence Scale) differently, left-hemisphere lesions in women depressed both
1800
IQ scores equally, and right-hemisphere lesions in women failed to depress either score.
A clear sex difference emerged in which males with left-hemisphere lesions exhibited a
depression in verbal IQ, whereas males with right-hemisphere exhibited a complementary
deficit in performance IQ. In contrast, females with right-hemisphere lesions showed no
significant depression in either IQ scale.
Thus, Inglis and Lawson (1982) found an equivalent effect of left-hemisphere lesions
on verbal IQ in both sexes, but men with right-hemisphere lesions were more disrupted
than woman were.
Work of Kimura (1999) shows that the pattern of cerebral organization within each
hemisphere also differs between the sexes. Men and women are almost equally likely to
be aphasic subsequent to left-hemisphere lesion. But apraxia is associated with frontal
damage to the left-hemisphere in women and with posterior damage in men. Aphasia
develops most often when damage in to the front of the brain in women but to the rear of
the brain in men (Kimura, 1999).
Thus, men are likely to be aphasic and apraxic after damage to the left posterior
cortex, whereas women are far more likely to experience speech disorders and apraxia
after anterior lesion.
Kimura (1999) also suggests an analogous sex-related difference subsequent to right-
hemisphere lesions.
Anterior, but not posterior lesions in women impaired their performance of the block-
design and object-assembly subtests of WAIS, whereas men were equally affected on
these tests by either anterior or posterior lesions.
Kolb and Stewart (1991) have found parallel results in their studies of rats with
prefrontal lesions: male rats with these lesions have much smaller deficits in various tests
of spatial navigation than do female rats with similar lesions. This finding may suggest
a fundamental difference between the sexes in the intracerebral organization in mammals.
Kolb and Stewart (1991), in an anatomical study, show a large difference between
male and female rats in the dendritic organization of neurons in the prefrontal cortex.
This sex difference was affected by treatment that either increased or decreased
testosterone levels during development (Kolb and Stewart, 1991).
Strauss et al. (1992) gave sodium amobarbital to 94 epileptic patients who were
being considered for elective surgery after infant brain damage. Left-hemisphere injury
in infancy leads to the shifting of language to the right hemisphere: so Strauss expected
this shift in those patients with left-hemisphere injury. The unexpected result was a sex
difference in the likelihood of cerebral reorganization subsequent to left-hemisphere
injury after one year of age: girls were unlikely to show reorganization, whereas boys
appeared likely to shift language, perhaps as late as puberty. This suggests that the male
brain may be more plastic after cortical injury.
According to Kolb and Stewart (1991), males showed a better recovery and more
synaptic changes than females did.
Thus, unilateral cortical lesions have different effects on male and female brain.
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Explanation of sex differences

Kolb and Whishaw (2003) identified five explanations for sex differences: (1)
hormonal effects on cerebral function; (2) genetic sex linkage; (3) maturation rate; (4)
environment; and (5) preferred cognitive mode.
Hormonal effects. In birds and mammals, the presence of testosterone at critical
times in the course of development has unequivocal effects on the organization of both
hypothalamic and forebrain structures, and the observed morphological effects are
believed to be responsible for the behavioral dimorphism (Kolb and Whishaw, 2003).
However, the hormones may have an organizing effect on the brains of mammals
only during development, although they can still influence neuronal function later in life.
Regions of the human brain that have clear sex-related differences in adulthood are the
same ones that have a high density of estrogen receptors during development. Women
have significantly higher volumes in the major frontal and medial paralimbic regions
than those of men, whereas men have larger relative volumes in the medial frontal cortex
and the angular gyrus. These areas correspond to region in which there are higher levels
of estrogen receptors and to regions high in androgen receptors during development
(Goldstein et al., 2001).
Androgens appear to be converted into estradiol (female hormones) in the brain, and
the binding of this estradiol to receptors leads to masculinization of the brain. Estradiol
receptors have been found in the cortexes of developing rodents and nonhuman primates,
but they are not found in the adults.
However, there is a relation between behavior and the level of hormones observed
at different times in adult of each sex. Hampson (1990) and Hampson and Kimura (1992)
showed that the performance of women on certain tasks changes throughout the menstrual
cycle as estrogen levels rise and fall. High estrogen levels are associated with relatively
depressed spatial ability as well as enhanced articulatory and motor capability.
Woolley et al. (1990) showed that, during the female rat’s estrous cycle, there are
large changes in the number of dendritic spines on hippocampal neurons. Thus, the
number of synapses in the female rat’s hippocampus goes up and down in 4-days cycles.
Similarly, female rats that have their ovaries removed in middle age show a dramatic
increase in dendrites and spines of cortical neurons (Stewart and Kolb, 1988). Thus,
estrogen has direct effects on cerebral neurons in the adult animal.
On the other hand, testosterone affects cognition in men. Kimura (1999) showed
that men’s spatial scores fluctuate with testosterone levels: men with lower testosterone
levels get the highest scores. Testosterone levels in men are higher in the autumn than in
the spring, and they are higher in the morning than in the evening. Thus, men do better
at the spatial tests in the spring and in the evening. Furthermore, men with lower average
levels of testosterone do better on both spatial tests and on mathematical reasoning tests
than do those with higher levels.
In the early part of the twentieth century, testosterone was believed to be able to
reverse senescence, but there is little evidence that the hundreds of given testicular
implants actually benefited from this treatment (Hamilton, 1986).
1802
Nonetheless, some evidence suggests that testosterone treatments may influence

spatial cognition in older men. Janowsky et al. (1994) gave retired men testosterone (or
placebo) in scrotal patches and found a significant improvement in the performance of
spatial tasks but not in verbal or other cognitive measures.
When the researchers measured blood-hormone levels, they found a decrease in
estradiol as well as an increase in testosterone. Hampson (1990) found that the low
estradiol levels correlated with the improved spatial performance. Thus, the suppression
of estrogen is more beneficial than the presence of testosterone.
However, the estrogen treatment in postmenopausal women improves verbal
memory.
In sum, gonadal hormones alter the brain and make male and female brains more or
less responsive in different environments. Thus, Juraska (1986) has demonstrated that
exposure to gonadal hormones perinatally determines the later ability of environmental
stimulation to alter the synaptic organization of the cerebrum. On the other hand, she
showed that environmentally induced changes in the hippocampus and neocortex are
affected differently by gonadal hormones. Thus, the female hippocampus is far more
plastic in new environments than the male hippocampus, and this plasticity depends on
estrogen.
This type of hormonally mediated selective effect of experience on the brain is
important because experimental factors (including social factors) could influence the
male and female brain differently, leading to sex-related various in brain and behavior.
So, the cognitive functions of the two sexes may diverge functionally at puberty and
begin to converge again after menopause (Kolb and Whishaw, 2003).
Genetic sex linkage. If a gene for particular trait, such as spatial analysis, is
recessive, the trait will not be expressed in a girl unless the recessive gene is present on
both X chromosomes. However, the recessive gene need to be present only on one
chromosome if the child is a boy. Thus, if a mother carries the gene on both X
chromosomes, all her sons will have the trait, but her daughters will possess it only if
their father also carries the recessive gene on his chromosome. However, a thorough
review by Boles (1980) concludes that it has yet to be proved.
Maturation rate. It has long been known that girls begin to speak sooner than the
boys, develop larger vocabularies in childhood, and, as children, use more complex
linguistic construction than the boys do (Kolb and Whishaw, 2003).
Findings from dichotic and tachistoscopic studies often indicate an earlier evolution
of cerebral asymmetry in girls than in boys. Because girls attain physical maturity at an
earlier age than boys do, it is responsible to propose that the male brain matures more
slowly than the female brain and that maturation rate is a critical determinant of brain
asymmetry.
That is, the more slowly a child matures, the greater is the observed cerebral
asymmetry (Weber, 1976; Kolb and Whishaw, 2003).
Weber (1976) found that, regardless of sex, early-maturing adolescents performed
better on tests of verbal abilities than on tests of spatial ones, whereas late-maturing
adolescents did the opposite.
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Because the girls mature faster than boys, superior spatial abilities in boys may be
directly related to their relatively slow development (Weber, 1976).
Environment. In regard to spatial ability, boys are expected to exhibit greater
independence than girls and thus to engage in activities such as exploring and
manipulating the environment.
Harris (1978) concluded that, although a few studies can be found to support the
environmental view, the bulk of the evidence fails to do so.
In the study, by Thomas et al. (1973), on the horizontality of a liquid, women who
failed the task were repeatedly shown a bottle half-filled with red water that was tilted at
various angles. Women stated that “water is level when the bottle is upright but inclined
when the bottle is tilted”.
Men and women who performed correctly stated that “water is always level”.
Thus, although environmental theories may be appealing, there is no evidence that
environmental or social factors can solely account for the observed sex differences in
verbal and spatial behaviors (Kolb and Whishaw, 2003).
Preferred cognitive mode. According to Kolb and Whishaw (2003), the difference
in strategies used by men and women to solve problems may be at least partly responsible
for the observed sex differences in behavior.
Genetic maturational and environmental factors may predispose men and women to
prefer different modes of cognitive analysis.
Women solve problems primarily by using a verbal mode. Because this cognitive
mode is less efficient in solving spatial problems, women exhibit an apparent deficit
In sum, at least six significant behavioral differences are related: verbal ability,
visuospatial analysis, mathematical ability, perception, motor skills, and aggression (Kolb
and Whishaw, 2003).
Harshman et al. (1983), in a very ambitious study of the interaction of sex and
handedness in cognitive abilities, found a significant interaction between sex and
handedness; that is, sex-related differences in verbal and visuospatial behavior vary as a
function of handedness.
Witelson (1985, 1989) found that callosal size also varies by sex and handedness.
Anatomical studies
Generally, the left-hemisphere of the brain controls the right side of the body and
the right hemisphere of the brain controls the left side of the body.
Broca (1861) discovered that the major language production center in the brain is
located in the left hemisphere of the brain. Another speech center called Wernicke’s area
(Wernicke, 1874), that is associated with speech comprehension, is also located in the
left hemisphere of the brain.
The fact that the right-hand and primary speech functions are controlled by the same
half of the brain has fuelled speculations attempting to link brain organization language
functions, and handedness. Thus, Broca introduced the notion of the “dominant
1804
hemisphere”, by which he meant the hemisphere that directs not only the movements of
writing, drawing, and other fine movements but also language and perhaps even major
aspects of logical thought. He then suggested that left-handers might: have a brain that
is organized in a mirror image to that of right-handers, with language control on the right
side of the brain.
The data, however, suggest that this relationship is unfounded. So, acquired a
pathology that damages the left side of the brain, or an injection of sodium amytal into
the left side of the brain results in the development of aphasia.
Although virtually all right-handers have language area in their left hemisphere,
Coren (2002) did not find the mirror imaged brain that we expected in left-handers.
The data show that the vast majority of left-handers have the same brain organization
as right-handers, with their language control exclusively confined to the left hemisphere.
According to Coren (2002), only about 2 of 10 left-handers have language exclusively
in the right hemisphere, as had been predicted by Broca.
There is also a small group of individuals who seem to have their language control
split between both sides of the brain or duplicated on both sides of the brain (Springer
and Deutsch, 1995; Coren, 2002).
The overwhelming number of studies with the new technology (positron emission
tomography, functional magnetic resonance imaging, magnetoencephalography) have
found that there is a remarkable similarity between brains, regardless of handedness, with
the only major difference being that hand control regions are somewhat larger and more
active on the side opposite to the dominant hand.
However, right-handers seem to have brains that are slightly more asymmetrical, in
terms of both their structure and their functional specialization.
A larger proportion of left-handers seem to have more symmetrical brains and are
more likely to have functions equally represented in both hemispheres (Corballis, 1991;
Springer and Deutsch, 1995; Toga et al., 2006).
Certain cerebral anatomical asymmetries are apparent at both the macroscopic and
histological levels.
Hand preference is correlated with differential patterns of right - left asymmetry in
the parietal operculum, frontal cortex, occipital region, vascular patterns, and cerebral
blood flow (Carmon et al., 1972; Hochberg and Le May, 1975; Le May, 1977).
Thus, in comparison with right-handers, a higher proportion of left-handers show
no asymmetry.
Ratcliffe et al. (1980) correlates the asymmetry in the course of the sylvian (lateral)
fissure, as revealed by carotid angiography, and with the results of carotid sodium
amobarbital speech testing. They found that left- and right-handers with speech in the
left hemisphere had a mean right - left difference of 27º in the angle formed by the vessels
leaving the posterior end of sylvian fissure. In the left- and right-handers with speech in
the right hemisphere or with bilaterally represented speech, the mean difference shrank
to 0º. Thus, the anatomical asymmetry in their population was related to speech
representation and not necessarily to handedness.
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The location of speech proved a better predictor of individual variation in cerebral

organization than handedness.
Asymmetries in areal size, cytoarchitecture or neurocytology occur elsewhere in the
cerebral cortex as well as subcortically.
For example, many brains have a wider right frontal pole and a wider left occipital
pole. Brodmann’s area 45 in the inferior frontal lobe, corresponding to Broca’s area,
contains a population of large pyramidal neurons that are found only on the left side. The
cortical surface surrounding the central sulcus is larger in the left hemisphere, especially
in the areas containing the primary somatosensory and motor maps of the arm, suggesting
that one cerebral manifestation of hand preference is a larger amount of neural circuitry
in the relevant parts of the cortex. Histological asymmetries are also found in areas that
are not usually considered to be closely related either to language or handedness.
The left entorhinal cortex has significantly more neurons than the right one (Toga
et al., 2006; Crossman, 2008).
Handedness may appear to be more closely related to anatomical anomalies because
left-handers display more variation in lateralization of speech.
In a study of more than 300 cases, Yakovlev and Rakic (1966) found that, in 80%,
the pyramidal tract that is descending to the right hand contains more fibres than does
the same tract going to the left hand. Apparently, more fibres descend to the right hand
both from the contralateral left hemisphere and from the ipsilateral right hemisphere
than to the left hand. In addition, the contralateral tract from the left hemisphere crosses
at a higher level in the medulla than does the contralateral tract from the right
hemisphere.
Thus, lateralized central differences may also occur at the level of cellular organi-
zation (Pelet et al., 1998; Anderson et al., 1999; Galuske et al., 2000; Gazzaniga, 2000 b).
As early as 1963, Hécaen and Angelergues, on careful review of the neuro-
psychological symptoms associated with lesions of the right or left hemisphere,
speculated that neural organization might be more closely knit and integrated on the left,
more diffuse on the right.
For example, the extent of higher order dendritic branching seems to be greater in
certain speech areas of the left hemisphere (e.g., Broca’s area) than in the corresponding
regions of the right hemisphere. Conversely, lower order dendritic branches seem to be
longer in the right hemisphere than in the left hemisphere (Hellige, 1993, 2000; Zaidel
and Iacobini, 2002).
A difficulty in accounting for variations in anatomical asymmetries is that some left-
and right-handers show a marked dissociation between morphological (structural) and
functional asymmetry. Kolb and Whishaw (2003) suggest that other variables, still
unknown, may also account for individual differences in both left and right-handers.
Witelson (1977, 1985, 1989), Witelson and Goldsmith (1991), Witelson and Kigar
(1992), and Witelson et al. (1995) studied the hand preference of terminally ill subjects
on a variety of unimanual tasks. She later did postmortem studies of their brains, paying
particular attention to the size of the corpus callosum.
1806
She found that the cross-sectional area was 11% greater in left-handed and
ambidextrous people than in the right-handed people.
Although no two human brains are exactly alike in their structure, in most people
the right frontal area is wider than the left and the right frontal pole protrudes beyond the
left, while the reverse is true of the occipital pole: the left occipital pole is frequently
wider and protrudes further posteriorly than the right but the central portion of the right
hemisphere is frequently wider than the left (Damasio and Geschwind, 1984; Jäncke and
Steinmetz, 2003).
Men show greater degree of frontal and occipital asymmetry than women (Bear et
al., 1986). These asymmetries exist in fetal brains (de Lacoste et al., 1991; Witelson, 1995).
The left sylvian fissure, the fold between the temporal and frontal lobes, is larger
than the right in most people (Witelson, 1995), even in newborns (Seidenwurm et al.,
1985). Most attention has focused on asymmetry of the posterior portion of the superior
surface of the temporal lobe, the planum temporale.
This region, which is involved in auditory processing, is larger on the left side in
most right-handers (Strauss et al., 1985; Beaton 1997).
Thus, for the right-handed individuals the planum temporale is larger in the left
hemisphere in approximately 65% of the cases, larger in the right hemisphere in
approximately 10% of the cases and approximately equal in 25% of the cases. The
corresponding percentages for non-right-handers are approximately 25, 10, and 65%
respectively. Similar distributions characterize asymmetry of the sylvian fissure (Hellige,
2000; Zaidel and Iacobini, 2002).
In sum, one of the most notable anatomical asymmetries is in the planum temporale,
which is usually larger on the left than on the right side.
Subtle asymmetries in the superior temporal lobe have been demonstrated in terms
of overall size and shape, sulcal pattern, cytoarchitecture, and at the neuronal level.
It seems reasonable to assume that these differences underlie some of the functional
asymmetries for language representation (Toga et al., 2006).
Handedness and the longevity

A significant number of left-handers arrived at their left-handedness through some
form of pathological event during their fetal development or associated with their birth,
and this same pathology also resulted in other physical or pathological problems (Coren,
2002).
A number of studies have examined handedness as a function of demographic
factors, such as age, sex, and race. These studies found a diminishing percentage of left-
handers in older age groups (Bishop, 1990; Springer and Deutsch, 1995). Forced
switching of left-handers to right-handedness in older age groups could explain this age-
related decline in the number of left-handers.
The alternative explanation for failing to find older left-handers might be that they
are simply no longer in the population. That is, left-handers have a shorter life span, and
the reason that we fail to find many older left-handers is because a large proportion of
them have died early (Coren, 2002).
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Although many left-handers were dying of factors traceable to the problems in

Table 23.4, there was a surprise in the data: left-handers were five times more likely to
die of accident-related injuries (Coren, 2002).
Table 23.4
Conditions That Two or More Research Reports Have Shown to Be Associated
with a Disproportionately High Number of Left-Handers
Negative conditions associated with left-handedness
Alcoholism Hashimoto’s thyroiditis Poor spatial ability

Allergies Hayfever Poor verbal ability
Asthma High and low extremes Predispositions toward aggression
in numerical ability
Attempted suicide Homosexuality Psychosis
Autism Hypopigmentation Reading disability
Bed-wetting Immune disorders Reduced adult height
Brain damage Impulsive aggression Reduced adult weight
Chromosomal damage Infection susceptibility Regional ileitis
Celiac disease Juvenile delinquency Schizophrenia or schizotypal thinking
Crohn’s disease Juvenile-onset diabetes School failure
Clinical depression Language problems Sleep difficulty
Criminality Learning disabilities Slow maturation
Deafness Lower intelligence scores Slow physical development
Depression Maniac-depressive phychosis Strabismus
Drug abuse Mental retardation Stuttering
Drug hypersensitivity Migraine headaches Sudden heart attack death
Emotionality Myasthenia gravis Transsexuality
Epilepsy Neural tube defects Ulcerative colitis
Excessive smoking Neuroticism Urticaria
Eczema Poor school performance
Positive conditions associated with left-handedness

Extremely high intelligence Good divergent thinking ability High spatial ability
High musical ability
Thus, the left-handers suffer injuries while playing sports, during the traffic, working
with tools and motorized equipment, working with kitchen and home implements and
devices, and even while engaged in military activities (Coren, 2002).
Left-handedness might be a marker (at least, statistically) for the possible existence
of some form of neural pathology, psychological deviance, or developmental abnormality.
Thus, the same pathology that caused the left-handedness might have also caused some
form of collateral damage that can reduce the individual’s physiological or psychological
fitness through direct or secondary mechanisms (Coren, 1993, 2002). So, a substantial
body of research found that left-handedness is frequently associated with a variety of
symptoms or syndromes. However, the number of findings in which left-handedness is
associated with positive outcomes in the research literature is much rarer.
A review of the literature indicated at least 60 negative pathological or undesirable
conditions associated with left-handedness as opposed to only 4 positive or desirable
1808
conditions. Table 23.4 provides an idea of the positive and negative conditions related to
an increased proportion of left-handers (Coren, 2002).
The research literature is repleted with suggestions that left-handedness is
predominantly associated with negative conditions, and with a range of pathological
antecedents. Example of rare traits include animals that are colored differently from the
vast majority of their species. For instance, a “blue-marl” collie, a white dog, or an albino
human often have major sensory deficits affecting their vision or hearing. These rare
traits could include rare palm crease patterns, rare fingerprint patterns, or rare distribution
of toe lengths, and even unusual ear shapes are often found to be associated with cognitive
or physical deficits.
Left-handedness, which affects only about 10% of the population, would also be
qualified as a rare trait (Coren, 2002).
Thus, the rare versus the common trait can be influenced by pathological factors.
According to Coren (2002), half of the resulting population of left-handers are
pathological, whereas only 1.2% of the right-handers are pathological. This means that
the relative risk of left-hander being pathological is approximately 41% greater than that
of right-hander being pathological.
Left-handedness might be seen as a soft sign indicating increased risk for many
problems: however, which specific problems an individual might suffer from, or which
neural loci are involved, is not determinable (Coren, 2002).
From the standpoint of behavioral medicine, we may view left handedness as a risk
factor that may well predict susceptibility to illness, physiological deficits, psychological
problems, and perhaps even a shortened life span (Coren, 2002).
Effects of hemispherectomy
The catastrophic epilepsies, in which panhemispheric syndromes are associated with
intractable seizures, include Rasmussen’s encephalitis, developmental syndromes (i.e.,
hemimegaencephaly, tuberous sclerosis, hamartomas, Sturge-Weber syndrome), and
congenital hemiplegia or porencephaly (Carson et al., 1996).
Although the original surgical approach of anatomic complete, en bloc hemi-
spherectomy with spearing of basal ganglia, hypothalamus, and diencephalon (Krynaw,
1950; Rasmussen, 1975) was successful from the standpoint of seizure control, the
immediate and delayed complications were daunting (Pilcher and Ojeman, 1993).
Postoperative complications were significantly reduced with the introduction, by
Rasmussen (1975), of the technique of modified or functional hemispherectomy, in which
a generous central and temporal resection is juxtaposed with deafferentation of the frontal
and occipital lobes (Rasmussen, 1987). With deafferentation rather than removal of the
frontal and occipital lobes, the volume of intracranial dead space is reduced, and in
7.3-year follow-up study of 14 patients, no hemosiderosis or hydrocephalus occurred,
and 10 of 14 patients were seizure free. Villemure and Mascott (1995) introduced the
peri-insular hemispherectomy, in which a smaller craniotomy and a much reduced peri-
insular (i.e., opercular frontal, parietal, and temporal) resection are combined with
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deafferentation of frontal, parietal, occipital and temporal lobes. In addition, to a favorable

seizure outcome (i.e., 9 of 11 patients were seizure free, and 1 of 11 improved 95%),
reduced operative time and preoperative and delayed complications were documented.
The trans-sylvian keyhole functional hemispherectomy advanced by Schramm et al.
(1995, 2001) represents a true minimalist approach to hemispheric deafferentation. A
linear scalp incision and 4 ´ 4 cm craniotomy provide the limited exposure required for
a trans-sylvian approach to the circular sulcus, through which access to the entire
ventricular system is gained. Transventricular hemispheric deafferentation and amygdalo-
hippocampectomy are performed, with significantly reduced blood loss and a mean
operating time of 3.6 hours.
For 20 patients, 88% were seizure free, and seizure improved for 6%.
Although most hemispherectomies are performed in the patient’s early adolescence,
the surgery is sometimes done in the first year of life, before the speech has developed.
If the hemispheres vary functionally at birth, then the left and right hemi-
spherectomies would be expected to produce different effects on cognitive abilities. If
they do not vary at birth, then no cognitive differences would result from left or right
hemispherectomies (Kolb and Whishaw, 2003).
Generally, results of studies of linguistic and visuospatial abilities in patients with
unilateral hemidecortications support the conclusion that both hemispheres are
functionally specialized at birth, although both hemispheres appear capable of assuming
some functions usually performed by the missing hemisphere (Kolb and Whishaw, 2003).
Thus, hemidecortication produces no severe deficit in visuospatial abilities. The left
hemisphere cannot completely compensate the right hemisphere.
Dennis and Whitaker (1976) found that both hemispheres understand the meaning
of words and both can spontaneously produce lists of names of things. However, the left
hemisphere has an advantage over the right.
In an analysis of reading skills, Dennis et al. (1981) found that both hemispheres
had almost equal ability in higher-order reading comprehension; however, the left
hemisphere is superior to the right in reading and spelling unfamiliar words and in using
sentence structure to achieve fluent reading. The left hemisphere also reads prose passages
with greater decoding accuracy, more fluency and fewer errors that violate the semantic
and syntactic structure of sentence, performances better with the right hemisphere in a
task that requires learning and association between nonsense words and symbols.
So, Dennis (1980) suggests that, if written language structure is thought as a
combination of meaning cues (morphology), sound cues (phonology), and picture cues
(logography), then the isolated left hemisphere will show superior performance with
morphology and phonology and inferior performance with logographic cues.
The isolated right hemisphere will show superior performance with logographic cues
and inferior performance with morphological and phonological cues (Dennis, 1980).
Kohn and Dennis (1974) found an almost analogous pattern of results on test of
visuospatial function.
Thus, although patients with right hemispherectomies performed normally on simple
tests of visuospatial functions such as drawing, they were significantly impaired in
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complex tests such as negotiating a maze and reading a map (Kohn and Dennis, 1974;
Kolb and Whishaw, 2003).
In sum, each hemisphere can assume some of its opposite’s functions if the opposite
hemisphere is removed in the course of development, but neither hemisphere is totally
capable of mediating all of the missing hemisphere’s function (Kolb and Whishaw, 2003).
There is convincing evidence against equipotentiality: both hemisphere appear to have a
processing capacity that probably has an innate structural basis (Kolb and Whishaw, 2003).
With few exception, patients undergoing hemispherectomy are of below-average or, at
least, average intelligence, and their proficiency at tests of the intact hemisphere’s function
is often less than normal (Dennis, 1980; Dennis et al., 1981; Kolb and Whishaw, 2003).
Although such children have severe behavioral difficulties after hemispherectomy,
they often compensate remarkably, communicating freely and, in some cases, showing
considerable motor control over the limbs opposite the excised hemisphere.
Using both fMRI and SEPs (somatosensory evoked potentials), Holloway et al.
(2000) investigated the sensorimotor functions of 17 hemispherectomy patients.
Ten patients showed SEPs in the normal hemisphere when the nerves of the limb
opposite the excised hemisphere were stimulated. Similarly, fMRI shows that, for at least
some of the patients, passive movement of the same limb produced activation in a region
of somatosensory cortex that normally responds to the opposite hand.
The Holloway’s team concluded that the responses to the hand ipsilateral to the
normal hemisphere must occur because direct ipsilateral pathways run from the normal
hemisphere to the affected limb.
However, the novel ipsilateral responses were found in patients with both congenital
and acquired disease, suggesting that although age at injury may be important, the ability
of nervous system to alter its organization to compensate for injury may influence the
cerebral reorganization.
Ontogeny of asymmetry
Generally, adultlike cerebral asymmetries are present before birth, a result that
supports an innate predisposition for cerebral asymmetry in humans.
In a MRI study, Sowell et al. (2002 a and b) confirm this general impression.
Thus, a basic template for cortical development appears to lay down an asymmetrical
organization prenatally, and the pattern progresses after birth.
The results of ERP studies by Dennis (1980), and Molfese and Molfese (1988)
confirm a functional asymmetry in which the left hemisphere showed a greater response
to speech stimuli as early as one week of age. There is apparently little change in this
difference during development.
However, initially it permits some flexibility or equipotentiality. The cognitive
functions of each hemisphere can be conceived as hierarchical. Simple, lower-level
functions are represented at the base of the hierarchy, corresponding to functions in the
primary sensor, motor, language, or visuospatial areas. More complex, higher-level
functions ascend the hierarchy, the most complex being at the top. These advanced
functions are the most lateralized (Kolb and Whishaw, 2003).
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At birth, the two hemispheres overlap functionally because each is processing low-
level behaviors.
By age of 5, the newly developing higher-order cognitive processes have very little
overlap, and each hemisphere becomes increasingly specialized. By puberty, each
hemisphere has developed its own unique functions (Kolb and Whishaw, 2003).
Thus, Moscovitch (1977) emphasized the possibility that one hemisphere actively
inhibits the other, thus preventing the contralateral hemisphere from developing similar
functions. This active inhibition presumably develops at about age of 5, as the corpus
callosum becomes functional. According to Moscovitch (1977), this inhibitory process not
only prevents the subsequent development of language processes in the right hemisphere
but also inhibits the expression of the language processes already in the right hemisphere.
The right hemisphere of commissurotomy patients appears to have greater language
abilities than expected from the study of normal patients, presumably because the right
hemisphere is no longer subject to inhibition by the left. Netley (1977) showed that people
born with no corpus callosum demonstrate little or no functional asymmetry as inferred
from dichotic listening, suggesting that the absence of interhemispheric connection results
in attenuated hemispheric asymmetry.
Popularized accounts of laterality have suggested that people can be classified as
“right-brained” or left-brained”, depending on whether they prefer to use strategies and
models of cognition associated with one hemisphere or another.
Thus, left-brained people are said to be rational and analytic, whereas right-brained
people are said to be intuitive, artistic, and creative.
However, there is individual variation on the various dimensions of laterality, but
there is no evidence that any neurologically intact individuals are functionally half-
brained in the manner referred to as hemisphericity. Individuals do differ reliably in
cognitive style, personality, creativity and so forth (Hellige, 2002).
However, hemispheric asymmetries are subtle, with no indication that aspects such
as rationality and creativity are the exclusive product of one brain hemisphere. Instead,
both hemispheres contribute to virtually everything we do (Hellige, 2000, 2002).
The discovery that both of disconnected hemispheres of split-brain patients have a
good deal of competence with respect to perception and motor control has led to
speculation about whether or not the surgery has produced a doubling of consciousness
or resulted in people with two minds.
Sperry (1986) believed that this was the case. In part, he based his conclusion on
the fact that the disconnected right hemisphere has its own perceptions, cognitions, and
memories of which the disconnected left hemisphere is completely unaware.
Others, however, have questioned whether the right hemisphere can truly think and
whether its limited abilities include the same level of awareness and consciousness that
seems typical on the left hemisphere.
Certainly, the disconnected right hemisphere is usually incapable of speech and other
forms of verbal communication that are uniquely human and that some have argued, are
essential for the concept of “mind”. There is much debate among philosophers and
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cognitive scientists about the extent to which language is essential for thinking, conscious
reflection, or mental life.
Le Doux and Gazzaniga (1978) hypothesized that an important function of an
individual’s verbal left hemisphere is the construction of internal, subjective reality or
ongoing narrative based on its observations of his or her own overt behavior.
In this view, observation of one’s own behavior is necessary because many processes
that influence behavior are not open to conscious experience. Le Doux and Gazzaniga
(1978) emphasize this with respect to behavior and bodily sensations produced by the
right hemisphere, of which the left hemisphere would have no direct knowledge.
However, even within the left hemisphere there appear to be a great many modules
whose processes may influence behavior but that are not themselves open to conscious
awareness.
Thus, the need to create an ongoing personal narrative by making inferences about
one’s own behavior is likely to extend to covert processes performed by both
hemispheres. Although, neither hemisphere is uniformly superior for processing
nonverbal perceptual information. Instead, both hemispheres contribute to perceptual
processing and do so in ways that could be described as complementary.
This chapter is not meant to solve all of the mysteries of lateralized functions, but
merely to highlight anatomical and functional asymmetries as they relate to language,
complex motor behaviors, and sensorimotor integration.
It is often assumed that anatomical asymmetries invariably reflect functional
asymmetries. However, physiological asymmetries, asymmetries in gene expression, or
subtle differences in neuronal cytoskeletal architecture may play a more significant role
in hemispheric specialization than gross anatomical or cytoarchitectonic asymmetries
(Geschwind and Iacoboni, 2007).
The intensification of morphological asymmetries associated with language is
important because of a wealth of evidence that these asymmetries are functionally
relevant (Witelson, 1977, 1992; Galaburda et al., 1978; Geschwind and Galaburda, 1985).
Furthermore, a number of studies support the general notion that the amount of
cerebral cortex dedicated to a particular function may reflect the brain capabilities in that
area (Eccles, 1977; Jerison, 1977; Garraghty and Kaas, 1992).
However, the size of a brain region is not always positively correlated with its
capabilities. Often, a larger cerebral hemisphere can be observed due to neuronal
migration abnormalities or other cortical malformations. In the domain of language more
specifically, the brains of individuals with dyslexia appear to be more symmetrical, with
a larger than usual planum temporale on the right, rather than a smaller planum temporale
on the left (Galaburda, 1993; Kushch et al., 1993).
Thus, anatomical asymmetries, whether gross or fine, cannot be viewed in isolation
and must eventually be considered in the context of physiology of the neuronal systems
to which they contribute (Geschwind and Iacoboni, 2007).
Handedness is of particular interest because it is a behavioral manifestation of brain
laterality for certain manual activities and it is also related to other, more cognitive
aspects of laterality.
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Direction and magnitude of hand dominance may even be determined by different

factors, with the magnitude being more heritable and with the direction being more
subject to environmental influence.
Handedness is at least moderately related to other form of laterality. Thus, there is
a greater proportion of left-handed individuals who show a laterality effect in a direction
opposite to that which is considered prototypical.
ASYMMETRY BETWEEN THE HEMISPHERES

in humans
Introduction
For more than a century, studies of behavioral defects produced by unilateral cerebral
lesions had focused on motor planning, language, perceptual analysis, and afterwards on
emotions and affects.
In reality, the emotional behavior of some patients affected by extensive lesions of
the right hemisphere is so striking that it had attracted the attention of such important
neurologists and psychiatrists as such Babinski (1914), Schilder (1935), and Critchley
(1955, 1957).
However, much current theorizing about the nature of cerebral asymmetry is based
on laterality research. The noninvasive studies are indirect measures of brain function
and are far less precise than anatomical measures.
Behavioral measures of laterality do not correlate perfectly with invasive measures
of cerebral asymmetry. However, laboratory studies of normal subjects and “split brain”
patients have shown which hemisphere processes are dependent on relative weighting of
many variables (Beaumont, 1997). In addition to underlying hemispheric organization,
these include the nature of the task (e.g., modality, speed factors, complexity), the
subject’s set of expectancies with the task, previously developed perceptual or response
strategies, and inherent subject variable such as sex and handedness (Bryden, 1978;
Bouma, 1990; Levine, 1995; Kuhl, 2000). Thus, in these subjects the degree to which
hemispheric specialization occurs at any given time is a relative phenomenon rather than
an absolute one (Hellige, 1995).
Before summarizing a number of the most well-established asymmetries, it is useful
to consider three general characteristics of laterality effects: ubiquity, subtlety, and
complementarity (Hellige, 2000 and 2001).
Ubiquitary refers to the fact that the two cerebral hemispheres have different levels
of ability and different processing propensities in a great many domains (motor activity,
language, perception, emotion, etc.).
Subtlety refers to the fact that it is rarely the case that one hemisphere can perform
a task or accomplish a specific process quite well, whereas the other hemisphere cannot
perform the task or process at all. Instead, both hemispheres typically have some ability,
though they may go about a task in different ways and one hemisphere may do a better
job than the other. A notable exception to this is speech production, which tends to be
controlled exclusively by a single hemisphere (usually the left).
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Complementarity refers to the fact that, in many domains, the role for which each
hemisphere is dominant can be described as complementary. Consequently, both
hemispheres normally play a role in virtually all complex activities, such as understanding
language or identifying faces, with their contributions fitting together like two pieces of
a puzzle (Hellige, 2000).
Individual differences in the behavior of normal subjects result, at least in part, from
individual differences in how the cerebral hemispheres are organized and how functions
are lateralized.
At one extreme, people who are logical, analytical, verbal, and meticulous are
assumed to rely more on their left hemispheres to solve problems in everyday life,
whereas people who are visual, intuitive and synthesizer are more concerned with
organizing concepts and visualizing meaningful wholes are assumed to rely more on their
right hemisphere.
Anyhow, factors other than brain organization probably contribute to preferred
cognitive mode.
On the one hand, strategies used by subjects can significantly influence tests of
lateralization, and, on the other hand, cognitive mode may be due to biases in socialization
or environmental factors in addition to neuronal, genetic, or constitutional biases.
Nevertheless, the idea that individual differences in behavior and cognition result
in part from individual differences in brain organization is a provocative assumption
worthy of serious study.
Clinical and neuroimaging studies, including PET, fMRI, ERP, and MEG, allowed
researchers to map cerebral activity as it takes place in normal subjects, and performances
related to left and right hemisphere functions.
Because both hemispheres are scanned, however, it is possible to assess left - right
differences in cerebral activation during a large range of behavioral measures.
Anyhow, clinical study has limitations of functional localization because “symptoms
must be viewed as expressions of disturbances in a system, not as direct expressions of
focal loss of neuronal tissue” (Benton, 1981).
Aphasics with similar symptoms may present lesions which vary in site or size. On
the other hand, cortical mapping by electrode stimulation (Ojemann, 1979) and neuro-
imaging techniques (Mazziota et al., 1997) demonstrates a great deal of interindividual
variability in cortical patterning. Examples from functional imaging studies show that
many different areas of the brain may be engaged during a cognitive task (Franckowiak
et al., 1997; Gazzaniga, 2000). For even the relatively simple task of telling whether
words represent a pleasant or unpleasant concept, the following areas of the brain showed
increased activation: left superior temporal cortex, posterior cingulate, left para-
hippocampal gyrus, and left inferior frontal gyrus (McDermott et al., 1999).
It is important to recognize that normal behaviors are functions of the whole brain
with important contributions from both hemispheres entering into every activity and
emotional state. Only laboratory studies on intact or split brain subjects or studies of
persons with lateralized brain damage demonstrate the differences in hemisphere function.
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Tradition and common sense favor verbal (left hemisphere) versus nonverbal (right
hemisphere) dichotomy. However, some theories see this dichotomy as unsatisfactory
because a number of facts have been brought forth to support their position. There is the
centuries-old observation that some aphasic patients, if primed, can recite familiar prayers
faultlessly (Benton and Joynt, 1960).
Some aphasic patients can sing a song (with its words) while some nonaphasic right
hemisphere-damaged patients cannot (Benton, 1977; Burkland and Smith, 1977). An
aphasic patient who does not understand the propositional content of an utterance may
appreciate the import of its prosodic component, i.e., he will know whether the examiner
is making a statement, asking a question, or issuing a command.
Conversely, the verbal functions of many right hemisphere-damaged patients are
not fully intact, with examination disclosing and at least modest decline in performance
level as measured by controlled word association and taken tests.
Another point that is brought up is the sizable number of subjects who show a left
ear (i.e., right hemisphere) superiority when processing verbal information in dichotic
listening studies.
Observations such as these have impelled some theories to look for a more basic
dichotomy. The leading candidates are the “serial-parallel” and “analytic-holistic” pairs.
The two human cerebral hemispheres are not simply mirror images of each other.
Much information on the lateralization of cerebral function has come from studying
patients in whom the corpus callosum had been divided (commissurotomy) as a treatment
for intractable epilepsy, and from those rare individuals who lack part, or all, of their
corpus callosum.
Commissurotomy produces the “split-brain” syndrome, which has provided evidence
supporting the notion that abilities or functions are predominantly associated with one
or another hemisphere.
Thus, patients with chrome epilepsy, who have undergone surgical section of the
corpus callosum in order to relieve their seizures, portray few difficulties under normal
circumstances. However, when these “split brain” patients undergo psychological testing,
the two halves of the brain appear to behave relatively autonomously, e.g., visual
information directed to the right cerebral hemisphere alone does not evoke verbal
response, and consequently individuals cannot name objects or real words solely
presented to the left visual field. Destruction of the splenium of the corpus callosum and
its connections to the left occipital cortex, either by stroke or tumor, leads to the posterior
disconnection syndrome of “alexia without agraphia”. Such individuals speak and write
without difficulty but cannot understand written material (alexia). Disconnection of visual
processes in the right hemisphere from the verbal processes of the dominant left cerebral
hemisphere is thought to explain the syndrome.
Knowledge of such lateralization of function has been advanced more recently by
functional brain imaging techniques.
In sum, in the human brain, the left cerebral hemisphere is usually the dominant
hemisphere (in absolute 95% of the population), whereas the right hemisphere is the
nondominant hemisphere.
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The left hemisphere usually prevails for verbal and linguistic function, for problem
solving, for mathematical skills, and for analytical thinking.
The right hemisphere is mostly non-verbal. It is more involved in spatial and holistic
or “Gestalt” thinking, in recognition of faces, and in many aspects of musical and poetry
skills, and in some emotions (Table 23.5).
Table 23.5
Summary of data on cerebral lateralization
Function Left hemisphere Right hemisphere

Visual system Letters, words Complex geometric patterns
Faces
Auditory system Language / related Nonlanguage environmental sounds
sound Music
Somatosensory ? Tactile recognition of complex patterns
system Braille
Movement Complex voluntary Movements in spatial patterns
movement
Memory Verbal memory Nonverbal memory
Language Speech Prosody?
Reading
Writing
Arithmetic
Spatial processes Geometry
Sense of direction
Mental rotation of shapes
Note: Functions of the respective hemispheres that are predominantly mediated by one hemisphere in right-handed people.
Memory also shows lateralization. Thus, verbal memory is primarily of left

hemisphere function, while non-verbal memory is represented in the right hemisphere.
These asymmetries are relative, not absolute, and vary in degree according to the function
and individual concern. Moreover, they apply primarily to right-handed men. Those men
with left-hand preference, or mixed handedness, make up a heterogeneous group, which
(as an approximation) shows reduced or anomalous lateralization, rather than a simple
reversal of the situation in right-handers. For example, speech representation can occur
in either or both hemispheres. Women show less functional asymmetry, on average, than
men (Crossman, 2008).
Historical aspects
Bouillaud
Jean Baptiste Bouillaud (1796-1881) read a paper before the Royal Academy of
Medicine in France in which he argued from clinical studies that certain functions are
localized in the neocortex and, specifically, that speech is localized in the frontal lobes,
in accordance with Gall’s beliefs and opposed to Flourens’s beliefs. Beginning in 1825
1817
and for a half-century thereafter, Bouillaud was the great champion of Gall’s localization
of the centers of speech and language in the frontal lobes and he argued repeatedly,
vigorously and, at times, rancorously that aphasic disorders resulted only from lesions in
this territory. In his Traité … de l’encephalite (1825), he presented 29 cases with and
without aphasia and with and without lesions in the anterior, middle, and posterior lobes.
All of the aphasic patients had lesions that were in, or close to the anterior lobes.
Inspection of Bouillaud’s 29 cases shows that 25 had lesions confined to a single
hemisphere, 11 in the left hemisphere and 14 in the right. Eight (73%) of the 11 left
hemisphere cases were aphasic. Four (29%) of the right hemisphere cases were aphasic.
Reviewing his own autopsied cases as well as those in the literature, he typically presented
just a few words on the loci of the lesions and sometimes these few words were very
imprecise indeed. In some cases, the flat statement that the lesion was in one or the other
anterior lobes (or both) is made. However, in other cases, the locus of the lesions is
described as being in the “anterior” part of the hemispheres.
Perhaps one reason why Bouillaud did not perceive this trend toward a higher
frequency of aphasic disorder in his left hemisphere patients is that not only he was
obsessed with the frontal lobe localization of aphasic disorder but he also accepted Gall’s
dual localization of the centers of speech and language in both hemispheres.
Observing that acts such as writing, drawing, painting, and fencing are carried out
with the right hand, Bouillaud also suggested that a part of the brain that controls them
might possibly be the left hemisphere.
Marc Dax
Marc Dax was born in 1770 and died in 1837. He studied medicine in Montpellier,
his graduate thesis being an interesting survey of the incidence and nature of the diseases
occurring over a 5-year period in the small town of Aigues-Mortes. As Gibson (1962)
has pointed out, in this thesis Dax called attention to the occasional occurrence of post-
seizure focal paralysis in some children. This observation preceded by many years, those
of Bravais and Todd, who are usually credited with the first descriptions of the
phenomenon.
Dax had a keen interest in the study of language, and this may account for the special
attention which he paid to language disturbances. In 1836, 1 year before his death, he
wrote a paper (Dax, 1836, 1865) on the association between aphasic disorders and lesions
of the left hemisphere for presentation at a regional medical congress at Montpellier. He
was, thus, about 66 year old when he wrote his famous mémoire. It is a remarkable
document. Dax describes successive observations that led him gradually to the conviction
that aphasia was a product of left hemisphere disease. He collected cases over the ensuing
20 years, so that at the time of writing his paper he reported having a series of over 40
cases in which the diagnosis of left hemisphere disease had been made, primarily on
clinical ground, without pathological confirmation.
The paper was not published and, as it will be seen, there is no evidence that Marc
Dax actually presented it at the congress. When it was, belatedly, submitted for publication,
1818
in 1865, by his physician-son, Gustav Dax, 4 years after Broca’s initial observation (Broca,
1865), it initiated a controversy about priority which has persisted up to the present day. At
the same time, together with his father’s memoir, Gustav Dax (Dax, 1865) published a
summary of his own observations and views on aphasia (Joynt and Benton, 2000).
From a scientific standpoint, Marc Dax’s generalization on the role of the left
hemisphere in speech was hardly derived from well documented observations. The
clinical descriptions were scanty, and the pathological confirmation was entirely lacking.
Dax made no mention of handedness nor did he, in any way, link hand preference to
hemispheric localization of speech function. Nonetheless, Marc Dax did make, and for
the first time, a clinical observation of the highest importance.
Gustav Dax
Dax’s paper (M. Dax, 1865) was published in 1865 by his son, Gustav Dax (G. Dax,
1865), who stated that it had been read at a regional medical meeting in Montpellier in
1836. In fact, there is no evidence that he did present the paper on that occasion (Joynt
and Benton, 1964). It is not mentioned in account of the meeting, nor could anyone be
found who remembered having heard it. It seems almost certain that, if the paper had
been presented, it would not have been totally neglected and would have had some
repercussions (Benton, 2000).
The tone of Dax’s paper is personally modest but firm in conviction. Its style
indicates that it was meant to be a communication to his peer. He was quite aware of the
importance of his discovery and he made one or two copies which he sent to professional
friends. Why he did not make his discovery known at the time through publication or
oral presentation is not clear (Benton, 2000).
Anyhow, there is suggestive evidence that Gustav Dax, the son, did know of the
preferential involvement of the left hemisphere in aphasia prior Broca’s 1863 report.
Presumably, this knowledge was gained from his father – for Gustav Dax had prepared an
extensive treatise of his own on aphasia (Dax, 1877) entitled: “Observations intended to
prove the constant coincidence of the derangements of speech with a lesion of the left
cerebral hemisphere”. In the introduction, Gustav Dax pays respect to his father’s memory
and mentions his father’s views on the localization of lesions responsible for the loss of
speech. This work of Gustav Dax was received by the Academy of Medicine of Paris on
March 24, 1863. Broca’s statement on the eight cases of aphasia with left hemisphere lesions
was delivered on April 2, 1863. Unfortunately, the commission appointed by the Academy
to examine Gustav Dax’s essay did not publish a report on it until 2 years later. Additional
support for Dax’s claim was provided in 1879 by Caizergues, who reported he had
discovered a copy of Marc Dax’s memoir when classifying the papers of his grandfather
who had been dean of the faculty of Montpellier (Caizergues, 1879). There is, therefore,
excellent evidence that Marc Dax did make his observation prior to Broca.
In short, Marc Dax had made an observation for which he was unwilling to take
public responsibility, and hence he recorded it in the form of an essentially private
communication (Benton, 2000).
1819
Broca
In 1861, Pierre Paul Broca (1824-1880) reported two instances of aphasia with
lesions in the left third frontal convolution (Broca, 1861).
He made no mention at that time of the significance of both these lesions occurring
on the left side. Later, at a meeting of the Anthropological Society of Paris on April 2,
1863, Broca reported on eight autopsies (Broca, 1863) of patients with aphasia and noted
that they all had lesions in the third frontal convolution. In 1865, Broca expanded his
views of the special role of the left hemisphere in speech and also discussed his priority
in making these observations (Broca, 1865).
In consequence Broca located speech in the third convolution of the frontal lobe on
the left side of the brain. Thus, he discovered that functions could be localized to a side
of the brain, a property that is referred to as lateralization. Because speech is thought to
be central in human consciousness, the left hemisphere is frequently referred to as the
dominant hemisphere, to recognize its special role in language. Thus, the concept of
hemispheric cerebral dominance was born when Broca (1865) was led to conclude from
his observations that “we speak with the left hemisphere”. He had read Marc Dax’s paper
as published by his son in 1865 and, naturally, wished to read the original presentation
along with any discussion. He searched in vain throughout the medical literature for the
original report or even for a reference to the 1836 paper. He then asked the librarian of
the Montpellier Faculty of Medicine to make personal inquiries regarding the 1836
presentation. The librarian reported that he had interviewed 20 physicians who had
attended the 1836 congress at Montpellier, and none could recall such a presentation.
Hence Broca was, with good reason, quite skeptical that Marc Dax had actually presented
his paper at the congress.
The discussion on priority was reopened by Broca in 1877 (Broca, 1877). He stated
that he had obtained a manuscript of the Marc Dax paper, purportedly presented in 1836,
and compared it with the Gustav Dax manuscript on aphasia. Broca admits that the style,
the mode of expression and the discussion all demonstrated no difference in origin.
Therefore, he did not doubt that the paper was written in 1836 by Marc Dax for
presentation, but he did not believe that it was ever presented. Broca speculated that Marc
Dax probably felt ensure of his ground and did not have the courage to face a discussion
as there was no confirmation of his cases by autopsy findings (Benton, 2000).
However, Broca’s anatomical analysis was criticized by French anatomist Pierre
Marie, who reexamined the brains of Broca’s first two patients, Tan, and a Monsieur
Lelong, 25 years after Broca’s death. Marie pointed out in his article titled “The Third
Left Frontal Convolution Plays No Particular Role in the Function of Language” that
Lelong’s brain showed general nonspecific atrophy, common in senility, and that Tan
had additional extensive damage in his posterior cortex that may have accounted for his
aphasia. Broca had been aware of Tan’s posterior damage but concluded that, whereas
the posterior damage contributed to his death, the anterior damage had occurred earlier,
producing aphasia.
Anyhow, a lesion in Broca’s area resulted in a loss of motor memory-images and
hence produced a primarily expressive aphasia with preservation of the capacity to
1820
understand speech. The speech pattern is nonfluent: on beside examination, the patient
speaks hesitantly, after producing the principal, meaning-containing nouns and verbs but
omitting small grammatical words and morphemes. This pattern is called agrammatism
or telegraphic speech. Patients with acute Broca’s aphasia may be mute or may produce
single words, often with dysarthria and apraxia of speech, naming is deficient, but the
patient often manifests a “tip of the tongue” phenomenon, getting out the first letter or
phoneme of the correct name.
Paraphasic errors in naming are more frequently of literal than verbal type (Kirshner,
2000).
Auditory comprehension seems intact, but detailed testing usually reveals some
deficiency, particularly in the comprehension of complex syntax. Repetition is hesitant
in these patients, resembling their spontaneous speech. Reading is often impaired. Broca’s
aphasics may have difficulty with syntax in reading, just as in auditory comprehension
and speech. Writing is virtually always deficient in Broca’s aphasias. Most patients have
a right hemiparesis necessitating use of nondominant, left hand for writing. Many patients
can scrawl only a few letters.
Associated neurological deficits of Broca’s aphasics include right hemiparesis,
hemisensory loss, and apraxia of the oral apparatus and the nonparalyzed left limbs.
An important clinical feature of Broca’s aphasia is its frequent association with
depression (Robinson, 1997).
The lesions responsible for Broca’s aphasia usually include the traditional Broca’s
area in the posterior part of the inferior frontal gyrus, along with damage to adjacent
cortex and subcortical white matter.
Lesions involving the traditional Broca’s area (Brodmann’s areas 44 and 45) resulted
in difficulty initiating speech, and lesions combining Broca’s area, the lower precentral
gyrus, and subcortical white matter yielded the full syndrome of Broca’s aphasia.
Aphemia, a rare variant of Broca’s aphasia, is a nonfluent syndrome in which the
patient is initially mute and then able to speak with phoneme substitutions and pauses.
Aphemia may be equivalent to pure apraxia of speech (Kirshner, 2000).
Wernicke
Broca himself was not greatly concerned with the neurological mechanisms
underlying speech and its disturbance. It was left to a younger physician, German ana-
tomist Carl Wernicke (1848-1904), to develop a mature theory of the nature of aphasic
disorders. In a monograph appeared in 1874, Wernicke demonstrated that a fluent aphasic
disorder, characterized by impaired understanding of speech and disordered expressive
speech, was specifically associated with disease in the territory of the posterior temporal
lobe of the left hemisphere (Wernicke, 1874). Wernicke was aware that the part of the
cortex that receives the sensory pathway, or projection, from the ear – and this is called
the auditory cortex – is located in the temporal lobe, behind Broca’s area. He, therefore,
suspected a relation between the functioning of hearing and speech, and he described cases
of aphasic patients with lesions in this auditory projection area that differed from those
1821
described by Broca. Like Broca, he conceived aphasia as a disorder of the sign function
of language. He denied that aphasic patients were necessarily impaired in intellect even
though, as a clinician, he knew that many aphasics, perhaps a majority, did in fact show
cognitive defects that extended beyond the realm of language. But he insisted that
“nothing could be worse for the study of aphasia than to consider the intellectual
disturbance associated with aphasia as an essential part of the disease picture”.
However, Wernicke went beyond his empirical discovery and his restriction of
aphasia to a disorder of the sign function of language to create a model of the neurological
mechanisms, derangements of which produced aphasic disorder. His model, and the
revision of it, developed by other neurologists, postulated the existence of interconnected
cerebral centers of speech in which memory-images of the different modalities of speech
were stored. A center for memory-images of the movement patterns of expressive speech
was located in Broca’s area in the posterior frontal region. A center for auditory memory-
images of words was located in Wernicke’s area in the posterior temporal lobe. A center
for visual memory-images of words was located further back in the angular gyrus.
Whether or not there was a specific center for memory-images of the movements patterns
of writing was a subject of debate. Those who believed in the existence of such a center
placed it either in the second frontal gyrus above Broca’s area or in the supramarginal
gyrus close to the center for visual memory-images of words (Benton, 2000).
In any case, Wernicke provided the first model for how language is organized in the
left hemisphere. It hypothesizes a programmed sequence of activities in Wernicke’s and
Broca’s language areas. Wernicke proposed that auditory information is sent to the
temporal lobes from the ear. In Wernicke’s area, sounds are turned into sound images or
ideas of objects and stored. From Wernicke’s area, the ideas can be sent through a
pathway called the arcuate fasciculus to Broca’s area, where the representations of speech
movements are retained. From Broca’s area, instructions are sent to muscles that control
movements of the mouth to produce the appropriate sound.
If the temporal lobe were damaged, speech movements could still be mediated by
Broca’s area, but the speech would make no sense, because the person would be unable
to monitor the words.
Because damage to Broca’s area produces loss of speech movements without the
loss of sound images, Broca’s aphasia is not accompanied by a loss of understanding
Wernicke’s aphasia may be considered a syndrome opposite to Broca’s aphasia, in
that expressive speech is fluent but comprehension is impaired. The speech pattern is
effortless and sometimes even excessively fluent (logorrhea). A speaker of a foreign
language would notice nothing amiss, but a listener who shares the patient’s language
detects speech empty of meaning, containing verbal paraphasias, neologisms, and jargon
productions. Neurologists refer to this pattern as paragrammatism. In milder cases, the
intended meaning of an utterance may be discerned, but the sentence goes away with
paraphasic substitutions (Kirshner, 2000). Naming in Wernicke’s aphasia is deficient,
often bizarre with paraphasic substitutions for the correct name. Auditory comprehension
1822
is impaired, sometimes even for the simple nonsense questions. Auditory perception of
phonemes is deficient in Wernicke’s aphasia, but deficient semantics is the major cause
of the comprehension disturbance; disturbed access to semantics and to the internal
lexicon is central to the deficit of Wernicke’s aphasia. Although the patients were able
to hear, they could not understand or repeat what was said to them. Reading compre-
hension is usually affected, but occasional patients show greater deficit in one modality.
Writing is also impaired, but in a manner quite different from that of Broca’s aphasia
(Kirshner, 2000).
The diverse symptom-pictures of aphasia encountered in clinical practice were
explained in terms of either a lesion in one or more centers (i.e., the “central” aphasia) or
a lesion in the connections between them (i.e., the “conduction” aphasia). Temporal lobe
aphasia is sometimes called fluent aphasia, to emphasize that the person can say words.
It is more frequently called Wernicke’s aphasia, however, in honor of Wernicke’s
description. The region of the temporal lobe associated with the aphasia is called
Wernicke’s area.
Most patients have no elementary motor or sensory deficits, although a partial or
complete right homonymous hemianopsia may be present.
The psychiatric manifestations of Wernicke’s aphasia are quite different from those
of Broca’s aphasia.
Depression is less common; many Wernicke’s aphasics seem unaware of, or
unconcerned about their communicative deficits. With time, some patients become angry
or paranoid about the inability of family members and medical staff to understand them.
The lesions of patients with Wernicke’s aphasia are usually in the posterior portion
of the superior temporal gyrus, sometimes extending into the inferior parietal lobe.
Damage to Wernicke’s area (Brodmann’s area 22) has been reported to correlate
most closely with persistent loss of comprehension of single words, although others
(Kertesz et al., 1993) have found only larger temporoparietal lesions in patients with
lasting Wernicke’s aphasia.
A receptive speech area in the left inferior temporal gyrus has been suggested by
electrical stimulation studies and by a few descriptions of patients with seizures involving
this area (Kirshner et al., 1995), but aphasia has not been recognized with destructive
lesions of this area.
Extension of the lesion into the inferior parietal region may predict greater
involvement of reading comprehension.
Wernicke also predicted a new language disorder although he never saw such a case.
He suggested that, if the arcuate fibres connecting the two speech areas (Wernicke‘s and
Broca’s area) were cut, disconnecting the areas but without inflicting damage on either
one, a speech deficit that Wernicke described as conduction aphasia would result.
Conductive aphasia has been advanced as a classical disconnection syndrome. Geschwind
later pointed to the arcuate fasciculus, a white matter tract traveling from the deep
temporal lobe, around the sylvian fissure to the frontal lobe, as the site of disconnection
(Geschwind, 1965). Conduction aphasia is an uncommon but theoretically important
1823
syndrome that can be remembered by its striking deficit of repetition. Most patients have
relatively normal spontaneous speech, although some make literal paraphasic errors and
hesitate frequently for self-correction. Naming may be impaired, but auditory
comprehension is preserved. A patient who can express himself at a sentence level and
comprehend conversation may be unable to repeat even single words. Reading and
writing are somewhat variable, but reading aloud may share some of the same difficulty
as repeating.
Associated deficits include hemianopsia in some patients; right-sided sensory loss
may be present, but right hemiparesis is usually mild or absent (Kirshner, 2000).
The lesions of conduction aphasia are usually in either the superior temporal or
inferior parietal regions. Patients with limb apraxia have parietal lesions (supramarginal
gyrus). The supramarginal gyrus appears to be involved in auditory immediate memory
and in phoneme generation. Lesions in this area are associated with conduction aphasia
and phonemic paraphasic errors.
Wernicke proposed that, although different regions of the brain have different
function they are interdependent in that to work, because they must receive information
from one another. Using this same reasoning, French neurologist Joseph Déjérine (1849-
1917), in 1892, described a case in which the loss of the ability to read (alexia, meaning
“word blindness”, from Greek lexia, for “word”) resulted from a disconnection between
the visual area of the brain and Wernicke’s area. So, Déjérine (1892) elucidated the
neuroanatomic substrate of pure alexia on the basis of autopsy study of a patient with
this disorder. His patient, an educated man and an accomplished musician, suddenly lost
the ability to read musical scores as well as conventional written material. Yet he could
write, perform music from memory, and showed no difficulty in the expression or
understanding of oral speech. He had a right visual field defect – in all probability a
hemiachromatopsia, not a hemianopsia. Autopsy study disclosed infarctions in the
territory of the left posterior cerebral artery, specifically, the mesial occipital area and
the splenium of the corpus callosum. Déjérine inferred that the lesions had the effects of
preventing the transmission of visual information to the language centers of the left
hemisphere, thus making reading impossible while leaving the interpretation of nonverbal
visual stimuli intact.
Déjérine and others accept the proposition that aphasia involves a defect in
intelligence.
Neurolinguists and cognitive psychologists have divided alexias according to
breakdowns in specific stages of the reading process. The linguistic concepts of surface
structure versus the deep meanings of words have been instrumental in these new
classifications. Four patterns of alexia (or dyslexia, in British usage) have been
recognized: letter-by-letter, deep, phonological, and surface dyslexia.
Like reading, writing may be affected either in isolation (pure agraphia) or in
association with aphasia (aphasic agraphia). In addition, writing can be impaired by motor
disorders, by apraxia, and by visuospatial deficits. Isolated agraphia has been described
with left frontal or parietal lesions.
1824
Disconnection is an important idea because it predicts that complex behaviors are

built up in assembly-line fashion as information collected by sensory systems enters the
brain and travels through different structures before resulting in an overt response of
some kind. Furthermore, the disconnection of structures by cutting connecting pathways
can result in impairments that resemble those produced by damaging the structures
themselves (Kolb and Whishaw, 2003).
The conflict between the “noetic” and “connectionist” school on the issues of the
nature of aphasic disorder and its underlying neural substrate continued through the early
decades of the twentieth century.
The decades since World War II have witnessed a tremendous surge of interest in
the aphasic disorders.
Pitres and amnesic aphasia

Clinicians such as Batteman (1870), Kussmaul (1876) and Banti (1886) identified
patients whose most prominent (and, sometimes, only) disability was their incapacity to
produce the names of objects and persons. Applying the old term “amnesic aphasia” to
this symptom-picture, they regarded it as a distinctive type of speech impairment and
included it as such in their classification of the aphasic disorders.
Broadbend (1878) proposed that amnesic aphasia resulted from destruction or
dysfunction of a “naming centre” in the posterior region of the left hemisphere, and Milles
and McConnell (1895) localized this centre in the third and second temporal gyri.
In 1898, Pitres began by describing what he considered to be a case of pure amnesic
aphasia. He distinguished between three forms of amnesic aphasia. The first is
antonomasia (word substitution) in which the patient fails to recall and produce
substantives within setting of adequate conversational speech and understanding. The
second is agrammatism, i.e., inability to formulate acceptable sentences. The third is
differential loss of language in polyglots. The anomic patient is less severely impaired
than the agrammatic patient who has difficulty in recalling verbs and connectives as well
as substantives. The differential loss in polyglots is attributable to differences in the depth
of a patient’s knowledge of the languages. Thus, Pitres’ concept of amnesic aphasia was
fairly broad, extending beyond anomia to encompass the lexical and syntactical
impoverishment of agrammatism.
Pitres indicated that the causative lesion is most frequently found to be in the inferior
parietal lobule, sometimes with extension into the angular gyrus. Amnesic aphasia is
produced by breaks in the outflow from psychosensory centers to the whole cortex and
hence there cannot be an absolutely constant localization of the responsible lesion. The
patient with amnesic aphasia should not only experience difficulty in producing words
corresponding to his ideas but also be unable to grasp the ideas represented by words
said to him. Anyhow, pure amnesic aphasia is rare. The disorder in naming is usually
accompanied by other disabilities.
“The existence of a clinical form of aphasia, uniquely determined by the loss of the
evocation of words”, cannot be questioned. The syndrome cannot be identified with any
1825
major category in current classifications and its autonomy should be recognized. It is an

associative aphasia that may be placed between the motor or emissive and sensory or
receptive aphasias.
Amnesic or anomic aphasia has figured prominently in modern classifications of the
aphasic disorders (Albert et al., 1981). However, reservations about its neuropathologic
significance are often expressed and not uncommonly it is described as being merely a
symptom-complex that appears in the course of recovery from a more pervasive fluent,
non-fluent or transcortical aphasic disorder. Finally, modern neurodiagnostic techniques
have yet to be brought to bear on the question of lesional localization and underlying
neurological mechanisms. Thus, whether or not Pitres’s amnesic aphasia is a useful and
meaningful neuropsychological concept remains to be determined.
In summary, anomic aphasia refers to aphasic syndromes in which naming, or access
to the internal lexicon, is the principal deficit.
Isolated, severe anomia may indicate focal left hemisphere pathology. Alexander
and Benson (1991) refer to the angular gyrus as the site of lesions producing anomic
aphasia, but lesions there usually produce other deficits as well, including alexia and the
four elements of Gerstmann’s syndrome: agraphia, right - left disorientation, acalculia,
and finger agnosia, or inability to identify fingers. Isolated lesions of the temporal lobe
can produce pure anomia, and positron emission tomography studies of naming in normal
subjects have also shown consistent activation of the superior temporal lobe.
Anomic aphasia thus serves as an indicator of left hemisphere or diffuse brain disease
(mass lesions elsewhere in the brain, and diffuse degenerative disorders), but it has only
limited localization value.
Geschwind
Norman Geschwind (1926-1984) presented his ideas in a now classic paper,
“Disconnexion Syndromes in Animals and Man”, which was published in 1965. This
comprehensive analysis, some 100 pages in length, presented the concept of discon-
nection and illustrated its far-reaching implications. Its impact was immediate and far-
reaching. In a real sense, it brought neuroanatomy back into the field of aphasia, apraxia,
and agnosia, and it provided a fruitful approach to the understanding of these types of
disorders, as well as other behavioral manifestations of brain disease.
Today, when we undertake to analyze the mechanisms underlying aphasic disorders,
amnesic syndromes, perceptual defects, and visuomotor disabilities, we think in terms
of disconnection – not simple disconnection, to be sure, but rather of disturbances of
progression and interaction in information processing that are based on the destruction
of specific pathways (Benton, 2000).
Wernicke’s speech model was updated by American neurologist Norman Geschwind
in the 1960s and is now sometimes referred to as the Wernicke-Geschwind model.
Aphasia and thought

A majority of aphasic patients do show impairment on one or another measure of
cognitive functions and their defects are by no means restricted to tests of abstract
1826
reasoning or symbolic thinking. They are generally more impaired than are nonaphasic
patients with left-hemisphere disease.
Among aphasic patients, those with significant defects in oral verbal comprehension
are most likely to show defective nonverbal test performance.
Moreover, certain nonverbal tasks, such as the identification of environmental
sounds and pantomime recognition, are failed only by aphasics (and perhaps severely
demented patients) but not nonaphasics with brain disease (Vignolo, 1969; Duffy et al.,
1975; Varney, 1978; Varney and Benton, 1982; Dănăilă and Golu, 2006).
However, the overriding finding (often overlooked in intergroup comparisons) is
one of extreme interindividual variability among aphasic patients, even among those with
severe disturbances in comprehension. This variability indicates that in virtually every
sample of aphasics some will perform normally, a fact which has been convincingly
documented in case reports (Alajouanine and Lhermitte, 1964; Zangwill, 1964).
In addition, there is no evidence for a significant relationship between the degree of
deficit in nonverbal task performance and the severity of aphasic disorder (Basso et al.,
1973), in part because stroke-produced aphasia is such an important cause of socio-
economic disability. At the same time, neurodiagnostic procedures, such as CT, magnetic
resonance imaging, functional magnetic resonance imaging, magnetoencephalography,
and positron-emission tomography, permit investigators to collect a substantial amount
of clinicopathologic data fairly quickly and new discoveries have modified concepts
about classification and lesional localization.
ASYMMETRIES OF THE HUMAN FRONTAL LOBES

In the course of the brain evolution, the frontal lobes developed most recently to
become its largest structures. It was natural to conclude that the frontal lobes must
therefore be the seat of the highest cognitive functions. Thus, when Hebb reported in
1939 that a small series of patients who had undergone surgical removal of frontal lobe
tissue showed no loss in IQ score on a standard intelligence test, he provoked a contro-
versy. Afterwards, Klebanoff (1945) noted the seemingly unresolvable discrepancies
between studies reporting on the cognitive status of patients with frontal lobe lesions. He
found that since Fritsch and Hitzig (1870) first reported mental deterioration in patients
with traumatic frontal lesions, more authors had described cognitive deficits in patients
with frontal lobe damage than denied the presence of such deficits in their patients. The
large number of World War II missile wound survivors and the popularity of
psychosurgery on the frontal lobes for treatment of psychiatric disorders in the 1940s and
1950s ultimately provided enough cases of frontal brain damage to eliminate speculative
misconceptions about frontal lobe functions (Dănăilă and Golu, 1988; Lezak et al., 2004).
The frontal lobes are the closest neural representation of popular notions of “intelligence”
or Spearman’s g factor because of their important role in contributing to success on
diverse cognitive tasks (Duncan et al., 2000). Thus, we know now that many cognitive
and social behaviors may be disrupted by frontal lobe damage. The three major divisions
of the frontal lobes (precentral division, premotor division, and prefrontal division) differ
1827
functionally, although each is involved more or less directly with behavior output (Stuss
and Benson, 1986; Pandya and Barnes, 1987; Goldberg, 1990; Damasio, 1991; Stuss et
al., 1994; Pandya and Yeterian, 1998).
Asymmetries in language
In the last two decades, functional imaging has provided a revealing view of areas
involved in healthy and neurologically impaired subjects (Roland, 1984; Petersen et al.,
1988; Binder et al., 1995; Klein et al., 1995; Warburton et al., 1996). Most observant
clinicians have remarked on the variability and overlap of aphasic syndromes, especially
in the immediate period following brain injury, as well as the individual differences in
symptoms between patients with apparently similar lesions (Benson, 1986; Galaburda et
al., 1990). In light of the individual variability in gross morphology in humans
(Andrianov, 1979; Rajkowska and Goldman-Rakic, 1995) there is a left-hemisphere
superiority and proficiency for the majority of vocal, motor, and language function
(Geschwind, 1970; Benson, 1986).
However, some language capacity exists in most right hemispheres (Dănăilă and
Golu, 1987; Iacoboni and Zaidel, 1996). Especially, is the predominance of the right
frontal lobe in the production of the melodic components that contribute to prosody, as
well as the expression of the emotional content of language.
Because spoken and written language are human specializations, detailed animal
models of the role of different frontal subregions serving language are not available
This is in contrast to frontal lobe participation in other cognitive functions, such as
working memory and sensorimotor integration, in which studies in primates have vastly
accelerated our knowledge of regional subspecializations and provided models that can
be tested in humans (Goldman-Rakic, 1987; Funahashi et al., 1989; Wilson et al., 1993;
Petrides, 1994).
Broca’s original belief that lesions confine to the posterior portion of the third left
frontal gyrus caused loss of articulatory function (aphémie) occurred on the background
of conviction (Broca, 1861 a, b, c; 1864 a, b; 1865), shared by his contemporaries, that
the left and right frontal lobes were identical in size and anatomy (Flourens, 1824; Broca,
1865; Berker et al., 1986).
The recovery of language function occurred through the compensatory effort of
homologous, essentially equipotential regions in the right frontal lobe (Geschwind and
Iacoboni, 2007). Following Broca, numerous cases supported the left hemispheric loca-
lization of language in right-handers, while expanding the cerebral territory responsible
for language functions (Wernicke, 1874; Jackson, 1880, 1915; Broca, 1888).
Jackson (1868) presented the first case of the left-handed man with aphasia and right-
sided lesions, further supporting between hand dominance and language lateralization.
Afterwards studies have confirmed the functional localization of language to the left
hemisphere in 99% of right-handers (Hécaen et al., 1981; Annett, 1985; Benson, 1986).
However, this relationship is less certain in left-handers, with most demonstrating either
1828
left-hemisphere or bilateral language, and, less frequently, right-hemisphere language

(Geschwind, 1970; Hécaen et al., 1981; Geschwind and Galaburda, 1985).
Anyhow, removal of the first two to three gyri of the left frontal operculum pars
opercularis (area 44) and triangularis (area 45) anterior to Brodmann’s area 4 on the left
in epilepsy surgery resulted in nonfluent aphasia in every case except one (Penfield and
Roberts, 1959).
Cortical stimulation studies by these same investigators demonstrated speech arrest
from stimulation of the first two opercular gyri on the left, but never on the right.
Stimulation of the left supplementary motor area (SMA), and not of the right,
produced speech arrest (Penfield and Roberts, 1959). Lesions of the SMA can produce
transcortical motor aphasia, whereas similar lesions on the right do not, consistent with
the proposed role of the SMA in speech initiation (Masdeu, 1978; Freedman et al., 1984).
Thus, in the left hemisphere, lesions in the portion of the motor association area that
mediates the motor organization and patterning of speech may result in speech distur-
bances that have as their common feature disruption of speech production with intact
comprehension. These deficits may range in severity from total suppression of speech
(Caplan, 1987; Jonas, 1987; Eslinger and Reichwein, 2001) to mild slowing and reduced
spontaneously of speech production (Stuss and Benson, 1990). Other alterations in speech
production may include stuttering, poor or monotonous tonal quality, or diminished
control of the rate of speech production.
Luria (1970) and Dronkers et al. (2000) demonstrated a motor pattern apraxia of
speech (oral apraxia) which may include difficulty imitating simple oral gestures in
connection with lesions in this area, although this condition can also occur with somewhat
more posterior lesions (Tognola and Vignola, 1980).
Lesion studies support the presence of an anterior frontal lobe language area that
encompasses Broca’s area and additional perisylvian areas more posteriorly. In a series
of patients there are lateralized left-sided lesions of the posterior part of the inferior gyrus,
17 out of 19 patients had difficulties in language fluency (Hécaen and Consoli, 1973).
Patients with lesions largely confined to the cortical surface corresponding to Broca’s
region did not have significant agrammatism, or writing difficulties, whereas those with
deeper lesions tended to have more profound language impairment. None of 15 patients
with a homologous right-sided lesion demonstrated any language or articulatory deficits,
confirming the relative specialization of the left inferior frontal gyrus for language output
Numerous case studies have underscored the relationship between the extension of
lesion into cortical regions adjacent to the third frontal gyrus and the severity of the
Broca’s aphasia (Tonkonogy and Goodglass, 1981). Articulatory disturbances (dysarthria
and dysprosody) are typically associated with lesions that extend into the opercular
precentral gyrus (Alexander et al., 1990).
A combination of word-finding difficulties, paraphasias, and slowness in speech is
observed with lesions of the pars triangularis and pars opercularis. Involvement of both
regions typically leads to a more severe and lasting nonfluent aphasia. Mohr et al. (1978)
1829
have also demonstrated that lesions localized to Broca’s area lead to nonfluent aphasia
or nonmotor articulatory disturbance, as well as persistent apraxia and dysprosody, but
not frank agrammatism, as is paradigmatic in many current formulations of nonfluent
(Broca’s) aphasia. Those with typical Broca’s aphasia have larger lesions that encom-
passed deeper white matter structures, anterior insula, and adjacent perisylvian regions
(Mohr et al., 1978; Alexander et al., 1990).
Morphological asymmetries. Comparison of the weights of both hemispheres
yielded variable and inconclusive results (Thurman, 1866; Broca, 1875; Aresu, 1914;
Von Bonin, 1962). However, the left hemisphere is greater than the right, suggesting
more cortical surface area overall on the left (Von Bonin, 1962). Indirect measurements
taken of indentations in the skull, called petalias, reflect outgrowth of the adjacent cerebral
hemisphere. Thus, the presence of marked left occipital petalia, the nature of frontal lobe
asymmetries has been less obvious (Tinley, 1927; Hadziselmovic and Cus, 1966).
However, most careful quantitative studies in adequate numbers of cases show a predo-
minance of the right frontal petalia (Hadziselmovic and Cus, 1966; Geschwind and
Galaburda, 1985).
Le May and Kido (1978) made direct measurements of the frontal lobes and
demonstrated that the width of the right frontal region was greater in 58% of right-
handed patients and extended further in 31%, as opposed to only 14% that extend
further forward on the left. This gross structural asymmetry has been consistently
observed in more recent studies (Geschwind and Galaburda, 1985; Bear et al., 1986;
Glickson and Myslobodsky, 1993).
However, the meaning of these observations is unclear, because they do not reflect
the total extent of cortical surface area because much of cortical surface area is contained
in the sulcal folds. This explanation is likely to hold for the studies of Wada et al. (1975),
that demonstrated a right-side size advantage when only the lateral cortical surfaces of
areas 44 and 45 were measured (Fig. 23.1).
Fig. 23.1. Cerebral structures concerned with language

output and articulation.
B = Broca’s area; C = pre- and postcentral gyri;
S = striatum. Areas 43, 44, and 45 are Brodmann’s
cytoarchitectonic areas. A lesion in any of the components
of this output network (B, C, or S) can produce a mild and
transient Broca’s aphasia.
Large lesions, damaging all three components, produce
severe persistent Broca’s aphasia with sparse, labored,
agrammatic speech but
well-preserved comprehension. (Illustration by
courtesy of Dr. Andrew Kertesz).
1830
One of the first detailed measurements based on cytoarchitectonic divisions of the

frontal lobes were carried out by Kononova (1935, 1949).
This work on five right-handed subjects not only showed that the total area of the
left frontal lobe was larger than the right by 16%, but also that Brodmann’s areas 45 and
47 were larger on the left by a margin of 30% and 45% respectively.
Kononova also observed a larger amount of individual variation in these and other
regions of frontal lobe, highlighting the difficulty in drawing firm conclusions from this
study of only six cases.
Galaburda’s (1980) detailed study of the magnocellular region of the pars
opercularis, which largely coincides with area 44, demonstrated the left side to be larger
than the right, in the majority of 10 cases.
Hayes and Lewis (1993) have demonstrated a population of magnopyramidal
neurons that are 15% larger in left Brodmann’s area 45 than in the right.
No difference was seen between similar large pyramidal neurons in area 4 (Hayes
and Lewis, 1995). However, in area 46 of the dorsolateral prefrontal cortex, the magno-
pyramidal neurons were about 10% smaller on the left. These differences are not large.
Other investigators have demonstrated consistent morphological asymmetries in more
extensive regions of the third or inferior frontal gyrus using autopsy material and MRI in
living patients (Falzi et al., 1982; Albanese et al., 1989; Foundas et al., 1995, 1996).
Foundas et al. (1996) demonstrated a striking correlation between the direction of
pars triangularis (area 45) asymmetry and hemispheric language lateralization, providing
the most convincing evidence to date of the correspondence between language and
anatomical asymmetries in the frontal lobe. Nine of 10 patients with Wada test-proven
lateralization of language to the left hemisphere displayed asymmetry in favor of the left
pars triangularis.
Although it is most likely that an increased neuron number underlies the larger areas
44 and 45 of the left hemisphere (Galaburda, 1993), an increase in neuropil size could
also account for the left-hemispheric predominance.
Scheibel et al. (1985) and Simonds and Scheibel (1989) emphasize that pars trian-
gularis and pars opercularis have been shown to have increased complexity of higher-
order dendritic branching on the left relative to the primary motor cortex in both
hemispheres, and pars triangularis and pars opercularis on the right. However, signi-
ficance of dendritic branching is uncertain.
Functional imaging
Positron emission tomography (PET) and functional magnetic resonance imaging
(fMRI) have supported the functional specialization of the left frontal cortex in language
and language-related tasks (Frith et al., 1991; Mc Carthy et al., 1993; Binder et al., 1995;
Klein et al., 1995; Just et al., 1996). Indeed, widespread areas of lateral frontal
hypometabolism are even seen in patients with aphasia and lesions in parietal and
temporal cortex, further implicating the lateral left frontal cortex in language function
and recovery (Metter, 1991).
1831
Even simple language tasks, although highly lateralized, activate a network of widely
distributed left-hemisphere cortical areas (Petersen et al., 1988; Binder et al., 1995; Just
et al., 1996). In most careful PET of fMRI studies of language, homologous regions are
often activated on the right side, although typically at far lower levels than those on the
left (Habib et al., 1996; Just et al. 1996; Warburton et al., 1996). The left-hemisphere
activations are highly variable and extend beyond Broca’s region, including the supple-
mentary motor area, and cingulate medially, and the dorsolateral prefrontal cortex and
the premotor area laterally.
One of the factors confounding the interpretation of PET language data is the
variability in activated areas across different studies. In spite of this variability, left
perisylvian regions in general, and Broca’s area in particular show consistent activation
in language tasks. So, the Broca’s area is a critical structure dedicated solely to language
output. Since Broca’s region comprises cytoarchitectonically and physiologically diverse
areas, it may serve several language-related functions (Poppel 1996).
Thus, lesions studies, intraoperative electrical stimulation, and PET imaging studies
confirm its role in phonological process (Lecours and Lhermitte, 1970; Denny-Brown
1975; Ojemann and Mateer, 1979; Demonet et al., 1994; Zatorre et al., 1996).
PET data indicate that Broca’s region is activated in a wide variety of non-output-
related language tasks, including listening tasks (Roland, 1984).
Phonological discrimination tasks often engage verbal working memory functions,
which are typically associated with left frontal lobe predominance as well (Milner and
Petrides, 1984; Paulescu et al., 1993; Petrides et al., 1993).
Thus, Broca’s region comprises contiguous area serving separate functions that can
be simultaneously engaged in the same task.
Denny-Brown (1965, 1975) emphasize the importance of visual input in language
acquisition and visual influences on aphasia caused by lesions of Broca’s area.
Thus, disruption of the integration of these visual inputs is a component of the lateral
alexia that can sometimes be observed in patients with Broca’s area lesions (Benson,
1977; Boccardi et al., 1984).
In sum, the functional supremacy of one cerebral hemisphere is crucial to language
function. There are many ways of determining that the left side of the brain is dominant:
(1) by the loss of speech that occurs with disease in certain parts of the left hemisphere
and its preservation with lesions involving corresponding parts of the right hemisphere;
(2) by preference, for greater facility in the use of the right hand, foot, and eye; (3) by
the arrest of speech with magnetic cortical stimulation or a focal seizure or with electrical
stimulation of the anterior language area during surgical procedure; (4) by the injection
of sodium amytal into the left internal carotid artery (Wada test – a procedure that
produces mutism for a minute or two, followed by misnaming, including preservation
and substitution; misreading; and paraphasic speech – effects lasting 8 to 9 min in all);
(5) by the dichotic listening test, in which different words or phonemes are presented
simultaneously to two ears (yielding a right ear – left hemisphere advantage); (6) by
observing increases in cerebral blood flow during language processing: (7) by
1832
lateralization of speech and language function following commissurotomy (Adams et al.,

1997); and (8) by studies with PET, fMRI and magnetoencephalography.
Asymmetry of prosody and emotion

Despite its minimal contribution to the purely linguistic as well as propositional
aspects of language, the right hemisphere does have an important role in the com-
munication of feelings and emotion. It has long been known that globally aphasic patients
can shout a curse, when angered. These aspects of language are subsumed under the term
prosody, by which is meant the melody of speech, its rhythm, intonation, inflection, and
pauses that transmit emotional overtones. The prosodic components, and gestures that
accompany them, enhance the meaning of the spoken word and endow language with its
richness and vitality (Adams et al., 1997).
Thus, speech involves not only the communication of vocabulary and grammatical
content, but also social and emotional content.
The critical role of the right hemisphere in the melodic and musical aspects of speech
and language output is supported by the observation of preservation of simple singing
ability in many patients with nonfluent aphasia (Yamadori et al., 1977).
Syndromes of loss of emotional aspects of speech are termed aprosodias. Motor
aprosodia involves loss of expressive emotion with preservation of emotional com-
prehension; sensory aprosodia involves loss of comprehension; sensory aprosodia
involves loss of comprehension of affective language, also called affective agnosia.
Several studies show that patients with right-hemisphere lesions can demonstrate
deficiency in interpreting and expressing the emotional content of speech (Ross and
Mesulam, 1979).
The lesions described in loss of expressive prosody mostly involve large portions
of the frontal lobe and often extend into the parietal lobe, hindering precise anatomical
localization (Dordain et al., 1971; Ross and Mesulam, 1979).
The involvement of the basal ganglia in prosody is demonstrated by lesion studies
(Cancelliere and Kertesz, 1990; Starkstein et al., 1994).
A PET study supports the role of the right lateral prefrontal cortex in simple pitch
discrimination, analogous to the role of Broca’s area in phoneme perception (Zatore et
al., 1994). Another PET study of emotional prosody comprehension also suggests that
right prefrontal cortex is preferentially active in tasks requiring perception and
interpretation of emotional prosody, and is not simply dedicated to prosodic expression
(George et al., 1996).
The deficit in prosody observed after right frontal lesions is not entirely limited to
the expression of emotional and melodic content, however, and can extend into
nonemotional semantic aspects, such as syllable stress (Weintraub et al., 1981; Dănăilă
and Golu, 1987).
In addition, prosodic elements of speech comprehension and expression can also be
impaired in anterior left-hemisphere lesions resulting in Broca’s aphasia (Danny and
Shapiro, 1982; Benson, 1986).
1833
In the foreign accent syndrome, which can result from left frontal lesions involving
Broca’s area, and neighboring cortical and subcortical regions, inappropriate syllable
stress, phoneme misproduction, rhythm, and pauses occur, changing a patient’s accent
often without chronically altering other aspects of language (Monrad-Krohn, 1947).
Exaggerated prosody, sometimes observed in nonfluent aphasia, reflects the
speaker’s attempts to communicate using retained right frontal abilities in the face of
minimal linguistic capabilities (Geschwind and Iacoboni, 2007).
The role of orbital frontal lobes in the regulation of emotion and mood has been well
established in studies of patients with brain injury (Benson and Stuss, 1986) and tumors.
The orbitofrontal cortex is the cortex of the ventral aspect of the frontal lobe. It
comprises mainly areas 11 and 13. The orbital prefrontal syndrome can ensue from a
variety of disease processes, including tumors (Fig. 23.2), and aneurisms of the anterior
communicating artery (Fig. 23.3).
Attention is disturbed mainly in its exclusionary aspect. The patient is unable to
suppress interference from external stimuli or internal tendencies.
Imitation of other and utilization behavior – the compulsion to utilize objects or tools
prompted simply by their presence – may be symptoms related to that lack of interference
control (Lhermitte et al., 1986)
Orbitofrontal hypermotility is the opposite of the hypomotility and aspontaneity of
the apathetic syndrome from lateral and medial lesions. In a substantial number of patients
the prevalent effect is euphoria, often accompanied by irritability and a contentious,
paranoid stance (Cummings, 1985).
A B
Fig. 23.2. A preoperative contrast enhanced computed tomographic (CT) scan of a 56-year-old man shows a giant
size olfactory grove meningioma and displacement of anterior and fronto-basal frontal lobes (A). The patient presents
an orbitofrontal syndrome. Postoperative contrast-enhanced CT-scan showing no residual tumor (B) and orbitofrontal
syndrome disappeared.
1834
A B
Fig. 23.3 (A) The left carotid angiogram demonstrates an ACoA aneurysm which projects inferiorly.
(B) Postoperative angiography demonstrated complete obliteration of the aneurysm with a clip.
Instincts are disinhibited and normal judgement impaired. These patients may show
by their behavior a blatant disregard for even the most elementary ethical principles.
Thus, orbitofrontal syndrome is oftentimes undistinguishable from mania.
Criminal sociopathy is another psychiatric condition analogous in some respect to
the orbitofrontal syndrome (Gorenstein, 1982; Lapierre et al., 1995).
Left frontal damage, especially damage to the anterior frontal lobes, is far more likely
to cause depression than similar lesions on the right (Gainotti, 1972; Sackeim et al., 1982;
Robinson et al., 1984; Starkstein et al., 1991). Lesions on the right more frequently lead
to mania (Jorge et al., 1993), especially regions of the orbitofrontal cortex (Starkstein et
al., 1987, 1989). In healthy subjects, left prefrontal cortex cerebral blood flow increases
when patients induce a state of dysphoria by thinking sad thoughts (Pardo et al., 1993;
George et al., 1995).
A transcranial magnetic stimulation (causing transient hypofunctioning) of the left,
but not right prefrontal cortex, resulted in decreased self-report of happiness and a
significant increase in sadness rating (Pascual-Leone et al., 1996).
Electrophysiological evidence suggests that the left frontal lobe is more specialized
for positive emotions related to approach and exploratory mechanisms and the right for
negative avoidance-related reactions (Davidson, 1992; Davidson and Sutton, 1995).
Lateral wall (prefrontal, premotor and primary motor cortex)

The lateral wall of frontal lobe can be subdivided in three main sectors along the
anterior-posterior axis: prefrontal, premotor, and primary motor.
Each of these sectors can be further subdivided in subsectors that are anatomically
and functionally differentiated (Matelli et al., 1985; Cavada and Goldman-Rakic, 1989;
Stepniewska et al., 1993; Petrides, 1994; Fogassi et al., 1996; Fujii et al., 1996; Geyer et
al., 1996; Rizzolatti et al., 1996 a, b).
1835
Prefrontal cortex
The lateral prefrontal cortex is the prefrontal cortex of the lateral convexity of frontal
lobe. It comprises part or entirely of areas 8, 9, 10 and 46. It is known to be primarily
involved in working memory processes (Goldman-Rakic, 1987). Working memory is the
ability to retain an item of information for the prospective execution of an action that is
dependent on that information. It is an essential cognitive function for the mediation of
cross-temporal contingencies in the temporal integration of reasoning, speech, and goal-
directed behavior (Fuster, 2009). Working memory, however, can fail in many patho-
logical conditions of the brain. The reason why is failure especially evident and
consistently found in the frontal patient is because that kind of memory is necessary for
prospective action, whether the action is a motor act, a mental operation, or a piece of
spoken language (Fuster, 2009).
Judging from the effects of a prefrontal lesion, working-memory of all modalities
seems distributed through lateral cortex, without anatomical compartmentalization for
spatial working memory (Müller et al., 2002; Müller and Knight, 2006).
However, the reversible transient lesions by transcranial magnetic stimulation (TMS)
have been reported to segregate spatial and non-spatial deficits to the dorsal and ventral
lateral cortex, respectively (Mottaghy et al., 2002).
A frontal eye-field (area 8) lesion leads to deficit of working memory for ocular
saccades (Ploner et al. 1999). Left-frontal patients have the most difficulty with working
memory of verbal items, and right-frontal patients with non-verbal areas.
Right-visuospatial specialization, in patients with right frontal lesions is more likely
to demonstrate poor use and representation of visuospatial data in a variety of tasks that
require working memory, and those with left frontal lesions are more likely to have
disordered memory for episodic information (Kolb and Whishaw, 1985; Milner, 1995).
Of patients with unilateral frontal damage, those with right frontal damage show the
poorest performance in design fluency tasks (Benson and Stuss, 1986).
Frontal patients, unlike temporal patients, have been noted to perform poorly in
spatial as well as nonspatial conditional association tests probably because of the working
memory component that those tests contain (Petrides, 1985).
Interference and the failure to control interference clearly play a role in the memory
deficit of the frontal patients.
This has been demonstrated by use of memory tasks with proper control of
interference factor (Oscar-Berman et al., 1991; Stuss, 1991; Chao and Knight, 1995; Ptito
et al., 1995).
So, in patients with brain injury, left frontal lobe damage typically leads to more
profound verbal recall deficits than right-sided damage, whereas right frontal damage
causes deficits primarily in categorization (Milner and Petrides, 1984; Incisa della
Rocchetta, 1986; Incisa della Rocchetta and Milner, 1993).
Deficits in the retrieval of verbal material in patients with left frontal damage may
be specific to certain lexical categories, in that injury to the left, but not to the right,
premotor areas produced a specific deficit in verb, but not noun retrieval (Damasio and
Tranel, 1993).
1836
However, left-hemisphere deficits in short-term or working memory are not limited

to the sphere of language and suggest the importance of the left prefrontal cortex in
programming strategies, control of executive function, and motor responses (Milner and
Petrides, 1984).
Patients with frontal lesions that spare the dorsolateral prefrontal cortex do not
exhibit these deficits (Goldman-Rakic, 1987). So, specialization of the left hemisphere
is for language and of the right for visuospatial information.
Thus, according to Fuster (2009), frontal patients show deficits in working memory,
especially if their lesions include lateral prefrontal cortex. The magnitude and qualities
of one such deficit depend on the context of testing, and most important, on the degree
to which the test requires the suppression of interference.
A specific framework of the neural substrates of human planning and executive
functions comprising working memory suggests that the dorsolateral prefrontal cortex
serves mechanisms of active manipulation and monitoring of sensorimotor information
within working memory. In this model, the ventrolateral prefrontal cortex serves only
working memory mechanisms that support simple retrieval of information for sensory-
guided sequential behavior (Petrides, 1994).
The lateral prefrontal cortex receives strong input from extrastriate cortical areas of
visual significance (Milner and Goodale, 1995).
The occipitofugal corticocortical pathways consists of a dorsal occipitoparietal
stream concerned with the processing of spatial relationships, and a ventral occipito-
temporal stream mainly concerned with the processing of object identity (Ungerleider
and Mishkin, 1982). This view has been refined, in that the dorsal stream is thought to
be primarily related to pragmatic aspects of spatial behavior, whereas the ventral stream
is primarily related to semantic aspects of spatial behavior (Goodale and Milner, 1992,
Jeannerot et al., 1995).
Thus, working memory for spatial locations is served by the dorsolateral prefrontal
cortex, whereas working memory for object identity is served by the ventrolateral
prefrontal cortex (Funahashi et al., 1993; Wilson et al., 1993).
Spatial information, for instance, can be readily coded with language. It is probably
for such reasons (Milner and Teuber, 1968) that early studies of frontal patients in spatial
delay tasks yielded negative results (Ghent et al., 1962; Chorover and Cole, 1966).
Other early studies, using delay task with complex spatial or nonspatial cues and
appropriate delays, clearly demonstrated that frontal patients, unlike patients with
posterior cortical lesions, have trouble with performance of delay tasks (Konorski, 1959;
Milner, 1964). Delays were of up to 60 seconds, and stimuli were such that verbal
rehearsal was extremely difficult.
In that nonspatial working memory task, patients with unilateral frontal damage made
significantly more errors than normal subjects or than patients with temporal lobe damage.
Lewinsohn et al. (1972) demonstrated similar deficits with visual, auditory, and
kinesthetic stimuli. Thus, frontal patients with unilateral right or left lesions showed
poorer performance than normal subjects. The authors concluded that the frontal deficit
was supramodal, and reflected both faulty registration and faulty retention.
1837
Later, even conventional delay tasks were shown to be impaired after a frontal lesion
(Milner et al., 1985; Freedman and Oscar-Berman, 1986; Oscar-Berman et al., 1991;
Pierrot-Deseilligny et al., 1991; Verin et al., 1993; Dubois et al., 1995).
Other neuropsychological studies, further substrate the prefrontal working-memory
deficits in digit span tests (Vidor, 1951; Hamlin, 1970, Janowsky et al. 1989 a; Stuss,
1991), in certain recognition tests (Milner and Teuber, 1968), and in temporal order and
recency tests (Milner, 1971, 1982; Milner et al., 1985; Shimamura et al., 1990; Kesner
et al., 1994; Jurado et al., 1997, 1998; Marshuetz, 2005).
PET studies have shown that listening to digits activates the left dorsolateral
prefrontal cortex in normal subjects when active monitoring and manipulation of external
information held in memory are required only to make judgements about the same stimuli,
and no active manipulation is required (Petrides et al., 1993). Similarly, visuospatial
information activates the right dorsolateral prefrontal cortex in normal subjects when
active manipulation and monitoring of information are required.
The same visuospatial information activates only the right ventrolateral prefrontal
cortex when only “reproduction” of information without active manipulation and
monitoring is demanded by the task (Owen et al., 1996).
The general patterns of lateralization of verbal working memory function to the left
frontal lobe and of visuospatial working memory function to the right frontal lobe, are
consistent with the clinical lesion data (Smith et al., 1996).
The dorsolateral prefrontal cortex seems to be a critical structure in a number of
delayed response and conditional sensorimotor learning tasks in nonhuman primates
(Goldman-Rakic, 1987).
Neurophysiological evidence showed that the neuronal discharge in dorsolateral
prefrontal neurons of monkeys performing conditional sensorimotor tasks is dependent
upon the learning component of the task (Fuster, 1995).
Learning related rCBF (regional cerebral blood flow) increases seem to be lateralized
to the left dorsolateral prefrontal cortex even when learning effects in conditional motor
tasks are largely parallel in both hands (Iacoboni et al., 1996 b). This suggests that transfer
of learning might occur through the anterior regions of the corpus callosum, intercon-
necting the prefrontal cortex of the two cerebral hemispheres (Iacoboni and Zaidel, 1995).
Working memory can be characterized as sustained attention to an internal
representation (Fuster, 2009).
Working memory is subject to destructibility and interference, which are likely after
prefrontal damage.
In a “rich” environment, with plentiful stimuli and distractors the frontal patient’s
memory is more likely to fail than in a quiet and simple environment. Just as critically,
interference may come from whithin – that is from the reservoir of memories and alter-
natives that the subject has experienced or is likely to experience in that particular context.
The greater the similarity between these and the memory currently “on line“, the
greater is the probability that they will interfere with it (Fuster, 2009).
1838
Callosal lesion in primates interfere with transfer of visuomotor conditional learning

(Eacott and Gaffan, 1990). The lateralization of conditional sensorimotor learning to the
left prefrontal cortex may not be specific to the human brain. Indeed, a lateralized left
prefrontal-dependent activity during sensorimotor learning has been reported in a
nonhuman primate (Gemba et al., 1995). Different from the frontal lobe receive
segregated cortical inputs from a variety of cortical areas of sensory significance. In
addition, the frontal lobe controls voluntary actions through planning of movements in
prefrontal areas, preparation of movements in premotor areas and execution of
movements in primary motor areas (Fuster, 1995).
However, little relevant data on structural asymmetries relate to functional
asymmetries in sensory motor integration, first in the lateral wall, and then in the medial
wall of the frontal lobe.
Premotor cortex
Situated just anterior to the precentral area, the premotor (area 6) and supplementary
motor areas have been identified as the site in which the integration of motor skills and
learned action sequences takes place (Kolb and Whishaw, 1996; Nilson et al., 2000;
Eslinger and Geddes, 2001; Damasio and Anderson, 2003). The concept of a premotor
cortex was first proposed in 1905 by Campbell, who called it the intermediate precentral
cortex. The term premotor cortex was first used by Hines in 1949.
Independent anatomical and physiological evidence in nonhuman primates (Matelli
et al., 1985; Fogassi et al., 1996; Fujii et al., 1996; Rizzolatti et al., 1996) and PET data
in humans (Iacoboni et al., 1996 a; Rizzolatti et al., 1996) support the division of premotor
cortex into four fields: a rostral (PMdr) and a caudal (PMdc ) field in the dorsal premotor
cortex, and a rostral (PMvr) and a caudal (PMvc) field in the ventral premotor cortex.
Neurophysiological evidence from studies of nonhuman primates suggests that PMdr
is associated with saccade-, arm-, and eye-, eye position-, and stimulus-related activity,
whereas PMdc is associated with arm motor preparation- and arm movement-related activity
(Fujii et al., 1996). The ventral premotor cortex seems to be associated with grasp
representations and action recognition in PMvr (Rizzolatti et al., 1996), and with peripersonal
space coding of somatosensory and visual stimuli in PMvc (Fogassi et al., 1996).
The medial premotor cortex is the so-called supplementary motor area (SMA) of
Woolsey et al. (1952). In both premotor areas, arcuate (prearcuate area 8 and postarcuate
area 6) and SMA, there is a degree of somatotopical organization – that is, differential
representation of the body (Woolsey et al., 1952; Muakkassa and Strick ,1979). Premotor
areas participate in afferent / efferent loop with the basal ganglia and the thalamus: the
looped interconnections are probably targeted to specific sites on both cortical and
subcortical structures (Passingham, 1997; Middleton and Strick, 2000).
The dorsal premotor cortex is traditionally associated with neglect in extrapersonal
space with selection and preparation of movements guided by external sensory stimuli,
and with the retrieval of responses associated with specific sensory stimuli (Halsband
and Freund, 1990; Passingham, 1993).
1839
The ventral premotor cortex is associated with neglect in peripersonal space

(Rizzolatti et al., 1983).
PET evidence seems to suggest a left-hemisphere lateralization in the human PMvr
(inferior frontal gyrus, Brodmann’s area 45) for the observation / execution matching
system of grasping action (Grafton et al., 1996; Rizzolatti et al., 1996). This functional
lateralization seems consistent with the hypothesis that primate communicative gestures
could be the precursors of human language and that the “grammar of communicative
gestures” could be represented in nonhuman primate PMvr, considered as the anatomical
homologue of human Broca’s area (Rizzolatti et al., 1996).
However, in these PET studies the subjects were required to grasp objects or to
imagine grasping objects, or to observe other grasping objects, only with the dominant
right hand.
Also, it has been shown with PET that the left PMvr (Brodmann’s area 45) is
activated in normal subjects while observing other making silent monosyllable mouth
movements (“lip reading”), whereas no acoustic or language receptive areas were
activated (Grafton et al., 1996). This would be consistent with the hypothesis that visual
information feeds forward directly to Broca’s area in the left hemisphere, as emphasized
by Denny-Brown (1975).
PET studies of dorsal premotor cortex in humans showed that left PMdr superiority
in establishing explicit stimulus - response association, and the left PMdc superiority in
implicit sensorimotor learning (Iacoboni et al., 1996 a). This would suggest a functional
rostrocaudal fractionation of human dorsal premotor cortex similar to the one observed
in nonhuman primates.
The lateralization to the left dorsal premotor cortex, suggested by chronometric
investigations, showed that the human left hemisphere is superior in tasks in which
stimulus - response associations and response selection are required (Anzola et al., 1977).
In the dorsolateral prefrontal cortex, sensorimotor learning seems to be associated
only with blood flow increase in PMdc. This suggests that, in contrast with other types
of learning that may be associated with blood flow decreases, frontal lobe mechanisms
of sensorimotor learning are generally associated with blood flow increases that
correspond to an increase in neural activity (Raichle et al., 1994).
Primary motor cortex

Motor cortex is located in the posterior part of the frontal lobe or frontal cortex, just
anterior to somatosensory cortex. Motor cortex includes a primary area, M1, where
electrical stimulation of neurons evokes muscle contraction at low levels of current (Jinnai
and Matsuda, 1979). M1 is characterized by large pyramidal or Betz cells and the lack of
an obvious layer 4 of granular cells.
Thus, M1 is referred to as agranular cortex and as area 4 of Brodmann’s classical
terminology. The pyramidal cells in M1 project via the pyramidal tract to motor neurons
pools in the contralateral brain stem and spinal cord (Brodal, 1978; Iwatsubo et al., 1990;
Kaas and Stepniewska, 2002).
1840
The primary motor cortex is the site of origin of about 30% to 40% of the fibres in
the pyramidal tract.
Furthermore, all the large-diameter axons (approximately 3% of pyramidal fibres)
originate from the giant motor neurons (of Betz) in the primary motor cortex.
Most of the neurons contributing fibres to corticospinal tract have glutamate or
aspartate as their excitatory neurotransmitter (Holmes and May, 1909; Levin and
Bradford, 1938; Lassek, 1940, 1954).
Stimulation of the motor cortex in conscious humans gives rise to discrete and
isolated contralateral movement limited to a single joint or a single muscle.
Bilateral responses are seen in extraocular muscles and muscles of the face, tongue,
jaw, larynx, and pharynx.
Thus, the primary motor area corresponds to the precentral gyrus (area 4 of
Brodmann). On the medial surface of the hemisphere, the primary motor area comprises
the anterior part of the paracentral lobule.
The contralateral half of the body is represented in the primary motor area in a
precise but disproportionate manner, giving rise to the motor homunculus in the same
way as that described for the primary somesthetic cortex.
The primary motor cortex functions in the initiation of highly skilled fine movements.
The motor area receives fibres from the ventrolateral nucleus of the thalamus, the
main projection area of the cerebellum. The motor area also receives fibres from the
somesthetic cortex (areas 1, 2 and 5) and the supplementary motor cortex.
The connections between the primary motor and somesthetic cortices are reciprocal.
Although the primary motor cortex is not the sole area from which movement can
be elicited, it is nevertheless characterized by initiating highly skilled movement at a
lower threshold of stimulation than the other motor areas.
One of the most striking lateralized behaviors in humans is hand preference, which
is typically associated with manual skill (Annett, 1985). Fine manual coordination is
lateralized to the left motor cortex in most right-handed individuals (Liepmann and Mass,
1907; Annett, 1985; Goldberg, 1985).
Some fMRI studies in human demonstrate asymmetric activation of primary motor
cortex during volitional fine movements of the hand (Kawashima et al., 1993; Kim et
al., 1993).
Stepniewska et al. (1993) and Geyer et al. (1996) demonstrated that the primary
motor cortex in human and nonhuman primates is divided functionally into a rostral sector
and a caudal sector. However, the functional asymmetries of the primary motor cortex
do not differentiate between rostral and caudal sectors (Fuster, 2007).
Hemispatial neglect is typically associated with right temporal-parietal lesions, but
it is observed with right frontal lobe lesions as well (Heilman and Valenstein, 1972;
Heilman et al., 1993).
Patients with right pre-Rolandic lesions, often encompassing primary motor areas,
tend not to move the hand ipsilateral to the lesion in the contralateral hemispace (Bisiach
et al., 1990) and exhibit motor impersistences well, which is thought to reflect an
1841
attentional deficit (Benson and Stuss, 1986). Paradoxically, these patients tend to neglect
lines seen on the left under free vision, and lines seen on the right under mirror-reversed
vision (Bisiach et al., 1995). Furthermore, a double dissociation in patients with unilateral
neglect is often seen.
Some patients have unilateral neglect only for near space; others have unilateral
neglect only for far space (Halligan and Marshall, 1991). This double dissociation
suggests that the representations of extrapersonal and personal space are differentiated
and segregated in the human brain.
In the nonhuman primate, there is evidence for two parietal-frontal circuits sub-
serving extrapersonal and personal space. A dorsal parietal-frontal circuit comprises area
7a, lateral intraparietal area, and dorsal premotor cortex, and codes extrapersonal space.
A ventral parietal-frontal circuit comprises area 7b, anterior intraparietal area, and
ventral premotor cortex, and codes personal space.
These two circuits are anatomically largely independent, but both input to primary
motor cortex (Passingham, 1993).
A PET observation has suggested that the right motor cortex is a critical structure in
mapping extrapersonal onto personal space (Iacoboni et al., 1997).
A number of fMRI studies have suggested a major role for the primary motor cortex
in motor learning (Grafton, 1995). Most of these studies have resulted in lateralized
activation of the left primary motor cortex. The only fMRI studies of which Iacoboni et
al. (1996) are aware that have used an unbiased learning paradigm in which left- and
right-hand motor activity was completely counterbalanced (Iacoboni et al., 1996 a, b;
Iacoboni et al., 1997) have resulted in blood flow increases consistently lateralized to the
left frontal lobe. These blood flow increases occurred mainly in dorsal premotor cortex
and in dorsolateral prefrontal cortex and only sporadically in primary motor cortex
(Iacoboni et al., 1996 b).
Medial wall (anterior cingulate cortex and SMA)

The medial prefrontal cortex comprises parts of the areas 8 through 10, and areas
12, 24 and 32. The latter two areas constitute the anterior cingulate cortex (Fig. 23.4).
It has important influences on attention, response selection, and emotional behavior
(Rolls, 1999; Brunia and Van Boxtel, 2000; Chelazzi and Corbetta, 2000).
Anterior and posterior portions have different projections and roles.
In general, the disorders due to medial lesions are poorly defined except for the case
of large lesions (Cummings, 1985, 1993).
Anterior cingulate cortex. Together with the lateral prefrontal cortex, the anterior
cingulate cortex controls behavior by detecting errors and signaling the occurrence of
conflicts during information processing. These functions are critical for the regulation of
behavior according to self-determined intention. The relative contribution of the two
structures is a matter of debate (Cohen et al., 2000; Gehring and Knight, 2000).
1842
Fig. 23.4. Modern rendition of the

cytoarchitectural map showing
Brodmann’s areas on the medial
surface of the human brain (figure
provided by Mark Dubin, University of
Colorado, 2006).
In the macaque, three areas, buried in the cingulate sulcus, seem to have significance
in sensorimotor processes: the rostral cingulate motor area, located anterior to the genu
of the arcuate sulcus, and the dorsal and the ventral cingulate motor areas, located caudal
to the genu of the arcuate sulcus (Picard and Strick, 1996).
PET findings have suggested at least two cortical fields in the human anterior
cingulate cortex: a large rostral one, anterior to the anterior commissure, associated with
complex sensorimotor tasks and with a somatotopic arrangement; and a small caudate
one, posterior to the anterior commissure, associated with simple tasks and not showing
a clear somatotopy (Picard and Strick, 1996).
Area 24 is at the crossroads of pathways linking the limbic system with the frontal
lobe, and, at the same time, is one of the so-called “suppressor areas”, which upon
stimulation induce general muscular hypotonia (Smith, 1945).
The anterior cingulate has been associated with attentional functions (Bench et al.,
1993; Posner and Dehaene, 1994). However, asymmetries in the anterior cingulate in
attentional mechanisms have not been systematically described (Pardo et al., 1991).
Furthermore, widespread areas of right dorsolateral prefrontal cortex are preferentially
activated during a variety of attentional tasks (Bench et al., 1993; Vendrell et al., 1995;
Lewin et al., 1996).
Picard and Strick (1996) observed a slower learning in right hand in subjects
practicing in a random fashion, associated with blood flow increases in the left SMA-
proper and the left rostral anterior cingulate area, in a region overlapping with the arm
representation in the human anterior cingulate cortex. Thus, behavioral data and rCBF
findings suggest a greater sensitivity of the left rostral cingulate region to contextual cues.
This is in line with a general role of the cingulate cortex in context-specific learning in
other mammals (Freeman et al., 1996).
The most striking asymmetry in the anterior cingulate region is at morphological
level. In the left hemisphere, there are often two cerebral sulci in the cingulate region,
the cingulate sulcus and the paracingulate sulcus, whereas in the right hemisphere, there
1843
is generally only one sulcus, the cingulate sulcus. It has been speculated that this
asymmetry might be related to certain aspects of effortful versus automatic vocalization
(Paus et al., 1996).
Indeed, the PET study that compared reversed speech (effortful) with overpracticed
speech, foci of activation were largely observed overlapping with the paracingulate sulcus
in the left hemisphere (Paus et al., 1993).
Lesions of the anterior cingulate region generally lead to hypokinesia or akinesia,
depending on their size (Kreindler, Macovei, Cardas and Dănăilă, 1966; Meador et al.,
1986; Verfaellie and Heilman, 1987). They are also frequently accompanied by defective
self-monitoring of behavior and of the ability to correct errors.
Akinetic mutism often results from massive bilateral lesions (Kreindler, Macovei
Cardas and Dănăilă, 1966). It is usually accompanied by severe neurovegetative
deterioration (Fuster, 2009). Some patients with lesions of the anterior cingulate region
have been noted to suffer from cataplexy (Ethelberg, 1950) – that is the paroxysmal and
general loss of muscle tonus commonly induced by strong emotion (Levin, 1953).
Once, the global adynamia results from irritation of area 24 (Fuster, 1955).
Mutism and apathy are the most prevalent disorders of medial frontal damage,
especially if that damage is large. Thus, subjects with a large medial lesion appear
characteristically unaware of their own condition (Nielsen and Jacobs, 1951; Barris and
Schuman, 1953).
Supplementary motor area. The supplementary motor area (SMA) is located on
the medial surface of the frontal lobe, anterior to the medial extension of the primary
motor cortex (area 4). It corresponds roughly to the medial extension of area 6 of
Brodmann. Although the existence of a motor area in the medial aspect of the frontal
cortex rostral to the precentral area of primates has long been known.
Penfield and Welch (1951) were the first to call this portion of the cortex the
supplementary motor area.
A homunculus has been defined for the supplementary motor area in which face and
upper limbs are represented rostral to the lower limb and trunk. Stimulation in humans
give risk to complex movement in preparation for the assumption of characteristic
postures (Brinkman and Porter, 1979; Tanji, 1994).
Two distinct areas can be differentiated in SMA: a rostral area called pre-SMA and
a caudal area called SMA-proper. In macaques, the pre-SMA is located mainly anterior
to the genu of the arcuate sulcus, whereas SMA-proper is located posterior to the genu
of the arcuate sulcus. In the human brain, the pre-SMA is located rostral to the level of
the anterior commissure, and the SMA-proper is located caudal to the level of the anterior
commissure. Anatomical and neurophysiological evidence suggest that the pre-SMA is
related to selection and preparation of movements, whereas the SMA-proper is more
related to aspects of motor execution (Picard and Strick, 1996). Although simple motor
tasks are elicited from stimulation of the supplementary motor area, the role of this area
in simple motor tasks is much less significant and is likely to be subsidiary to that of the
primary motor area. On the other hand, the supplementary motor area assumes more
1844
significance in executing simple motor tasks as a compensatory mechanism when the

primary motor area is destroyed (Tanji, 1994).
The supplementary motor area seems crucial in the temporal organization of
movement, especially in sequential performance of multiple movements, and in motor
tasks that demand retrieval of motor memory.
When subjects perform sensorimotor tasks, practice in blocked fashion (where each
task pattern is practiced separately from the others) produces a faster learning slope than
practice in random fashion (where each practiced task pattern is mixed with the others;
Stelmach, 1996).
In a PET experiment on sensorimotor conditional learning, Iacoboni (2000) has
observed that contextual interference affects learning in the right hand more than in the
left hand. This was associated with blood flow increases in the left SMA-proper
(Iacoboni, 2000). Thus, the left SMA-proper seems to be more sensitive to contextual
interference than the right SMA-proper, which might suggest that the differential
contextual effect observed in patients with left and right SMA lesions occurs more
specifically at the level of the SMA-proper (Geschwind and Iacoboni, 2007).
Lesions in the medial aspects of area 6 (SMA), and 8, frequency lead to difficulties
in initiation and performance of limb, eye, or speech movements.
Patients with long-term unilateral medial frontal lobe lesions in the left hemisphere
benefit from preparatory information regarding a motor response and can inhibit
inappropriate responses.
In contrast, patients with similar long-term lesions in the right hemisphere cannot
benefit from preparatory information regarding a motor response and cannot inhibit an
inappropriate motor response (Verfaellie and Heilman, 1987).
Thus, it seems there is a differential effect of contextual cues on motor performance
in the left and right SMA. On the other hand, in right-handed neurological patients with
unilateral SMA lesions, functional asymmetry is related to the temporal control of
movement sequences.
This function is generally subserved by the SMA (Tanji and Shima, 1994).
Patients with left SMA lesions are much more impaired in reproducing rhythm
patterns using the left hand, the right hand, or both hands in an alternating manner, than
patients with right SMA lesions (Halsband et al., 1993). Furthermore, patients with left
SMA lesions are more disturbed in the chronology of memory-guided saccade sequences
than patients with right SMA lesions (Gaymard et al., 1993).
This differential role of the left and right SMA in sequential control of movements,
at least in right-handers, explains why strategically placed callosal lesions producing
motor disconnection tend to be associated with alien syndrome in the nondominant hand,
but not the dominant hand in right-handers (Geschwind et al., 1995).
If the motor areas of the right hemisphere that control the left hand do not receive
inputs on sequential control of movements from the right SMA because of callosal
disconnection, then motor control disturbances in the left hand are likely to appear
(Geschwind et al., 1995). They propose that this pathophysiological mechanism might
1845
be a unitary mechanism of praxis disturbances following callosal lesions (Gonzales-Rothi

et al., 1994).
In sum, one model of frontal specialization proposes a dichotomy in which the right
frontal lobe is specialized for novelty and the left frontal lobe for the routine (Goldberg
and Podell, 1995). That the right frontal lobe is predominant in novelty processing fits
with its role in attentional mechanism (Heilman et al., 1993).
PET studies in healthy volunteers demonstrate strikingly increased blood flow and
metabolic activity in the right prefrontal cortex, including Brodmann’s areas 8, 9, 44, and
46 during selective attention tasks in different sensory modalities (Roland, 1984; Pardo
et al., 1991; Bench et al., 1993; Lewin et al., 1996).
According to Geschwind and Iacoboni (2007), the specialization of one hemisphere
for a given function does not require that the contralateral hemisphere be involved in that
function. Thus, any attempt to unify lateralized frontal lobe functions under one model
is simplistic and likely to be flawed (Geschwind and Iacoboni, 2007).
The only functional asymmetry for which a corresponding structural asymmetry is
that of language and Broca’s area.
Asymmetry in the motor system

The most obvious behavioral asymmetry in humans is handedness, with
approximately 92% of woman and 88% of men favoring and being more proficient with
the right hand for performing a variety of skilled activities, such as writing, drawing,
eating, and using a needle to sew.
Of the remaining non-right-handed individuals a few exhibit strong and consistent
left-handedness, a few are truly ambidextrous, and others show hand preferences that
vary from one skilled activity to another (Vallortigara, 2000).
In general, for both right-handed and left-handed individuals, hand differences are
weaker for unskilled activities as picking up a small object.
Furthermore, for tasks that require the coordinated activity of both hands, their roles
are often complementary (Corballis, 1997).
Generally, for right-handed individuals the left hand (controlled by the right
hemisphere) performs movements of relatively low spatial and temporal frequency,
whereas the right hand (controlled by the left hemisphere) performs movements of
relatively high spatial and temporal frequency.
An example of this complementary arrangement is handwriting, during which the
left hand arranges and steadies the paper while the right hand makes more frequent and
smaller movements with the writing instruments.
Though handedness is the most obvious example, there are also other motoric
asymmetries.
For example, for right-handed individuals the left side of the body is frequently
preferred for postural support. In addition, the right side of the face (controlled by the
left hemisphere) is superior for making certain oral movements associated with language
and other precisely sequenced activities, whereas the left side of the face (controlled by
the right hemisphere) is more emotionally expressive (Provins, 1997).
1846
Anyhow, two different types of experiments have been devised to assess motor
asymmetries: 1) direct observation of motor asymmetry; and 2) interference tasks (Kolb
and Whishaw, 2003).
1) Direct observation
If asymmetry in the control of movement is inherent, this asymmetry might be
observable when people are engaged in other behavior.
For example, perhaps the right hand is more active during the performance of verbal
tasks, which do not require a manual response, and the left hand is more active during
the performance of nonverbal tasks, such as listening to music, which also do not require
a manual response. To examine this possibility, Kimura (1964 and 1973) videotaped
subjects talking or humming. They found that right-handed people tend to gesture with
their right hands when talking but are equally likely to scratch, rub their noses, or touch
their bodies with either hand. Kimura interpreted the observed gesturing with the limb
contralateral to the speaking hemisphere to indicate a relation between speech and certain
manual activities.
Differences in gesturing, which favor the right hand in right-handed subjects, could
simply be due to a difference in preferred hand rather than to functional asymmetry in
motor control.
A second observed motor asymmetry was reported in the performance of complex
movements of the mouth. Wolf and Goodale (1987) did single-frame analyses of
videotaped mouth movements produced when people make verbal or nonverbal sounds.
These observations support the idea that the left hemisphere has a special role in the
selection, programming, and production of verbal and nonverbal oral movements.
Considerable evidence shows that the left side of the face displays emotions more
strongly than the right side, and Wolf and Goodale (1987) showed that the onset facial
expressions occur sooner on the left side of the face. Thus, it is not the control of
movement itself that is asymmetrical but rather movement for a particular purpose.
2) Interference tasks
A variety of interference tasks examine a well-known phenomenon that most people
manifest: the difficulty of doing two complex tasks at the same time. Perhaps the most
interesting interference study known to us is an unpublished experiment by Robert Hicks
and Marcel Kinsbourne (Kolb and Whishaw, 2003). They persuaded several unemployed
musicians to come to their laboratory daily to play the piano. The task was to learn a
different piece of music with each hand so that the two pieces could be played simul-
taneously. When the musicians had mastered this very difficult task, the experimenters
then asked them to speak or to hum while playing.
Speaking disrupted playing with the right hand, and humming disrupted playing
with the left.
Interference studies provide a useful way to study the roles of two hemispheres in
controlling movement, but much more work is needed before researchers can identify
1847
the complementary roles of the two hemispheres (see reviews by Murphy and Peters,
1994, and by Carosseli et al., 1997). It will be necessary to identify which types of
movements each hemisphere is especially good at controlling, because these movements
will probably be resilient to interference effects.
Studies of interference effects are intriguing because they may be sources of fresh
insights into the cortical organization of the motor system, but interference effects are
poorly understood and appear to be capricious. In addition, as we become proficient at
motor tasks, we are less prone to interference effects (Kolb and Whishaw, 2003).
The left hemisphere as interpreter

The left hemisphere is considered to be the “dominant” hemisphere in most right-
handed people. The term dominant is usually taken to mean language-dominant, but
Gazzaniga (1995) has suggested that the left hemisphere is not only superior in terms of
language function, but also in the ability to make simple inferences and to interpret its
own behavior and emotions (Gazzaniga and Smylie, 1984).
Such observations strongly suggest that the left hemisphere is not only more able
than the right to express itself verbally but that it plays a dominant role in interpreting
behavior and providing a rationale for events in the world.
These observations can also yield insight regarding the confabulatory behavior seen
in some amnesic patients who are unable to encode new information.
Finding themselves in situations for which they cannot remember the antecedents,
they may be compelled to explain them in the same way that the left hemisphere explains
behavior motivated by right hemisphere (Baynes and Gazzaniga, 1997).
Asymmetries for the language in humans
Introduction
The most obvious functional difference between the hemispheres is that, for most
people, the left hemisphere is the primary mediator of verbal function, including reading
and writing, understanding and speaking, verbal ideation, verbal memory, numerical
symbol system, and even comprehension of verbal symbols traced on the skin. Processing
the linear and rapidly changing acoustic information needed for speech comprehension
is better with the left than with the right hemisphere (Schwartz and Tallal, 1980; Haward
1997; Beeman and Chiarello, 1998).
Males show a stronger left hemisphere lateralization for phenological processing
than females (Shaywitz et al., 1995; Zaidel et al., 1995).
So, left hemisphere dominance for many aspects of language is the most obvious
and cited asymmetry outside of the motor domain. From clinical neurological data as
well as other sources, it is estimated that speech production is limited to the left
hemisphere in approximately 95% of right-handed individuals. Left hemisphere is also
dominant for many aspects of language perception and for the verbal processing of
stimulus material.
1848
Moreover, left hemisphere lateralization extends to control of posturing and of

sequencing hand and arm movements, and of the musculature of speech, although
bilateral structures are involved (Lezak et al., 2004).
One of the most obvious cognitive aspect associated with left hemisphere damage
is aphasia. This complex of disorders reflects a very basic underlying capacity of the left
hemisphere that is not dependent on hearing, as deaf persons who sign can develop an
aphasia for their nonauditory language in the areas associated with aphasia in hearing
persons (Bellugi et al., 1983; Posner et al., 1990).
Other left hemisphere disorders include verbal memory or verbal fluency deficits,
concrete thinking, specific impairments in reading or writing, and impaired arithmetic
ability characterized by defects or loss of basic mathematical concepts of operations and
even of numbers (Grafman and Rickard, 1997; Delazer and Bartha, 2001; Dănăilă and
Golu, 2006).
Right hemisphere language capacities have been demonstrated for comprehension
of speech and written material. One significant contribution is the appreciation and
integration of relationships in verbal discourse and narrative materials (Delis et al., 1983,
Beeman and Chiarello, 1998; Kiehl et al., 1999), which is a capacity necessary for
enjoying a good joke (Beeman, 1998; Gardner, 1994). The right hemisphere also appears
to provide the possibility of alternative meaning, getting away from purely literal
interpretations of verbal material (Bottini et al., 1994; Brownell and Martino, 1998; Fiore
and Schooler, 1998).
The right hemisphere appears to have a reading lexicon (Bogen, 1997; Coslett and
Saffran, 1998), but the more verbally adept left hemisphere normally blocks access to it
so that the right hemisphere’s knowledge of words becomes evident only in laboratory
manipulations or left hemisphere damage (Landis et al., 1983; Landis and Regard, 1988).
The right hemisphere seems to be sensitive to speech intonations (Borod et al., 1998,
Ivry and Lebby, 1998) and is necessary for voice recognition (Van Lancker et al., 1989).
Following commissurotomy, when speech is directed to the right hemisphere, much
of what is heard is comprehended so long as it remains simple (Searleman, 1977; Bayness
and Eliassen, 1998). Although functional imaging studies show a preponderance of left
cerebral activity in reading (Price, 1997), not surprisingly, given its visuospatial
components, reading also engages the right hemisphere, activating specific areas
(Ornstein et al., 1979; Gaillard and Converso, 1988; Huettner et al., 1989; Banich and
Nicholas, 1998; Indefrey and Levelt, 2000). In contrast to the ability for rapid, automatic
processing of printed words by the intact left hemisphere, the healthy right hemisphere
takes a slower and generally inefficient letter by letter approach (Chiarello, 1988; Burgess
and Lund, 1998), which may be useful when word shapes have unfamiliar forms (Banich
and Nicholas, 1998).
Less can be said fore the verbal expressive capacities of the right hemisphere since
they are quite limited, as displayed – or rather, not displayed – by split brain patients who
make few utterance in response to right brain stimulation (Zaidel, 1978; Baynes and
Gazzaniga, 2000).
1849
The right hemisphere appears to play a role in organizing verbal production

conceptually (Joanette et al., 1990; Browell and Martino, 1998), with specific temporal
and prefrontal involvement in comprehending story meanings (Nichelli et al. 1995).
It may be necessary for meaningfully expressive speech intonation (prosody) (Filley,
1995; Borod et al., 1998; Ross, 2000). The right hemisphere contributes to the
maintenance of context-appropriate and emotionally appropriate verbal behavior (Joanette
et al., 1990; Brownell and Martino, 1998), although this contribution is not limited
communication but extends to all behavior domains (Lezak, 1994).
That the right hemisphere has a language capacity can also be inferred in aphasic
patients with left-side lesions who showed improvement from their immediate post-stroke
deficits accompanied by measurably heightened right hemisphere activity (Papanicolaou
et al., 1988; Murdoch, 1990; Dănăilă et al., 1990; Franckowiak, 1997; Heiss et al., 1999;
Gold and Kertesz, 2000).
Based on the data obtained following the investigation of patients with organic
pathological foci in the right hemisphere, Dănăilă et al., (1990) demonstrate the thesis of
bilateral integration of the language system by the interaction of the two cerebral
hemispheres.
The study of aphasic patients showed that the dominance of the left hemisphere for
language was of a relative rather than an absolute nature.
It had been noted that, although the aphasic patients were incapable of truly
proportional language, they did produce automatic, interjectional, and emotional speech;
these positive features of an aphasic’s language behavior were interpreted as reflecting
the operation of mechanisms in his unaffected minor hemisphere (Benton, 2000).
In a stressful situation, an aphasic patient might produce perfectly intelligible
propositional speech which he could not utter under ordinary circumstances. It was
presumed that this speech was produced by the minor hemisphere. This meant that in the
course of language learning, verbal engrams were laid down in the right hemisphere as
well as in the left. These minor hemisphere engrams remained inactive because of the
specialization of the major hemisphere for language (Benton, 2000).
The same explanation was applied for recovery from aphasic disorder. It seemed
clear that the minor hemisphere must have participated in the original learning of
language.
So, the right hemisphere has been erroneously called the “minor” or “nondominant”
hemisphere because the often subtle character of right hemisphere disorders led early
observers to believe that it played no specialized role in behavior. However, although
limited linguistically, the right hemisphere is “fully human with respect to its cognitive
depth and complexity” (Levy, 1983).
When we consider understanding language for the purpose of communication, this
is growing evidence that both hemispheres make important contributions. Whereas the
left hemisphere is dominant for the perception of phonetic information, for the use of
syntax and for certain aspects of semantic processing, the right hemisphere is dominant
for processing the sort of information cues and prosody that communicate such things as
1850
emotional tone. So, the right hemisphere is superior to the left in using the intonation
cues of speech to identify emotional tone of voice. The right hemisphere is also involved
in processing narrative-level linguistic information (Hellige, 2001). Some of these
complementary language-related asymmetries may be related to hemispheric difference
in the efficiency of processing different aspects of acoustic signals.
For example, identification of many spoken phonemes requires efficient processing
of rapid changes in the acoustic signal over brief periods of time, a type of processing
for which the left hemisphere is hypothesized to be superior.
In contrast, identification of the emotional tone of voice requires efficient processing
of much slower modulations of the acoustic signal over longer periods of time, a type of
processing for which the right hemisphere is hypothesized to be superior (Heilman, 1997;
Christman, 1997; Hellige, 2000).
So, patients with right hemisphere damage may be quite fluent, even verbose
(Brookshire, 1978; Rivers and Love, 1980; Cutting, 1990), but illogical and given to lose
generalization and bad judgment (Stemmer and Joanette, 1998). They have difficulty in
ordering, organizing and making sense out of complex stimuli or situations, and thus
many display planning defects (Lezak et al., 2004). Verbal comprehension may be
compromised by confusion of the elements of what is heard by personalized intrusions,
by literal interpretations, and by generalized loss of gist in a morass of details (Beeman
and Chiarello, 1998). Their speech may be uninflected and aprosodic, paralleling their
difficulty in comprehending speech intonations (Ross, 2003).
These patients are vulnerable to difficulty in maintaining a high level of alertness
(Ladavas et al., 1989), which may be akin to the association of right hemisphere lesions
with impersistence – the inability to sustain facial or limb posture (Pimental and
Kingsbury, 1989).
Dănăilă et al. (1990) evaluated speech disorders at 15 patients with tumors and
strokes localized in the right hemisphere. They noted there main categories of speech
impairments: disturbances of contents of “semantic structure”, disturbances of forms of
the logical-grammatical structure, and disturbances of dynamics – volume, output,
fluency, rhythm, intonation and writing.
The two hemispheres also appear to access word meanings in complementary ways.
When a word is present, the left hemisphere restricts processing very quickly to one
possible meaning, usually the dominant meaning or the meaning most consistent with
the present context, whereas the right hemisphere maintains activation of multiple
meanings and remote associated words for a more expended period of time (Springer and
Deutsch, 1998).
Anyhow, viewed in retrospect and taken in their totality these clinical contributions
would seem to have produced at least suggestive evidence for the view that the right
hemisphere should not be considered simply as a minor hemisphere with no distinctive
functional properties (Benton, 2000).
1851
Asymmetry in visuospatial functions

The expected right hemispheric superiority in visuospatial function has been demon-
strated in callosotomy patients (Bogen and Gazzaniga, 1965; Milner and Taylor, 1972).
In contrast, superior use of visual imagery has been demonstrated in the left
hemisphere, using a letter-based task (Farah et al., 1985).
The use of tactile information to build spatial representations of abstract shapes also
appears to be better developed in the right hemisphere (Milner and Taylor, 1972).
Tasks such as Block Design from the Wechsler Adult Intelligence Scale (WAIS),
however, which are typically associated with the right parietal lobe, appear to require
integration between the hemispheres in some patients (Gazzaniga, 1989). Furthermore,
while the right hemisphere is better able to analyze unfamiliar facial information than
the left hemisphere (Levy et al., 1972; Gazzaniga and Smylie, 1983) and the left is better
able to generate voluntary expressions (Gazzaniga and Smylie, 1990), both hemispheres
share in the management of facial expression when spontaneous emotions are expressed.
Although the right hemisphere demonstrates superior levels of performance on a
variety of perceptual and spatial tasks, the left hemisphere appears to have at least some
competence in most areas and some cases are essential for the solution of complex visual
problems.
The left hemisphere is superior at all language tasks and in a variety of tasks that
require interferences (Baynes and Gazzaniga, 1997).
Moreover, verbal IQ appears to be stable following callosotomy, although perfor-
mance IQ may decline (Zaidel, 1990).
Gazzaniga (1995) suggests that the hemisphere is also dominant for intelligent
behavior, although that conclusion assumes a contemporary concept of intelligence that
rests heavily on verbal abilities.
Hemispheric isolation of visual and tactile information

Subjects can independently report visual material that has been isolated to one
hemisphere or other, but they cannot make comparison between the two hemifields.
Performance is at or near chance levels in simple same / different comparison when
items are presented in different visual fields (Holtzman et al., 1981; Seymour et al., 1994;
Baynes and Gazzaniga, 1997).
Despite reports of integration of higher-order information following callosotomy
(Sergent, 1983, 1990), such results have not always been replicated or have proved
explicable through the patient’s strategic maneuvers (Seymour et al., 1994; Corballis,
1994; Kingstone and Gazzaniga, 1995).
At present, it appears that if visual or tactile information is presented so that it is
initially perceived by only one hemisphere, the perception remains isolated within that
hemisphere.
The animal literature, however, has documented that information from areas close
to the visual midline is shared by both hemispheres (Stone, 1966; Fukuda et al., 1989).
1852
It appears that this observation is also true for the human species in an area no more
than 2º from the vertical meridian ( Fendrich and Gazzaniga, 1989).
Although represented the visual information in this area has little utility, as neither
detailed shape comparisons nor brief displays could be reliably compared across the
meridian ( Fendrich and Gazzaniga, 1989).
Sharing of attention control

Although both higher cognitive function and basic perceptual information appear to
be isolated within each hemisphere, there is some evidence for sharing the control of
visual attention. The hemispheres appear to share control of the “attentional spotlight”
via their subcortical connections (Baynes and Gazzaniga, 1997). That is, if attention is
directed to particular position in the visual field a cue in one field, that information can
be used by both hemispheres (Holtzman et al., 1981, 1984). Nonetheless, explicit inter-
field comparisons of spatial location cannot be made accurately (Holtzman et al., 1981),
nor can attention be simultaneously directed to different points in each visual field
(Holtzman et al., 1984).
It also appears that attentional resources are limited despite the “splitting” of
conscious. Holtzman and Gazzaniga (1982) demonstrated that increasing processing
demands in one hemisphere had a deleterious effect on performance in the other
hemisphere. Nonetheless, in comparison with normal subjects, there was less decrement
in a dual-task condition for callosotomized subjects (Holtzman and Gazzaniga, 1985).
Thus, although the two hemispheres may compete for cognitive resources, there is
evidence for independence of function. This latter finding is consistent with the observation
of Luck et al. (1989) that visual search is independently mediated by both hemispheres.
Mangun et al. (1994) demonstrated differential processing of spatial cues, with only
the left visual field (right-hand) trials yielding an advantage for validly cued trials.
According to Baynes and Gazzaniga (1997), although the behaving is remarkably
intact following callosotomy, investigation reveals hemispheric capacities that refine and
confirm hypotheses based on normal subjects and patients with focal lesions.
The isolated right hemisphere usually cannot read, write, or speak, despite displaying
a variety of conscious behaviors. Dissociation like left-handed tactile anomia or agraphia
may be an indication of less language-competent right hemispheres.
However, the ability to comprehended auditory and visual language may be present
and can contribute to the presentation of aphasic and alexic patients. Observations indicate
that the right hemisphere may participate in long-term recovery from aphasia (Baynes
and Gazzaniga, 1997).
Independent function of the hemispheres was demonstrated as a result of which the
important role played by the verbal left hemisphere in allowing the organism to observe
and interpret its own actions and emotional states was recognized. Insights regarding the
components of perception, memory, attention, and language continue to arise from this
population and to inform models of normal perceptual and cognitive processing (Baynes
and Gazzaniga, 1997).
1853
Asymmetries in processing spatial informations

Tradition and common sense favor the verbal (left hemisphere) vs. nonverbal (right
hemisphere) dichotomy.
Speech expression and comprehension, as well as reading text and writing, take
place serially in a fixed temporal order. In contrast, the appreciation of a spatial display,
whether it is a form, an object, or face, permits parallel information processing and hence
an almost instantaneous grasp of the complex stimulus (Benton, 2000).
Matching of unfamiliar face is regarded as a configurational task par excellence. In
accord with expectation, one finds a right frequency of failure in patients with right
hemisphere disease, particularly those with posterior temporo-occipital lesions where the
frequency of failure is about 50%. However, there is a subgroup of patients with posterior
left hemisphere lesions and impaired understanding of speech who also show a notable
frequency of failure, in this instance, 35% to 40% (Hamsher et al., 1979). Similarly,
tachitoscopic visual field studies of facial recognition in normal subjects find a highly
significant left field advantage, indicating a major participation of the right hemisphere
in the performance. But again, there is a substantial minority of normal right, handed
subjects who exhibit a left field advantage, the proportion being 20-25% (Helliard, 1973;
St. John, 1981).
Anyhow, the right hemisphere dominates the processing of information that does
not readily lend itself to verbalization. This includes the reception and storage of visual
data, tactile and visual recognition of shapes and forms, perception of spatial orientation
and perspective, and copying and drawing geometric and representational designs and
pictures. The left hemisphere seems to predominate in metric distance judgments (Hellige,
1988; Mc Carthy and Warrington, 1990), while the right hemisphere has superiority in
metric angle judgments (Benton et al., 1994; Mehta and Newcombe, 1996).
Thus, both hemispheres contribute to processing spatial information, with some
differences in what they process most efficiently (Sergent, 1991; Banich, 1995).
In the spatial domain, the brain computes at least two kinds of a spatial relation
representation – a categorical representation used to assign a spatial relation to a category
such as “connected to” or “above” and a coordinate representation used to represent
precise distances and locations. The right hemisphere makes more effective use of this
latter coordinate system, whereas there is either no hemispheric difference or a left
hemisphere advantage for processing categorical spatial relationships. Neural network
simulation suggests that hemispheric asymmetry for making categorical versus coordinate
judgments may be related to the nature of visual information that is most useful for
processing categorical versus coordinate properties.
It is interesting that categorical spatial processing is disrupted by manipulations
(blurring of stimuli) that selectively interfere with information carried by channels with
small, discrete receptive fields, whereas coordinate spatial processing is disrupted by
manipulations (use of a diffuse red background) that selectively interfere with information
carried by channels with large overlapping receptive fields (Beeman and Chiarello, 1998;
Hellige, 2001).
1854
The same networks that favored coordinate spatial processing also favored coding the
identify of specific shapes, whereas the same networks that favored categorical spatial
processing also favored the assignment of shapes to categories. Interestingly, there is
evidence of right hemisphere superiority for processing the sort of specific shape information
that would be needed to distinguish among the exemplars of single category, but left
hemisphere superiority for classifying the prototypes used to define different categories.
Arithmetic calculations (involving spatial organization of the problem elements or
distinct from left hemisphere – mediated linear arithmetic problems involving) have a
significant right hemisphere component (Grafman and Rickard, 1997; Dehaene, 2000).
Arithmetic failures are most likely to appear in written calculations that require
spatial organization of the problems’ elements (Grafman and Rickard, 1997; Dănăilă and
Golu, 2006).
Visuospatial and other perceptual deficits show up in these patients’ difficulty
copying designs, making constructions, and matching or discriminating patterns or faces.
Prosopagnosia (inability to recognize faces) occurs only when the cortex on the
undersides of the occipital and temporal lobes is damaged bilaterally (Mesulam, 2000;
Dănăilă and Golu, 2006). Patients with right hemisphere damage may have particular
problems with spatial orientation and visuospatial memory such that they get lost, even
in familiar surroundings, and can be slow to learn their way around a new area. Visual
functions have to do with dorsal-ventral distinction. Two now well-identified visual
systems have separate pathways with different cortical loci (Mesulam, 2000; Goodale,
2000; Dănăilă and Golu, 2006).
Their constructional disabilities may reflect both their spatial disorientation and
defective capacity for perceptual or conceptual organization. Stereoscopic vision may be
affected (Benton and Hécaen, 1970).
The distinctive processing qualities of each hemisphere become evident in the
mediation of spatial relations. In the right hemisphere the tendency is to deal with the
same visual stimuli as a spatially related whole.
Patients with left hemisphere damage may make defective constructions largely
because of tendencies toward simplification and difficulties in drawing angles, but
they also may display deficits in visuospatial orientation and short-term recall (Mehta
et al., 1989).
The ability to perform complex manual – as well as oral – motor sequences may be
impaired (Harrington and Haaland, 1992; Meador et al., 1999; Schluter et al., 2001).
The distinctive processing qualities of each hemisphere became evident in the
mediation of spatial relations. Left hemisphere processing tends to break the visual
percept into details that can be identified and conceptualized verbally in terms of number
or length of lines, size and direction of angles, etc. Together, the two processing systems
of the left and the right hemisphere provide recognition, storage and comprehension of
discrete and continuous, serial and simultaneous, detailed and holistic aspects of
experience across at least the major sensory modalities of vision, audition and touch
Thus, model has clinical value, because loss of tissue in a hemisphere tends to impair
its particular processing capacity. A diminished contribution from one hemisphere may
1855
be accompanied by augmented or exaggerated activity of the other when released from

the inhibitory or competitive constraints of normal hemispheric interactions (Novelly et
al., 1984; Lezak, 1994; Starkstein and Robinson, 1997; Shimizu et al., 2000). This
phenomenon appears in the verbosity and overwriting of many right hemisphere damaged
patients (Lezak and Newman, 1979; Yamadori et al., 1986; Cutting, 1990).
The functional difference between hemispheres also appears in the tendency for
patients with left-sided damage to be more accurate in remembering large visually
presented forms than the small details making up those forms; but when the lesion is on
the right, recall of details is more accurate than recall of the whole composed figure (Delis
et al., 1986). These examples suggest that one hemisphere’s function is enhanced when
the other hemisphere is impaired. In an analogous manner, patients with left hemisphere
disease tend to reproduce the essential configuration but leave out details when copying,
drawing, and they may perform some visuo-perceptual tasks better, intact subjects (Kim
et al., 1984; Wasserstein et al., 1987).
Perceptual deficits, particularly left-sided inattention phenomena and those
involving degraded stimuli or unusual presentation, are not uncommon (McCarthy and
Warrington, 1990).
Asymmetry in memory and learning

Along with the limbic system, many regions of the temporal lobes are critical for
normal learning and retention. Anyhow, memory and learning show hemispheric dif-
ferences.
Awake patients undergoing brain surgery report vivid auditory and visual recall of
previously experienced scenes and episodes upon electrical stimulation of the exposed
temporal lobe cortex (Penfield, 1958; Gloor et al., 1982). Nauta (1964) speculated that
these memories involve widespread neural mechanisms and that the temporal cortex and,
to a lesser extent, the occipital cortex play roles in organizing the discrete components
of memory for orderly and complete recall.
Thus, retrieval of visual information is impaired by lesions of the visual association
cortex of the occipital lobe, impaired retrieval of auditory information follows lesions of
the auditory association of the temporal lobe, and so on.
Anyhow, memory and learning show hemispheric differences. So, loss of the left
hippocampus and nearly cortical areas impairs verbal memory, and destruction of the
right hippocampus results in defective recognition and recall of “complex visual and
auditory patterns to which a name cannot readily be assigned” (Milner, 1970, Morris et
al., 1995; Sass et al., 1995; Abrahams et al., 1997; Pillon et al., 1999). In some cases,
lesions of the temporal neocortex may impair retention and learning by disconnecting
the hippocampus from cortical input (Jones-Gotman et al., 1997). Cortical regions appear
to be organized for long-term storage of memories (Fuster, 1999).
The subjects for most studies of memory and the temporal lobe are patients who
have had portions of one or both temporal lobes excised, usually for seizure control.
These studies show that memory deficits with temporal lobe lesions also differ according
1856
to the side of the lesion (Milner, 1972; Lee et al., 1989; Smith, 1989; Morris et al., 1995,
Pillon et al., 1999).
Impaired verbal memory appears with surgical resection of the left temporal lobe
(Seidenberg et al., 1998), and nonverbal (auditory, tactile, visual) memory disturbances
accompany right temporal lobe resection (Lezak et al., 2004). With left temporal
lobectomies, deficits have been found for different kinds of verbal memory, including
episodic (both short-term and learning), semantic and remote memory (Smith, 1989; Frisk
and Milner, 1990; Loring and Meador, 2003).
These patients also lag behind normal controls in learning designs, although once
learned their retention is good unlike patients with right temporal lesions who fail both
aspects of this memory task (Jones-Gotman, 1986).
Same patients with cortical lesions have shown selective deficits in retrieving highly
specific types of information, such as items in certain categories, but not others (Martin
et al., 1997; Gabrieli, 1998). This finding suggests that cortical representation of
knowledge is highly organized.
Reduced access to verbal labeling may explain the left temporal patients’ slowed
learning. Learning manual sequences becomes more difficult following left but not right
lobectomy (Jason, 1987).
Cortical stimulation of the anterior left temporal cortex interferes with verbal
learning without affecting speech, while stimulation of the posterior left temporal cortex
is more likely to result in retrieval (word finding) problems and anomia (literally, no
words) (Fedio and Van Buren, 1974; Ojemann, 1978).
Lesions in different areas of the left temporal lobe differentially affect the degree
and nature of impairment in immediate auditory recall of tones or digits (Gordon, 1983).
Memory deficits documented for patients with right temporal lobectomies and other
temporal lobe lesions involve designs, faces, melodies, and spatial formats such as those
used in maze learning (Abrahams et al., 1997).
In short, these patients display memory impairments when perceptions or knowledge
cannot be readily put into words (Shapiro et al., 1981; Smith, 1989). This left - right
difference has been found in brain activation studies comparing the effect of stimulus
material on temporal lobes (Ojemann, 1978; Dolan et al., 1997), and on the prefrontal
cortex’s role in memory (Wagner et al., 1998; Mc Dermott et al., 1999; Lee et al., 2000).
However, current evidence suggests that the relationship between the type of material
(verbal vs. nonverbalizable) to be learned or modality of stimulus input and hemisphere
involvement is not simple. Functional neuroimaging data demonstrate that both
hemispheres may be activated by a verbal memory task (Buckner et al., 1998; Johanson
et al., 2001).
This finding suggests that cortical representation of knowledge is highly organized.
Loss of facts, knowledge of objects, and meaning of words have been reported with
selective damage to the inferolateral temporal gyri of one or both temporal lobes, with
sparing of the hippocampal and parahippocampal gyri (Graham and Hodges, 1997).
1857
Thus, while the hippocampus and medial limbic structures are involved in the
processing of newly learned information that has not been consolidated yet, the temporal
cortex appears to house old learned information.
Asymmetry in the information process

The supramodal nature of hemisphere specialization shows up in a number of ways:
one is the organization of the left hemisphere for “linear” processing of sequentially
presenting stimuli such as verbal statements, mathematical proposition, and the
programming of rapid motor sequences. The right hemisphere is superior for “configu-
rational” processing required by material that cannot be described adequately in words
or strings of symbol, such as the appearance of a face or three-dimensional spatial
relationship (Bogen, 1969 a and b; Lezak, 1994, Carlesimo and Caltagirone, 1995;
Swithenby et al., 1998). The two hemispheres process global / local or whole / detail
information differently (Robertson and Rafael, 2000; Rossion et al., 2000), what Delis
et al. (1988) refer to as the level or hierarchical analysis. When asked to copy or read a
large-scale stimulus such as the shape of a letter or other common symbol composed of
many different symbols in a small scale, patients with left hemisphere disease will tend
to ignore the small bits and interpret the large-scale figure; those whose lesions are on
the right are more likely to overlook the big symbol but respond to the small ones. This
can be interpreted as indicating a left hemisphere superiority in processing detailed
information, a right hemisphere predilection for large-scale or global percepts (Fig. 23.5)
Yet another processing difference between the hemisphere has to do with stimulus
familiarity, as the right hemisphere appears to be best suited to handle novel information
while the left tends to be more adept with familiar material such as “well-routinized
codes” (Goldberg and Costa, 1981; Goldberg, 1990).
Other studies have associated the right hemisphere with early less detailed stages of
processing, which may also be those that emerge first in the course of development,
leaving the left hemisphere to perform later stage operations on more detailed features
(Sergent, 1984, 1988; Bouma, 1990).
Asymmetry in the attention

Data from a variety of sources suggests right hemisphere dominance for spatial
attention specially, if not attention generally: patients with compromised right hemisphere
functioning tend to have diminished awareness of or responsiveness to stimuli presented
to their left side; reaction times mediated by the right hemisphere are faster than those
mediated by the left; and the right hemisphere is activated equally by stimuli from either
side in contrast to more exclusively contralateral left hemisphere activation (Heilman
and Van Den Abell, 1980; Meador et al., 1988; Mesulam, 2000; Heilman and Rothi
2003).
1858
Fig. 23.5. Functions associated with the dominant and nondominant cerebral hemispheres.
(Modified from Noback CR et al. (1996), The Human Nervous System, 5th edn., Williams and Wilkins, Baltimore).
However, other studies suggest that neither hemisphere has an attentional advantage,
but rather each hemisphere directs attention contralaterally (Mirsky, 1989; Posner, 1990),
1859
and that they are equally capable of detecting stimuli (Prather et al., 1992). The right
hemisphere directs attention to far space while the left hemisphere directs attention to
near space (Heilman et al., 1995). The appearance of right hemisphere superiority for
attention in some situations may stem from its ability to integrate complex, nonlinear
information rapidly.
Asymmetry in the music

Musical perception may be considered in terms of the reception of those perceptual-
acoustic characteristics that define the basic elements of musical sounds, such as
frequency, pitch, consonance, timbre, duration, intensity, and spatial location.
The sparing of musical abilities in patients with congenital, acquired language
defects or aphasic was noted by Dalin (1745), Bouillaud (1865), Proust, 1866 and 1872),
Finkelnburg (1870).
Conversely, instance of loss of musical skills were also described in patients who
showed left hemiparesis and without aphasia (Mann, 1898; Jossmann, 1926, 1927). Loss
of the capacity to sing hum or whistle a tune is one of the more frequently described
forms of amusia. Anyhow, neural mechanism underlying disorders of receptive functions
and those of expressive functions of music, and the nature of their relationship to
cognitive and linguistic activity remains obscure.
Nevertheless, despite the close qualitative and quantitative association between
disorders of music and language, there is incontrovertible evidence that the two spheres
of activity are mediated by distinctive neurobehavioral systems.
The long-standing observation that patients with severe expressive language disorder
are able to sing is in itself sufficient proof of this. The same dissociation may be observed
in patients with receptive language disorder.
The fact that disturbances in musical function can occur in patients who are free of
any aphasic disorder is equally cogent evidence for the independence of a two “language”
system (Benton, 2000).
Patients with purely or predominantly oral-expressive impairment are about as likely
to be nonaphasic as aphasic. However, it must be remarked that most of them do in fact
show dysprosodic speech which might be interpreted as another expression of a general
defect in the oral production of sounds, rhythms, and melodic intonations.
Clinopathological correlations with respect to disturbances in musical function are
much less abundant than for the aphasic disorders and only a limited amount of
information about the site of lesions associated with the amusias has been amassed.
Lesions in either hemisphere can produce both expressive and receptive disorders
of musical function in a right-handed patient while aphasia in such a patient is almost
invariably an expression of left hemisphere disease.
Analysis of the clinical literature suggests that “pure” expressive amusia (vocal or
instrumental) with preservation of receptive function and without aphasia is most likely to
be associated with anterior lesions of the right hemisphere. The case reports of Mann (1898),
Jossmann (1926, 1927), and Botez and Wertheim (1959) illustrate this relationship.
1860
A predominantly expressive amusia in combination with a predominantly expressive

aphasic disorder is associated with anterior lesion of the left hemisphere, as illustrated
by the inability of many Broca aphasics to reproduce a heard tone or sing a tune. Here
appears to be no hemispheric bias in respect to the lesions that may produce a disorder
of expressive musical function (Benton, 2000).
Anyhow, the most fundamental musical motor activity is singing. Perry et al. (1999),
measured increased cerebral blood flow (CBF) during simple singing using positron
emission tomography (PET). Repetitive singing of a single pitch was contrasted with
listening to complex tones at the same pitch rate. The set of regions activated overlapped
those previously observed during speech (SMA, anterior cingulate, insula / frontal
operculum, and precentral gyrus). The main differences were in the direction of
hemisphere asymmetry within a subset of these regions. First, the CBF increase was much
greater in the right primary auditory region, a result that Zatorre and Binder (2000) and
Zatorre and Peretz (2001) later replicated for singing a single pitch continuously on each
breath in contrast to listening to playback of that singing.
They hypothesized that this asymmetry may be related to deriving the fundamental
frequency of one’s own voice for feedback guidance of vocal motor production (given a
right auditory cortex preference for spectral analysis).
The fundamental frequency of subjects’ vocalization was measured. When the total
amount of pitch excursion within each continuously sung note was quantified and
covaried against CBF in the whole brain, a region of positive covariation was observed
in the right primary auditory region.
Second, though less striking, an asymmetry favoring the right hemisphere was also
observed within the right ventral precentral gyrus or the orofacial region. The classsic
correspondence between the region activated by singing and speaking suggests that both
may have evolved from a complex system for the voluntary control of vocalization. Their
divergences suggest the lateral evolution of complementary hemispheric specialization
for both the perception and production of singing and speech (Perry et al., 1999).
The simple acts of motor production require the execution of learned motor program
or an integrated sequence of movements. More complex sequences that follow a precise
temporal plan and involve multiple vocal instrumental pitches and variable timing and
intensity are integrated to musical expression. Such sequential movements performed as
a unit require advance programming prior to their execution (Pascual-Leone et al., 1995;
Blood and Zatorre, 2001). The cortical areas involved in the control of manual motor
output in a quasi-musical context, is consistent with what would be expected for timed
manual movements in general.
In an experiment, Perry et al. (1999), asked their subjects to listen to a two-note
sequence drawn from a major scale and either imagine it in their heads, or hum it out
loud. When they hummed out loud, in contrast to just listening to the sequences, activation
was seen not only in motor cortex, SMA, and the right putamen as seen during imaging
but also in the left putamen, cerebelum, right primary auditory region, and more ex-
tensively in motor cortex bilaterally. Thus, this simple act of musical motor programming
1861
activated the same areas through to be involved in the execution of movement sequences
generally (i.e., primary and premotor cortex, SMA, basal ganglia, and the cerebellum).
Musical perception
Musical perception may be considered in terms of the reception of those perceptual-
acoustic characteristics that define the basic elements of musical sounds, such as
frequency, pitch, consonance, timbre, duration, intensity and spatial localization.
Disturbance in receptive musical capacities in combination with aphasic disorder
have been found to be associated with lesions involving the middle and posterior parts
of the first and second temporal gyri, the transverse temporal gyri, and the anterior
temporal region of the left hemisphere.
The three surgically explored cases of Dorgeuille (1966) may be cited to illustrate
this point.
They showed a fluent aphasia, impairment in the discrimination of tones, expressive
musical defects, defective reproduction of sounds and rhythmic patterns and defects in
singing melodies with which thay had been quite familiar.
Receptive amusia without concomitant aphasic disorder has been found to be
associated with temporal lobe disease of either hemisphere or of both hemispheres
(Schuster and Taterka, 1926; Pötzl and Uiberall, 1937; Pötzl, 1939, 1943; Spreen et
al., 1965).
A plausible interpretation is that some individuals show dissociated dominance, i.e.,
thay are left hemisphere dominant for language but right hemisphere dominant for music.
Henschen (1920) localized a center for singing in the upper part of the third frontal gyrus,
a venter for oral musical comprehension in the left temporal pole and a center for reading
music in the angular gyrus.
The idea that each hemisphere makes a distinctive contribution to receptive and
expressive musical performance has been proposed. For example, Barbizet et al. (1969)
and Barbizet (1972) have advanced the concept that the right hemisphere participates
primarily on the perceptual and executive levels of musical activity while the left
hemisphere mediates the recognition and memory of musical structures, the symbolic
processes in reading and writing music, and the higher level integrative functions involved
in musical composition. It is clear that there can be a dissociation between expressive
and receptive functions.
But why one aphasic patient with focal lesion will show concomitant disturbances
in musical function while another patient with a similar type of disorder and lesion will
show no musical disabilities is a complete mystery (Benton, 2000). It is possible that the
contribution which each hemisphere makes to the mediation of musical function varies
quantitatively from one individual to another.
Reliable knowledge about interhemispheric relations in this respect no doubt would
go far toward helping us understand a cognitive problem, namely, why some patients are
rendered amusic as a consequence of disease of the right hemisphere while the majority
of patients in this category are not affected (Benton, 2000).
1862
A number of questions remain unanswered. Investigation in the field of the aphasic

disorders has generated findings that have given much insight into the relations between
handedness and hemispheric cerebral dominance for the language functions (Benton,
1965; Subirana, 1969; Hécaen, 1972).
Asymmetry in the visual perception and language

of temporal-lobe lesions
TH and TF at the posterior end of temporal lobe are often referred to as the parahip-
pocampal cortex. The fusiform gyrus and inferior temporal gyrus are functionally part
of the temporal cortex.
Functionally, mesial structures of the temporal lobe (amygdala, hippocampus, and
rhinal cortex) all have demonstrated role in some aspects of the establishment of new
memories.
The amygdala, in particular, has been seen as contributing to normal and abnormal
emotional responses and experiences. Bilateral amygdaloid destruction causes a severe
disturbance of normal affective behavior (Kluver-Bucy syndrome, schizophrenia, and
bipolar disorder).
The contribution of the temporal lobe to visual perception has been clarified by the
division of visual projection from the occipital lobe in two directions or “streams”: a
dorsal route into parietal lobe that is involved in spatial localization and a ventral route
into the temporal lobe that is involved in the appreciation of the qualities of objects (and
their identification) in visual scene.
Damage to posterior inferior temporal lobe, especially when bilateral, and when
portions of inferior areas 18 and 19 are involved, can lead to a condition called
prosopagnosia.
Patients with this disorder can see a face but do not recognize the person from the
face alone.
Prosopagnosia can usually recognize and correctly interpret facial expressions, and
they may be able to recognize a person from other visual but nonfacial cues, such as gait
or posture. It is clear that the disorder caused by IT (inferior temporal) lesions has to do
with conscious recognition.
The disorder may be accompanied by difficulty in recognizing (naming) famous
buildings, and such individuals may also have difficulty with texture discriminations and
color perception.
When the damage is on the left posterior inferior temporal lobe, the person may
identify the face incorrectly but still give an answer in the correct category (e.g., naming
a different figure in politics or entertainment). This is called “deep” prosopagnosia in
analogy with “deep” dyslexia in which the person reads a word semantically related to a
word on the page.
Milner (1968) found that her patients with right temporal lobectomies were impaired
in the interpretation of cartoon drawings in the Mc Gill Picture – Anomalies Test. But,
although patients with right temporal lesions can describe the contents of the cartoon
1863
accurately, they are impaired at recognizing the anomalous aspects of this picture and
others. So, when the damage is on the right, the person may be slow and erratic at
recognizing faces but not profoundly prosopagnosic.
Language. Electrical stimulation of the superior temporal sulcus (especially in the
posterior half) in the left hemisphere of typical right-handers often causes speech arrest
or other alterations of language abilities. PET findings show bilateral activation of
Heschel’s gyrus and unilateral activation of Wernicke’s area (left hemisphere only) when
typical right-handed subjects listen to a verbal material such as a narrative.
Speech-related areas are occasionally found in the middle temporal gyrus, although
it is possible that such unusual patterns of speech representation might be found
predominantly in patients with preexisting brain damage.
Damage to the anterior parts of the inferior and lateral portions of the temporal lobe
of the speech hemisphere causes problems with confrontational naming, but repetition
and grammar are usually unaffected.
An inferior speech area has been seen in some patients (speech arrest following
electrical stimulation) and surgeons have usually assumed that these areas can be removed
without significant loss of language ability.
Some patients have isolated naming deficits (e.g., proper names) with unilateral
lesions of the anterior and lateral tip of the temporal lobe.
Damage to the anterior parts of the inferior and lateral portions of the temporal lobe
of the right hemisphere has been associated with memory deficits for autobiographical
episodes, although other retrograde memory functions may remain intact.
Using functional activation with PET or fMRI has confirmed the hypothesis that
visual analysis extends into the inferior portions of the temporal lobes. The activation
appears to be bilateral in most cases, but there is a predominance of left-sided activation
if the object’s name is being sought.
Anyhow, it is worth mentioning that one of the disadvantages of functional brain
scans is that patterns of activation reveal what is activated not what must be activated for
successful completion of the task.
The following symptoms are associated with disease of temporal lobes: disturbance
of auditory sensation and perception; impaired long-term memory; altered personality
and affective behavior: disorders of music perception; disorders of visual perception;
disturbance in the selection of visual and auditory input; inability to use contextual
information; impaired organization and categorization of sensory input; and altered sexual
behavior (Kolb and Whishaw, 2003).
Asymmetry in the auditory system

The temporal lobes comprise all the tissue that lies below the sylvian sulcus and
anterior to the occipital cortex. They share borders with the occipital and parietal lobes,
but the precise boundaries are not clearly defined by landmarks.
Subcortical temporal-lobe structures include the limbic cortex, the amygdala, and
the hippocampal formation. Connection to and from the temporal lobe extents throughout
the brain.
1864
We can divide the temporal regions on the lateral surface into those that are auditory
(Brodmann’s areas 41, 42, and 22) and those that form the ventral visual stream on the
lateral temporal lobe (areas 20, 21, 37 and 38). The visual regions are often referred to
as inferotemporal cortex.
The medial temporal region (limbic cortex) includes the amygdala and adjacent
cortex (uncus), the hippocampus and surrounding cortex (subiculum, entorhinal cortex,
perirhinal cortex), and the fusiform gyrus. The entorhinal cortex is Brodmann’s area 28,
and the perirhinal cortex comprises Brodmann’ areas 35 and 36.
In contrast with the visual-system, pathways, the projections of the auditory system
provide both ipsilateral and contralateral inputs to the cortex; so there is bilateral
representation of each cochlear nucleus in both hemispheres.
In the early 1960s, Doreen Kimura (1961 and 1967) studied neurological patients while
they performed dichotic listening tasks. Pairs of spoken digits (say, “two” and “six”) were
presented simultaneously through headphones, but one digit only was heard in each ear. The
subjects heard three pairs of digits and then were asked to recall as many of the six digits as
possible, in any order. Kimura and Folb (1968) noticed that subjects recalled more digits
that had been presented to the right ear than had been presented to the left.
This result led Kimura to propose that, when different stimuli are presented
simultaneously to each ear, the pathway from the right ear to the speaking hemisphere
has preferred access and the ipsilateral pathway from the left ear is relatively suppressed.
Thus, during a dichotic task, the stimulus to the left ear must travel to the right
hemisphere and then across the cerebral commissures to the left hemisphere. This longer
route puts the left ear at a disadvantage, and words played to the right ear are recalled
more accurately.
Having found a right ear advantage for the perception of dichotically presented
speech stimuli, an obvious next step was to search for tasks that gave a left-ear superiority.
In 1964, Kimura reported just such an effect in the perception of melodies. Two excerpts
of instrumental chamber music were played simultaneously through headphone, one to
each ear. After each pair, four excerpts (including the two that had been played
dichotically) were presented binaurally (to both ear), and the subject’s task was to identify
the two that had been heard previously. Amazingly, Kimura (1964) found a left ear
advantage on this task.
Not all normal subjects show the expected ear advantages in dichotic studies, the
effects are not large when they occur (seldom exceeding a twofold difference in accuracy
in the two ears), and dichotic results are apparently affected by various contextual and
practice effects.
Patients with damage to the corpus callosum exhibit an almost complete inhibition
of words presented to the left ear, even though they can recall words presented to this ear
if there is no competing stimulus to the right ear.
The Kimura’s experiments imply that the left hemisphere is specialized for
processing language related sounds, whereas the right hemisphere processes music-
related sounds.
1865
Papcun et al. (1974) showed that Morse-code operators have a right-ear superiority
for the perception of the code, even though the sounds are distinguished only by their
temporal structure. Thus, the results of this study might be taken as evidence that the left
hemisphere is not specialized for language so much as for “something else”.
Asymmetry in the somatosensory system of parietal-lobe lesions

The postcentral gyrus, at the most forward part of the parietal lobe, contains the
primary sensory (somatosensory) projection area. Kinesthetic and vestibular functions
are mediated by areas low on the parietal lobe near the occipital and temporal lobe
boundary regions. Anyhow, the parietal lobe can be divided into three functional zones
for somatosensory processes, movement, and spatial cognition. The most anterior zones
take part in somatosensory functions.
Sensory information undergoes extensive associative elaboration through reciprocal
connections with other cortical and subcortical areas (Kolb and Whishaw, 1996; Mesulam
1998; Dănăilă and Golu, 2006). The superior parietal region primarily controls the visual
guidance of movements of the hands and fingers, limbs, head, eyes. The region has
expanded in humans to include regions controlling not only the actual manipulation of
objects, but also the mental manipulation of objects. Movements around the body, or in
the imagination, necessarily include the space around the body and the object. Thus, the
posterior parietal region can be conceived of as having a “spatial” function, although the
precise nature of this spatial function is far from clear.
The inferior parietal region has a role in processes related to spatial cognition and in
what have been described as quasi-spatial processes, such as are used in arithmetic and
reading.
Thus, the posterior parietal region can be conceived of having a “spatial” function
but no clear-cut demarcation exists among any of the functions localized on the posterior
cortex.
Rather, although the primary centers of the major functions served by the posterior
cerebral regions are relatively distant from one another, secondary association areas
gradually fade into tertiary overlap, or heteromodal, zones in which auditory, visual, and
body-sensing components commingle (Lezak et al., 2004).
Anyhow, the parietal cortex processes and integrates somatosensory and visual
information, especially with regard to the control of movement.
The anterior parietal zone processes somatic sensations and perceptions; the posterior
parietal zone is specialized primarily for integrating sensory input from the somatic and
visual regions and, to a lesser extent, from other sensory regions, mostly for the control
of movement.
Somatosensory system, like the others, is not a single sensory system, but a multiple
one composed of several submodalities. Three major submodalities are: pain and
temperature; the perception of objects using fine touch and pressure receptors, or hapsis;
and the perception of body awareness, called proprioception.
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Somatosensory cortex is composed of a primary area S I (somatosensory area I, or

Brodmann’s area 3-1-2) and a number of secondary areas (somatosensory area II or S II)
areas 5 and 7. Area SI also sends projections into the adjacent motor cortex, area 4.
Penfield and Boldrey (1958) created a map that topographically represented the body
surface on the primary somatosensory cortex. The regions representing feeling in the
mouth and eyes were in the ventral part of S I, the regions representing hand and finger
sensation were in the middle, and the regions corresponding to feet were in the dorsal
area. The map is called homunculus. In humans, the areas representing the hands and
tongue are extremely large, whereas the areas representing the trunk and legs are small.
The results of subsequent studies, mainly using monkeys and making use of smaller
recording electrodes, suggest that the primary somatosensory cortex contains a number
of homunculi, one for each of its four known subregions, 3a, 3b, 1, and 2.
Each of these areas is dominated by responses to one type of body receptor, although
there is overlap. Area 3a represents muscle sense (position and movement of muscle),
area 3b represents both slowly and rapidly adapting skin receptors, area 1 represents
rapidly adapting skin receptors, and area 2 represents deep pressure and joint sense. Thus,
the body is represented at least four times in S I (Kolb and Whishaw, 2003).
The primary somatosensory system is almost completely crossed, which allow an
easy behavioral comparison of the two sides testing the right and left limb separately.
One line of somatosensory research compares the performance on the left and right
hands in the recognition of shapes, angles and patterns. The left hand of right-handed
subjects is superior at nearly all tasks of this type (Kolb and Whishaw, 2003).
Rudel et al. (1974) found that both blind and sighted subjects read Braille more
rapidly with the left hand. Some children are actually fluent readers with the left hand
but are totally unable to read with the right. Because Braille patterns are spatial
configurations of dots, this observation is congruent with the proposal that the right
hemisphere has a role in processing spatial information that is not shared by the left.
Another type of somatosensory test which employs an analogue of the dichotic
listening procedure, is the dichaptic test. Subjects feel objects and then look at an array
of objects and select those that they had previously touched. Using this, Gibson and
Bryden (1983) presented subjects with cutouts of irregular shapes or letters made of
sandpaper, which were moved slowly across the fingertips. Their subjects showed a right-
hand advantage for identifying letters and a left-hand advantage for identifyng other
shapes.
Milner et al. (1994), suggest that the brain operates on a “need to know” basis.
Having too much information may be counterproductive for any given system.
Somatosensory symptoms associated with damage to the postcentral gyrus and the
adjacent cortex are very different. Within the brain, no other territory supposes the parietal
lobes in the rich variety of clinical phenomena that are exposed under conditions of
disease.
However, the clinical manifestations of parietal lobe disease may be subtle, requiring
special techniques for their elicitation.
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Somatosensory symptoms of parietal-lobe lesions

Semmes et al. (1960 and 1963), Semmes and Turner (1977) and Corkin et al. (1970),
found that lesions of the postcentral gyrus produced abnormally high sensory thresholds,
impaired position sense, and deficits in stereognosis (tactile perception). In Corkin study,
patients performed poorly at detecting a light touch to the skin (pressure, sensibility), at
determining if they were touched by one or two sharp points (two point threshold), and
at localizing points of touch on the skin on the side of the body contralateral to the lesion.
Anyhow, the classical doctrine that somatic sensation is represented only in the
contralateral parietal lobe is not absolute.
Beginning with Oppenheim (1898), there have been sporadic reports of patients who
showed bilateral astereognosis or loss of tactile sensation as a result of an apparently
unilateral cerebral lesion. Semmes et al. (1960 and 1963) found that the impairment of
sensation (particularly, discriminative sensation) following right and left-sided lesions
was not strictly comparable: the left hand as will as the right tended to be impaired by
injury to the left sensorimotor region, whereas only the left hand tended to be affected
by injury to the right sensorimotor region.
These observations with minor qualifications were confirmed by Carmon (1971)
and also by Corkin et al. (1970), who investigated the sensory effects of cortical excision
in patients with focal epilepsy. More recently, Caselli (1991) has described six patients
with extensive right-sided cerebral infarction, associated in each case with bilateral
impairment of tactile object recognition but without impairment of primary sense
modalities in the right hand. In each of these patients, there was also a profound
hemineglect, which confounded the interpretation of left side sensory signs.
Thus, it appears that certain somatic sensory functions are mediated not only by the
contralateral hemisphere, but also by the ipsilateral one, although the contribution of the
former is undoubtedly the more significant.
The traditional concept of the left hemispheric dominance in respect to tactile
perception has been questioned by Carmon and Benton (1969), who found that the right
hemisphere is particularly important in perceiving the direction of tactile stimuli. Also,
Corkin et al. (1964) and Corkin (1965) observed that patients with right-hemisphere
lesions show a consistently greater failure of tactile-maze learning than those with left-
sided lesions, pointing to a relative dominance of the right hemisphere in the mediation
of tactile performance involving a spatial component. Noteworthy in this respect is that
the phenomenon of sensory inattention or extinction is more prominent with the right
than with the left parietal lobe lesions and is most informative if the primary and
secondary sensory cortical areas are spared.
Lesion of the postcentral gyrus may also produce a symptom that Luria (1973) called
afferent paresis.
Movements of the finger are clumsy because the person has lost the necessary
feedback about their exact position.
Head and Holmes (1911) drew attention to a number of the interesting points about
patients with parietal sensory deficits – the easy fatigability of their sensory perception;
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the inconsistency of responses to painful and tactile stimuli; the difficulty in distin-
guishing more than one contact at a time; disregard of stimuli on the affected side when
the healthy side is stimulated simultaneously (tactile inattention or extinction); the
tendency of superficial pain sensation to outlast the stimulus and to be hyperpathic; and
the occurrence of hallucinations of touch.
More precise testing is possible by using a von Frey hair. By this method, a stimulus
of constant strength can be applied and the threshold for tactile sensation determined by
measuring the force required to bend a hair of known length.
Thus, the defect is essentially one of sensory discrimination, i.e., an impairment or
loss of the sense of position and passive movement and the ability to localize tactile,
thermal and noxious stimuli applied to the body surface; to recognize figures written on
the skin; to distinguish between single and double contacts (two point discrimination);
and to detect the direction of movement of a tactile stimulus. In contrast, the perception
of pain, touch, pressure, vibratory, and thermal stimuli is relatively intact. This type of
sensory defect is sometimes referred to as “cortical”, although it can be produced just as
well by lesions of the subcortical connections.
In tests of pressure sensibility, two points discrimination, point localization, position
of sense, and tactile object recognition, Semmes and Turner (1977) and Corkin et al.
(1970) found bilateral disturbance in nearly half of their patients with unilateral lesions,
but the deficits were always more severe contralaterally and mainly in the hand.
A pseudothalamic pain syndrome on the side deprived of sensation has also been
described by Biemond (1956). The discomfort (burning or constrictive pain, identical to
the thalamic pain syndrome) resulted from vascular lesions restricted to the cortex.
Another somatosensory symptom is simultaneous extinction that can be
demonstrated only by special testing procedures. The logic of this test is that a person is
ordinarily confronted by an environment in which many sensory stimuli impinge
simultaneously, yet the person is able to distinguish and perceive each of these individual
sensory impressions.
To offer more-complicated sensory stimulation, two tactile stimuli are presented
simultaneously to the same or different body parts. The objective of such a double
simultaneous stimulation is to uncover those situations in which both stimuli would be
reported if applied single, but only one would be reported if both were applied together. A
failure to report one stimulus is usually called extinction and is most commonly associated
with damage to the somatic secondary cortex, especially in the right parietal lobe.
Blind touch
Paillard et al. (1983), reported the case of a woman who appears to have a tactile
analogue of blindsight. This woman had a large lesion of areas PF, PE (area PE is
equivalent to area 5 and PF to area 7b in Felleman and van Essen’s flat map of cortical
areas in the macaque) and some of PG (area PG in the monkey includes areas 7a, VIP,
LIP, IPJ, PP, MSTc, and MSTp), resulting in a complete anesthesia of the right side of
the body so severe that she was likely to cut or burn herself without being aware of it.
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Nevertheless, she was able to point with her left hand to location on her right hand where
she had been touched, even though she failed to report feeling the touch.
Anyhow, the PG areas are primarily visual.
The presence of a tactile analogue of blindsight is important because it suggests the
existence of two tactile systems – one specialized for detection and an other for
localization. Such specialization may be a general feature of sensory system organization
Object recognition
Warrington and Taylor (1973) described a common symptom of right-parietal-lobe
lesion, in which patients having these lesions badly impaired at recognizing objects shown
in unfamiliar view. They wrote that the deficit is not in forming a gestalt, or concept, but
rather in perceptual classification.
Such allocation can be seen as a type of spatial matching in which the common view
of an object must be rotated spatially to match the novel view.
Warrington and Taylor suggested that the focus for this deficit is roughly the right
inferior parietal lobule, the same region proposed as the locus of contralateral neglect.
Pseudocerebellar syndrome
With anterior parietal lobe lesions there is often an associated hemiparesis, since the
position of the parietal lobe contributes witch a considerable number of fibres to the
corticospinal tract. Or, there is only a poverty of movement of the opposite side as part
of the somatic neglect. The affected limbs, if weakened, tend to remain hypotonic and
the musculature undergoes atrophy of a degree not explained by inactivity alone.
Exceptionally, at some phase in recovery from the hemisensory deficit, there is
incoordination of movement and intention of tremor of the contralateral arm and leg,
simulating a cerebellar deficit (pseudocerebellar syndrome) (Adams et al., 1997).
Somatosensory agnosias
There are two major types of somatosensory agnosias: astereognosis and
asomatognosia.
Astereognosis
Astereognosis (Greek: a, priv.; + stereos, solid; + gnosis, knowledge) refers to the
loss of the power of judging the form, shape and size of an object by touch, based on the
impressions from deeper receptors.
Ahylognosia (Greek: a, priv.; + hyle, matter; + gnosis, recognition) is the inability
to recognize differences of density, weight, texture and roughness of objects by touch. It
depends mainly on cutaneous impressions.
The lack of recognition of texture, shape and form is frequently a manifestation of
cortical disease but a similar clinical defect will occur if tracts that transmit tactile and
proprioceptive sensation are interrupted by lesions of the spinal cord and brain stem (and,
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of course, of the peripheral nerves). The latter type of sensory defect is called
stereoanesthesia and must be distinguished from astereognosis, which connotes an
inability to identify an object by palpation, even though the primary sense data (touch,
pain, temperature and vibration) are intact. In practice, a pure astereognosis is rarely
encountered, and the term is employed when the impairment of superficial and vibratory
sensation in the hand seems to be of insufficient severity to account for the defect. Defined
in the way, astereognosis is either right- or left-sided, and, with the qualifications
mentioned below, is the product of a lesion in the opposite hemisphere, involving the
sensory cortex, particularly S 2, or the thalamoparietal projections.
Finally, there is a distinction to be made between astereognosis and tactile agnosia.
Casselli (1991) defined tactile agnosia as a strictly unilateral disorder, right or left, in
which the impairment of tactile object recognition is unencumbered by a disturbance of
the primary sensory modalities. Such a disorder would be designated by other as a pure
form of astereognosis. In accordance with Adams et al. (1997), tactile agnosia is a
disturbance in which a one-sided lesion lying posterior to the postcentral gyrus of the
dominant parietal lobe results in an inability to recognize an object by touch in both
hands.
According to this view, tactile agnosia is a disorder of apperception of stimuli and
of translating them into symbols akin to the defect in naming parts of the body, visualizing
a plan or a route, or understanding the meaning of the printed or spoken words (visual or
auditory verbal agnosia).
Asomatognosia
The idea that visual and tactile sensory information are synthesized during
development into a body schema or image (perception of one’s body and of the relations
of bodily parts to one another) was first clearly formulated by Pick (1908) and extensively
elaborated by Brain (1941).
The formation of the body schema is believed to be based on the constant influx and
storage of sensations from our bodies as we move about; hence, motor activity is
important in its development. Always, however, a sense of extrapersonal space is
involved as well, and this dependents upon visual and labyrinthine impulses. The
mechanisms upon which these perceptions depend are best appreciated by studying their
derangements in the course of neurological disease (Adams et al., 1997).
Asomatognosia refers to the loss of knowledge or sense of one’s own body and
bodily condition. Unilateral asomatognosia (Anton-Babinsky syndrome) include:
anosognosia (the unawareness or denial of illness); anosodiaphoria (indifference to
illness); autotopagnosia (inability to localize and name body parts or inability to recognize
any part of the body, a condition resulting from a lesion of the minor hemisphere);
allocheiria (one-sided stimuli are felt on the other side); and asymbolia for pain (the
absence of normal reaction to pain, such as reflexive withdrawal from a painful stimulus).
These conditions resulting from a lesion of the minor hemisphere in which are included
right parietal lobes. Anyhow, unilateral asomatognosia is seven times as frequent with
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right (nondominant) parietal lesions as with the left-sided ones, according to Hécaen’s
statistics (Hécaen, 1962). The apparent infrequency of right sided symptoms is
attributable in part to their obscuration by an associated aphasia.
The observation that a patient with a dense left hemiplegia may be indifferent to, or
unaware of the paralysis was first made by Anton. Babinsky named this disorder
anosognosia. It may express itself in several ways: The patient may act as if nothing were
the matter. If asked to raise the paralyzed arm, the patient may raise the intact one or do
nothing at all. If asked whether the paralyzed arm has been moved, the patient may say
yes. If the failure to do so is pointed out, the patient may admit that the arm is slightly
weak. If told it is paralyzed, the patient may deny that this is so or offer an excuse: “My
shoulder hurt” (Adams et al., 1997).
Some patients report that they feel as though their left side had disappeared, and
when shown their paralyzed arm, they may deny it is theirs and assert that it belongs to
someone else or even take hold of it and fling it aside.
This mental derangement, obviously includes a somatosensory defect, and loss of
the stored engrams of the body schema as well as a conceptual negation and neglect of
half of the body.
Anosognosia is usually associated with a blunted emotionality. The patient looks
dull, is inattentative and apathetic, and shows varying degrees of general confusion. There
may be an indifference to failure, a feeling that something is missing, visual and tactile
illusions when sensing the paralyzed part, hallucinations of movement, and allocheiria
(one sided stimuli are felt on the other side).
Weintraub and Mesulam (1987) indicated that patients with right parietal lesions
show elements of ipsilateral neglect in addition to the striking degree of contralateral
neglect, suggesting that, in respect to spatial attention, the right parietal lobe is truly
dominant.
Neglect presents obstacles to understand. Heilman et al. (1993), examined 13 patients
with neglect and noted that the area of lesions was the right inferior parietal lobule.
Anyhow, they wrote that contralateral neglect is occasionally observed subsequent
to lesions to the frontal lobe and cingulate cortex, as well as to subcortical structures
including the superior colliculus and lateral hypothalamus. Neglect is caused by either
defective sensation or perception, or defective attention or orientation. The strongest
argument favoring the theory of defective sensation or perception is that a lesion to the
parietal lobes, which receive input from all the sensory regions, can disturb the integration
of sensation into perception. Denny-Brown and Chambers (1976) termed this function
morphosynthesis and its disruption amorphosynthesis. A current elaboration of this theory
proposes that neglect follows a right parietal lesion because the integration of the spatial
properties of stimuli becomes disturbed. As a result, although stimuli are perceived, their
location is uncertain to the nervous system and they are consequently ignored.
In the absence of right hemisphere function, the left hemisphere is assumed to be
capable of some rudimentary spatial synthesis that prevents neglect of the right side of
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the world. This rudimentary spatial ability cannot compensate, however, for the many
other behavioral deficits resulting from right parietal lesions (Kolb and Whishaw, 2003).
Critchley (1953) and others suggested that neglect results from defective attention
or orientation.
Heilman et al. (1993), propose that neglect is manifested by a defect in orienting to
stimuli: the defect results from the disruption of a system whose function is to “arise”
the person when new sensory stimulation is present.
The lesion responsible for the various forms of unilateral asomatognosia lies in the
cortex and white matter of the superior parietal lobe but may extend variability into the
postcentral gyrus, frontal motor areas, and temporal and occipital lobes, accounting for
some of the associated abnormalities.
Rarely, a deep lesion of the ventrolateral thalamus and juxtaposed white matter of
the parietal lobe will produce contralateral neglect.
Another aspect of parietal lobe physiology, revealed by human disease, is the loss
of exploratory and orienting behavior with the contralateral arm and even a tendency to
avoid tactile stimuli.
Mori and Yamadori (1989) call this “rejection behavior”. Denny-Brown and
Chambers (1976) attribute the released grasping and exploring that follow frontal lobe
lesions to a disinhibition of parietal lobe automatism.
Left parietal syndrome

Generally, the dominance of the left hemisphere was amplified to encompass some
important forms of nonverbal mental activity. Truly, the left hemisphere was, as the
French neurologists characterized it, “the intellectual hemisphere”, dominant in thought
as well as in speech (Lhermitte, 1929).
In 1924 and 1927, Josef Gerstmann described finger agnosias as “a circumscribed
disturbance of orientation towards one’s body”. Lange (1930) and Stengel (1944)
suggested that this rather peculiar deficit as well as the other elements of the Gerstmann
syndrome (right - left disorientation, agraphia, acalculia) should be considered as part of
a more comprehensive syndrome of spatial disorientation involving external space and
constructional praxis as well as the body schema.
Gerstmann and other argued that these symptoms accompany a circumscribed lesion
in the left parietal lobe, roughly corresponding to the angular gyrus.
These four symptoms (fingeragnosia, right - left confusion; agraphia; and acalculia)
became known as the Gerstmann syndrome, and the lesions could be localized in the
angular gyrus. One or more of these manifestations may be associated with word
blindness (alexia) and homonymous hemianopsia, or a lower quadrantanopsia, of which
the patient is usually unaware.
Some authors believe that right - left confusion, digital agnosia, agraphia and
acalculia have special significance, being linked through a unitary deficit in spatial
orientation of finger, body sides, and numbers.
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Apraxia and the parietal lobe

The term apraxia is applied to a state in which a clear-minded patient with no
weakness, ataxia or other extrapyramidal derangement and no defect of the primary
modes of sensation loses the ability to execute highly complex and previously learned
skills and gestures.
In 1871, Heymann Steinthal first used the term “apraxia” for a loss of motor skills
(cited by Heilman et al., 1997). Steinthal thought that apraxia was a defect in “the
relationship between movements and the objects with which the movements were
concerned”. Afterwards, Liepmann (1900) described three forms of apraxia: limb kinetic,
ideomotor and ideational. His anatomic data indicated that planned or commanded action
is normally developed not in the frontal lobe, but in the parietal lobe of the dominant
hemisphere, where visual, auditory, and somesthetic information is integrated.
Presumably, the formation of engrams of skilled movements depends on the integrity of
this part of the brain; if it is damaged, the engrams cannot be activated at all or the
movements are faltering and inappropriate. On the other hand, we know that a significant
portion of the pyramidal tract originates in neurons of the parietal cortex. Also, the parietal
lobes are important sources of visual and tactile information necessary for the control of
movement.
Paus et al. (1989), have described the motor disturbances due to the lesions of the
parietal cortex. The patient is unable to maintain stable posture of the outstretched hand
when his eyes are closed and cannot exert a steady contraction. Exploratory movements
and manipulation of small objects are impaired, and the speed of tapping is diminished.
Posterior parietal lesions (involving areas 5 and 7) are more detrimental in this respect
than anterior ones (areas 1, 3, and 2), but with the most severe deficits both regions are
affected.
To successful manipulate environmental stimuli the pyramidal motor neurons must
be guided by movement programs. The programs must instruct the motor neurons how
to position one’s hand and arm to interact with a tool or object, to orient the limb toward
the target of the limb’s action, to move the limb in space, to determine the speed of the
movement, to imitate a movement, to solve a mechanical problem and to order
components of an act.
Disorders of these praxic systems are called apraxis. There are six major forms of
limb apraxia: 1) ideomotor; 2) ideational; 3) conceptual; 4) limb kinetics; 5) dissociation;
and 6) conduction. Each of these forms of apraxia is defined by the nature of errors made
by the patient, and each of these disorders also has different mechanisms.
Ideomotor apraxia (IMA)

Failure to correctly position a limb, to move the limb correctly in space, and to
properly orient the limb is called ideomotor apraxia.
IMA is probably the most common type of apraxia.
When patients with IMA perform learned skilled movements, including pantomimes,
imitations, and use of actual objects, they make spatial and temporal errors.
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In right-handed individuals, IMA is almost always associated with left hemisphere

lesions, but, in left-handers, IMA is usually associated with right hemisphere lesions.
IMA is associated with lesions in a variety of structures, including the corpus callosum,
the inferior parietal lobe, the premotor areas, basal ganglia and white matter.
From sensory areas 5 and 7 in the dominant parietal lobe there are connections with
the supplementary and premotor cortices of both cerebral hemispheres, wherein reside
the innervatory mechanisms for patterned movement. The patient may know and
remember the planned action, but because these connections are interrupted, he cannot
execute it with either hand. This was Liepmann’s concept of ideomotor apraxia.
Kimura (1977) showed that the patients with left posterior parietal lesions often
present ideomotor apraxia. He also revealed that the deficits in such patients can be
quantified by asking them to copy a series of arm movement. Patients with left-parietal
lobe lesions are grossly impaired at this task, whereas people with right-parietal-lobe
lesions perform the task normally.
Ideational apraxia
The inability to carry out a series of acts or sequence of action – an ideational plan
that leads to goal – has been called ideational apraxia.
When performing a task that requires a series of acts, these patients have difficulty
sequencing the acts in the proper orders. To determine its presence, patients should be
tested for their ability to perform multistep sequential tasks. Failure to perform each step
in the correct order suggests ideational apraxia.
Patients who select the wrong movement (content errors) have also been diagnosed
as having ideational apraxia, but in order to avoid confusion these errors may be classified
as conceptual apraxia (Heilman et al., 1997).
Ideational apraxia may occur with more diffuse brain diseases such as those
associated with degenerative disorders or with focal lesions of the left hemisphere,
particularly in the parietal lobe. In general, however, patients with frontal lesions have
the most difficulty with sequencing.
Conceptual apraxia
To perform a skilled act, two types of knowledge are needed: conceptual knowledge
and production knowledge.
Whereas dysfunction of praxis production system induces IMA, defects in the
knowledge needed to successfully select and use the tools and objects are called
conceptual apraxia.
Therefore, patients with IMA make production errors (e.g., spatial and temporal
errors), and patients with conceptual apraxia make content and tool selection errors.
Patients with conceptual apraxia may not recall the type of actions associated with
specific tools, utensils, or objects (tool-object action knowledge) and therefore make
content errors (Heilman et al., 1997). For example, when asked to demonstrate the use
of a screw driver by pantomiming as by using the tool, the patient with the loss of tool-
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object action knowledge may pantomime a hammering movement or use the screw driver
as if it were a hammer.
Unfortunately, use of the term ideational apraxia has been confusing; with the term
erroneously used to label other disorders (Heilman et al., 1997). The term ideational
apraxia has been used to describe patients who make conceptual errors.
Patients with conceptual apraxia may be unable to recall which tool is associated
with a specific object (tool-object association knowledge).
For example, when shown a partially driven nail, they may select a screw driver
rather than a hammer from an array of tools. This conceptual defect also occurs in the
verbal domain, which has these results (Heilman et al., 1997): when a tool is shown, the
patient may be able to name it (e.g., hammer), but when the patient is asked to name or
point to a tool when its function is described, he cannot. The patient may also be unable
to describe the functions of tools.
Patients with conceptual apraxia may also have impaired mechanical knowledge
(Heilman et al., 1997). Mechanical knowledge is also important for tool development,
and patients with conceptual apraxia may be unable to correctly develop tools.
In 1920, Liepmann thought that conceptual knowledge was located in the caudal
parietal lobe, but in 1989, Ochipa et al., placed it in the temporal-parietal junction.
Later, a patient was reported with left-handed and rendered conceptual apraxia by
lesion in the right hemisphere, suggesting that both production and conceptual knowledge
have lateralized representation and that such representations are contralateral to the
preferred hand. Further evidence that these conceptual representations stored in the
hemisphere that is contralateral to the preferred hand drives from the observations of a
patient who had a callosal disconnection and demonstrated conceptual apraxia of the
nonpreferred (left) hand (Ochipa et al., 1992).
Researchers studying right-handed patients who had either right or left hemisphere
cerebral information found that conceptual apraxia was more commonly associated with
left than right hemisphere injury (Heilman et al., 1997). However, they did not find any
anatomic region that appeared to be critical, suggesting that mechanical knowledge may
be widely disturbed in the left hemisphere of right-handed people. Although conceptual
apraxia may be associated with focal brain damage, it is perhaps most commonly seen in
degenerative dementia of the Alzheimer’s type. It was also noted that the severity of
conceptual and IMA did not always correlate.
The observation that patients with IMA may not demonstrate conceptual apraxia
and patients with conceptual apraxia may not demonstrate IMA provides support for the
postulate that the praxis production and praxis conceptual systems are independent.
However, for normal function these two systems must interact (Heilman et al., 1997).
Limb kinetic apraxia

In 1920, Liepmann found that patients with limb kinetic apraxia have a loss of the
ability to make finely graded, precise individual finger movements. Tasks such as finger
tapping and pegboard may be impaired. The patient may have difficulty picking up a
straight pin from the top of the deck using a pincer grasp of the thumb and forefinger.
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Limb kinetic apraxia usually affects the hand that is contralateral to a hemispheric
lesion.
Liepmann (1920) thought that limb kinetic apraxia was induced by lesions that injured
the primary motor and sensory cortex. In 1986, it was demonstrated that monkeys with
lesions confined to the corticospinal system show similar errors (Watson et al., 1986).
Conduction apraxia
Patients with IMA are generally able to imitate better than they can pantomime to
command. However, one patient was reported who was more impaired when imitating
than when pantomiming to command. Because this patient was similar to the conduction
aphasic who repeats poorly, this disorder was termed conduction apraxia (Heilman and
Rothi, 1985).
Whereas the lesions that induce conduction aphasia are usually in the supramarginal
gyrus or Wernicke’s area, the lesions that induce conduction apraxia are unknown.
The mechanism of conduction apraxia may be similar to that of conduction aphasia,
such that there is a disconnection between the portion of the left hemisphere that contains
the movement representation (input praxicon) and the part of the left hemisphere that are
important for programming movements (output praxicon) (Heilman, 1997).
Dissociation apraxia
In 1973, Heilman described patients who, when asked to pantomime to command,
looked at their hand but failed to perform any recognizable actions. Unlike patients with
ideomotor and conduction apraxia, these patients’ imitation and use of objects were
flawless. In addition, when they saw the tool or object they were to pantomime, their
performance was also flawless.
When asked to pantomime in response to visual or tactile stimuli, some patients were
unable to do so, but these patients could pantomime to verbal command.
Patients with dissociation apraxia may have callosal lesions. In those patients with
callosal lesions, it has been proposed that whereas language was mediated by their left
hemisphere, the movement representations (praxicon) were stored bilaterally (Heilman,
1997). Therefore, their callosal lesion induced a dissociation apraxia only of the left hand
because the verbal command could not get access to the right hemisphere’s movement
representations.
Not only can callosal lesions be associated with an IMA, but also callosal
disconnection can cause dissociation apraxia. The subjects of Gazzaniga and associates
(1967) and the patient described by Geschwind and Kaplan (1962) had disassociation
apraxia of the left hand.
With the left hand, they could not gesture normally to command but performed well
with imitation and actual tools, because these tasks do not need verbal mediation and the
movement representations stored in their right hemisphere can be activated by tactile or
visual input.
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Right-handed patients who have both language and movement formulas represented
in their left hemisphere may show combination of dissociation and IMA with callosal
lesions.
When asked to pantomime with the left hand they perform no recognizable
movement (dissociation apraxia), but when imitating or using actual tools, they may
demonstrate the spatial and temporal errors seen with IMA (Heilman, 1997).
Not all callosal lesions cause IMA of the left hand, which suggests that not all right-
handers have movement formulas entirely represented in their left hemisphere. Apraxia
from right hemisphere lesions in a right-hander is rare but has been reported, suggesting
that hand preference is not entirely determined by the laterality of movement
representation and may be multifactorial (Heilman et al., 1997).
Left-handers may demonstrate an IMA without aphasia from a right hemisphere
lesion. These left-handers are apraxic because their movement representations are stored
in their right hemisphere and their lesions destroyed these representations. These left-
handers were not aphasic because their left hemisphere mediated language (as in the
majority of left-handers).
If these left-handers had callosal lesions, they may have demonstrated a dissociation
apraxia of the left arm and on IMA of the right arm.
The dissociation apraxia from left hemisphere lesions that Heilman (1973) described
was, unfortunately, incorrectly termed ideational apraxia. These patients probably had
an intrahemispheric language-movement formula, visual-movement formula, or
somesthetic-movement formula dissociation (Heilman, 1973). The location of lesions
that cause intrahemispheric dissociation apraxia is not known.
Facial-oral apraxia
Facial-oral apraxia is probably the most common of all apraxias (Adams et al., 1997).
It may occur with lesions that undercut the left supramarginal gyrus or the left motor
association cortex and may be associated with apraxia of the limbs.
Such patients are unable to carry out facial movement to command (lick the lips,
blow out a match, etc.), although they may do better when asked to imitate the examiner
or when holding a lighted match.
With lesions that are restricted to the facial area of the left motor cortex, the apraxia
will be limited to the facial musculature and may be associated with a verbal apraxia or
cortical dysarthria.
Dressing apraxia
A particularly common group of parietal symptoms easily tested at the bedside,
consists of neglect of one side of the body in dressing and grooming (“dressing apraxia”),
recognition only on the intact side of bilaterally and simultaneously presented stimuli
(“sensory extinction”), deviation of head and eyes to the side of the lesion and torsion of
the body in the same direction (failure of directed attention to the body and to
extrapersonal space on the side opposite the lesion).
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The patient may fail to shave one side of the face, apply lipstick or comb the hair
only on one side, or find it impossible to put on eyeglasses, insert denture, or put on a
dressing gown when one of its sleeves has been turned inside out.
Unilateral spatial neglect is brought out by having the patient bisect a line, draw a
daisy or a clock, or name all the objects in the room.
Homonymous hemianopsia and varying degrees of hemiparesis may or may not be
present (Adams et al., 1997).
Constructional apraxia
Disturbance of the perception of space, other than language-related ones, are most
evident in patients with lesions of the right, nondominant parietal lobe. These include
disorders of topographic (extrapersonal) orientation and topographic and geographic
memory, with resulting difficulties in route finding and an inability to reproduce
geometric figures (“constructional apraxia”).
A number of tests have been designed to elicit these disturbances, such as indicating
the time by placement of the hands of a clock, drawing a map, spontaneous (free)
drawing, copying a complex figure, reproducing stick-pattern constructions and block
designs, three-dimensional constructions, and reconstructions of puzzles (Adams et al.,
1997). In the majority of cases, as remarked above, the lesions responsible for these
deficits prove to be in right hemisphere, though the unilateral dominance is not as striking
as that of language and language-associated functions. In the most severe disturbances
of visual-spatial perception, described by Holmes and Horrax in 1919, both parietal lobes
were affected.
The terms dressing apraxia and constructional apraxia are sometimes used to
describe certain symptoms of unilateral extinction or neglect (amorphosynthesis) that
characterize parietal lobe lesions. These abnormalities are not apraxias in the strict sense
as defined above but an imperception of the body.
In sum, from the above description it is evident that the left and right parietal lobes
function differently. The most obvious difference, of course, is that language and
arithmetical functions are centered in the left hemisphere. It is hardly surprising, therefore,
that verbally mediated or verbally associated spatial functions are more affected with
left-sided than with right-sided lesions. It must also be realized that language function
involves cross-modal connections and is central to all cognitive functions.
Hence, cross-modal matching tasks (auditory-visual, visual-auditory, visual-tactile,
tactile-visual, auditory-tactile, etc.) are most clearly impaired with lesions of the dominant
hemisphere. Indeed, this is what Butters and Brody (1968) have found. Similarly, faults
in what Luria (1973) has called logicogrammatical and syntactic aspects of language
(which he considers to be quasispatial) occur with left parietal lesions. Such patients can
read and understand spoken words, but cannot grasp the meaning of a sentence if it
contains elements of relationship (e.g., “the mother’s daughter” versus “the daughter’s
mother”; “the father’s brother’s son”). There are similar difficulties with calculation, as
just described. The recognition and naming of parts of the body and the distinction of
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right from left and up from down are other learned, verbally mediated spatial concepts
that are disturbed by lesions in the dominant parietal lobe.
Damage to the somatosensory regions of the parietal lobe produces deficits in tactile
functions, ranging from simple somatosensation to the recognition of objects by touch.
Posterior parietal-lobe injury interferes with the visual guidance of hand and limb
movements. Thus, effects of unilateral disease of the dominant parietal lobe (left
hemisphere in right-handed patients) include: disorders of language (especially, alexia);
Gerstmann syndrome; tactile agnosia (bimanual astereognosis); bilateral ideomotor,
ideational, and limb apraxia; deficits in arithmetic and writing.
Effects of unilateral disease of the nondominant parietal lobe (right hemisphere in
right-handed patients) includes: deficits in visual-spatial cognition topographic memory
loss; Anton-Babinski syndrome, dressing and constructional apraxia; and contralateral
neglect. These disorders may occur with lesions of either hemisphere but have been
observed more frequently with lesions of the nondominant one.
Effects of unilateral disease of the parietal lobe, right or left, include: cortical sensory
syndrome and sensory extinction (or total hemianesthesia with large acute lesions of
white matter); mild hemiparesis; unilateral muscular atrophy in children; hypotonia;
poverty of movement; hemiataxia; visual inattention; and sometimes anosognosia; neglect
of one-half of the body and of extrapersonal space (observed more frequently with right
than with left parietal lesions).
Effects of bilateral disease of the parietal lobes include: visual spatial imperception,
optic ataxia, spatial disorientation, severe forms of constructional apraxia and confusion.
Generally, posterior parietal-lobe injury interferes with the visual guidance of hand
and limb movements.
Localization and lateralization of language

Philosophers who argue that the mind controls behavior see “the mind” as
indivisible. They suggest that the brain or mind does its work as a unified whole.
Thus, by the close of the first half of the nineteenth century there was still uncertainty
about whether or not there was differentiation of function within the cerebral hemispheres
of the human brain as opposed to the holistic concept that the hemispheres operated as a
unit as envisioned by Flourens (1824). The influential physiologist Flourens insisted that
the cerebral hemispheres operated as a unit, that each region subserved the same
functions, and that the severity of behavioral impairment after brain insult was related to
the quantity of tissue destroyed and not to its locus. Nevertheless, most victims of brain
damage find that some behavior is lost and some survives, suggesting that different parts
of the nervous system have different functions. For example, the physicians of the
Salpêtrière and the Pitié pointed to the discretic deficits produced by stroke – e.g.,
monoplegia of an arm or of a leg, hemiplegia with or without sensory impairment, without
paralysis – as evidence that specific cerebral centers governing those functions must exist.
Postmortem examination did indeed disclose limited areas of hemorrhage or infarction
in those patients. Nevertheless, it was not possible to achieve agreement about the precise
location of the presumed centers.
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Asymmetry in emotional system

Emotions are internal states of higher organisms that serve to regulate, by behavior
and psychological changes, an organism’s interaction with a definite object or its social
environment. Evaluation has three main components: 1) the subjective experience;
2) the physiological response; and 3) the behavioral expression. On the other hand,
emotions can be divided into three functionally distinct but interacting sets of processes:
1) the evaluation of a stimulus or event with respect to its value to the organism; 2) the
subsequent triggering of an emotional reaction and behavior; and 3) the representation
of 1 and 2 in the organism’s brain, which constitutes emotional feeling. On the one hand,
emotions are continuous with more basic motivational behaviors, such as responses to
reward and punishment; on the other hand, emotions are continuous with complex social
behavior. The former serves to regulate an organism’s interaction and homeostasis with
its physical environment, whereas the latter serves an analogous role in regard to the
social environment (Le Doux, 1996).
Studies in animals have focused on the first of the two previously mentioned aspects
of the emotion and have investigated the neuronal systems whereby behavior is guided
by the reinforcing properties of stimuli. Structures such as the amygdala, orbitofrontal
cortex, and ventral striatum have been shown to play critical roles in this regard.
In humans, these same structures have been shown to also participate in more
complex aspects of social behavior; additionally, there are structures in the right
hemisphere that may play a special role in the social aspects of emotion. Emotions
influence nearly all aspects of cognition, including attention, memory, and reasoning
(Adolphs, 2002).
Emotion refers to a variety of different aspects of nervous system function that relate
representations of the external environment to the value and significance these have for
the organism.
Such a value mapping encompasses several interrelated steps: evaluation of the
external event or situation with which an organism is confronted, changes in the brain
and body of the organism in response to the situation, behavior of the organism, and
mapping of all the changes occurring in the organism that can generate a feeling of
emotion (Rolls, 1999; Adolphs, 2002).
We can identify three components of emotion: 1) recognition / evaluation / appraisal
of emotionally salient stimuli; 2) response / reaction / expression of the emotion (inclu-
ding endocrine, autonomic, and motor changes); 3) feeling (the conscious experience of
emotion) (Davidson and Irwin, 1999; Adolphs, 2002).
Production of emotional facial expressions and other somatovisceral responses
directly causes changes in emotional experience, brain activity, and autonomic state.
Although basic emotions may rely on largely innate factors, they do not appear
immediately in infancy. Rather, like the development of language, emotions mature in a
complex interplay between an infant’s inborn urge to seek out and to learn certain things
and the particular environment in which this learning takes place.
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Brain structures studied in emotional behavior in humans

Natural structures that are important for emotional behavior in humans can be
divided into: 1) structures important for homeostatic regulation and emotional reaction,
such as the hypothalamus and the periaqueductal gray matter (PAG); and 2) structures
for linking perceptual representation to regulation and reaction, such as the amygdala
and orbitofrontal cortex (Le Doux, 1996; Rolls, 1999; Adolphs, 2002).
We will discuss the role of parietal and frontal regions in representing the organism’s
own changes in body state focusing on right fronto-parietal cortex right somatosensory-
related cortices as well as other somatosensory structures such as the insula.
It is important to remember that all these structures are heavily interconnected, and
that most play at least same role in multiple components of emotion.
The right hemisphere

Clinical and experimental studies have suggested that the right hemisphere is
preferentially involved in processing emotion in humans.
The configurational processing of the right hemisphere lends itself most readily to
the handling of the multidimensional and alogical stimuli that convey emotional tone,
such as facial expressions (Benowitz et al., 1983; Moreno et al., 1990; Borod et al., 1997;
Ivry and Lebby, 1998) and voice quality (Blumstein and Cooper, 1974; Ley and Bryden,
1982; Joanette et al., 1990).
Patients with right hemisphere damage tend to experience relative difficulty in
discerning the emotional features of stimuli, whether visual or auditory, with corres-
ponding diminution in their emotional responsivity (Cicone et al., 1980; Ruckdeschel-
Hibbard et al., 1986; Van Lancker and Sidtis, 1992; Borod et al., 1998; Adolphs and
Damasio, 2000).
While impairments in affective recognition appear to be supramodal, deficits in
recognizing different kinds of affective communication (e.g., facial expressions, gestures,
prosody) can occur independently of one another (Bowers et al., 1993). Patients with
such deficits are limited in both their comprehension and their enjoyment of humor
(Gardner et al., 1975; Gardner, 1994). Self-reference processing and self-evaluation
appear to have mostly right hemisphere involvement (Keeman et al., 2000), although
both hemispheres contribute to processing of aspects of personal information (Kircher et
al., 2001).
Differences in emotional expression can also distinguish patients with lateralized
lesions (Etcoff, 1986; Borod, 1993). Right hemisphere-lesioned patient’s range and
intensity of affective intonation are frequently inappropriate (Borod et al., 1985; Shapiro
and Danly, 1985; Borod et al., 1990; Joanette et al., 1990). In the controversy over
whether their facial behavior is less expressive than that of persons with left hemisphere
damage or of normal control subjects, Brozgold and associated (1998) and Montreys and
Borod (1998) say it is, while Pizzamiglio and Mammucari (1989) say it is not.
The preponderance of research on normal subjects indicates heightened expres-
siveness on the left side of the face (Sackeim et al., 1978; Dopson et al., 1984; Borod et
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al., 1998). These findings are generally interrupted as indicating right hemisphere
superiority for affective expression.
Recognition of emotional facial expressions can be selectively impaired following
damage to the right temporoparietal areas, and both PET and neuronal recordings
corroborate the importance of this region for processing facial expressions of emotions.
For example, lesions restricted to right somatosensory cortex result in impaired
recognition of emotion from visual presentation of face stimuli. These findings are
consistent with a model that proposes that we internally stimulate body state in order to
recognize emotions (Adolphs, 2002).
This is disagreement as to whether right hemisphere damaged patients experience
emotions any less than other people. Same studies have found reduced autonomic
responses to what would normally be an emotional stimulus (Gainotti, 2003).
Lezak and associates (2004) and others have observed strong – but not necessarily
appropriate – emotional reactions in patients with right-lateralized damage, leading to
the hypothesis that their experience of emotional communications and their capacity to
transmit the nuances and subtleties of their own feeling states differ from normal affective
processing (Barbizet, 1974; Morrow et al., 1981; Ross and Rush, 1981; Lezak, 1994),
leaving them out of joint with those around them.
Patients whose injuries involve the right hemisphere are less likely to be dissatisfied
with themselves or their performances than are those with left hemisphere lesions (Keppel
and Crowe, 2000) and less likely to be aware of their mistakes (Mc Glynn and Schacter,
1989). They are more likely to be apathetic (Andersson et al., 1999), to be risk takers
(Miller and Milner, 1985), and to have poorer social functioning (Brozgold et al., 1998).
At least in the acute or early stages of their condition, they may display an
indifference reaction tending to deny or make light of the extent of their disabilities
(Gainotti, 1972; Pimental and Kingsbury, 1989).
In extreme cases, patients are unaware of such seemingly obvious defects as
crippling left-sided paralysis or slurred and poorly articulated speech. These patients tend
to have difficulty making satisfactory psychological adaptations, with those whose lesions
are anterior being most maladjusted in all areas of psychosocial functioning (Tellier et
al., 1990).
Lesions in right temporal and parietal cortices have been shown to impair emotional
experience, arousal, and imagery. It has been proposed that the right hemisphere contains
systems specialized for computing effect from nonverbal information; these may have
evolved to subserve aspects of social cognition.
Lesions and functional imaging studies have corroborated the role of the right
hemisphere in emotion recognition from facial expressions and from prosody. There is
currently controversy regarding the extent to which the right hemisphere participates in
emotion: Is it specialized to process all emotions (the right hemisphere hypothesis), or is
it specialized only for processing emotions of negative valence while the left hemisphere
is specialized for processing emotions of positive valence (the valence hypothesis)? It
may well be that an answer to this question will depend on more precise specification of
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which components of emotion are under consideration (Panksepp, 1998; Rolls, 1999;
Adolphs, 2002).
In contrast to recognition of emotional stimuli, emotional experience appears to be
lateralized in a pattern supporting the valence hypothesis, in which the left hemisphere
is more involved in positive emotions and the right hemisphere is more involved in
negative emotions.
So, is reported a higher incidence of depression in patients with anterior lesions
2-4 months poststroke (Kim and Choi-Kwan, 2000; Singh et al., 2000) and with right
hemisphere lesions at six months poststroke (Mac Hale et al., 1998).
Gainotti (1993) suggests that the emotional processing tendencies of the two
hemispheres are complementary: “The right hemisphere seems to be involved
preferentially in functions of emotional arousal, intimately linked to the generation of
the autonomic components of the emotional response, whereas the left hemisphere seems
to play a more important role in functions of intentional control of the emotional
expressive apparatus”. These authors hypothesize that language development tends to
override the left hemisphere’s capacity for emotional immediacy, while, in contrast, the
more spontaneous and pronounced affective display characteristic of right hemisphere
emotionality gives that hemisphere the appearance of superior emotional endowment.
As awareness of deficit is often muted or lacking with right hemisphere lesions (Carpenter
et al., 1995; Meador et al., 2000), these patients tend to be spared of the agony of severe
depression particularly early in the course of their condition.
When the lesion is on the right, the emotional disturbance does not seem to arise
from awareness of defects so much as from the secondary effects of the patient’s
diminished self-awareness and social intensivity (Lezak et al., 2004). Patients with right
hemisphere lesions who do not appreciate the nature or extent of their disability tend to
set unrealistic goals for themselves or to maintain previous goals without taking their
new limitations into account. As a result, they frequently fail to realize their expectations
(Lezak et al., 2004). Depression in patients with right-sided cortical damage may take
longer to develop than it does in patients with left hemisphere involvement since it is less
likely to be an emotional response to immediately perceived disabilities than to a more
slowly evolving reaction to their secondary consequences. When depression does develop
in patients with right-sided disease, however, it can be more chronic, more debilitating,
and more resistive to intervention (Lezak et al., 2004).
Inappropriate euphoria and self-satisfaction may accompany lesions involving other
than right hemisphere areas of the cortex (Mc Glynn and Schacter, 1989). Further,
premorbid personality colors the quality of patients’ responses to their disabilities. Thus,
the clinician should never be tempted to predict the site of damage from the patient’s
mood alone.
The left hemisphere

The analytic, bit-by-bit processing of the left hemisphere deals best with the words
of emotion. Patients with left hemisphere lesions have less difficulty in appreciating facial
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expressions and voice intonation, and most are normally responsive to uncaptioned
cartoons but do as poorly as right hemisphere patients when the stimulus is verbal
(Heilman et al., 1995).
Hemispheric differences have been reported for the emotional and even personality
changes that may accompany brain injury (Sackeim et al., 1982; Prigatano, 1987;
Gainotti, 1993).
Patients with left hemisphere lesions can exhibit a catastrophic reaction (extreme
and disruptive transient emotional disturbance). The catastrophic reaction may appear as
acute – often disorganizing – anxiety, agitation, or tearfulness, disrupting the activity that
provoked it. Typically, it occurs when patients are confronted with their limitations, as
when taking a test (Prigatano, 1987; Robinson and Starkstein, 2002).
They tend to regain their composure as soon as the source of frustration is
removed. Anxiety is also a common feature of left hemisphere involvement (Gainotti,
1972; Galin, 1974). It may show up as under cautiousness (Jones-Gotman and Milner,
1977) or oversensitivity to impairments and a tendency to exaggerate disabilities
(Keppel and Crowe, 2000). Yet, despite tendencies to be overly sensitive to their
disabilities, many patients with left hemisphere lesions ultimately compensate for them
well enough to make a satisfactory adjustment to their disabilities and living situations
(Tellier et al., 1990).
Davidson and Irwin (2002) and Davidson and Henriques (2000) posited an approach
/ withdrawal dimension, correlating increased right hemisphere activity with increases
in withdrawal behaviors (including feelings such as fear or sadness, as well as depressive
tendencies) and left hemisphere with increases in approach behaviors (including feelings
such as happiness).
Patients whose left hemisphere has been inactivated from use of the Wada technique
(intracarotid injections of sodium amytal for pharmacological inactivation of one side of
the brain to evaluate lateralization of function before surgical treatment of epilepsy)
(Wada and Rasmussen, 1960) are tearful and tell of feeling of depression more often than
their right hemisphere counterparts, who are more apt to laugh and feel euphoric. In the
same vein, Regard and Landis (1988) found that pictures exposed to the left visual field
were disliked and those to the right were liked.
Since the emotional alterations seen with some stroke patients and in lateralized
pharmacological inactivation have been interpreted as representing the tendencies of the
disinhibited intact hemisphere, some investigators have hypothesized that each
hemisphere is specialized for positive (the left) or negative (the right) emotions, sugges-
ting a relationship between the lateralized affective phenomena and psychiatric disorders
(Flor-Henry, 1986; Lee et al., 1990).
However, studies of depression in stroke patients have produced inconsistent results
(Sato et al., 1999; Carson et al., 2000; Singh et al., 2000).
Shimoda and Robinson (1999) found that hospitalized stroke patients with the
greatest incidence of depression were those with left anterior hemisphere lesions. At
short-term follow-up (3-6 months), proximity of the lesion to the frontal pole and lesion
1885
volume correlated with depression in both right and left hemisphere stroke patients. At
long-term follow-up (1-2 years), depression was significantly associated with right
hemisphere lesion volume and proximity of the lesion to the occipital pole.
Moreover, the incidence of depression in patients with left hemisphere disease
dropped over the course of the first year (Robinson and Manes, 2000).
Impaired social function was most evident in those patients who remained depressed.
Women are more likely to be depressed in the acute stages of left hemisphere stroke
than men (Paradiso and Robinson, 1998). With left hemisphere damaged patients,
depression seems to reflect awareness of deficit; the more severe the deficit and acute
the patient’s capacity for awareness, the more likely is that the patient will be depressed.
The occurrence of deviant emotional reaction in the course of disease is associated
with lesions in some parts of the nervous system more regularly than in others. These
have been grouped in the term limbic and are among the most complex and least
understood parts of the nervous system. As defined by Broca (1878) and later by Papez
(1937), the limbic system generally consists of the group of structures around the medical
edge of the cerebral hemisphere.
These structures include the amygdala, the hippocampus, the parahipocampal gyrus,
and related structures, such as the orbital / medial (orbitofrontal) cortex, cingulate cortex,
anterior and mediodorsal thalamic nuclei, the ventromedial corpus striatum (i.e., the
accumbens and medial caudate nucleus), and the nucleus basalis of Meynert. These
structures have important roles in emotion, motivation, and memory.
Next we discuss those structures for which the most data are available from humans;
the amygdala and the orbitofrontal cortex.
The human amygdala

The amygdala is a complex of several nuclei in the rostromedial part of the temporal
lobe. There are several deep nuclei (lateral sulcus, basal sulcus and accessory basal
nucleus) with differing input and output pathway with cerebral cortex, hippocampus,
basal ganglia, thalamus, hypothalamus and brain stem nuclei.
The amygdala receives input from all the sensory systems (olfactory system, taste,
visceral system, visual, and somatosensory systems). Functional imaging studies (e.g.,
positron emission tomography and functional magnetic resonance imaging) provided
evidence that the amygdala responds to emotionally salient stimuli in the visual auditory,
olfactory, and gustatory modalities.
In the dorsal part of the amygdala are the central nucleus and medial nucleus, which
have connections with the hypothalamus and autonomic brain stem nuclei.
On the surface there are a number of modified cortical areas, many of which are
interconnected with the olfactory system (olfactory bulbs) (Shepherd and Greer, 1998).
The outputs from the amygdala can be divided into three categories:
1. Return projections back to the sensory areas that project into the amygdala: In
the case of the visual system, these return projections even extend back to the primary
visual cortex.
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2. Descending projections to the visceral control centers of hypothalamus and brain-

stem: The central amygdaloid nucleus projects to a wide variety of autonomic related
cell groups, including the lateral hypothalamus, the periaqueductal gray, the parabrachial
nucleus, the nucleus of the solitary tract, the dorsal vagal sulcus, and the ventrolateral
medulla. Through these projections, the amygdala can influence heart rate and blood
pressure, and gut bowel function, respiratory function, bladder function, etc.
3. Interactions with the orbital and medial frontal cortex, both via direct
amygdalocortical projections and via connections with the mediodorsal thalamic nucleus
and the ventromedial parts of the basal ganglia: This circuit appears to be involved in
determination of the affective “sign” of sensory stimuli (e.g., whether it is rewarding or
aversive) and in setting mood.
Damage to the amygdala’s interconnecting structures (e.g., the posterior septum
lying between the hemispheres in front of the anterior commissure) has been associated
with both hypersexuality and diminished aggressive capacity (Brodal, 1981; Gorman and
Cummings, 1992).
The most prominent inputs are derived from higher order sensory association cortex,
especially from the visual areas in the inferior temporal cortex (i.e., the temporal visual
processing stream important for analysis of form and color and recognition of complex
stimuli such as faces.
Seizure activity and experimental stimulation of the amygdala provoke visceral
responses, particularly those concerned with feeding (e.g., chewing, salivating, licking,
and gagging), with the visceral components of fear reactions, with facial expression of
fear and with fright (Rolls, 1999).
Removal of the amygdala from both hemispheres can have a “taming” effect on
humans and other animals alike, with loss of the ability to make emotionally meaningful
discriminations between stimuli (Cahill and Mc Gaugh, 1998; Killcross, 2000; Pincus
and Tucker, 2003). Amygdalectomized humans become apathetic showing little
spontaneity, creativity, or affective expression (Lee et al., 1989; Aggleton, 1993).
In addition, the ability to make social interpretation of facial expressions is impaired
in patients with bilateral amygdala lesions (Adolphs et al., 1998). Baron-Cohen et al.
(2000), implicated dysfunction of amygdala in autism.
Bilateral destruction of the amygdala in humans does not produce a prominent
amnestic disorder (Lee et al., 1988; Markowitsch et al., 1994), Material learned by
amygdalectomized patients tends to be retained but they become more dependent on
context and external structure for learning new material, for retrieval generally, and for
maintaining directed attention and tracking than prior to surgery (Andersson, 1978).
Kluver-Bucy syndrome results from total bilateral temporal lobectomy (bilateral
destruction of the uncus and amygdala) in adult rhesus monkeys. These animals were
rather placid and lacked the ability to recognize objects visually (they could not
distinguish edible from inedible objects), they had a striking tendency to examine
everything orally, were unusually alert and responsive to visual stimuli (they touched or
mouthed every object in their visual fields), became hypersexual, and increased their
food intake.
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This constellation of behavioral changes has been sought in human beings, but the
complete syndrome has been described only infrequently (Marlowe et al., 1975). Pillieri
(1967), has collected some of the cases that come closest to reproducing syndrome.
Orbitofrontal cortex
The importance of the frontal lobes in social and emotional behavior was
demonstrated in the mid-1800s by the famous case of Phineas Gage. In 1850, Bigellow
published this famous “crowbar case”, originally described by Harlow (1848).
Gage, a railroad construction foreman, had sustained the passage of an iron bar
(1.25 inches in diameter at the larger end, 3.5 feet in length and 13.5 pound in weight),
which entered the left frontal lobe, emerged from the right frontal bone near the sagittal
suture, leaving a circular opening of about 3.5 inches in diameter and destroying the
left frontal lobe and anterior temporal pole, as well, in all probability, some right frontal
tissue.
Phineas Gage did not appear to have suffered intellectual impairment in the narrow
sense of the term. Four years after his injury, he went to South America where he worked
for 8 years before returning to the United States, a year before his death. However, be-
ginning about one month after his injury, he exhibited a remarkable change in personality.
Before the injury, Gage was considered a honest, reliable, polite, deliberate person
and a good businessman.
Subsequently, he became uncaring, profane, childish, capricious, obstinate, showed
poor judgment, used profane language, socially inappropriate in his conduct and was
inconsiderate of others.
In short, he showed a distinctive type of personality change that later authors, such
as Welt (1888), associated with prefrontal lobe disease.
The studies of Jastrowitz (1888), Welt (1888) and Oppenheim (1890) established
that distinctive changes in personality and behavior could be related to disease of the
prefrontal region, and Welt specifically implicated involvement of the orbital and mesial
sectors of the region. The terms moria (turpidity) and Witzelsucht (addiction to joking)
are linguistic residues of their observations.
In discussing frontal lobe symptomatology, Moritz Jastrowitz (1888) stated that he
had seen a specific form of dementia, characterized by an oddly cheerful agitation, in
patients with tumors of the frontal lobe, which he referred to as “so-called moria”.
Leonore Welt (1888) wrote a paper in which she reported a personally observed case
and presented a detailed review of earlier literature. Her patient, a 37-year-old man, had
sustained a severe penetrating frontal fracture after a fall from a fourth storey window.
Physical recovery was swift and uneventful after an operation for removal of bone from
the brain. Beginning about 5 days after the traumatic event, the patient showed a
remarkable change in personality. He was aggressive and malicious and given to making
bad jokes. He teased other patients unmercyfully and played mean tricks on the hospital
personnel. He showed no respect for the physicians and threatened to “expose” them in
the daily press. He exhibited this objectionable behavior for about a month, at which time
his behavior gradually improved.
1888
Some months later, he died from a pleuritic infection. Autopsy disclosed destruction
of the gyrus rectus in both hemispheres as well as the mesial sector of the right inferior
frontal gyrus.
Analyzing the eight autopsied cases showing personality change, she found that
invariably there was involvement of the orbital gyri.
In 1890, Hermann Oppenheim wrote a comprehensive paper on the clinical
manifestations of brain tumors. Four patients who exhibited Witzelsucht (addiction to
joking) proved to have tumors of the right frontal lobe, three of which had invaded the
mesial and basal area.
Extensive study of modern-day patients with similar anatomical profile (i.e., bilateral
damage to ventromedial frontal lobe) has shed more light on this case. These patients
show a severely impaired ability to function in society, even with normal IQ, language,
perception, and memory.
Damasio (1994) and others have illuminated the importance of ventromedial frontal
cortices in linking stimuli with their emotional and social significance.
So, orbitofrontal cortex plays a key role in impulse control and regulation and
maintenance of set and of ongoing behavior (Stuss et al., 1983; Malloy et al., 1993). In
healthy persons, this region is involved in the expression of aggressive behavior (Pietrini
et al., 2000). Damage here can give rise to disinhibition and impulsivity, with such
associated behavior problems as aggressive outbursts and sexual promiscuity (Grafman
et al., 1996; Eslinger, 1999).
Lesions here also can disrupt a patient’s ability to be guided by future consequences
of their actions (Bechara et al., 1994) and lead to poor decisions (Bechara et al., 1999).
Left-sided traumatic damage to this area has been associated with prolonged
unconsciousness (Salazar et al., 1987). Frontal lobe disturbances thus tend to have
repercussions throughout the behavioral repertoire.
Emotional and social functions bear same resemblance to that of the amygdala, but
with two important differences. First, it is clear that the ventromedial frontal cortices play
an equally important role in processing stimuli with either rewarding or aversive
contingencies, whereas the amygdala’s role, at least in humans, is the clearest for aversive
contingencies. Second, reward-related representations in ventromedial frontal cortex are
less stimulus driven than in the amygdala and thus can play a role in more flexible
computations regarding punishing or rewarding contingencies (Adolphs, 2002).
Temporal lobe connections to the orbitobasal forebrain are further implicated in
cognitive functioning. Patients with lesions here are similar to patients with focal temporal
lobe damage in displaying prominent modality, specific learning problems along with
some less severe diminution in reasoning abilities (Salazar et al., 1986).
Because the structures involved in the primary processing of olfactory stimuli are
situated at the base of the frontal lobe, odor discrimination is affected by orbitofrontal
lesions – in both nostrils, when the lesions is on the right, but only in the left nostril, with
left-sided lesions (Eslinger et al., 1982; Zatorre and Jones-Gotman, 1991).
1889
Thus, impaired odor detection frequently accompanies the behavioral disorders

associated with orbitofrontal damage (Malloy et al., 1993; Stuss, 1993; Varney and
Menefee, 1993; Eslinger, 1999).
Diminished odor discrimination may also occur with lesions in the temporal lobes
and with damage to temporal lobe pathways connecting these formations to the
orbitofrontal olfactory centers. This effect appears with right but not left temporal
pathway lesions (Martinez et al., 1993).
Anyhow, the amygdala and the orbitofrontal cortex function as components of neural
system that can trigger emotional responses. The structure of such a physiological
emotional response may also participate in attempts to reconstruct what it would feel like
to be in a certain dispositional (emotional or social) state and hence to stimulate the
internal state of another person (Adolphs, 2002).
As in the amygdala, single-neuron responses in the orbitofrontal cortex are
modulated by the emotional significance of stimuli, such as their rewarding and punishing
contingencies, although the role of the orbitofrontal cortex may be more general and less
stimulus bound than that of the amygdala. Amygdala and orbitofrontal cortex are
bidirectionally connected, and lesion studies have shown that disconnecting the two
structures results in the impairments similar to those following lesions of either structure,
providing further support that they function as components of a densely connected
network.
1890
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THE NEURAL BASIS
OF CONSCIOUSNESS
Introduction
Consciousness is an universal set of neurologic and mental or spiritual processes
produced by the brain in awake state, which allows people to understand the mind of
others (mind reading); it also allows an optimal social living to perform any kind of high
normal behavior activity (social, political, professional, moral, ethic, religious, etc.)
related to the self and the environment (family, society).
So, the two separate forms of consciousness are neurologic and mental or spiritual.
The neurologic form of consciousness is based on interactions between the brain stem,
midbrain, diencephalon, limbic system and the cerebral cortex. There is the idea of being
conscious versus unconscious.
Consciousness may be also defined as our awareness of our environment, our bodies
and ourselves (Hobson, 2007). Awareness of ourselves implies an awareness of
awareness, that is the conscious recognition that we are a conscious being. Awareness of
ourselves implies meta-cognition (Hobson, 2007).
Although many theorists treat consciousness as single, all-or-nothing phenomenon,
others distinguish between first-order consciousness and a meta-level of consciousness.
For example, they may distinguish between consciousness and metaconsciousness
(Schooler, 2002), primary consciousness and higher-order consciousness (Edelman and
Tononi, 2000), or core consciousness and extended consciousness (Damasio, 1999).
Animals possess primary (core) consciousness which comprises sensory awareness,
attention, perception, memory (or learning), emotion and action (Edelman, 1992).
According to Hobson (2007), what differentiates humans from their fellow mammals and
gives humans what Edelman defines as secondary consciousness, depends upon language
and the associated enrichment of cognition that allow humans to develop and to use verbal
and numeric abstraction. Spoken and written language are human specializations. These
mental capacities contribute to our sense of self as agents and as creative beings. It also
determines the awareness of awareness that we assume our animal “collaborators” do
not possess (Hobson, 2007).
Many factors are involved in the establishing levels of consciousness commonly
referred to as wakefulness and sleep. Such factors include the enormous driving of the
cerebral cortex over the ascending activating and inhibiting systems and the influence of
1928
24. The neural basis of consciousness
cyclic limbic activation of cerebral cortical areas. There are complex interconnections
between these areas of the nervous system: the hypothalamus, thalamus and hippocampal
formation. Our state of consciousness includes accompanying autonomic responses such
as changes in respiration, heart rate, or body temperature. Injuries that involve a
considerable part of tegmentum of the midbrain result in a profound coma because of the
interruption of ascending multisynaptic activating system (AAS) as well as descending
hypothalamotegmental and dorsal longitudinal fasciculus path.
In humans, the complex system of mental and spiritual processes depends on and is
produced by the highest psychical activities, i.e., it depends on and is produced by the
brain, making people: use symbolic representation and language; reflect on the past and
anticipate and plan for the future; transform thought into speech and action; logically
record the personal experience and transmit it orally by writing and / or by drawing;
participate in the progress and civilization; read through other people’s thoughts, judge
correctly their intentions and act consequently; use abstractization and generalization to
make new discoveries; know, spread and protect the ethical, moral and religious standards
in order to live an optimal social life; organize behavior and extrapolate it in time; deal
with cognitive novelty.
The prediction and comprehension of others’ behavior are evidently very important
aspects of social functioning.
The consciousness processes belong, in essence, to people who act by control
mechanisms of psychological activities, generalization and abstractization mechanisms,
exploring and handling of mental images to solve all the problems man is facing with.
In humans, the level of consciousness depends on the complexity of the brain
ontogenetic evolution; the human brain makes culture and technology possible. We believe
that the cerebral cortex is absolutely necessary for this function; machines that are
responsive to sensory events and are capable of complex movements are not conscious.
According to this view, the brain stem occupies the bottom of the totem pole, providing
the basic arousal mechanism without which the higher brain regions cannot operate.
On the other hand, consciousness must be a function of numerous interacting
systems. The major structures supposed to play a key role in the neural correlates of
consciousness are: the brain stem, the midbrain, the diencephalon (especially the
hypothalamus and thalamus), the limbic system, and the cerebral cortex.
Thus, the brain “language” can be conceptualized as the transmission of neural
signals (Yamazaki and Tanaka, 2007). The “grammar” of the brain’s language system
concerns the proper timing of neuronal impulses. Neuronal impulse timing is based upon
proper integration and balance of excitatory and inhibitory processes (Hatta et al., 2004).
Patients and method

In our attempt to demonstrate the presence of the ascending inhibitory system, of
the consciousness disorders and its modular aspect, a group of nine patients has been
subject to evaluation and surgery within the Neurosurgery department of the National
Institute of Neurology and Neurological Diseases in Bucharest. Eight of the patients have
1929
been diagnosed with brain tumors, and one patient with encephalitis; patient mean age
was 42,88 years, the youngest being 21 and the oldest 73 years.
Six (66,66%) of the patients were males and three (33,33) females. In 8 patients, the
main examination was computed tomography (CT) and magnetic resonance imaging
(MRI). In the patient presenting multiple brain metastases, the brain was subject to
examination after death.
In this section we will present the clinical symptomatology of the above patients.
Case 1. A 21-year-old man presented with a history of sudden onset of coma.
MRI-scan revealed a bilateral ponto-mesencephalic hemorrhage triggered by a
cavernoma. After total resection of the cavernoma and hematoma, patient’s status has
improved significantly, presenting only a remaining minimal right side weakness and
hemisensory deficit. Now the patient is a student, and has an excellent state.
Case 2. A 38-year-old woman presented with logorrhea syndrome, with hyper-
kinesia, hyperwakefulness and hyperprosexia. The patient could sleep for only a short
time, and then awake and was unable to fall back asleep. MRI-scan revealed a petroclival
meningioma which significantly compresses the superior part of the brain stem.
Case 3. A 36-year-old man presented with intermittent increased intracranial
pressure, paralysis of the conjugate upward gaze (Parinaud’s sign) and pseudo-Argyll
Robertson pupil. A contrast-enhanced CT-scan revealed a tumor of the pineal area. Only
15% of the patients with tumors of the pineal area, which are compressing the dorsal area
of the mesencephalon, also experience arousal disorders.
Case 4. A 29-year-old woman presented with left hemiparesis by compression of the
adjacent internal capsule, palsies of vertical and lateral gaze, absence of convergence,
retraction nystagmus, and mild sensory deficit in the opposite side of the body, including
the trunk. Pain and thermal sensation was more affected than touch, vibration and position.
Involvement of ventral posterolateral and posteromedial nuclei of the thalamus
causes loss or diminution of all forms of sensation on the opposite side of the body.
Contrast medium-enhanced coronal and axial MRI shows a big right thalamic tumor.
The tumor was fully resected and after the surgery the patient remained with a mild
sensory deficit and a hemiparesis, but she returned to an independent life.
Case 5. A 56-year-old man presented with a sudden onset of coma and fever.
Coronal and axial Tl-weighted MRI-scans revealed edematous, demyelination
symmetrical changes infra- and supratentorial which involved the entire midbrain, both
thalamic formations, bilateral basal ganglia, two-side temporo-occipital convolution and
hippocampus, determined by encephalitis (limbic encephalitis). After 9 days of coma the
patient died.
Case 6. A 56-year-old man with a history of severe headaches, presented with taste
and smell disorder, excessive euphoria accompanied by peculiar kind of compulsive,
shallow and childish humor (moria), irritability, hypomania and puerilism.
The patient also shows disorders of attention and motility, distractibility, hyper-
reactivity, hyperkinesia, perseveration, emotional lability, cognitive dysfunction that
impede the initiation and temporal organization of actions and lacks of initiative, wrong
decision and instinctual disinhibition.
1930
Contrast enhanced computed tomography (CT) scan shows a giant size olfactory
groove meningioma and displacement of anterior brain.
Post surgery, after complete resection of the tumor, the orbitofrontal syndrome
disappeared almost completely.
Case 7. A 35-year-old woman was admitted to our department of neurosurgery with
a bilateral meningioma of the anterior falx who compressed dorsolateral premotor and
prefrontal cortex (Brodmann’s areas 6, 8, 9, 10, and 46).
As symptoms, she had attention disorder directed to a particular item of sensorium
or inner experience and incapacity to suppress from inner experience items that can
interfere with what is currently on focus.
She was apathetic, disinterested in herself and the world around her. Visuospatial
neglect along with gaze abnormalities were also present because the lesion encroaches
on area 8. According to our experience, the apathy is present in all lateral-damage
conditions, and is mostly apparent after large bilateral lesions of the frontal convexity.
Perseveration, dysexecutive syndrome with attention, working-memory and planning
disorders were among the symptoms. Language disorders were directly linked to failure
of temporal integration.
In this patient, depression was secondary to cognitive disorder.
Case 8. A 46-year-old man was admitted to our department of neurosurgery with
olfactory hallucination (“uncinate fit”) often accompanied by a dreamy state of mind,
auditory elementary hallucination, when the patient heard the sound of running water,
impaired recognition of melodies in the absence of words, the usual tendency for the
patient to report the current date as an earlier one and prosopagnosia.
Coronal Tl-weighted, gadolinium-enhanced MRI prior to surgery showed a large
right-sided temporobasal tumor (a).
Post surgery coronal Tl-weighted, gadolinium-enhanced MRI (b) obtained after
complete removal of the tumor (astrocytoma). The patient improved very much and was
discharged after 2 weeks.
Case 9. Patient, aged 73, was admitted to our neurosurgery department with a coma
and deceased within 18 hours. On autopsy, more than 110 bilateral cortical and
intracerebral metastases have been discovered, originating from a melanocarcinoma
situated in the right abdominal area, previously subject to surgery 7 months earlier.
Results
Starting from clinical neuropsychology, we present our results, along with the
comments made on the main cerebral formation, which play an important role in
understanding this extremely complex problem, which is the consciousness.
BRAINSTEM
The brain stem is the portion of the central nervous system rostral to the spinal cord
and caudal to the cerebral hemispheres.
1931
The net-like appearance of the brain stem neurons led to the designation “reticular
formation”, a term that was originally used in a purely descriptive anatomical sense.
The reticular formation

The reticular formation (RF), beginning in the medulla and extending to the
midbrain, plays a major role in the sleep-wakefulness cycles of animals and humans. It
occupies a significant portion of the dorsal brain stem and forms a network of reticular
fibres that synapse with and modulate many ascending and descending fibre tracts.
Nuclei of RF receive afferent information from all sensory (visual, auditory, etc.)
and motor systems as well as from other major structures of the brain, and project their
axons upwards and downwards to virtually all parts of the nervous system. Through their
connections with the thalamus, hypothalamus and directly to the cerebral cortex they can
send information to, and receive it from all areas of the cortex. There are ascending (or
forward) and descending (or backward) connections between them.
The RF is also known as the reticular activating system and the reticular inhibitory
system (Dănăilă, 1972; Arseni and Dănăilă, 1977; Dănăilă and Pascu, 2009).
The role of reticular formation is to awake or to get to sleep the cerebral cortex.
After waking, the cortex allows all modes of sensory processing (sight, hearing,
touch, etc.) to combine with conscious thought and experience in order to focus on some
inputs and suppress others.
Neuroscientists now recognize that the various nuclei within the brain stem serve
many functions and that only a few take part in waking and sleeping.
Instead of being used in a descriptive analogical way, the reticular formation was
promoted to a functional concept, a brain stem system which, by virtue of its nonspecific
connectivity, could act as a kind of volume control for the degree of conscious arousal
and sleeping and as a homeostatic system.
Ascending (reticular) activating system (AAS)

In 1929, Hans Berger reported a technologic innovation, the electroencephalogram
(EEG) which is correlated closely with the level of consciousness of the patients. Since
Berger’s first observation, the various ongoing brain oscillations have been used
successfully to characterize mental status such as sleep, the waking state or vigilance and
mental pathologies such as epilepsy. Sensory evoked potentials (EEG signals triggered
by an external stimulation) have demonstrated that such mental factors as sensation,
attention, intellectual activity, and planning of movement, all have distinctive electrical
correlates at the surface of the skull (Zeman, 2001). Afterwards, in 1935 and 1936,
Bremer examined the EEG waveforms in cats into which he had placed lesions of the
brain stem. He found that after a transection between the medulla and the spinal cord, a
preparation that he called the encephale isolé, or isolated brain, animals showed a
desynchronized (low-voltage, fast-wave) EEG pattern and appeared to be fully awake.
When he transected the neuraxis between the superior and inferior colliculus, a
preparation he called the cerveau isolé, or isolated cerebrum, the EEG showed a
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synchronized, or high-voltage, slow-wave pattern indicative of deep sleep and the animals
were behaviorally unresponsive. Bremer concluded that the forebrain fell asleep due to
the lack of somatosensory and auditory sensory inputs.
The reticular activating system obtained this designation in 1949, when Moruzzi
and Magoun stimulated it electrically in anesthetized cats and found that the stimulation
produced a waking pattern of electrical activity in cat’s cortex. When Moruzzi and
Magoun placed lesions in the paramedian reticular formation of the midbrain, the animals
showed cortical-evoked responses to somatosensory or auditory stimuli, but the back-
ground EEG was synchronized and the animals were behaviorally unresponsive. These
observations emphasized the midbrain reticular core as relaying important arousing
influences to the cerebral cortex and this pathway was labeled the ascending reticular
activating system (initially called ARAS, but today named AAS).
The most important reticular nuclei for arousal and consciousness are the raphe
nuclei and the central nuclei. These groups receive significant converging sensory input
from all sensory modalities and project to the thalamus (i.e., intralaminar nuclei),
cholinergic basal forebrain nuclei, and the entire cerebral cortex. An important component
of the central reticular activating system is thought to be the noradrenergic nuclei,
particularly the locus ceruleus, at the pontomesencephalic junction.
The centromedian and parafascicular nuclei, two of the intralaminar nuclei of the
thalamus representing the rostral extent of the AAS receive inputs from the spinothalamic,
trigeminothalamic and multisynaptic ascending pathways (of the reticular formation)
relaying pain sensation. As a result of their diffuse cortical connections, they are involved
in the maintenance of arousal.
The neurons of the locus ceruleus project to the thalamus, hypothalamus, basal
cholinergic nuclei, and the neocortex (Moore and Bloom, 1979).
Immediate coma results from the destruction of the central reticular nuclei at or
above the upper pontine level (Fig. 24.1, case 1).
Anyhow, AAS acts on the cerebral cortex through the thalamus, directly, and through
the arousal caudal hypothalamic neurons (tuberomammillary nucleus) which are
connected with suprachiasmatic nuclei (Fig. 24.2).
As a result, the reticular formation comes to be known as the reticular activating
system to maintain general arousal, and as the reticular inhibitory system for sleeping.
However, an exact physiologic role of the reticular activating system in
consciousness is unclear. The awake condition like the sleep has many phases: a quick
short phase which is determined by the direct action of AAS on the cerebral cortex, a
longer phase during the 24 hours, determined by indirect action of AAS on the cortex
through the thalamus; and a rhythmical phase determined by the AAS action on the
cerebral cortex through the hypothalamus awaking system under the influence of the
suprachiasmatic nucleus. These nuclei are serially interconnected with AAS not only in
the forward, but also in the reverse direction (backward).
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A B
C D
E F
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Fig. 24.2. The Ascending Reticular Activating System (ARAS) is found in the brain stem (1), and sends projections
throughout the cortex: directly (2), through the thalamus (3), or through the hypothalamus (4), tuberomammillary
neurons (5), which receive influence from suprachiasmatic nucleus (6).
It is generally agreed that a key component of the reticular activating system is a

group of cholinergic nuclei near the pons-midbrain junction that project to thalamocortical
neurons. The relevant neurons in the nuclei are characterized by high discharge rates
during the waking. When stimulated, these nuclei cause “desynchronization” of the
electroencephalogram (that is, a shift of EEG activity from high-amplitude, synchronized
waves to lower amplitude, higher-frequency, desynchronized ones).
In 1980, McGuiness and Krauthamer have concluded that the intralaminar nuclei
acted not only as a thalamic pacemaker and as a relay for cortical arousal but was
characterized also by the presence of cells responding to visual auditory and somesthetic
stimuli. Schiff and Plum (1999) wrote “cortical and subcortical innervations of the
intralaminar nuclei place them in a central position to influence distributed networks
◄ Fig. 24.1. A 21-year old man who presented with a history of sudden onset of coma.
Sagittal (A), axial (B) and coronal (C) T1-weighted magnetic resonance imaging (MRI) scans revealed a gross
pontine hemorrhage (1.9 cm) from a cavernous malformation that reached the surface of the floor of the fourth
ventricle and in the cerebelopontine angle.
The lesion was resected through a suboccipital approach. Sagittal (D), axial (E), and coronal (F) MRI scans,
one year later, reveal no recurrence. Two months after surgery, the patient presented with minimal right sided
weakness and hemisensory deficits. Now the patient is a student, and has an excellent state.
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underlying arousal, attention, intention, working memory and sensorimotor integration,

including gaze control”. Thus, there are three main types of thalamic projections: the
specific (for vision, audition), the diffuse and the projection to striatum (essentially, all,
from intralaminar nuclei). Diffuse intralaminar nuclei efferents are widely, though
sparsely, distributed to most of neocortex: it is this diffuse projection that has to do with
consciousness. One can understand how intralaminar nuclei could directly influence
ideation, as ideation is a function of cortex (Bogen, 2007).
Activity of these neurons is not, however, the only neuronal basis of wakefulness:
there are also involved, the noradrenergic neurons of the locus ceruleus; the serotonergic
neurons of the raphe nuclei; and histamine-containing neurons in the tuberomammillary
nucleus (TMN) of the hypothalamus. The locus ceruleus and raphe nuclei are modulated
by the TMN neurons located near the tuberal region that synthesize the peptide orexin (also
called hypercretin). Orexin promotes waking, and thus may have useful applications in jobs
where operators need to stay alert. On the other hand, antihistamines inhibit the histamine-
containing TMN network, and thus tend to make people drowsy (Willie et al., 2003).
Arousal systems are regulated not only by external stimuli, but also by control
systems of the brain. For example, the frontal cortex, particularly the orbitofrontal area,
regulates the thalamic reticular nucleus and the cholinergic, basal forebrain structures.
Patients with lesions in this area show deficits in arousal (Marrocco and Field, 2002).
Cortical control is not limited to cholinergic modulation. In a work on the norepinephrine
system, Minzenberg et al. (2008) demonstrated the role of locus ceruleus-norepinephrine
system in the prefrontal cortex function and cognitive control.
The frontal cortex also exerts an influence on the limbic system, which regulates
emotional arousal. The anterior cingulate region is important in the self-regulation of arousal
through its connections with the cholinergic basal forebrain (Marrocco and Field, 2002).
In sum, AAS can exert both direct and indirect action on the cerebral cortex.
However, the reticular formation which appears to be responsible for maintaining cortical
arousal is not the same with consciousness.
Ascending (reticular) inhibitory system (AIS)

According to case 2, it is impossible that the two important functions of the central
nervous system, arousal and sleep, or activation and inhibition, depend only on AAS.
The two compulsory conditions (arousal and sleep) cannot be determined or explained
by the AAS activity or inactivity only.
Dănăilă (1972), Arseni and Dănăilă (1977) and Dănăilă and Pascu (2009) have
clinically demonstrated that, besides the AAS, there is an ascending reticular inhibitory
system (AIS) as well, of which lesion leads to the appearance of the logorrhea syndrome
with hyperkinesia, hyperwakefulness, and hyperprosexia.
Normally, during the 24 daily hours, after arousal follows sleep, which is based on
AIS. The two reticular systems (AAS and AIS) are under the influence of the
suprachiasmatic nucleus and of the awake and sleep centers in the hypothalamus.
As much as awake is determined by AAS, sleep, considered the most profound
natural alteration of consciousness, is determined by AIS. It acts on the cerebral cortex
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directly, through the thalamus, through the ventrolateral preoptic (VLPO) nucleus of the
hypothalamus, which in its turn is under the influence of the suprachiasmatic nucleus,
and through the basal ganglia.
The lateral group of the reticular formation, localized in the pons and rostral part of
the brain stem, gives origin to AIS. When AIS is activated, the cerebral cortex becomes
inactive and the person asleep. This system receives inhibitory signals from the
cerebellum and sends output signals to the thalamus, to the hypothalamic sleeping center,
and directly to the cerebral cortex (Fig. 24.3).
Fig. 24.3. The Ascending Reticular Inhibitory System (ARIS) is found in the brain stem, and sends projections
throughout the cortex: directly (1), through the thalamus (2), or through the hypothalamus;
ventrolateral preoptic nucleus-VLPO, (3), which receives influence from suprachiasmatic nucleus.
The raphe nuclei, in the midline of the brain stem, use serotonin as their primary
neurotransmitter and have diffuse connections to the cerebral cortex and subcortical gray
matter (Moore et al., 1978).
Thus, the correlated activity between reticular neurons leads to a strengthened
connection, both excitatory and inhibitory. In the absence of inhibition, any external input,
weak or strong, would generate more or less the same one-way pattern, an avalanche of
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excitatory stimuli involving the whole population (Hopfield and Tank, 1986). Cortical
networks gain their nonlinearity and functional complexity primarily from the inhibitory
interneuronal system (Pouille and Scanziani, 2001). The specific firing patterns of
principal cells in a network depend on the temporal and spatial distribution of inhibition.
Without inhibition and dedicated neural formation, excitatory circuits cannot accomplish
anything useful (Buzsaki, 2006). Fast coupling of the excitatory and inhibitory influences
can bring about a submillisecond precision of spike timing (Pouille and Scanziani, 2001).
Anyhow, reticular nucleus efferents terminate in the immediately underlying
thalamic nuclei and the reticular nuclei efferents are GABA-ergic (the neurons in reticular
nuclei are exclusively inhibitory, using GABA as their transmitter) (Bogen, 1997, 2001).
Thus, thalamocortical communication can be simultaneously inhibited by this reticular
nucleus efferents that terminate in the underlying thalamic nuclei. In the brain and
particularly in the cerebral cortex, there are multiple influences, both inhibitory and
facilitatory. When a performance has been lost because the competence has lost some
facilitation, re-emergence of the performance can result simply from the subsidence of
inhibition (Sherrington, 1932). The same suggestion was made by von Monakow in 1911.
The main point is that a loss of performance is not necessarily the result of damage to
the competence for that performance; it may result from unbalanced or excessive
inhibition of the competence (Bogen, 2001).
Generally, the reticular formation of the brain stem is, in turn, influenced by
circadian clocks located in the suprachiasmatic nuclei and the arousal (tuberomammillary
nucleus) and sleeping (ventrolateral preoptic nucleus) centers of the hypothalamus. The
clock adjusts periods of sleep and wakefulness to appropriate duration during the 24-
hours cycle of light and darkness. So, in all structures of the nervous system, inhibition
plays a pivotal role.
Thus, brain uses not only excitation, but also inhibition during its normal operations
and behaviors. With no inhibitory cells in a network, depending on the temporal and spatial
distribution and dedicated interneurons, excitatory circuits cannot accomplish anything
useful (Buzsaki, 2006). Excitatory potentials dominate on the dendrites of principal cells,
whereas only inhibitory postsynaptic potentials impinge upon the cell body (soma).
Interneurons provide autonomy and independence to neighboring principal cells but they
offer, at the same time, useful temporal coordination. The functional diversity of principal
cells is enhanced by the domain-specific actions of GABA-ergic interneurons which can
dynamically alter the qualities of the principal cells (Buzsaki, 2006). The separation of
inputs in a network with only excitatory connections and circuits is not possible. Like all
somatic functions at all levels of the system, executive functions, beginning with attention,
make use of inhibition for focus, contrast suppression of interference, order, and timeliness
(Fuster, 2009). Inhibition enhance saliency and contrast. Inhibition appears essential for
the control of impulsivity and a wide array of instinctual drives.
So, there are two opposing active processes that could summate, algebraically, a
control excitatory reticular system and a control inhibitory one. Thus, the brain uses not
only excitation, but also inhibition during its normal function.
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Ascending output of the brain stem reticular formation not only subserves arousal
and sleep but also contains information about other bodily states and other neural
formation outside the reticular formation. This is why ARAS and ARIS might be named
ascending activatory system (AAS) and, respectively, ascending inhibitory system (AIS).
Clinical aspects
It is important to distinguish between alertness and impairment of the wakeful state.
It is possible to be awake and not conscious, but it is impossible to be conscious and not
awake. A combination of clinical lesion studies and animal data has identified the
following major mechanisms through which alterations in consciousness are produced:
disturbance of the ascending reticular system; bilateral lesions of the midbrain and
diencephalon; and bilateral involvement of the cerebral cortex (hemispheres). To what
degree same damage will render unconsciousness of a person remains to be clarified.
Coma
Destructive lesions of the brain stem may occur as a result of vascular disease, tumor,
infection, or trauma. Unlike compressive lesions, which can often be reversed by
removing a mass, destructive lesions cannot be reversed. Between the conscious state of
mind and coma there are multiple intermediary stages that manifest through: confusion
or lethargy, drowsiness, stupor, semicoma (light coma), locked-in syndrome persistent
vegetative state, loss of conscious in concussion (diffuse axonal injury). We will shortly
discuss below the most important of them.
Persistent vegetative state

The term persistent vegetative state was introduced by Jannet and Plum in 1972, to
describe the state of preservation of autonomic function and primitive reflexes, without
the ability to interact meaningfully with external environment.
The vegetative state has been differentiated from the newly introduced category of
minimally conscious state (MCS; Giacino et al., 2002). MC patients may show islands
of relatively preserved brain response (Schiff et al., 2002; Bly et al., 2004), as well as
fragments of behaviors interpretable as signs of perception and voluntary movement that
preclude the diagnosis of vegetative state (Zeman, 2001). Both, the vegetative and
minimally conscious state need to be distinguished from the locked-in syndrome in which
the patient is fully conscious but, due to a circumscribed brain stem lesion, is unable to
communicate in any way other than by lid closure and vertical eye movements. Overall,
brain metabolism is less reduced in locked-in patients (Levy et al., 1987).
Diffuse axonal injury (loss of consciousness in concussion)

The mechanism of loss of consciousness with a blow to the head is not completely
understood.
Brief loss of consciousness, which in humans is usually not associated with any
changes in CT and MRI scan, may be due to the shearing forces transiently applied to
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the ascending arousal system at the mesodiencephalic junction. Physiologically, the

concussion causes abrupt neural depolarization and promotes release of excitatory
neurotransmitters. There is an efflux of potassium from cells with calcium influx into
cells and sequestration in mitochondria leading to impaired oxidative metabolism. There
are also alterations in cerebral blood flow and glucose metabolism, all of which impair
neuronal and axonal function (Giza and Hovda, 2001).
Concussion or hemorrhage into the dorsolateral mesopontine tegmentum may be
visible on MRI, but diffuse axonal injury is generally not. Magnetic resonance spectroscopy
may be useful in evaluating patients with diffuse axonal injury, who typically have a
reduction in N-acetylaspartate as well as elevation of glutamate / glutamine and choline /
creatinine ratio (Adams et al., 2000; Brooks et al., 2001; Schutter et al., 2004).
Logorrhea syndrome with hyperkinesia

The activity in the reticular formation is the mechanism that induces the sleep and
awakens you from sleep and brings you back to full consciousness.
Thus, damage in the reticular formation typically sends a person into coma because
this is an on / off switch for all higher brain centers or determines the logorrhea syndrome
with hyperkinesia (Dănăilă, 1972; Arseni and Dănăilă, 1977; Dănăilă and Pascu, 2009).
In a study on the behavior of patients with brain stem tumors and another neurosurgical
condition, Dănăilă (1972), Arseni and Dănăilă (1977) observed that, apart from the
locked-in syndrome, persistent vegetative state or coma, the patients may also manifest
various other aspects, especially logorrhea syndrome with hyperkinesia, hyperwake-
fulness and hyperprosexia (Fig. 24.4, case 2). In our opinion, the logorrhea syndrome
A B
Fig. 24.4. MRI studies of a petroclival meningioma (A) which compresses from outside the brain stem provoke
logorrhea syndrome with hyperkinesia and hyperwakefulness. Postsurgery (B) this syndrome disappears.
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with hyperkinesia, hyperwakefulness and hyperprosexia reflect a hyperconsciousness or,

in other words, a super-arousal determined by eliberation of the AAS from the influence
of AIS which is damaged.
Thus, the logorrhea syndrome with hyperkinesia is produced by the lesion of the
AIS and is an argument in favor of the existence of AIS.
The lesions found in our cases (pons, rostral part of the brain stem) mark the location
of the AIS. Trillet et al. (1995) have described a syndrome of hemiballisme and logorrhea
determined by a hematome of the left subthalamic nucleus. The right hemiballisme is
explained by the influence on the subthalamic nucleus, but not the logorrhea. In our
opinion, the image given in Fig. 1 of theirs article shows multiple subthalamic lesions
which affect zona incerta; one knows that zona incerta has an inhibitory role (Jones, 2007).
In conclusion, we think that the logorrhea syndrome is, in this case, given by the
lesion produced to the zona incerta which is located in the immediate neighborhood of
the subthalamic nucleus. AIS passes through zona incerta.
In sum, besides the other homeostatic systems, the reticular system (AAS and AIS)
represents an actual regulator system of the entire neuraxis, as proven by its participation
in the regulation of all the psychical processes (attention, memory, reasoning, behavior,
etc.), speech, muscular tonus, and the physiognomy of movement.
MIDBRAIN (Mesencephalon)
The midbrain is the short portion of the brain between the pons and the cerebral
hemispheres. It consists of tectum, contains the four corpora quadrigemina and two
cerebral peduncles with tegmentum and crus cerebri.
The cerebral aqueduct, surrounded by the central gray matter, separates the tectum
from the tegmentum. The cerebral peduncle consists of two parts: 1) a dorsal part, the
tegmentum; and 2) a ventral part, the crus cerebri. These two parts are separated from
each other by substantia nigra.
The midbrain tegmentum contains the trochlear and oculomotor nuclei, neural
structures concerned with ocular and visual reflexes, the mesencephalic reticular
formation, the red nuclei and many scattered collections of cells.
Dorsal midbrain syndrome

The midbrain may be forced downward through the tentorial opening by a mass
lesion impinging upon it from the dorsal surface (Fig. 24.5, case 3).
The most common causes are masses in the pineal gland, in the posterior thalamus,
or in upward transtentorial herniation which kinks the midbrain.
Primary midbrain hemorrhages, which may be of either type, are rare. Most of such
patients present acutely with headache, alteration of consciousness and abnormal eye
signs. Most of them recover completely from bleeds from cavernous angiomas, but some
remain with mild neurologic deficit.
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A B
Fig. 24.5. A) A contrast-enhanced axial CT-scan of a 36-year-old man with hydrocephalus and a large pineal region
tumor, that was totally resected. Postsurgery, the patient remains clinically intact. B) Axial CT-scan, 3 months
postsurgery confirming total removal of the tumor (germinoma).
Pressure from this direction produces the characteristic dorsal midbrain syndrome,
manifested first by limited upgaze. In severe cases, the eyes may be fixed in forced,
downward position. There may also be a deficit of convergent eye movements and
associated pupilloconstriction. The presence of retractory nystagmus, in which all of the
eye muscle contracts simultaneously to pull the globe back into the orbit, is characteristic.
Motor responses are difficult to obtain or result in extensor posturing. Motor tone and
tendon reflexes may be heightened, and plantar responses are in extension.
If the cerebral aqueduct is compressed sufficiently to cause acute hydrocephalus,
however, an acute increase in supratentorial pressure may ensue.
This may cause an acute increase in downward pressure on the midbrain, resulting
in sudden lapse into deep coma (Posner et al., 2007).
Most patients in whom the herniation can be reversed suffer chronic neurologic
disability (Brendler and Selverstone, 1970; Zervas and Hedley-Whyte, 1972).
After the midbrain stage becomes complete, it is rare for patients to recover fully.
DIENCEPHALON
The diencephalon contains the hypothalamus, thalamus, subthalamus (substantia
nigra, the zona incerta, the nucleus of the tegmental fields of Forel, ansa lenticularis,
Forel’s field H1 – thalamic fasciculus – Forel’s field H2 – lenticular fasciculus-, and
subthalamic fasciculus), metathalamus (medial geniculate body and lateral geniculate
body), and epithalamus (pineal body, habenular trigones, stria medullaris, and roof of
the third ventricle).
In the following, we study only the role of the hypothalamus and thalamus in sleep,
arousal, and circadian rhythm.
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The hypothalamus
The hypothalamus is composed of about 22 small nuclei, the fibre system that passes
through it and the pituitary gland. Although the hypothalamus comprises only about 0.3%
of the brain weight, it takes part in nearly all aspects of motivated behavior, including
sleeping, arousal, temperature regulation, emotional behavior, endocrine function,
metabolism, sexual behavior, and movement.
From our point of view, the ventrolateral preoptic nucleus (sleeping system), the tubero-
mammillary nucleus (arousal system), and the suprachiasmstic nucleus (day - night cycle
system) are important.
The sleep is a circadian function, and although the suprachiasmatic nuclei are not
essential for its generation, they are responsible for consolidation of sleep in cycles that
occur within a circadian framework.
According to Hobson (2007), when humans go to sleep they rapidly become less
conscious. The initial loss of awareness of the external world that may occur when we
are reading in bed is associated with the slowing of the EEG that is called Stage I. At
sleep onset, although awareness of the outside world is lost, subject may continue to have
visual imagery and associated reflective consciousness. Even in the depths of stage IV
non-REM sleep, when consciousness appears to be largely obliterated, the brain remains
highly active and it is still capable of processing its own information. From PET and
single neuron studies, it can safely be concluded that the brain remains about 80% active
in the depths of sleep. Most of the brain activity is not associated with consciousness.
Non-REM, Stage IV is characterized by low-frequency, high-amplitude EEG in which
subjects may report not only some thought-like mentation but also movie-like dreams
(Bosinelli, 1995).
The circuitry through which AIS influences the sleep, being localized in the upper
pons and rostral parts of the brain stem, includes the hypothalamic ventrolateral preoptic
nuclei, suprachiasmatic nuclei, the thalamus, and the cerebral cortex. Saper et al. (2005)
provide very good arguments regarding the sleep and arousal. Nevertheless, in our
opinion, the explanation of the sleep / wakefulness given by them as due to a flip-flop
switch, to the influence of suprachiasmatic nucleus, to the homeostatic mechanism and
to the allostatic mechanism is not enough. It is our opinion that the explanation should
also include the existence of the AAS and AIS which are working also under the influence
of the suprachiasmatic nucleus, homeostatic mechanisms and allostatic mechanism and
which control the sleep.
The arousal, like sleep, exhibits more steps: a rapid one, which has a short lifetime
and which is determined by the direct action of the ascending activating system on the
cerebral cortex; another, with a longer lifetime, within the 24 hours, which is caused by
indirect action of AAS on the cerebral cortex via thalamus; and the third, which is
rhythmic and it is determined by the AAS action on the cerebral cortex via the
hypothalamic arousal system which, in its turn, is found under the influence of the
suprachiasmatic nucleus.
Some studies have demonstrated that the influence of the hypothalamus on arousal
is not restricted to the tuberomammillary neurons in caudal hypothalamus. In particular,
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a prominent group of neurons confined to the lateral hypothalamus has been implicated
in the sleep disorder known as narcolepsy (Card et al., 1999).
These neurons express novel neuropeptides known as hypocretins or orexins and are
differentially concentrated within the perifornical nucleus that surrounds the fornix in the
tuberal hypothalamus. Mapping studies have shown that hypocretin (orexin) neurons are
similar to tuberomammillary neurons in that they are confined to the hypothalamus and give
rise to extensive projections throughout the neuraxis (Parent, 1997).
Human sleep occurs with circadian periodicity. Thus, humans have an internal “free-
running clock” that operates even in the absence of information about the period of 24
hours (Aschoff, 1965; Hobson, 1989; Colwell and Michel, 2003). This clock is controlled
by the suprachiasmatic nucleus.
So, circadian rhythms provide temporal organization and coordination for
physiological, biochemical, and behavioral variables in all eukaryotic organisms and in
some prokaryotes. Circadian rhythms that are genetically determined, not learned (Hall,
1990, Rosato et al., 1997; von Schantz and Archer, 2003), are generated by an
endogenous self-sustained pacemaker.
The pineal body synthesizes the sleep-promoting neurohormone melatonin and
secretes it into the bloodstream where it modulates the sleep.
The thalamus
The physiological understanding of the human thalamus is limited. The fundamental
function of the thalamus is that of relay and it modulates peripheral information to the
cerebral cortex and to the basal ganglia, keeping the somatosensory, mental, and
emotional activity of a living individual in harmony.
With the exception of the thalamic reticular nucleus, all thalamic subnuclei possess
thalamic projection neurons that relay processed information to the cerebral cortex. In
addition, the thalamic subnuclei also have inhibitory GABA-ergic interneurons whose
cell bodies and processes are confined to a single subnucleus. The reticular nucleus of
the thalamus is a continuation into the diencephalon of the reticular formation of the brain
stem. It receive inputs from the cerebral cortex and thalamic nuclei. The former are
collaterals of corticothalamic projections and the latter are collateral of thalamocortical
projections. The reticular nucleus projects to other thalamic nuclei. The inhibitory
neurotransmitter of this projection is GABA. The reticular nucleus is unique amongst the
thalamic nuclei because its axons do not leave the thalamus. Based on its connections,
the reticular nucleus plays a role in integrating and gating activities of the thalamic nuclei.
As the termination site for the reticular ascending system is considered, it is not
surprising that the thalamus has an important arousal and sleep-producing function (Green
1987; Steriade et al., 1990; La Berge, 2000; Jones, 2007) and that it alerts, activates or
inhibits a specific processing and response system. Its involvement in attention shows
up in diminished awareness of stimuli impinging on the side opposite to the lesion
(unilateral inattention) (Dănăilă, 1972; Arseni and Dănăilă, 1977; Ojemann, 1984; Posner,
1988; Heilman et al., 2003).
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The ascending input to intralaminar nuclei can help explain consciousness of primitive
percepts (non-cognitive component). So, ascending output of the brain stem reticular
formation not only subserves arousal but also contains information about other states. Thus,
other input to reticular formation comes from the spinothalamic system, and trigeminal
complex, and from dentate nuclei in the cerebellum conveying proprioceptive signals. There
are also ascending inputs to intralaminar nuclei from deep layers of the periaqueductal gray,
substantia nigra and amygdala with affective information, and from the vestibular nuclei
with information about body position (McGuiness and Krauthamer, 1980; Kaufman and
Rosenquist, 1985; Royce et al., 1991; Jones, 2007).
Intralaminar nuclei. These nuclei, embedded in the internal medullary lamina,
consist of centralis, lateralis, paracentralis, central medial nuclei (anterior group), and
centromedial and parafascicular nuclei (posterior group) (Ohye, 2002). The latter are
often called the centromedian-parafascicular complex.
The anterior group receives different projections from the spinothalamic tract, deep
cerebellar nucleus, brain stem reticular formation, etc.
The posterior group has a reciprocal connection with the basal ganglia. The efferent
connection with the cerebral cortex is very wide and was thought to be a diffuse
projection. The intralaminar nuclei were classified as representatives of the “nonspecific
system” rather than of the “specific system”, such as the thalamic station for the visual,
auditory, or somatosensory system with definite modality-specific peripheral input.
Reticular nucleus. This nucleus is considered to be related to arousal, attention,
cognitive function, etc. As discussed later, it plays a role in maintaining cortical activity
in a disease state of epilepsy (Ohye, 1990; Ohye, 1998; Jones, 2007).
Ohye (2002) studied the human thalamus using microrecordings during stereotactic
thalamotomy for dyskinesia and found verbal command neurons in this nucleus and
adjacent area.
Surround-type inhibition mediated by thalamic reticular nuclei may selectively gate
out extraneous stimuli while allowing focused relay important sensory data to the
thalamocortical circuits, which endow a given neural activity pattern with the property
of conscious perception (Ames and Marshall, 2003). But how is this neurophysiologic
activity coordinated in time to produce a somewhat unified conscious stream? Data
suggest the answer may lie in the acquisition of gamma synchrony, most commonly at
approximately 40 Hz (Gray and Viana di Prisco, 1997).
Gamma synchrony has also been hypothesized to “bind” disparate features of a given
object, such as color, size, texture, and motion, into a temporally unified sensory stimulus
(Singer and Gray, 1995).
On the other hand, thalamocortical neurons receive ascending projections from the
locus ceruleus (noradrenergic), raphe nuclei (serotonergic), reticular junction (cholin-
ergic), TMN (histaminergic) and project to cortical pyramidal cells.
In the tonic firing state, thalamocortical neurons transmit information to the cortex
that is correlated with the spike trains encoding peripheral stimuli (Steriade, 1992, 1999).
In brief, the control of sleep and wakefulness depends on the brain stem and
hypothalamic modulation of the thalamus and cortex.
1945
The epithalamus
The function of the epithalamus is not well understood.
Production of the pineal hormone melatonin is cyclic, with high levels of synthesis
occurring at night and low levels during the day.
A destructive disease of the diencephalon

Unilateral thalamic or diencephalic lesions (tumors, hemorrhage, etc.) do not
determine coma.
A B
C D
Fig. 24.6. Contrast medium-enhanced coronal (A) and axial (B) magnetic resonance imaging showing a big right
thalamic tumor that proved to be an astrocytoma. Thirteen months following resection and radiotherapy, coronal (C)
and axial (D) magnetic resonance imaging demonstrates the absence of tumor.
The patient was conscious and in good state.
1946
A B
Fig. 24.7. A 56-year-old man who presented with a sudden onset of coma and fever. Coronal (A) and axial (B) T1-
weighted magnetic resonance imaging (MRI) scans revealed edematous, demyelination symmetrical changes infra-
and supratentorial, which involve entire midbrain, both thalamic formations, bilateral basal ganglia, two-side
temporooccipital convolution and hippocampus, determined by encephalitis. After 9 days of coma, the patient died.
We had the case of a 29-year-old woman whose CT demonstrated a spontaneous

hypodense tumor, located in the right thalamus. On MRI the tumor appeared hypointense
in T1-weighted image and hyperintense in T2-weighted image, surrounded by a moderate
edema (Fig. 24.6, case 4). At the operation, the tumor was totally resected. The
histological exam showed an astrocytic cell population. Thirty-five days after surgery,
the patient started radiation therapy using a 10 MeV photons energy linear accelerator.
The clinical examination, performed thirteen months after surgery, demonstrated a very
good health condition of the patient. Control cerebral MRI showed the absence of any
intracerebral tumor mass and reduced hydrocephalus.
Bilateral destructive lesions of the diencephalic region result in deep coma and death,
despite an intact cortex.
Occasional inflammatory and infectious disorders may have a predilection for the
diencephalon (Fig. 24.7, case 5). Fatal familial insomnia, a prior disorder, is reported to
affect the thalamus selectively, and this has been proposed as a cause of the sleep disorder,
although this produces hyperwakefulness, not coma (Della Porta et al., 1964). Humans
with bilateral damage to the region of the dorsal pons, midbrain, and thalamus (by trauma,
brain tumor, viral or bacterial infection, ischemic or hemorrhagic stroke) may exhibit an
impaired state of alertness, possibly becoming stuporose or comatose.
LIMBIC SYSTEM AND HIPPOCAMPUS

Broca (1878) first described and named the limbic lobe. In a subsequent phase in
speculation on the limbic lobe by observers such as Papez (1937) and Brodal (1947), it
was suggested that, in humans, this lobe is partially olfactory and is mainly concerned
with emotional behavior. In addition, the amygdala was seen as part of limbic lobe.
Finally, Papez showed that the hippocampus projects, via the fornix, back to the
1947
hypothalamus. Nauta (1958) developed this concept further, insisting on the functional
importance of certain regions of the neural axis, such as the septum, cingulate gyrus,
orbitofrontal cortex, preoptic area, “limbic striatum” (including the nucleus accumbens,
mesolimbic dopaminergic tract), nonspecific thalamic nuclei, hypothalamus and midbrain
tegmental area, regions closely related to the amygdala and hippocampus. These regions
form a ring, or “limbus”, around the base of the brain. Anterior cingulate cortex (ACC)
is part of a neural circuit that mediates outcome-contingent changes in behavior (Ito et
al., 2003; Kerns et al., 2004; Kennerley et al., 2006) and processes fictive information in
human (Chiu et al., 2008). The ACC is interconnected with the orbitofrontal cortex which
mediates fictive thinking in humans (Camille et al., 2004; Ursu and Carter, 2005).
Hayden et al. (2009) hypothesized that neurons in the ACC, which monitors the
consequences of actions and mediates subsequent changes in behavior, would respond
to fictive reward information.
Generally, the hypothalamus makes a link between the limbic and endocrine system
reasonable. The limbic system is now considered to be a functional unit. Areas around
the limbic system are called paralimbic and have a more complex histologic structure.
Anyhow, the limbic system makes a link between external and internal world.
The Hippocampus. The hippocampus occupies the medial part of the floor of the
temporal horn and is divided into three parts: head, body and tail.
Structure. The hippocampus is bilaminar, consisting of the cornu Ammonis (or
hippocampus proper) and the gyrus dentatus (or fascia dentata), with one lamina rolled
up inside the other.
Functions and connections: the possible functions of the hippocampus are divided
into four categories: (1) learning and memory, (2) regulation of emotional behavior,
(3) certain aspects of motor control; and (4) regulation of hypothalamic functions
(Duvernoy, 2005). The hippocampus and related diencephalic structures form and
consolidate declarative memories that are ultimately stored elsewhere.
The hippocampus is also involved in the regulation of the hypothalamo-hypophysial
axis. Through its projections to the paraventricular hypothalamic nucleus, it may inhibit
the hypophysial secretion of adrenocorticotrophic hormone (ACTH) (Jacobs et al., 1979;
Teyler et al., 1980; Herman et al., 1989; Diamond et al., 1996).
The amygdala: amygdala is a complex mass of gray matter buried in the anterior-
medial portion of the temporal lobe, just rostral to the hippocampus.
The amygdala and its interconnections with an array of neocortical areas in the
prefrontal cortex and anterior temporal lobe, as well as several subcortical structures,
appear to be especially important in the higher order processing of emotion.
The amygdala links cortical regions that process sensory information with
hypothalamic and brain stem effector systems. In a review of the role of the amygdala in
emotional processing, Phelps and Le Doux (2005) identified five areas in which there is
evidence from studies of cognition-emotion interactions involving the amygdala:
1) implicit emotional learning and memory;
2) emotional modulation of memory;
1948
3) emotional influences on perception and attention;

4) emotion and social behavior;
5) emotion, inhibition and regulation.
CEREBRAL CORTEX
The cerebral cortex of the cerebral hemispheres, the convoluted outer layer of gray
matter composed of tens billions of neurons and their synaptic connections, is the most
highly organized correlation center of the brain, but the specific of cortical structures in
mediating behavior is neither clear-cut nor circumscribed (Collins, 1990; Franckowiak
et al., 1997). This multitude of neurons send a large number of axons in all directions,
covered by supportive myelin. This forms the white matter of the cortex which fills the
large subcortical space.
The cerebral cortex receives sensory information from internal / external environ-
ment of the organism, processes this information and then decides on and carries out the
response to it.
Generally, the hemispheres supply much of the content and registration function of
consciousness, including language, abstract reasoning, somatosensory visual and spatial
abilities, map of the physical dimensions of the self, executive function, complex emotion,
feelings, memory and ability to read other’s mind.
While the cortex is vital for cognitive functions, it interacts constantly with major
satellite organs, notably the thalamus, basal ganglia, hypothalamus, cerebellum, brain-
stem and limbic regions, among others.
In order to be conscious, to operate at normal parameters, to record and potentiate
the internal and external sensory data, and to correctly process them based on the previous
individual experience, and to answer adequately, it is necessary that the cerebral cortex
should be integer and aroused by the ascending activating system.
These considerations suggest that there might be multiple conscious awareness
systems, each supporting conscious awareness in different mental domains.
Unilateral and diffuse, bilateral cortical destruction

Different regions of the cerebral cortex have modular specific functions (somatic
sensory and motor, visceral sensory and motor, integrative cognitive functions, speech
functions, etc.) responsible for the high-order cognitive processing or conscious mind.
These correspond to the Brodmann areas, as well to each of the four cerebral lobes.
Being aware of the somatic and visceral ego refers to the ability of being conscious
of the components of one’s body, concrete activities and their status. Thus, a lesion of
the parietal lobe leads to a destruction of the ego, which manifests through agnosia, such
as asomatognosia (denial of one’s own body part), finger agnosia, tactile agnosia,
hemiasomatognosia.
The ideational consciousness refers to the ability of one person to be aware of their
concrete activities, ideas and thoughts that are expressed through spoken or written words.
A lesion of the frontal, parietal, occipital, temporal lobe and the callous body leads to
1949
apraxia, Gerstmann’s syndrome, Balint’s syndrome, akinetic mutism, aphasia and

agraphia. Emotional consciousness refers to the ability of being aware of emotions. The
frontal lobe and the left parietal lobe coordinate positive emotions, whereas ones on the
right side coordinate negative emotions.
A B
Fig. 24.8. A presurgery contrast enhanced computed tomographic (CT) scan of a 56-year-old man shows a giant size
olfactory groove meningioma and displacement of anterior brain (A). The patient presents an orbitofrontal syndrome.
Postsurgery contrast-enhanced CT scan showing no residual tumor (B) and orbitofrontal syndrome disappeared.
A B
Fig. 24.9. A presurgery contrast enhanced computed tomographic (CT) scan of a 35-year-old woman shows a bilobed
meningioma of the anterior falx. She has a dorsolateral frontal syndrome (A). Postsurgery contrast-enhanced
computed tomography scan showing no residual tumor (B) and frontal syndrome disappeared.
1950
We want to stress the existence of the same discrete modules in the brain for each
possible neuropsychological capacity. Adjacent modules communicate with each other
more than do non-adjacent modules. So, the term of modular or functional localization
of consciousness is used to indicate that certain functions can be localized to particular
areas of the cerebral cortex. The mapping of cortical function began with inference made
from the deficits produced by cortical lesions in humans.
A B
Fig. 24.10. (A) Preoperative coronal T1-weighted, gadolinium-enhanced magnetic resonance images obtained for a
46-year-old man who presented prosopagnosia and memory disturbance. It demonstrated a large right-sided
temporo-basal astrocytoma. (B) Image was obtained after complete removal of the tumor.
After two months the symptoms disappeared.
A B
Fig. 24.11. Bilateral, cortical and subcortical, more than 110 cerebral metastases (A and B).
The primitive tumor was a melanocarcinoma.
1951
As we have noticed, partial lesion of some Brodmann specialized areas or of one of

the lobes leads to the modular loss of consciousness (Fig. 24.8, case 6), (Fig. 24.9, case 7),
(Fig. 24.10, case 8). When all the cerebral cortex is destroyed as well as the white matter
of the two hemispheres that globally depress neuronal activity, the consciousness level
decreases and coma is produced. These causes of diseases include cortical and subcortical
tumors (Fig. 24.11, case 9), hypoxia, sedatives, hypnotics, neurotransmitter receptor
antagonists, neural toxins, infectious disease and metabolic disease. Careful studies of
split-brain patients make it clear that the right hemisphere has a consciousness of its own,
even if it lacks the ability to communicate its experiences verbally.
Discussion
The consciousness processes belong to people who act by control mechanisms of
psychological activities, generalization and abstractization mechanisms, as well as by
exploring and handling of mental images to solve all the problems man is facing with.
The consciousness level depends on the complexity of the brain ontogenetic evolution.
It must be a function of numerous interacting systems. Data based on our experience
support this statement.
According to Tononi and Laureys, consciousness can be dissociated from other brain
function, such as responsiveness to sensorial inputs, motor control, attention, language,
memory, reflection, spatial frames of reference, the body and perhaps even the self
(Tononi and Laureys, 2009). We consider this point of view to be incorrect because
consciousness cannot appear without these function. It cannot be dissociated from them.
The respective functions represent modules of the consciousness. The consciousness
results from the respective cerebral activities. Lesions of some functions lead to modular
disorder of the consciousness.
The major structures supposed to play a key role in the neural correlates of
consciousness are: the brain stem, the diencephalon (the hypothalamus and thalamus),
the limbic system (especially the hippocampus and amygdala), basal ganglia, cerebellum,
and the cerebral cortex. The brain stem is the source of massive reticular formation
pathways that activate or inhibit higher and lower brain centers. They are the core of the
basic arousal and sleeping cycle.
The hypothalamus, the thalamus and the cerebral cortex are likely closely intertwined
with RF which plays a key role in consciousness. Generally, there are an ascending
activating system (AAS) and an ascending inhibitory system (AIS).
However, AAS which appears to be responsible for maintaining cortical arousal is
not the same with consciousness.
Sleep is based on ascending reticular inhibitory system. The two reticular systems
(AAS and AIS) are under the influence of the suprachiasmatic nucleus and of the awake
and sleep centers in the hypothalamus. So, as much as awake is determined by AAS,
sleep, considered the most profound natural alteration of consciousness, is determined
by AIS. AAS and AIS are not neurological basis of consciousness but they rather
constitute the necessary substrate for consciousness to emerge.
1952
Lesions of the ascending reticular inhibitory system produced the logorrhea

syndrome with hyperkinesia, hyperwakefulness and hyperprosexia.
Bilateral lesions / destructions of the neurological formations (brain stem, midbrain,
diencephalon, limbic system and cerebral cortex) lead to the loss of consciousness.
The ascending inhibitory system is important in explaining the sleep and many other
behaviors.
On the other side, the cerebral cortex and consciousness have a modular structure.
AAS and AIS reach the cerebral cortex directly, through the thalamus and the
hypothalamus. In order to be conscious, it is necessary that the cerebral cortex should be
integer and aroused.
Thus, to be conscious is equivalent of having access to information about the self
and the environment and to have the capacity to read another individual’s intention. The
consciousness is the most developed form of expressing the personality. The self similar
to the ego, the spirit, the soul is the main expert or primary knower. So, consciousness is
not equal to the awakened state of mind, as it involves functions of almost the entire
brain. But different brain structures and functions have a certain role in generating
consciousness. Consciousness, as a result of functions from almost entire brain, is
composed by modules which have different important values and features.
Injuring one module only leads to partial modification of the conscious state. Thus,
attention, memory, sensorial input, motor output, language, introspection / reflection,
space, body and self, perception, imagination, gnosias etc. are necessary prerequisite of
consciousness. The measurement scale of the (actual) level of consciousness of a current
person in the awakened state of mind and under ordinary life condition is composed of
several modules such as: being aware of the somatic, visceral, cognitive, emotional and
spiritual ego, and being aware of the physical, spatial, social, socio-relational extra ego.
Conclusions
– Bilateral destruction of the reticular activating nuclei at the rostral pons and
midbrain lead to loss of consciousness and the induction of coma.
– The damage of the ascending reticular inhibitory system lead to the appearance of
the logorrhea syndrome with hyperkinesia, hyperwakefulness, and hyperprosexia.
– The ascending inhibitory system is very important in explaining the sleep and
many other behaviors.
– AAS and AIS reach the cerebral cortex by three distinct ways: directly, through
the thalamus and through the hypothalamus.
– The sleep is controlled by action of the AAS-AIS dipole.
– With respect to its functioning, the cerebral cortex may be compared to a
continuous chess game between of the two systems, AAS and AIS, which act in perfect
equilibrium in order to perform all functions and behaviors of the individual.
– The cerebral cortex and consciousness have a modular structure.
1953
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1957
INDEX
A Ascending reticular inhibitory system 426

Asomatognosia 1871
Abducent nucleus and nerve 272 Association (cognitive) loop 780
Acetylcholine-releasing neurons 771 Association areas of the cortex 1600
Activation of inferior temporal neurons 1380 Astereognosis 1870
Selective attention to auditory input 1381 Asymmetries of the human frontal lobes 1827
Afferent fibres to the medullary RF 391 Anterior cingulate cortex 1842
Afferent projections (input) to the vestibular nuclei Asymmetries for the language in humans 1848
234 Asymmetries in language 1828
Afferents to the cerebellum 456 Asymmetries in processing spatial informations
Afferents to the RF 404 1854
Agenesis of the cerebellum 525 Asymmetry in memory and learning 1856
Agnosia and alexia 1537 Asymmetry in the attention 1858
Akinetic mutism 376 Asymmetry in the information process 1858
Alien hand syndrome 1538 Asymmetry in the motor system 1846
Alzheimer’s disease 951 Asymmetry in the music 1860
Amygdala 989 Asymmetry in visuospatial functions 1852
Afferent connections 995 Asymmetry of prosody and emotion 1833
Anatomical organization of the amygdala 990 Direct observation 1847
Connections 993 Functional imaging 1831
Connections with the hippocampal formation Hemispheric isolation of visual and tactile infor-
1000 mation 1852
Connections with the neocortex 1000 Interference tasks 1847
Connections with the olfactory system 1000 Medial wall (anterior cingulate cortex and SMA)
Efferent connections 997 1842
Erasing fear memories 1016 Morphological asymmetries 1830
Functions of the amygdala 1006 Prefrontal cortex 1836
Major pathways 994 Premotor cortex 1839
Neurochemical modulation 1005 Primary motor cortex 1840
Subcortical connectivity 995 Sharing of attention control 1853
The fear system and the seeking system 1012 Supplementary motor area 1844
The seeking system 1018 The left hemisphere as interpreter 1848
Amygdala and learning 1024 Asymmetry between the hemispheres in humans
Amygdala in normal aging 1019 1814
Anatomy of hearing 255 Aphasia and thought 1826
Central transmission 258 Bouillaud 1817
Anatomy of the corpus callosum 1493 Geschwind 1826
Body (trunk) 1495 Gustav Dax 1819
Genu 1495 Historical aspects 1817
Isthmus 1497 Marc Dax 1818
Rostrum 1495 Pitres and amnesic aphasia 1825
Splenium 1498 Asymmetry in emotional system 1881
Andral, Gabriel 63 Asymmetry in the auditory system 1864
Anterior commissure 1484 Asymmetry in the somatosensory system of parietal-
Anterior corpus callosum vascular malformations lobe lesions 1866
1563 Asymmetry in the visual perception and language of
Anterior temporal neocortex 1395 temporal-lobe lesions 1863
Apraxia and the parietal lobe 1874 Language 1864
Arachnoid cisternae 1765 Athetosis 805
Arachnoid granulations and villi 1766 Auditory association cortex 1330
Ascending reticular activating system 417 Anatomy 1330
i
Leon DănăiLă – Functional neuroanatomy of the brain
Auditory object recognition and scene analysis Ascending (reticular) activating system (AAS)
1342 1932
Auditory processing 1338 Ascending (reticular) inhibitory system (AIS)
Binaural properties 1340 1936
Complex response properties 1339 Clinical aspects 1939
Functional studies in humans 1331 Coma 1939
Functional studies in monkeys 1330 Diffuse axonal injury (loss of consciousness in
Neurophysiology 1336 concussion) 1939
Sound localization 1340 Logorrhea syndrome with hyperkinesia 1940
Spatial attention 1341 Persistent vegetative state 1939
Spatial localization 1338
Reticular formation 1932
The left temporal lobe and verbal memory 1335
Brain structures studied in emotional behavior in hu-
The right temporal lobe, nonverbal memory, and
musical perception 1335 mans 1882
The role of the planum temporale in sound de- Broca 6, 33, 61, 62, 65-76, 80, 120, 122-124, 128,
coding 1340 129, 136, 509, 585, 676, 739, 843, 849, 851-
The role of the primary auditory cortex 1338 853, 877, 908, 915, 967, 998, 1086, 1089,
Tonotopy 1339 1122, 1141-1147, 1182, 1225, 1226, 1229,
Unilateral lesions 1333 1236, 1239, 1248, 1303, 1349, 1352, 1365,
Auditory cortex 268, 1697 1366, 1383, 1481, 1482, 1485, 1497, 1537,
Acoustic startle reflex, orientation, and attention 1568, 1577, 1591, 1615, 1630, 1638, 1648,
1706 1657, 1664, 1665, 1668, 1704, 1705, 1715-
Area 20 1706 1717, 1725, 1726, 1731, 1743, 1804-1806,
Area 21 1705 1819-1823, 1828-1830, 1832-1834, 1840,
Auditory association cortex 1704 1846, 1861, 1886, 1891, 1893-1895, 1898,
Descending auditory pathways 1706 1902, 1906, 1915, 1927, 1947, 1954
Primary auditory cortex 1697 Brodmann 88, 90-93, 123, 125, 128, 129, 132, 134,
Auditory pathway through the reticular formation
135, 139, 152, 154, 242-244, 268, 300, 309,
270
328, 357, 367, 448, 557, 563, 565, 567, 571,
Auditory pathways 261
575, 576, 753, 780, 844, 851, 852, 857, 892,
Ballisme 805
893, 911, 914, 915, 919, 966, 1001, 1114,
1124, 1125, 1128, 1137, 1139, 1142, 1144,
B
1147, 1152, 1154, 1155, 1157, 1163, 1165,
Basal ganglia 731
1181, 1186, 1205, 1225, 1226, 1229, 1234,
Basal ganglia – anatomical organization 732
1255-1259, 1261, 1262, 1282, 1299, 1300-
Basal ganglia – subcortical loop 782
1302, 1313, 1321, 1323, 1325, 1326, 1328,
Basal ganglia and automatic processing 798
1330, 1332, 1364, 1384, 1410, 1415, 1417,
Basal ganglia and cerebellum in motor function 801 1418, 1448, 1469, 1553, 1594-1596, 1611,
Basal ganglia and learning 792 1615, 1617, 1627, 1628-1630, 1632, 1633,
Basal ganglia circuitry 773 1639, 1641, 1642, 1648, 1649, 1654-1657,
Basal ganglia functions 788 1660-1662, 1664, 1668-1670, 1672, 1674,
Cognitive function 790 1677, 1678, 1680, 1681, 1685, 1686, 1690-
Gating function 791 1700, 1704-1706, 1714, 1715, 1720-1722,
Motor function 789 1726, 1730, 1806, 1821, 1823, 1829-1831,
Basal nuclei or basal ganglia 146 1840, 1841, 1843, 1844, 1846, 1865, 1867,
Basal portion of the midbrain 357 1931, 1949, 1952
Basic division of the brain stem 142
Blind touch 1869 C
Bony labyrinth 224
Bouillaud 62, 63, 64, 67, 68, 73, 75, 122, 138 Callosal agenesis 1557
Brain modules 1432 Callous fibres 1499
Brain organization in nonhearing people 1789 Cardiovascular activity 415
Brain stem 1931 Caudal pons 272
ii
INDEX
Caudate nucleus 736 Circuits that modulate activity of the basal ganglia
Central auditory system 1323 786
Auditory cortex 1325 Claude’s syndrome 372
Auditory cortical anatomy 1326 Climbing fibres 468
Connectivity 1329 Clinical effects and symptoms 1448
Cytoarchitecture of auditory cortex 1328 Achromatopsia 1457
Central nervous system 1480, 1586, 1722, 1758, Apperceptive agnosia 1451
1759, 1770, 1774, 1931, 1936 Associative agnosia 1451
Central pathways 232 Color agnosia 1458
Cerebellar circuitry 479 Color anomia 1458
Cerebellar cortex 484 Cortical blindness and Anton’s syndrome 1460
Granular layer 493 Defects in constructional skills 1463
Molecular layer 486 Disorder of color processing 1456
Purkinje cell layer 488 Disorder of reading 1455
Cerebellar cortex – pharmacologic considerations Lesions in the association with visual areas 1469
495 Lesions in the primary visual area 1469
Cerebellar cortex – physiology 496 Other visuospatial anomalies 1460
Cerebellar peduncles 450 Prosopagnosia 1452
Internal structure 452 Simultanagnosia 1452
Cerebellum 143, 439 Topographical disorientation 1461
Cerebellum and behavioral syndrome 523 Visual agnosia 1450
Visual field defects 1448
Cerebellum and cognition 504
Visual hallucinations 1466
Cerebellum and language 506
Visual illusions (metamorphopsias) 1465
Cerebellum and psychiatric disorders 522
Visual imagery 1467
Cerebellum and writing 508
Visual neglect 1459
Cerebellum, working memory, creativity and gifted-
Visual object agnosia 1454
ness 508
Clinical effects of temporal lobe lesions 1382
Clinical aspects 511
Apperceptive deficits 1384
Cerebral asymmetry in nonhumans 1776
Associative deficits 1384
Asymmetry in birds 1781
Auditory agnosia 1384
Asymmetry in nonhuman primates 1782 Auditory hallucinations 1386
Asymmetry in rats 1779 Auditory illusions 1386
Handedness and functional asymmetry 1785 Behavioral aspects of auditory agnosia 1385
The evolution of handedness 1786 Cortical deafness 1383
Cerebral cortex 151 Disorder of memory, emotion and behavior 1387
Cerebral cortex 1592, 1949 Disturbances of time perception 1389
Discussion 1952 Neurological substrate of the disorder 1385
Unilateral and diffuse, bilateral cortical destruc- Nonauditory syndromes 1389
tion 1949 Smell and taste 1388
Cerebral hemispheres 150, 1414, 1480, 1483-1485, Vestibular disturbances 1388
1493, 1503, 1505, 1508, 1511, 1557, 1576, Visual disorders 1382
1578, 1580, 1583, 1588-1590, 1592, 1593, Word deafness (auditory verbal agnosia) 1385
1596, 1597, 1628, 1634, 1657, 1749, 1750, Cochlear nerve and nuclei 252
1753, 1761, 1777, 1781, 1798, 1814-1816, Cochlear nuclei 259
1838, 1850, 1859, 1875, 1880, 1898, 1902, Cognitive affective syndrome 520
1906, 1911, 1914, 1922, 1926, 1931, 1941, Columnar organization of the striate cortex 1434
1949 Color 1436
Cerebral peduncle 357 Cue invariance 1438
Cerebro-cerebellar circuit 482 Form 1437
Chemical specified systems 400 Functional subsystem 1436
Chorea 804 Motion perception 1436
iii
Commissural connections of the hippocampus 903 Cortical layers, afferents and efferents 1625
Complete callosotomy 1554 Cortical localization of music 1717
Conceptual apraxia 1875 Cortical-striatal-pallidal-thalamo-cortical circuits
Conduction apraxia 1877 774
Connections between cortical areas and binding Corticocortical connectivity 1431
problems 1604 Corticoreticular fibres 409
Connections of the basal ganglia 752 Corticoreticulocerebellar pathway 465
Corticostriate fibres 753 Cranial arachnoid 1764
Fibres from the brain stem pedunculopontine Cranial nerve nuclei of the medulla 178
tegmental nucleus 756 Clinical considerations 181
Fibres from the ventral tegmental area 756 Cytoarchitectonic organization of the hippocampus
Globus pallidus pathway 763 893
Nigrostriate fibres 755 Interneurons 896
Pallidohabenular fibres 767 Molecular layer 895
Pallidonigral fibres 766 Polymorphic layer 896
Pallidosubthalamic fibres 764 The pyramidal layer 893
Pallidotegmental fibres 767 Cytoarchitecture of the temporal lobe cortex 1364
Pallidothalamic fibres 766 Asymmetry of temporal lobes 1366
Striatonigral fibres 761 Connections of the temporal cortex 1365
Striatopallidal fibres 760, 764
Striatum 753 D
Subthalamopallidal fibres 764
Thalamostriate fibres 755 Dale 8, 100, 101, 102, 103, 104, 105, 107, 122, 123,
The ansa system 757 124, 125, 643, 711, 1478
The lenticular fasciculus 757 Darwin 61, 126
The thalamic fasciculus 759 Decerebrate rigidity 376
Ventral (limbic) striatum 762 Dentate gyrus 904
Constructional apraxia 1879 Afferents to the dentate gyrus 908
Control of eye movements and other cranial nerve Efferents from the dentate gyrus 910
functions 410 Depth and the analysis of space 1439
Control of visceral functions 413 Descartes, René 36, 47, 94, 95, 130, 544, 1898, 1954
Cornu Ammonis (hippocampus proper) 886 Descending auditory projections 270
Regional variations 891 Details of cerebellar circuitry 481
Corpus callosum 1431, 1484-1486, 1492-1495, Diencephalon 144, 540
1497-1509, 1511-1516, 1518, 1520, 1523- Direct and indirect pathways (loops) 783
1528, 1530-1547, 1550, 1552, 1554, 1555- Dissociation apraxia 1877
1564, 1567, 1568, 1571-1573, 1575 Dopamine-releasing neurons 769
Corpus callosum and attention 1541 Dorsal pons (pontine tegmentum) 214
Corpus callosum and its visuospatial aptitudes 1527 Dorsal surface of the pons 211
Corpus callosum and memory 1540 Dressing apraxia 1878
Corpus callosum and reading 1526 Dystonia 807
Corpus callosum and the emotional function 1542 E
Cortical areas 1632
Cortical areas controlling motor activity 1640 Efferent connections of the diencephalon 620
Cortical columns spots and stripes (microarchitec- Adenohypophysis 631
ture) 1619 Diencephalic periventricular system 621
Cortical connectivity 1614 Dorsal longitudinal fasciculus 622
Afferent connections 1614 Fasciculus mammillary princeps 620
Cortical language areas 1714 Fornix 621
Broca’s area 1715 Hypophysial portal system 634
Wernicke’s area 1714 Hypothalamocerebellar fibres 624
Cortical layers 1611 Hypothalamocortical fibres 624
iv
INDEX
Hypothalamoprefrontal fibres 624 Hitzig 62, 78-80, 82, 83, 85, 127, 129,1128,
Hypothalamospinal tract 623 1233
Hypothalamothalamic fibres 624 Frontal commissurotomy 1544
Mammillointerpeduncular tract 621 Frontal lobes 1122
Affect 1188
Mammillotegmental tract 621
Ambiguity and decision 1190
Mammillothalamic tract 620
Attention 1185
Medial forebrain bundle 622 Attention deficit / hyperactive disorder (ADHD)
Neurohypophysis 628 1218
Periventricular bundle 624 Autobiographical memory 1202
Pituitary gland 626 Broca’s aphasia 1144
Supraopticohypophysial tract 625 Brodmann’s area 8 1147
Tuberohypophysial tract 625 Cingulate motor cortex 1153
Efferent fibres from the medullary RF 392 Connections 1158
Corticostriatal connections 1158
Efferent projections (output) from the vestibular nu-
Cytoarchitecture 1156
clei 238
Depression 1188
Efferents from the cerebellum 471 Disorders due to lesions of the upper motor
Efferents from the RF 404 neurons 1134
Egyptian physician Imhotep 9 Disturbance in self-awareness 1219
Emotion and motivation function of the basal gan- Dorsolateral frontal syndrome 1211
glia 793 Dorsolateral prefrontal cortex (DLPFC) 1162
Encephalitis and the hippocampus 941 Dorsomedial prefrontal cortex 1163
Environmental accident 1790 Empathy 1198
Environmental deprivation 1790 Euphoria 1188
Executive control 1179
Epithalamus 542
Executive function, actions and plans 1176
Functions 544 Frontal lobe syndromes 1211
Habenular nuclei 542 Frontal-subcortical aphasias 1146
Posterior commissure 546 Function and localization within rostral pre-
Stria medullaris thalami 542 frontal cortex 1169
The pineal gland 542 Functional organization 1128
Extrastriate visual areas – outside of V1 1419 Hypokinesia 1189
Lesions in Broca’s area 1225
F Lesions in the frontal eye field 1226
Lesions in the motor cortex 1226
Loss of dexterity 1135
Facial nucleus and nerve (CN VII) 277
Medial prefrontal cortex 1169
Facial-oral apraxia 1878 Medial syndrome 1216
Fast synaptic subcortical control of hippocampal cir- Memory 1200
cuits 939 Memory of the future 1199
Ferrier 7, 62, 82-86, 93, 121, 127-129, 1057, 1697, Mental flexibility 1187
1729, 1732, 1776, 1900 Monitoring 1185
Figure-ground segmentation 1438 Motivation and cognitive control in the human
Complex forms 1438 prefrontal cortex 1175
Motor functions of somatosensory cortex 1154
Fissures, sulci, and gyri 1597
Neuropsychological functions of the prefrontal
Flourens 60, 79, 80, 127
cortex 1162
Forebrain 144, 1480, 1485, 1578, 1586, 1587, 1589, Novelty and routine 1199
1592, 1601, 1606, 1614, 1616, 1626, 1727, Orbitofrontal cortex 1165
1737, 1761, 1802, 1889, 1921, 1933, 1936 Orbitofrontal syndrome 1213
Fritsch and Hitzig 62, 78-80, 82, 83 Pathological hyperreflexia 1135
v
Planning 1193 Secondary neurons 1110

Precentral division 1125 Taste receptors 1103
Prefrontal cortex and intelligence 1206 Taste transduction 1107
Prefrontal division 1155 Thalamic neurons 1112
Prefrontal dysfunction 1209 The ascending gustatory path 1112
Premotor division 1138 Goltz, Friedrich L. 80
Pseudobulbar (spastic bulbar) palsy 1136
Response inhibition 1184 H
Reticulofrontal disconnection syndrome 1218
Retrieval 1201 High-order cognition and working memory 794
Rostro-caudal axis of PFC 1182 Hindbrain 1753, 1761
Social behavior 1206 Hippocampal commissure 1486
Source of memory 1201 Hippocampal connections 899
Spasticity 1135 Afferent fibres 899
Supplementary motor area (SMA) 1150 Efferent fibres 901
Temporal sequencing 1201 Hippocampal formation 883
Theory of mind: empathy 1196 Anatomy 883
Weakness 1136 Structure 886
Working memory 1203 Hippocampal sclerosis 942
Function of the corpus callosum 1504 Hippocampus and human diseases 940
Functional approach of the cerebellum 444 Histology of the cerebral cortex 1605
Functional areas of the cerebral cortex 1639 History of the brain and mind 1
Functional aspects of the cerebral cortex 1634 Human amygdala 1886
Functional cerebral organization of left-handers Human amygdala and fear 1020
1790 Human amygdala and memory 1024
Anatomical theories 1791 Human amygdala dysfunctions 1037
Genetic theories 1793 Human amygdala in Alzheimer’s disease 1045
Hormonal theories 1792 Human amygdala in autism 1040
Functional organization of extrastriate visual areas Human amygdala in schizophrenia 1044
1421 Human amygdala in social function 1033
Connectivity 1424 Huntington’s disease 806
Intrinsic circuitry 1428 Hyperkinetic disorders 804
Visual input 1425 Hypertonicity and dyskinesias 803
Functions of the RF 405 Hypokinetic disorders 810
Descending influences 405 Hypothalamic functions 638
Somatic motor function 405 Affective-emotional behavior control 683
Circadian regulation on metabolism 697
G Circadian regulation on sleep 698
Diabetes insipidus 677
GABA-releasing neurons 769 Disorder of water balance 676
Gall 56 Drinking and thirst 673
Phrenology 56 Essential hypernatremia syndrome 678
Galvani 54, 55, 56, 124, 139 Hypothalamic regulation of sleep 701
Globus pallidus 743 Hypothalamus, anorexia and emaciation 671
Glutamate-releasing neurons 768 Other hypothalamic functions 681
Gray and white matter 449 Regulating the circadian rhythm 689
Gustatory system 1103 Regulation of body temperature 657
Cortical neurons 1114 Regulation of hunger and the amount of food in-
Disorders of the gustatory system 1116 take 664
Extralingual taste buds 1107 Regulation of memory 688
Lingual taste buds 1105 Regulation of the autonomic nervous system and
Primary neurons 1109 of vegetative functions 650
vi
INDEX
The hypothalamic neurons participate in four re- I

flex classes 645
The hypothalamus and motivation 656 Ideational apraxia 1875
The hypothalamus and the obesity 668 Ideomotor apraxia (IMA) 1874
The parvocellular neurosecretory system 643 Implicit learning 504
Inferior colliculi 342
The regulation of the neuroendocrine system 639
Afferent connections 342
The reproduction function has a complex inte-
Efferent connections 343
gration 648 Inferior colliculus 265
The syndrome of increased release of antidi- Influence on the endocrine system 417
uretic hormone (ADH) and normal thirst 680 Inhibitory interneurons in the neocortex 1609
Hypothalamus 591 Innervation of the cranial dura mater 1763
Afferent pathways to the hypothalamus 614 Insula 1709
Amygdalohypothalamic tract 616 Connections 1711
Anterior hypothalamic nucleus 600 Functional aspects 1713
Arcuate (infundibular) nucleus 606 The insular cortex of the primates 1711
Cerebellohypothalamic fibres 617 Interhemispheric transfer of elaborate behavior 1542
Connections of the hypothalamus 613 Median fusion 1543
Interhemispheric transfer time 1544
Corticohypothalamic fibres 618
Interictal disorders 1395
Dorsal longitudinal fasciculus of Schütz 617
Internal capsule and corona radiata 1486
Dorsomedial nucleus 605 Internal structure of the pons 212
Extrinsic connections 614 Intracerebellar nuclei 452
Fibres from the reticular formation 617 Intrinsic circuitry of the hippocampal formation 902
Fornix 614 Introduction in the nervous system 141
Hypothalamic regions 593 Ischaemic damage to the hippocampus 942
Hypothalamic zones 608
Inferior mammillary peduncle 617 J
Interstitial nuclei of the anterior hypothalamus
600 Jackson, Hughlings 75, 77, 128, 129, 533, 1730,
Lateral hypothalamic nucleus 605 1828, 1908
Lateral zone 610
L
Local connections 613
Mammillary region 607 Lancisi 39, 40, 41, 112, 121, 126, 128, 129, 132
Medial forebrain bundle 618 Lateral lemniscus 264
Medial zone 610 Lateral organization 1597
Nuclei of the hypothalamic regions 594 Left parietal syndrome 1873
Pallidohypothalamic fibres 617 Leptomeninges and CSF space 1763
Periventricular zone 609 Lesions in the auditory association area 1395
Preoptic region 597 Lesions of the cortical vestibular area 1395
Retinosuprachiasmatic tract 616 Level of motor (pyramidal) decussation 160
Spinohypothalamic fibres 618 Dorsal column nuclei 160
Stria medullaris thalami 619 Other tracts 168
Spinal trigeminal nucleus and its tracts 166
Stria terminalis 616
Level of olive 172
Suprachiasmatic (supraoptic) region 599
Level of sensory (lemniscal) decussation 169
Thalamohypothalamic tract 616 Accessory cuneate nucleus 171
The paraventricular and supraoptic nuclei 601 Arcuate nuclei 171
Tuberal region 604 Area postrema 172
Ventrolateral preoptic nucleus 613 Cranial nerve nuclei 172
Ventromedial nucleus 605 Medial lemniscus 169
vii
Medial longitudinal fasciculus (MLF) 170 Membranous labyrinth 225

Levi-Montalcini 107-109, 124, 131, 1403 Mesencephalic dopaminergic cell groups 362
Limb kinetic apraxia 1876 Mesencephalic reticular formation 378, 398
Limbic functions 865 Mesencephalon 1485, 1930, 1941
Negative and positive reinforcement 870 Microstructure of the vestibular system 226
The limbic system and emotion 866 Midbrain (Mesencephalon) 143, 334, 1941
The limbic system and memory 870 Diencephalon 1942
Limbic lobe 843 Dorsal midbrain syndrome 1941
Limbic lobe and limbic system 843 Epithalamus 1946
Limbic loop pathway 780 Hypothalamus 1943
Limbic system 847 Thalamus 1944
Indusium griseum 863 Midbrain clinical correlates 370
Parts of the limbic system 849 Midcallosal section 1546
The alveus, fimbria, and fornix 858 Middle Ages 3, 24, 26, 101, 123
The cingulate gyrus and cingulum 855 Avicenna 3, 4, 25-31, 34, 121, 134, 135, 137,
The dorsal longitudinal fasciculus 863 138
The fasciola cinerea 865 Esmail Jorjani 26, 121, 137
The habenular nuclei 863 Mondino De’ Liuzzi 31, 124, 133
The hypothalamus 862 Rhazes 3, 26, 27, 29, 124, 135, 137-139
The locus ceruleus and dorsal raphe nucleus 862 Middle pons 283
The olfactory bulb 850 Monoaminergic system 401
The olfactory system 849 Morphological approach of the cerebellum 440
The septum 852 Mossy fibres 466
The thalamus 861 Motor skills 1796
The ventral tegmental area 863 Munk 81, 84, 86-89, 120, 134
Limbic system and hippocampus 1947 Musical perception 1862
Limbic system disorder 873 Myeloarchitectonics 1617
Localization and lateralization of language 1880
Locked-in syndrome 374 N
Loewi 100, 102-105, 107, 125, 126, 132
Ways by which neurons communicate 106 Neuroanatomy of vomiting 204
Longitudinal organization 1598 Neuroanatomy of yawning 203
Neurogenesis 937
M Neurons of the RF 386
Neuropeptide-releasing neurons 772
Mapping the human cortex 1627 Neurotransmitter systems 948
Marc Dax 64-66 Adenosine 949
Gustav Dax 65, 66, 127 GABAergic mechanisms 948
Marchiafava-Bignami disease 1563 Galanin 950
Mathematical aptitude 1796 NPY (neuropeptide Y) 949
Medial geniculate nucleus 266 Opiod 949
Medial longitudinal fasciculus (MLF) 317 Neurotransmitters of the basal ganglia 768
Medial tegmental syndrome 277 Neurotransmitters of the cerebral cortex 1630
Medulla and cardiovascular control 202 Noradrenergic and serotoninergic system 771
Medulla and respiratory functions 201 Nothnagel’s syndrome 373
Medulla and sneezing 203 Nuclear groups 345
Medulla and swallowing 202 Nuclei associated with the basal ganglia 751
Medulla oblongata (or bulb) 142, 156 Amygdaloid nucleus (amygdala) 751
External structure 156 Thalamic nuclei 751
Internal structure 158 The claustrum 751
Medullary (lateral) reticulospinal tract 408 Nuclei associated with the RF 404
Medullary reticular formation 175, 389 Nucleus accumbens 739
viii
INDEX
O Human volition 1270

Left and right parietal lobes compared 1298
Object recognition 1870 Lesions in the parietal association area of the
Occipital lobe 1409 nondominant hemisphere 1302
Oculomotor loop 780 Lesions in the superior longitudinal fasciculus
Olfactory system 1077 1303
Cortical neurons 1095 Lesions in other afferent fibres terminating in
Disorders of the olfactory system 1096 Broca’s or Wernicke’s areas 1303
Efferent olfactory connections 1096 Lesions in the primary somesthetic area 1300
Olfactory bulb – secondary olfactory neurons Lesions in the secondary somesthetic area 1300
1084 Lesions in the supramarginal and angular gyri of
Olfactory cortex projections 1095 the dominant hemisphere 1302
Olfactory receptors 1078 Lesions in the supramarginal gyrus 1301
Olfactory striae 1090 Lesions in the Wernicke’s and Broca’s area 1303
Olfactory tract 1089 Lesions in the Wernicke’s area 1302
Olfactory transduction 1082 Movement intention 1268
Thalamic neurons 1094 Neglect of one-half of the body 1291
Olivocerebellar fibres 461 Object recognition 1265
One-and-a-half syndrome 276 Primary somatosensory cortex 1256
Opiod peptide precursor mRNA and opiod receptor Somatosensory association cortices 1259
levels in Parkinson’s disease (PD) and Spatial attention 1295
levodopa-induced dyskinesia (LID) 772 Spatial information 1265
Orbitofrontal cortex 1888 Subdivisions of the parietal cortex 1258
Organization of the cells of the cortex 1624 Summar 1299
Organization of the cerebellum 439 Symptoms of posterior parietal damage 1283
Organization of the RF 386 Symptoms of right parietal lesions 1286
Other circuits of the basal ganglia 781 Tactile agnosia 1282
Afferent fibres 781 Tactile inattention 1289
Efferent fibres 781 The Gerstmann syndrome and other left parietal
Substantia nigra 781 symptoms 1290
The SI syndrome: astereognosis 1281
P Visual inattention 1289
Volition and consciousness 1278
Pacchioni 38, 40, 123, 134, 1766, 1773, 1774 Voluntary action and decision making 1273
Parietal lobe 1254 Voluntary action as conditioned responding
“Attention neurons” in the monkey parietal cor- 1277
tex 1288 Voluntary action as exploratory behavior 1276
Apraxia 1293 Voluntary action as goal-directedness 1277
Autotopagnosia 1292 Voluntary action as random behavioral noise
Balint’s syndrome 1284 1277
Body-part phantoms 1296 Parinaud’s syndrome 373
Brain circuits 1271 Parkinson’s disease 811
Clinical somatosensory disorders 1280 Pathophysiology of basal ganglia disorders (Clinical
Conclusions 1280 considerations) 802
Contralateral neglect (inattention) 1286 Patterns of organization within the sensory cortices:
Disorders of spatial cognition 1295 Brain modules 1432
Drawing 1294 Peduncular hallucinosis syndrome 375
Early gamma oscillations synchronize develop- Pedunculopontine nucleus 782
ing thalamus and cortex 1273 Perception 1797
Guidance of movement 1265 Periaqueductal grey matter 377
Gustatory cortex 1264 Pia mater 1770
High-order cortical representation 1263 Plus-minus lid syndrome 373
ix
Point-to-point representation on the cortex 1599 R

Pons 143, 210
Pontine (medial) reticulospinal tract 407 Red nucleus 351
Pontine reticular formation 394 Regulation of the hypothalamo-hypophysial axis
Pontocerebellar fibres 464 935
Postcallosotomy mutism 1523 Renaissance 3-5, 24, 31, 134, 135, 137
Posterior commissure 355 Gabriele Fallopio 35, 46
Giulio Casserio 35, 44
Posterior commissure 1485
Jacopo Berengario Da Carpi 32, 131
Praxic and graphometric activities 1534
Leonardo Da Vinci 4, 31, 32, 139
Prefrontal cortex 800
Vesalius 3, 4, 8, 31-35, 46, 122, 126, 134, 135,
Premotor cortex 1649 137, 139, 335, 384
Cortex of the frontal pole 1669 Respiration 414
Dorsolateral area 1668 Reticular formation 385
Dorsolateral prefrontal cortex 1661 Reticulocerebellar fibres 464
Frontal eye field 1654 Reticulospinal tracts 388
Inferior or orbital prefrontal cortex 1669 Role of the human amygdala in perception and
Medial prefrontal cortex 1669 attention 1027
Mirror system: ventral premotor and parietal Rostral pons 316
cortex 1666 Ventral portion of the pons 317
Motor speech region 1664
Posterior parietal motor area 1654 S
Prefrontal cortex 1668
Supplementary eye fields 1661 Saccule 230
Schizophrenia and the hippocampus 942
Supplementary motor area (SMA) 1652
Sections of the pons 272
The lateral prefrontal cortex 1668
Sensory areas of the cerebral cortex 1670
Ventrolateral prefrontal area 1668
Primary sensory areas 1670
Pretectal area 336 Primary somatosensory (somesthetic) cortex
Primary gustatory cortex 1721 (S I) 1670
Primary motor area 1641 Secondary somatosensory cortex (S II) 1676
Corticospinal tract 1645 Sensory-motor loop 776
Secondary motor cortex 1648 Sex differences in behavior 1795
Primary vestibular cortex 1681 Sex differences in cerebral organization 1795
Awareness of voluntary action and the parietal Sex differences in the brain structure 1797
cortex 1684 Anatomical studies 1804
Primary visual cortex (V1) 1417, 1685 Effects of hemispherectomy 1809
Output from the primary visual cortex 1690 Environment 1804
Preoccipital areas involved in following ocular Explanation of sex differences 1802
movements 1695 Genetic sex linkage 1803
Secondary visual cortex (V2) 1690 Handedness and the longevity 1807
Hormonal effects 1802
The fifth visual area (V5) 1695
Influence of sex hormones 1798
The fourth visual area (V4) 1692
Maturation rate 1803
The third visual area (V3) 1692
Ontogeny of asymmetry 1811
Procedural learning 505 Preferred cognitive mode 1804
Projections from the mesopontine tegmentum to the Sherrington 43, 93-99, 103, 118, 122, 124, 126, 131,
forebrain 419 136, 138, 171, 209, 221, 330, 376, 383,
Pseudocerebellar syndrome 1870 1938, 1957
Pupillary reflexes 364 The discovery of neurotransmitters 98
Pupillodilation 368 Somatic sensory function 412
Putamen 740 Somatosensory agnosias 1870
x
INDEX
Somatosensory symptoms of parietal-lobe lesions Entorhinal cortex 915

1868 Extrinsic connections 917
Somesthesis 1527 Functional role of the human hippocampus 921
Audition 1530 Intrinsic connections 912, 914
Movement 1532 Learning and memory 921
Olfaction 1531 Motor control 934
Transfer of motor information 1532 Perforant and alvear pathway projections 917
Sound reflex 272 Presubiculum and parasubiculum 914
Spatial analysis 1796 Presubiculum projections to layer III of the en-
Specificity of callosal fibres 1511 torhinal cortex 914
Acute disconnection syndrome 1514 Subicular efferents and afferents 912
Chronic disconnection syndrome 1515 Transmitters and receptors of the hippocampal
Language 1521 formation 920
The disconnection syndrome 1511 Substantia nigra 358, 750
The effects of complete disconnection 1513 Subthalamic nucleus 782
The effects of partial disconnection 1513 Afferent fibres 782
Transfer of sensorial information 1516 Efferent fibres 782
Visual effects 1516 Subthalamic nucleus (nucleus of Luys) 747
Speech perception 1344 Subthalamic pathway 767
Auditory awareness during sleep and sedation Subthalamus 586
1363 Forel’s field H (prerubral field) 589
Auditory imagery 1364 Subthalamic nucleus 587
Consonance 1358 Zona incerta 590
Decoding speech 1346 Superior cerebellar peduncle 318
Disorder of music perception 1358 Superior colliculi 337
Duration 1358 Afferent connections 340
History 1346 Efferent connections 338
Intensity 1354 Superior olivary nuclei 264
Introduction 1344 Supranuclear pathways for accommodation 367
Mapping of speech and speech perception in the Swedenborg 44, 45, 79, 121, 138
brain 1348 Syndrome of Benedikt 372
Music perception 1353 Syndrome of Weber 371
Pitch 1355 Syndromes after callosotomy 1544
Plasticity and reorganization of the auditory cor-
tex 1361 T
Speech as a gestural language 1348
Timbre 1354 Tectum 337
Sperry 109-116, 118, 119, 126, 128, 131, 133, 134, Tegmentum 344
137-139, 1506-1508, 1512, 1514-1516, Temporal lobe epilepsy 1390
1518, 1521, 1523, 1524, 1532-1535, 1540- Temporal lobes 1319
1542, 1555, 1557, 1559, 1569, 1579, 1580, Anatomy 1321
1581, 1584-1586, 1588, 1589, 1591, 1812, Temporal-lobe functions 1367
1902, 1912, 1923 Allocation of episodic memories 1374
Spinocerebellar and trigeminocerebellar fibres 457 Emotion, affect and personality 1369
Splenial section 1546 Facial recognition and biological motion 1377
Striatum 735 Klüver-Bucy syndrome 1370
Stroke of the corpus callosum 1561 Memory 1370
Subiculum 911 Memory allocation in neural circuits 1372
Associational connections 917 Organization and categorization 1368
Commissural connections 914, 917 Phonoagnosia 1379
Cytoarchitectonic organization 915 Spatial navigation 1376
Emotional behavior 934 Synaptic selection and memory allocation 1373
xi
Visual perception 1376 Hippocrates 1, 2, 8, 12, 15, 17-21, 24, 25, 27, 29,
Thalamocortical fibres 1614 42, 129, 130, 138
Thalamocortical relationship 1615 Plato 2, 8, 15, 16, 22, 25, 41, 127, 134, 135
Efferent connections 1616 The Golden Age of Greece 13
Thalamus 546 The Hellenistic Era 20
Anatomy 547 Tic disorder 808
Anterior nuclei and lateral dorsal nucleus 554 Top of the basilar syndrome 373
Borders 549 Tourette’s syndrome 809
Clinical considerations 584 Transfer of complex asymmetrically organized in-
Functions of the thalamus 582 formation 1537
Intralaminar nuclei 556 Tremor 804
Lateral and external medullary laminae 550 Trigeminal nerve (CN V) 283
Medial nuclei 559 Trigeminal neuralgia 315
Median nuclei 561 Trigeminal reflexes 311
Metathalamic nuclei 562 Trigeminal tracts 297
Neuronal circuitry 582 Tumors and degenerative diseases of corpus callo-
Nuclear groups of the thalamus 551 sum 1561
Posterior nuclear complex 566
Pulvinar nuclei and lateral posterior nucleus 566 U
Reticular nucleus 568
Ventral nuclei 570 Unconscious perception 1443
Unilateral apraxia 1537
The 4 generations of the Meckel family
Unilateral MLF lesion: internuclear ophthalmoplegia
Johann Friedrich Meckel The Elder 45
276
August Albrecht Meckel 52
Utricle 229
Johan Friedrich Meckel The Younger 50
Johann Heinrich Meckel Von Hemsbach 53
V
Philipp Friedrich Theodor Meckel 48
The clinic of the corpus callosum 1506
Ventral (basilar) pons 212
The Ebers Papyrus 11
Ventral and dorsal pathways 1440
The neural basis of consciousness 1928
Ventral surface and midtemporal cortical areas 1718
Patients and method 1929 Anomic aphasia 1720
Results 1931 Automatisms 1719
The superior temporal sulcus and biological motion Hallucinations 1718
1379 Illusions 1718
Theories of cerebellar function 500 Ventral surface of the pons 210
Theories of hand preference 1787 Ventricular system and meninges 1748
Culture and language 1788 Anterior wall 1751
Environmental theories 1787 Aqueduct of Sylvius 1753
Sensory or environmental deficits 1789 Cavum trigeminale 1762
The left hemisphere 1884 Composition of CSF 1758
The right hemisphere 1882 Cranial dura mater 1760
There is an inverted U-shape function between the CSF absorption 1757
level of stress and memory 936 CSF function 1758
Three faces of Greece and Hippocrates 12 Diaphragma sella 1762
Alcmaeon of Croton 14 Emissary veins 1763
Aristotle 2, 4, 8, 14, 17, 22-24, 31, 37, 42, 43, Falx cerebelli 1762
121, 138 Falx cerebri 1761
Early Greece 12 Floor 1752
Galen 3, 4, 8, 20, 21, 23-27, 30, 31-34, 37, 42, Floor of the fourth ventricle 1754
121, 128, 129, 132, 135, 137, 138, 140, 544, Fourth ventricle 1753
546 Frontal horn 1749
xii
INDEX
Lamina terminalis 1751 W

Lateral ventricle 1749
Lateral wall 1753 Walleyed syndrome 374
Meninges 1759 Wepfer, Johann Jakob 36, 44
Posterior wall 1752 Wernicke 6, 71-75, 77, 89, 120, 132, 140, 269, 585,
Production of the cerebrospinal fluid (CSF) 1756 660, 1210, 1226, 1302, 1303, 1328, 1330,
Reflections of the meningeal layer of the dura 1333, 1340, 1342, 1349, 1351-1353, 1359,
mater 1760 1379, 1385, 1386, 1407, 1410, 1482, 1506,
Roof 1751 1551, 1553, 1568, 1590, 1615, 1638, 1639,
Roof of the fourth ventricle 1755 1657, 1680, 1704, 1705, 1708, 1714-1717,
Sinus pericranii 1763 1784, 1804, 1821-1824, 1826, 1828, 1864,
Tanycites 1758 1877, 1909, 1926
Tentorium cerebelli 1761 White matter of cerebral hemisphere 1480
The body or the central portion 1749 Association fibres 148
The choroid plexus 1750 Cingulum 1481
The inferior (temporal) horn 1750 Commissural fibres 1484
The posterior (occipital) horn 1749 Corticofugal fibres 1484
Third ventricle 1750 Corticopetal fibres 1483
Vascular and nerve supply 1762 Inferior longitudinal fasciculus 1482
Verbal ability 1797 Long arcuate fibres 1481
Vertical gaze 369 Projection fibres 1482
Vertical one-and-a-half syndrome 374 Short arcuate fibres 1481
Very pre-term infants 525 Superior fronto-occipital fasciculus (subcalosal
Vesalius 1504, 1766, 1775 bundle) 1482
De humani corporis fabrica 1590, 1775 Superior longitudinal fasciculus 1482
Vesling, Johann 36, 44, 46 The external capsule 1482
Vestibular apparatus 224 Uncinate fasciculus 1481
Vestibular nerve and nuclei 231 White matter of the cerebral hemispheres 153
Vestibular nuclear complex 233 Willis 5, 35, 41-47, 55, 94, 119, 124-126, 130, 132-
Vestibular system 223 135, 138-140, 306-309, 332, 530, 538, 678,
Vestibulocerebellar fibres 463 730
Vestibulocochlear nuclei and nerve 231 Wilson’s disease (hepatolenticular degeneration)
Visual attention 1445 821
Visual consciousness 1443 Written words and dyslexia 1439
Visual field topography 1412
Anatomy 1414 Z
Cytoarchitecture 1415
Visual pathways 1409 Zones of the RF 402
Volta 55, 56, 139
xiii

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LEON DĂNĂILĂ

GABRIEL ANDRAL ...................................................................................................................63

Cranial nerve nuclei ................................................................................................................172

Caudal pons ............................................................................................................................272

Vertical one-and-a-half syndrome ...........................................................................................374

Gray and white matter .............................................................................................................449

Retinosuprachiasmatic tract ....................................................................................................616

Essential hypernatremia syndrome ......................................................................................678

Efferent fibres (output) .........................................................................................................764

Extralingual taste buds ..........................................................................................................1107

Voluntary action as goal-directedness ..................................................................................1277

Functional studies in humans ................................................................................................1331

The superior temporal sulcus and biological motion .............................................................1379

Cue invariance ......................................................................................................................1438

Corticofugal fibres ..................................................................................................................1484

Interhemispheric transfer time ...............................................................................................1544

PREMOTOR CORTEX ..........................................................................................................1649

Facial-oral apraxia .................................................................................................................1878

Fig. 18.1. The circuitry

Pretectal neurons, in turn, project to the Edinger-Westphal nucleus, a small group

sensitive photopigment (melanopsin) and are capable of modulating their response to

Visual field topography

Fig. 18.3. Medical view of the occipital

Fig. 18.4. Topography of the visual cortex of the macaque

Fig. 18.5. Tomography of the human visual cortex. (A) A

Fig. 18.6. The visual cortex is highly laminated, as can be

This band of myelinated axons running horizontally in layer 4B demarcates the

Another surprising feature of area V1 is that, although it appears to be anatomically

Extrastriate visual areas – outside of V1

An example of the advantage of color vision can be seen in the type of

The functional organization of extrastriate visual areas

Alternate connectivity schemes based on the strength of response correlation among

Patterns of organization within the sensory cortices: Brain modules

Fig. 18.12. Examples of iterated, modular substructures in the

The columnar organization of the striate cortex

Written words and dyslexia

Depth and the analysis of space

Visual information allows us to direct our movements to objects in space and to

The ventral and dorsal pathways

2) These posterior parietal neurons can therefore be characterized as an interface

temporal sulcus. The superior temporal sulcus is characterized by polysensory neurons-

colliculus, which is known to play a role in orienting to visual information; so it may be

CLINICAL EFFECTS AND SYMPTOMS

Visual field defects

Fig. 18.15. A 56-years-old female patient

The traditional way to classify visual-object agnosia is to distinguish two broad

The clinical picture. Prosopagnosia refers to an impairment in familiar face

Visual object agnosia

Disorder of color processing

Other visuospatial anomalies

Cortical blindness and Anton’s syndrome

Defects in constructional skills

The mechanisms whereby a patient manifests defects in constructional abilities may

Visual illusions (metamorphopsias)

Visualization is crucial in problem-solving tasks such as mental arithmetic, map

Lesions in the association with visual areas

Wolpert J, Die Simultanagnosie-Storung der Gesamtauffassung. Z Gesamte Neurol Psychiatr 93;

Fig. 19.2. A coronal section of