Barker Revision Notes

Key point summaries
Part 1: Anatomical and functional organization
1. Development of the nervous system

The nervous system develops early in embryogenesis with the formation of the
neural plate.
The folding and subsequent development of the neural tube is tightly regulated
and forms the mature central nervous system (CNS).
The neural crest that is formed during this process gives rise to a number of
structures including the dorsal root ganglia as well as parts of the autonomic
nervous system (ANS).
Neurogenesis continues throughout life at certain sites in the adult brain.
2. Organization of the nervous system

There are a number of different components to the nervous system, including the
central, peripheral, autonomic and enteric nervous systems.
The autonomic nervous system comprises the sympathetic and parasympathetic
nervous systems.
The brain consists of a frontal, temporal, parietal and occipital lobe, along with a
range of subcortical structures, the brainstem and cerebellum.
The brainstem consists of the midbrain, pons and medulla.
The CNS is enclosed by a series of membranes called the meninges.
The spinal cord is divided into cervical, thoracic, lumbar and sacral parts, which
innervate the arm, trunk, legs as well as urogenital areas.
3. Autonomic nervous system (ANS)

The ANS consists of the, enteric (see Chapter 4) sympathetic and
parasympathetic nervous systems.
It is intimately related to and regulated by the hypothalamus.
The ANS has a vital role in controlling a large number of internal organs.
Abnormalities of the ANS can be focal or generalized.
Neuroanatomy and Neuroscience at a Glance, Fourth Edition. Roger A. Barker, Francesca Cicchetti, Michael J. Neal.
2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.
4. Enteric nervous system
The enteric nervous system is a complex integrated network of neurones in the
wall of the gut.
It is made up of Meissners and Auerbachs plexuses and interneurones.
It regulates the local activity of the gut, especially in the large and small bowel,
and in turn it is controlled by the ANS.
5. Meninges and cerebrospinal fluid

The meninges are made up of three distinct structures: the dura, the arachnoid
and the pia mater.
These structures help protect the brain and spinal cord and contain within them
the cerebrospinal fluid (CSF).
The brain is separated from the circulation by a blood--brain barrier (BBB) that
also protects the CNS from circulatory factors and gives it relative immunological
privilege.
The CSF is formed continuously by the choroid plexus and absorbed through the
arachnoid villi and abnormalities of the flow of this fluid can result in
hydrocephalus.
The most common disease process affecting the meninges is infection.
6. Blood supply of the central nervous system

The blood supply to the brain comes from the carotid and vertebral arteries.
At the base of the brain, the arteries form the circle of Willis, which can enable
cerebral perfusion to be preserved in some instances of arterial occlusion
The carotid arteries form the anterior circulation to the brain, whereas the
vertebral arteries merge to become the basilar artery (so called vertebrobasilar
system), which constitutes the posterior circulation.
Abnormalities of blood flow in the carotid arteries typically cause problems in the
cerebral hemisphere and subcortical structures.
Abnormalities of blood flow in the vertebral arteries cause problems in the
brainstem, cerebellum and posterior parts of the brain.
The commonest causes of blood flow problems in the brain are due to either
atherosclerosis and local thrombus formation or emboli.
7. Cranial nerves
There are 12 pairs of cranial nerves.
Two cranial nerves (the olfactory and optic nerves) do not originate in the
brainstem.
These nerves are responsible for conveying all the special senses to the brain as
well as sensation from the face, motor input to the eyes, face, mouth, pharynx
and some of the neck; in addition they also carry the local autonomic innervation
to the head.
Abnormalities of cranial nerves can be helpful in the accurate localization and
diagnosis of neurological problems affecting the brainstem.
8. Anatomy of the brainstem

The brainstem is made up of the midbrain, pons and medulla.
The midbrain contains structures important in the control of eye and body
movements and includes the third, fourth and part of the fifth cranial nerve nuclei.
The pons is important in relaying information to and from the cerebellum and in
some aspects of eye movement control and locomotion. It contains the sixth,
seventh and part of the fifth and eighth cranial nerve nuclei.
The medulla houses structures vital to respiration, cardiovascular stability and
movement, and contains the ninth, tenth, eleventh and twelfth cranial nerve
nuclei.
Lesions of the brainstem often give characteristic clinical syndromes and as such
when they present they can often be diagnosed with great anatomical accuracy.
Widespread damage to the brainstem is incompatible with life.
9. Organization of the spinal cord

The spinal cord is highly organized with ascending sensory pathways,
descending motor tracts, motor neurones that innervate muscles and
interneurones that modulate both sensory and motor information.
The cervical spinal cord innervates the arm and the lumbar spinal region, the leg.
Sensory information passes up the dorsal column system, which carries
information ipsilaterally on light touch and proprioception before the path
decussates in the brainstem.
Sensory information on pain and temperature is relayed by the
anterolateral/spinothalamic system and decussates around the level of entry of
the synapsing sensory fibres in the spinal cord.
There are a number of descending motor tracts. The corticospinal tract is most
involved with fine distal motor control.
Knowledge of the anatomy of the spinal cord can help localize lesions accurately.
10. Organization of the cerebral cortex and thalamus

The cerebral cortex is organized into six layers, the thickness of which varies
according to the functional role of that cortical area.
Sensory cortical areas have a large layer IV.
Motor cortical areas have a large layer V.
The cortex is organized into columns that relate to each other, which can best be
modelled in a distributed systems fashion.
The thalamus is made up of discrete nuclei that are important in relaying
information to and from the cortex.
11. Hypothalamus
The hypothalamus consists of a large number of nuclei that perform many
complex functions.
The hypothalamus is important in the regulation and coordination of a large
number of vital bodily functions, which involve the ANS and the endocrine
system.
It also has a role in the coordination of circadian rhythms and memory and in
regulating temperature control, satiety and thirst.
Damage to this small structure can have wide-ranging effects.
Part 2: Cells and neurophysiology
12. Cells of the nervous system I: neurones

The nervous system is made of neurones and glia, which are different in the
central and peripheral nervous systems.
The neurones consist of a cell body with a single axon that conveys action
potentials away from the cell body.
The axon then synapses on another cell, typically the dendrite of another
neurone.
The dendrites receive many synapses and relay the information to the cell body
where the information is integrated and translated into action potentials that
originate at the axon hillock.
13. Cells of the nervous system II: neuroglial cells

The CNS glia consist of astrocytes, oligodendrocytes, microglia and ependymal
cells, while in the peripheral nervous system the only glial cells are the Schwann
cells.
The astrocytes fulfil a number of functions, including a major homeostatic role in
the CNS.
The oligodendrocytes are important in myelinating axons in the CNS.
Microglia cells are derived from the reticulo-endothelial system and have a role in
the innate immune response.
14. Ion channels

Ion channels are protein complexes that span membranes and imbue cells with
excitability, and many different types exist in the mammalian nervous system.
The channels can either be opened by voltage changes or chemical substances.
On activation the channel opens and allows ions to flow through it, and the
selectivity of the channel for ions determines whether it either depolarizes or
hyperpolarizes the membrane.
The ion channel once opened either directly closes or goes through a series of
inactivation stages.
15. Resting membrane and action potential

The resting membrane potential is largely a function of the relative impermeability
of the membrane especially to sodium ions compared with potassium.
The resting membrane potential is therefore largely determined by the equilibrium
potential for potassium.
In contrast the peak of the action potential is largely determined by the
equilibrium potential for sodium.
Action potentials are an all or nothing phenomena.
The action potential once generated is followed by a refractory period, which is a
function of sodium channel inactivation and the delayed opening of voltage
dependent potassium channels.
16. Neuromuscular junction and synapses

Neurones communicate via synapses.
Synapses can be either electrical or chemical in nature.
Chemical synapses are the predominant type found in the CNS.
Chemical synapses have a presynaptic element that causes quantal
neurotransmitter release which is calcium dependent.
Neurotransmitters act via specific receptors.
Neurotransmitters are inactivated at the synapse by enzymic degradation or
selective uptake mechanisms.
17. Nerve conduction and synaptic integration

Nerve conduction is different in myelinated and unmyelinated nerves.
In myelinated nerves the action potential is generated at each node of Ranvier
leading to saltatory conduction, which allows for larger nerve cells to conduct
information accurately and efficiently over long distances.
The action potential on reaching the synapse leads to the release of
neurotransmitter(s) which can then bind to specific receptors in the pre- and/or
postsynaptic membrane.
This binding then causes a change in membrane potential that can be either
excitatory or inhibitory.
These synaptic inputs are then integrated by the postsynaptic cell over time
(temporal summation) and space (spatial summation) and the final integrated
signal coded by action potential generation at the axon hillock of the postsynaptic
neurone.
18. Neurotransmitters, receptors and their pathways

Many different types of neurotransmitter are used in the nervous system.
These neurotransmitters work by binding to specific receptors which then cause
changes in membrane excitability either directly or indirectly.
The receptors have a sensitivity that is modulated by the degree to which they
are exposed to the neurotransmitter such that they become desensitized if
constantly exposed to that transmitter, while the converse is true when there is
little activation of the receptor by the neurotransmitter.
The main excitatory neurotransmitter of the CNS is glutamate while the major
inhibitory one is -aminobutyric acid (GABA).
Abnormalities of certain neurotransmitter systems are associated with some

diseases, most notably dopamine in Parkinsons disease and schizophrenia.
19. Main CNS neurotransmitters and their function

The major excitatory neurotransmitter in the CNS is glutamate and the major
inhibitory one, GABA.
A number of diffusely projecting transmitter systems originating from the
brainstem and regulate several important functions within the CNS.
No one transmitter is associated with a single disease entity, however, some
diseases have abnormalities predominantly in one transmitter system.
20. Skeletal muscle structure

Striated muscle is a highly organized structure made up of thick and thin
filaments.
Thick filaments contain myosin.
Thin filaments contain actin and the regulatory proteins controlling muscle
contraction.
The two filaments bind in muscle contraction in response to local calcium release.
Disorders of structural proteins within the muscle typically underlie inherited
muscular dystrophies.
21. Skeletal muscle contraction

Skeletal muscle contraction relies on crossbridge formation between thick and
thin filaments.
This process involves the movement of the blocking tropomyosin on the thin
filament in response to a calcium influx from the sarcoplasmic reticulum (SR).
The calcium release from the SR occurs when the nicotinic acetylcholine receptor
(AChR) are activated at the neuromuscular junction by the release of ACh from
the innervating motor neurone.
The crossbridge once formed then pulls the filaments passed each other, and at
the end of this power stroke the crossbridge is broken by adenosine triphosphate
(ATP) hydrolysis.
The whole process is known as the sliding filament hypothesis.
Part 3: Sensory systems
22. Sensory systems: an overview

Sensory systems convey information from receptors to the CNS by transducing
that sensory stimulus into an electrical signal.
The transduced sensory stimulus then codes for the intensity, location and
modality of that stimulus and sends that information via a unique route into the
CNS, where it makes specific connections.
The signal is refined by a number of processes to ensure that its fidelity is
improved and that contrast is maintained as sensory systems are more interested
in changing sensory stimuli than continuous ones.
23. Sensory transduction

Sensory transduction involves converting the incident energy of the sensory
stimulus into an electrical code for transmission to the CNS.
Sensory transduction can be either a chemical or mechanical process.
All sensory receptors (with the exception of nociceptors) are more sensitive to
changes in sensory stimuli than their continued presence and as such can adapt.
Adaptation is the resetting of the sensitivity of the receptor in the presence of a
continuous sensory stimulus.
24. Visual system I: the eye and retina

The retina is a highly organized neural network and transmits highly processed
information to the CNS.
It has two main types of photoreceptor: rods, which are responsible for night
vision and found in greater numbers in the periphery of the retina, while the
cones, which are responsible for daytime vision, are found more at the fovea.
The fovea is the area of the retina that has the highest acuity and is used for all
targeted visual tasks.
There is a vertical organization of the retina that involves information passing
from the photoreceptors to the bipolar cells and ganglion cells, the axons from
which form the optic nerve. They convey information about the visual scene
including acuity and colour.
Two sets of cells integrate across this vertical series of cells: the horizontal and
amacrine cells. They generate the centre-surround receptive fields of the bipolar
and ganglion cells, which is important in visual discrimination functions. The
amacrine cells code for a range of complex stimuli.
The output of the retina in the optic nerve is highly organized.
25. Visual system II: the visual pathways and subcortical

visual areas
The retina projects to several different CNS sites.
The retinal projection to the thalamus and to cortical areas is important in visual
perception and the use of visual stimuli for motor/behavioural responses.
The retinal projection to the midbrain controls pupillary responses.
The retinal projection to the superior colliculus is important in orienting
responses.
The retinal projection to the suprachiasmatic nucleus of the hypothalamus is
important in the light entrainment of circadian rhythms.
26. Visual system III: visual cortical areas

The visual cortex is highly organized and processes information in two
complementary ways.
One involves serial processing and is best described by the Hubel and Wiesel
model.
The other is parallel processing that involves P and M channels for pattern and
motion detection, respectively.
The primary visual cortex is important for visual perception.
The extrastriate areas tend to perform specialized visual functions and work with
V1 in visual perception.
27. Auditory system I: the ear and cochlea
Sound is characterized by a number of different properties including loudness,
frequency and timbre among other qualities. Many of these properties are coded
for in the ear, with sound localization being more a property of the CNS
processing of the sound from both ears.
Sound enters the external ear and then passes across the small bones of the
middle ear before being converted into electrical codes in the cochlea of the inner
ear.
Problems with hearing due to abnormalities in the external and middle ear causes
conductive deafness; problems within the inner ear or the eighth cranial nerve
conveying that information to the brain causes a sensorineural deafness.
The mechanotransduction of the sound into an electrical code occurs in the organ
of Corti of the cochlea and is mediated by hair cells, of which there are two main
types (inner and outer).
Frequency coding is done along the cochlea while loudness is determined by the
number of receptors activated.
28. Auditory system II: the auditory pathways and

language
The auditory pathways are bilateral from the moment the information from the
vestibulocochlear nerve enters the brainstem.
Sound localization is a function of binaural inputs into the brainstem nuclei.
The primary auditory cortex is found in the superior temporal sulcus and is
important in many aspects of sound perception.
Language is typically located in the dominant left hemisphere.
Dysphasia indicates problems with language while dysarthria means problems
with speech articulation.
Abnormalities of language vary depend on the site of pathology.
29. Vestibular system

The vestibular apparatus is located in the inner ear and consists of the otolith
organs and semicircular canals.
It conveys information on head position and movement to the brain via the eighth
cranial nerve.
It projects into the vestibular nucleus which has multiple projections to other CNS
sites.
It is important in balance, gait and eye movement control.
Most disorders of the vestibular system are benign and affect the peripheral
vestibular apparatus.
30. Olfaction and taste

Olfactory transduction is a chemically mediated process in specific receptors
which then transmit that information directly to the olfactory bulb via the first
cranial nerve.
Processing of olfactory information in the olfactory bulb is complex, and the
information is then conveyed via the olfactory tract to a number of CNS sites
including structures in the temporal lobe.
Taste is mediated via a number of different receptor types, which then relay that
information via the seventh, ninth and tenth cranial nerves to structures in the
brainstem and from there to a number of CNS sites.
31. Somatosensory system

The skin is innervated by a range of different sensory receptors that can be
functionally classified in terms of the size of their receptive field and speed of
adaptation.
These receptors have their cell bodies in the dorsal root ganglia and project to
the brain via a number of pathways but most notably the dorsal columns.
The ascending pathway is organized in a somatotopic fashion and this is
maintained to the cortical level.
The sensory information passing up the dorsal columns synapses in the dorsal
column nuclei and from there the system projects to the thalamus as the medial
lemniscus.
The cortical areas involved in sensory perception are in the parietal lobe.
32. Pain systems I: nociceptors and nociceptive pathways

Nociception is different from pain.
Nociception involves tissue damaging stimuli and is subserved by its own
network of receptors and distinct centrally projecting pathways.
This pathway involves a synapse in the dorsal horn where gating of nociceptive
information can occur including an input from the brain by descending pathways.
The nociceptive pathways then cross in the spinal cord and project to a number
of CNS sites.
Nociceptors do not adapt; in the face of continuous stimulation, they can induce
changes within the CNS leading to chronic pain syndromes.
33. Pain systems II: pharmacology and management

Several different points on the nociceptive pathways are amenable to therapeutic
intervention; most of these are found in the dorsal horn, where the nociceptive
receptors first synapse.
The mainstay of therapy for pain management involves different drugs and nerve
stimulation; however, surgery has little role to play.
The best management of pain involves a multidisciplinary team.
34. Association cortices: posterior parietal and prefrontal

cortex
Association cortices correspond to those areas of cortex that do not have a
primary motor or sensory function and encompass the posterior parietal, frontal
and temporal lobes.
Damage to the posterior parietal cortex causes problems of neglect, dyspraxia
and constructional/route finding abilities.
Damage to the prefrontal cortex causes a change in personality with deficits in
attention, behaviour and taste.
Part 4: Motor systems
35. Organization of the motor systems

The motor systems can best be thought of in terms of different levels each of
which has a particular function.
These levels relate to each other to control movement going from the highest
level which involves planning movements to the lowest level that involves their
actual execution.
Damage at these different levels produces specific patterns of motor deficits
clinically.
This hierarchical ordering of motor control is a convenient model system for
understanding how different parts of the nervous system control movement, but it
is only one way by which to model this system.
36. Muscle spindle and lower motor neurone

The lower motor neurone is the nerve cell that has its cell body in the ventral horn
of the spinal cord and brainstem and directly innervates the muscles.
Lesions of the lower motor neurone cause a classical combination of features
including wasting, weakness, areflexia and fasciculations.
The muscle spindle is a highly organized structure that provides vital dynamic
and static information to the CNS on the state of the muscle and its degree of
contraction.
The monosynaptic stretch reflex involves an afferent Ia input from the spindle and
an excitatory output to the synergistic muscles and an inhibitory one to antagonist
muscles.
The Golgi tendon organ is important in reflexes as it prevents overstretching of
the muscles.
37. Spinal cord motor organization and locomotion

There are two main groups of descending motor pathways, the lateral and
ventromedial, which innervate the proximal and distal musculature, respectively.
The spinal cord contains central pattern generators, which are involved in
locomotion and are defined by the fact that they produce a patterned output in the
absence of any input.
The locomotive cycle has both a stance and swing phase and it can be
modulated by supraspinal and peripheral inputs.
Upper motor neurone lesions are characterized by increased tone, increased
reflexes, clonus and extensor plantars with a pattern of weakness that affects the
extensors more in the upper limb and flexor muscles in the lower limb.
38. Cortical motor areas

There are a number of different motor cortical areas which sit just in front of the
central sulcus with a major extension along the medial border of the frontal lobe.
The different motor cortical areas all have slightly different functions.
The more anterior cortical motor areas are involved to a greater extent with
planning movements while the more caudal ones have a greater role in
movement execution.
39. Primary motor cortex

The primary motor cortex sits just anterior to the central sulcus and corresponds
to Brodmann area 4.
There is tight input--output coupling in the motor cortex so that sensory
information can be used to modify fine movements.
The primary motor cortex provides a major descending influence to the brainstem
and spinal cord.
40. Cerebellum
The cerebellum can best be thought of as a series of parallel systems that control
different parts of the body.
The cerebellum has a fundamental role in coordinating movements.
It has a very clear repetitive structure and is a site of plasticity and motor
learning.
Damage to the cerebellum is not uncommon and can cause devastating
problems of balance with eye and speech abnormalities.
41. Basal ganglia: anatomy and physiology

The basal ganglia are made up of a collection of subcortical structures including:
caudate nucleus; putamen; globus pallidum; subthalamic nucleus and substantia
nigra.
Abnormalities in the basal ganglia classically cause problems of movement which
are collectively called extrapyramidal disorders.
It is now increasingly recognized that the basal ganglia subserve a number of
non-motor functions, including cognitive processes and a role in motivation.
42. Basal ganglia diseases and their treatment

A number of diseases specifically target the basal ganglia, of which the
commonest is Parkinsons disease (PD).
The movement disorders of the basal ganglia are often described as being hypo-
or hyper-kinetic and their pathogenesis can be predicted by understanding the
internal organization of the basal ganglia.
A number of drug therapies for treating Parkinsons disease mainly work to
restore the dopaminergic nigrostriatal pathway back to normal.
A number of drugs can help some aspects of Huntingtons disease, but they are
less effective than those currently available for PD.
Part 5: Consciousness and higher brain function
43. Reticular formation and sleep

The sleepwake cycle is tightly controlled by a number of CNS structures and
thus it is not uncommon for it to become disrupted in a range of illnesses.
Disorders of sleep are common and best diagnosed in a specialist sleep clinic
with formal polysomnography, including electroencephalography (EEG).
The EEG follows a distinct pattern of changes as animals move from wakefulness
through the different stages of sleep.
A range of drugs are now available to treat problems of sleep and daytime
somnolence although some can cause problems of tolerance and withdrawal
symptoms.
44. Consciousness and theory of mind

Consciousness is dependent on a number of CNS structures, including brainstem
and thalamic projections to the cortex.
Major injuries to the CNS can cause permanent states of reduced consciousness
vegetative state and minimally conscious state. These have to be distinguished
from the states in which patients are conscious but cannot respond because of a
major abnormality in their motor system (locked-in syndrome).
Theory of mind describes the capacity of individuals to understand the actions
and thoughts of others, involves the frontal lobe and is abnormal in conditions
such as autism. It is thought to be a function of the prefrontal cortex.
45. Limbic system and long-term potentiation

There are many different definitions of the limbic system.
In this chapter we have defined the limbic system as a collection of structures
that lie along the medial part of the temporal lobe.
The limbic system is important in memory and emotion.
The hippocampus has a well-described process of long-term potentiation, which
may underlie memory acquisition and storage.
Damage to the hippocampus is common and often leads to temporal lobe
epilepsy.
46. Memory
Memory covers a range of different cognitive and memory functions, and it is
important to define the different types of memory as they have different
anatomical sites.
Motor (implicit) memories are largely stored in the cerebellum.
Memory for episodes, events (explicit memory) are separate from the memory for
facts -- all of which are stored in the temporal lobes.
Working memory involves mainly frontostriatal circuitry.
Patients typically complain of memory deficits when they have any type of
cognitive problem.
47. Emotion, motivation and drug addiction

Emotional processing of stimuli is mainly performed by the amygdala.
Motivation is a function of the dopaminergic system, especially the ventral
tegmental area and its projection to the nucleus accumbens.
Drug addiction is complex and is different with different drugs, but often involves
the mesolimbic dopaminergic systems.
48. Neural plasticity and neurotrophic factors I: the

peripheral nervous system
The peripheral nervous system has a high degree of regenerative capacity.
The peripheral glia (Schwann cells) are important in nerve regeneration.
Many peripheral sensory nerves are dependent on neurotrophic factors for their
genesis and survival.
49. Neural plasticity and neurotrophic factors II: the central
nervous system
Plasticity of the CNS occurs throughout life but gets less as one gets older.
Plasticity ensures that sensory inputs create an appropriate CNS map by which
to optimally process that sensory information, and abnormalities of sensory inputs
early in life can cause long-term damage (e.g., amblyopia).
In adulthood, maladaptive plasticity may underlie some forms of dystonia and
chronic pain.
It is now known that in the adult mammalian CNS, new neurones are generated
in two main sites (the subventricular zone and dentate gyrus of the
hippocampus).
Part 6: Applied neurobiology: the principles of

neurology and psychiatry
50. Approach to the patient with neurological problems

The initial part of any neurological assessment involves a careful history, which
can be clarified by asking direct questions once the nature of the problem has
been described.
The history then guides the examination, following which a clear differential
diagnosis should be drawn up, bearing in mind that common things are common!
A history of rapidly evolving symptoms is often a feature of a major neurological
problem.
The commonest neurological problems that present to clinic are chronic
headaches, dizziness and sensory symptoms, and in most cases the cause for
these symptoms is benign.
51. Examination of the nervous system

The examination of the nervous system should be done in a structured way.
The best way to elicit clinical signs is through repeated practice of the
neurological examination.
The neurological signs elicited should be understood in the context of the history,
and a clear differential diagnosis drawn up at the end of the examination.
The history and examination should form a coherent whole; if not, a multifocal
disease process should be considered.
52. Investigation of the nervous system

The investigation is determined by the differential diagnosis.
The initial investigations should be the simplest and least invasive, but also the
most relevant to the presenting problem.
More invasive investigations should only be done after careful consideration and
when the results from the simpler tests are available.
All investigation results should be viewed in the context of the history and
examination, to make sure they are all form a coherent story.
53. Imaging of the central nervous system

There are many different ways to image the CNS, and the modality chosen
depends on what part of the neuro-axis needs imaging and what is being looked
for.
The commonest and most widely available scanning involves magnetic
resonance imaging (MRI), which can now be used to image most lesions in the
CNS.
Functional scanning is still largely reserved for research purposes or as a
presurgical assessment in patients having resective brain surgery.
54. Clinical disorders of the sensory systems

Clinical disorders of the sensory system can either present with positive
symptoms such as paraesthesiae or negative symptoms such as numbness.
Sensory abnormalities arise from both central and peripheral pathological
processes, and the distribution and type of sensory loss helps decide where the
lesion is most likely to be found.
A glove and stocking loss of sensation is typical of a peripheral neuropathy.
55. Clinical disorders of the motor system

Motor abnormalities can be defined in terms of problems of power and/or
coordination.
Power abnormalities can be due to lesions of the upper or lower motor neurones,
as well as at the neuromuscular junction or in the muscle itself.
Coordination problems arise when there are major sensory deficits, profound
weakness, or cerebellar problems.
56. Eye movements

Eye movement control involves a large number of CNS structures.
The brainstem has an intricate network of structures that accurately control eye
movements including gaze.
There is a major input to the brainstem eye movement motor machinery from the
cortex and basal ganglia.
Abnormalities of eye movements can lead to very accurate diagnoses, given
what is known about their CNS control.
57. Neurochemical disorders I: affective disorders

Affective disorders are common and can take the form of depression or a bipolar
disorder.
Depression can be endogenous or a response to circumstance (reactive).
The genetic basis of these disorders is being better described, and plays more of
a role in bipolar patients.
Affective disorders not only cause abnormalities of mood, but also disruptions of
basic biological functions such as sleep, eating and sexual drive.
There are many different effective approaches and drugs to treat patients with
affective disorders, the choice of which is dependent in part on the type of
depression being experienced.
58. Neurochemical disorders II: schizophrenia

Schizophrenia is a common psychiatric disorder that typically presents in late
adolescence/early adulthood.
It is characterized by a typical combination of symptoms, and patients often have
subtle motor signs and cognitive deficits, which in some cases become more
prominent as the disease enters a chronic phase.
The disease can be treated by drugs that typically target the dopaminergic
receptors. Although this supports the original dopamine hypothesis of
schizophrenia, the model is now thought to be more complex and to involve a
number of neurotransmitters.
The disease has a major genetic component which may lead to
neurodevelopmental abnormalities for example, a number of studies have
shown that pre-adolescent children have subtle behavioural abnormalities that
are predictive of developing the disease.
59. Neurochemical disorders III: anxiety

Anxiety disorders are common and are subdivided into four main types:
generalized anxiety disorder, panic disorder, stress reactions and phobias.
Their neural basis is not well described but a number of transmitters have been
implicated in their pathogenesis.
A number of drug therapies are available for treating anxiety disorders although
some of them bring problems of dependence.
Alternative therapeutic approaches involve psychotherapy and cognitive
behavioural therapy.
60. Neurodegenerative disorders

Neurodegenerative disorders are becoming more common as the population
ages.
The cause of most of these conditions is unknown, but rare mendelian forms of
these diseases have thrown insight into possible pathogenic mechanisms as has
the list of targets coming out of genome-wide association studies in large cohorts
of patients.
The drugs to treat these conditions are very limited, but the processes underlying
the mechanism of cell death are being better defined with the hope that new
disease-modifying agents will be tested in the clinic soon.
61. Neurophysiological disorders: epilepsy

Epilepsy is common -- about 1:20 people have a fit at some point in their life.
Epilepsy can be classified as being either generalized or partial; in the latter case
if there is an impairment of consciousness it is called complex partial.
Various models exist to explain how epilepsy starts and propagates in the brain,
but in most cases the cause is unknown.
Many drugs are available for treating epilepsy and their mode of action is
increasingly being understood and involves either an effect on receptors and/or
ion channels that mediate repetitive neuronal firing.
Surgical treatment for epilepsy can be very effective if targeted to patients with a
clear focal epileptogenic origin for their seizures.
62. Neuroimmunological disorders

The CNS has relative immunological privilege, but this can change in the face of
disease or injury.
The CNS is susceptible to immunological attack and increasing numbers of
disorders are now being found to have an immunological basis.
The most common immune disorder of the CNS is multiple sclerosis.
Many traditional neurodegenerative disorders of the CNS invoke an inflammatory
response including microglial activation, and so there is now much interest as to
whether this is driving the disease process in someway.
There is a relatively large number of immunological conditions that can target the
peripheral nerve, neuromuscular junction and muscle, causing disease.
63. Neurogenetic disorders

There are many genetic conditions that can affect the nervous system, many of
which affect only the nervous system.
Our ability to probe for the genetic cause of sporadic disorders of the CNS is
increasing as is our ability to routinely test for common genetic disorders (e.g.
Duchenne muscular dystrophy; Huntingtons disease).
Mitochondrial disorders can cause a range of neurological conditions and often
result from mutations in the mitochondrial genome that can be specifically looked
for.
A group of genetic disorders have now been described in which there is an
abnormal expansion of three bases in the genome (triplet repeat disorders),
which show specific patterns of inheritance including genetic anticipation.
64. Cerebrovascular disease

Cerebrovascular disease is common especially as one gets older.
Cerebrovascular accidents can affect any artery but each artery typically
produces a distinct clinical picture.
Anterior cerebral circulation strokes are usually due to local atherosclerosis and
embolism from that site while posterior circulation strokes have more of an
embolic basis from the heart.
Clear protocols now exist for the optimal investigation and treatment of strokes,
and this includes early interventional therapies.

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Key point summaries

Part 1: Anatomical and functional organization

1. Development of the nervous system

2. Organization of the nervous system

3. Autonomic nervous system (ANS)

5. Meninges and cerebrospinal fluid

6. Blood supply of the central nervous system

8. Anatomy of the brainstem

9. Organization of the spinal cord

10. Organization of the cerebral cortex and thalamus

Part 2: Cells and neurophysiology

12. Cells of the nervous system I: neurones

13. Cells of the nervous system II: neuroglial cells

14. Ion channels

15. Resting membrane and action potential

16. Neuromuscular junction and synapses

17. Nerve conduction and synaptic integration

18. Neurotransmitters, receptors and their pathways

Abnormalities of certain neurotransmitter systems are associated with some

19. Main CNS neurotransmitters and their function

20. Skeletal muscle structure

21. Skeletal muscle contraction

Part 3: Sensory systems

22. Sensory systems: an overview

23. Sensory transduction

24. Visual system I: the eye and retina

25. Visual system II: the visual pathways and subcortical

26. Visual system III: visual cortical areas

28. Auditory system II: the auditory pathways and

29. Vestibular system

30. Olfaction and taste

31. Somatosensory system

32. Pain systems I: nociceptors and nociceptive pathways

33. Pain systems II: pharmacology and management

34. Association cortices: posterior parietal and prefrontal

Part 4: Motor systems

35. Organization of the motor systems

36. Muscle spindle and lower motor neurone

37. Spinal cord motor organization and locomotion

38. Cortical motor areas

39. Primary motor cortex

41. Basal ganglia: anatomy and physiology

42. Basal ganglia diseases and their treatment

Part 5: Consciousness and higher brain function

43. Reticular formation and sleep

44. Consciousness and theory of mind

45. Limbic system and long-term potentiation

47. Emotion, motivation and drug addiction

48. Neural plasticity and neurotrophic factors I: the

Part 6: Applied neurobiology: the principles of

50. Approach to the patient with neurological problems

51. Examination of the nervous system

52. Investigation of the nervous system

53. Imaging of the central nervous system

54. Clinical disorders of the sensory systems

55. Clinical disorders of the motor system

56. Eye movements

57. Neurochemical disorders I: affective disorders

58. Neurochemical disorders II: schizophrenia