CNS Note
CNS Note
CNS Note
Figure 1-1: General view of the brain, spinal cord and spinal nerves
The central nervous system (the neural axis or neuraxis) consists of the
brain and the spinal cord.
Anatomically, the brain comprises the cerebrum which consists of two
cerebral hemispheres, the cerebellum, and the brain stem. The
brainstem consists of the midbrain, the pons and the medulla oblongata.
The CNS contains the nerve centers which receive and process the
nervous signals, then formulate the response to these signals. The
peripheral nerves are divided into cranial and spinal nerves. The cranial
nerves are twelve pairs of nerves, which arise from the brain and
emerge out through foramina in the bones of the cranium (skull). The
spinal nerves are 31 pairs of nerves that arise from the spinal cord and
emerge out through foramina in the vertebral column. Anatomically,
the spinal nerves are sorted out into 5 groups according to their site of
origin from the spinal cord which are 8 cervical pair, 12 dorsal pairs, 5
lumbar pairs, 5 sacral pairs and one cooccygeal pair.
The basic functional unit in the nervous system is the reflex action.
A reflex action is an involuntary action in response to a stimulus e.g. a.
painful stimulus applied to the hand leads to reflex withdrawal of the
arm (the withdrawal reflex).
The basic structural unit of the nervous system which is capable of
conducting a reflex action is the reflex arc (fig. 1-2). A reflex arc;
consists of 5 components:
2. POSTSYNAPTIC INHIBITION
Postsynaptic inhibition is inhibition of synaptic transmission by
induction of an inhibitory state in the postsynaptic neuron. It is induced
either by drugs or by inhibitory neurons.
Physiology
Dr. Basim Mohamad Alwan Lecture (2)
8. EFFECT OF pH
Alkalosis enhances synaptic transmission. A rise of arterial blood pH
from 7.4 to 7.8 leads to increased cerebral excitability and convulsions.
Acidosis depresses synaptic transmission. Breathing of air with high
C02 level will lead to hypercapnea and acidosis and then depression of
synaptic transmission in the brain resulting in drowsiness and sleep or
even anesthesia. A drop of arterial pH down to 7.0 produces coma
because of failure of synaptic transmission between various neurons in
the brain.
9. EFFECT OF HYPOXIA
Hypoxia depresses synaptic transmission and prolongs reflex time due
to accumulation of acidic metabolites.
2. RECIPROCAL INHIBITION
In reciprocal inhibition the activation of one output neuron is
accompanied by simultaneous inhibition of another output neuron. This
form of inhibition occurs, for example, during the flexor withdrawal
reflex. In this reflex, contraction of the flexor muscles is accompanied
by concomitant reflex relaxation of the extensor muscles. Reciprocal
inhibition helps to optimize the reflex response by inhibiting any
antagonistic contraction.
Physiology
Dr. Basim Mohamad Alwan Lecture 3
SENSORY NERVES
Sensory nerves (afferent nerves) are the nerves which convey the
sensory information from different parts of the body to the central
nervous system. They make the first order of neurons in the nervous
pathways of all sensations.
All the spinal sensory nerves enter the spinal cord through the dorsal
roots (sensory roots) of the spinal nerves. The cell bodies of these
nerves are in the dorsal root ganglia of the spinal nerves. As these
nerves carry impulses towards the cell bodies they are considered as
long dendrites of the ganglion cells.
BELL-MAGENDI LAW: It states that the dorsal roots of the spinal
nerves are sensory and the ventral roots are motor".
SENSORY UNIT: a primary afferent and the receptors that define its receptive
field.
DERMATOME
A dermatome is the area of skin which is supplied by a spinal dorsal
root i.e. it is the cutaneous receptive field of a spinal dorsal root (fig.
4-1). The dermatomes of different roots overlap with each other.
Figure 3 - 1: Dermatomes of the spinal ant. and post. roots
(B) EXCITABILITY
(THE GENERATOR OR THE RECEPTOR POTENTIAL)
When a receptor is stimulated, it increases the permeability of the
membrane of the nerve ending to Na+ so Na+ influx and membrane
depolarization is produced. The depolarization of the membrane of the
sensory nerve ending on stimulation of the receptor is called the
"generator potential" or the "receptor potential" (fig. 3-3). The
generator potential is characterized by:
Figure 3 - 4: The relationship between the magnitude of the generator potential and
the frequency of discharge of impulses in its afferent nerve.
Figure 3-8: The five types of receptors according to their adequate stimuli.
CODING OF SENSORY INFORMATION
All stimuli are transduced by the sensory receptors into nerve impulses
in the afferent nerves. These impulses reach the brain acting as code
signals specific for each sensation. The brain then deciphers these code
signals and identifies the modality (type), the locality and the
intensity of the stimulus.
This law states that "stimulation of any point along the course of a
sensory pathway produces the specific sensation served by this
pathway regardless of the type of the stimulus used",
2. CODING OF THE LOCALITYOF THE STIMULUS
Each locality sends sensory impulses to the brain via a specific sensory
pathway. Stimulation of any point along the course of this pathway
produces a sensation felt at this specific locality. So, the locality of the
stimulus is also coded by the specific sensory pathway which serves
this locality. This is called the "law of projection". It explains the
phantom limb phenomenon which occurs in amputees.
THE PHANTOM LIMB PHENOMENON
This is the false sensation from a limb when the limb does not really exist. It
occurs in amputees who complain of pain, touch, itching or pressure
sensation felt in the absent limb. This false sensation is due to irritation of
the cut ends of the afferent nerves of the amputated limb which send
impulses up to the brain. The brain projects the sensation on to the absent
limb as if it were existing.
MECHANORECEPT1VE SENSATIONS
These sensations produced by mechanical stimuli which stimulate
mechanoreceptors. It is a group of sensations which comprises several sensory
modalities.
MECHANORECEPTORS
Mechanoreceptors are receptors which are especially sensitive to mechanical
stimuli. They are classified into cutaneous and deep mechanoreceptors as
follows:
1. CUTANEOUS MECHANORECEPTORS
Cutaneous mechanoreceptors (fig- 4-1) are of three types:
i. Naked nerve endings; e.g. the free nerve endings and the basket endings
around hair follicles.
ii. Expanded nerve endings; e.g. Merkel discs and Ruffini corpuscles.
iii. Encapsulated nerve endings; e.g. Pacinian corpuscles and Meissner
corpuscles.
MECHANORECEPTIVE SENSATIONS
1. TOUCH (TACTILE) SENSATION
Touch is the cutaneous sensation produced by light mechanical stimuli. There are
two types of touch sensation;
Crude touch and fine touch.
(A) CRUDE TOUGH
This is touch sensation without accurate identification of the locality or the
number of stimuli.
TICKLE AND ITCH
Tickle is a sensation produced by mild tactile stimulation of certain areas of skin,
usually leading to reflex involuntary laughter.
Itch is a sensation of skin irritation which leads to the desire for scratching of the
skin (the scratch reflex). It is produced by either a moving tactile stimulus a
moving flea or by substances released in the skin as histamine. The powder of
cowhage plant produces itch by releasing an itch-producing substance in the skin.
The receptors for tickle and itch sensation are specialized, highly sensitive,
rapidly adapting free naked nerve endings. They are found exclusively in the
superficial layers of the skin. Tickle and itch signals are transmitted by the slowly
conducting type IV nerve fibers.
Scratching relieves itch by removing the irritating stimulus and by presynaptic
lateral inhibition of the central terminals of the primary itch-conducting fibers.
Nerve fibers carving scratch signals send collaterals inside the spinal cord to
inhibit fibers of itch sensation by presynaptic inhibition mechanism. So, scratch
conducting fibers inhibit the itch conducting fibers by lateral presynaptic
inhibition.
(b).TACTILE DISCRIMINATION
It is the ability to identify two tactile stimuli applied simultaneously as two separate
points of contact. It is tested by the compasses test or using discriminator. The two
blunt ends of test compasses are applied to the skin of a blind-folded subject. The
distance between the two ends of the compasses is increased step by step until the
subject feels the two ends of the compass as two separate points. Acuity of this
sensation is inversely proportionate to the two-point threshold which is the
minimal distance at which the two stimuli are felt as two separate points.
Figure 4-2: Two-point discrimination; a: The compasses test, b: Two-point threshold of different
parts of the skin.
Tactile discrimination is not equally developed in different parts of the skin (fig.
4-2). It is highly developed in the tips of the fingers and tongue (two-point
threshold = 2-3 mm) but poorly developed on the back of the trunk (threshold =
65 mm).
For two-point discrimination to occur, impulses from the two points on the skin
should reach two separate final sensory neurons in the sensory cerebral cortex.
Accordingly, there are three conditions which favor the development of high
degree of tactile discrimination in a skin area. These conditions are:
i. High density of touch receptors.
ii. Minimal convergence in the sensory pathway.
iii. Large area of sensory cortical representation in the sensory cortex; i.e. a
large number of final sensory neurons.
These conditions are all found in the skin of the lips and fingertips.
VIBRATION SENSE
This is a flickering (repetitive) tactile sensation. There are two types of vibration
receptors; the high frequency, rapidly adapting Pacinian corpuscles which
respond to vibration frequency up to 800 Hz, and the low frequency, slowly
adapting Meissner corpuscles which respond to vibration frequency up to 80 Hz.
Vibration sense is tested by putting the base of a vibrating tuning fork on the skin.
A sense of buzzing or thrill is felt. The tuning fork is usually put on a
subcutaneous bony prominence just to magnify the vibrations. Bone itself is
insensitive to vibrations.
Vibration sense is conducted by the gracile and cuneate pathway (the dorsal
column-lemniscal system). In cases of uncontrolled diabetes mellitus or
pernicious anemia, degeneration of the dorsal column occurs. An early sign of
this degeneration is decreased sensitivity or disappearance of the vibration sense.
2. PRESSURE SENSATION
This is the sensation produced by a strong, blunt, static mechanical stimulus.
There are two types of pressure receptors: the rapidly adapting Pacinian
corpuscles, and the slowly adapting Ruffini endings.
Pressure sensation may be divided according to the intensity of the mechanical
stimulus into two types; light pressure (pressure touch) sensed by cutaneous
receptors, and deep pressure sensed by receptors in deeper structures as fasciae
and connective tissues.
The acuity of pressure sensation is tested by applying different weights on a
supported hand of a blind-folded subject, then, the subject is asked to identify
which weight is heavier and which is lighter.
Like touch sensation, there are two types of pressure sensation:
A. CRUDE PRESSURE SENSATION
This is pressure sensation with low ability to discriminate different weights. This
sensation is conducted by the ventral spinothalamic pathway.
B. FINE PRESSURE SENSATION
This is pressure sensation with high ability to discriminate different weights. This
sensation is conducted by the gracile and cuneate pathway.
STEREOGNOSIS
It is the ability to identify objects by handling them without seeing them (e.g. a
key, a coin, a nail ...etc.). This ability depends on touch and pressure sensations
as well as the cortical sensory somatic association area of the parietal lobe
(Brodmann areas 5 and 7). This sensation is conducted by the gracile and
cuneate pathway.
3. MUSCLE TENSION SENSATION
This is the sensation produced by traction on muscle tendons. The receptors are
the Golgi tendon organs. It enables the person to discriminate different weights
by lifting them. It is tested by applying different weights on an unsupported hand
of a blind-folded subject, then, the subject is asked to identify the lighter and the
heavier weight.
THERMORECEPTORS
There are two types of thermoreceptors:
1. WARMTH RECEPTORS
Warmth receptors are specialized free nerve endings. They are stimulated at
temperatures between 25-50 oC with maximum frequency of discharge at about
40°C (fig. 4-3). At temperatures lower than 40oC the frequency of discharge
decreases and the discharged impulses take the separated impulses pattern
(ungrouped pattern). At temperatures higher than 40°C, the frequency decreases
and the discharged impulses take a grouped pattern, "volley pattern" (fig.
4-5). Warmth sensation is conducted by the thin, type IV fibers.
Figure 7-3: The frequency of discharge from thermoreceptors and thermal pain receptors at
different temperatures.
2. COLD RECEPTORS
Cold receptors are the Krause end-bulbs which are specialized, encapsulated
nerve endings (fig. 4-4). They are stimulated at temperatures between 10-35°C
with maximum frequency of discharge at about 25°C (fig. 7-3). At temperatures
lower than 25°C, the frequency of discharge decreases and the discharged
impulses take the grouped pattern (volley pattern).
STIMULATION OF THERMORECEPTORS
The effectiveness of a stimulus applied to thermoreceptors depends on two
factors:
1. The absolute temperature: In the temperature range of 10 - 50°C, anything
warmer than the skin is felt warm and anything colder than the skin is felt cold.
2. The rate of change of temperature; i.e. the rate of warming or cooling. A
rapidly changing temperature (rising or falling) is much more effective stimulant
to thermoreceptors than a slowly changing or a steady temperature.
NONSPECIFIC THERMORECEPTORS
Some pressure receptors (Ruffini endings) are stimulated also by cold. This
explains why a colder of two otherwise identical weights placed on the hand is felt
heavier than the warmer weight (Weber's illusion). This is because the colder
weight is a stronger stimulant of pressure receptors than the warmer weight
because it makes double stimulation of Ruffini pressure receptors, first by its
weight, and second by its coldness.
Physiology
Dr. Basim Mohamad Alwan Lecture (5)
PAIN
Pain is an unpleasant sensation produced by damage or impending damage of
tissues. It is a specific sensation produced by stimulation of specific pain
receptors (nociceptors). It is not due to overstimulation of other receptors as
mechano or thermoreceptors as was believed before. This is proved by:
1. Pain can be dissociated from other sensations; e.g. in syringomyelia (saccular
dilation of the spinal central canal) pain and temperature sensations disappear
from the affected areas but other sensations persist.
2. Some areas do not contain pain receptors and are insensitive to pain (e.g. the
center of the cornea, the inside of the cheek opposite the second molar tooth),
these areas are sensitive to other sensations.
3. Strong mechanical stimulation of light receptors of the eye (e.g. by a blow on
the eye) produces light sensation from the light receptors (flashes and stars) not
pain.
PAIN RECEPTORS
There are three types of pain receptors:
1. Mechanosensitive pain receptors: Which are stimulated by strong
mechanical stimuli?
2. Thermosensitive pain receptors: Which are stimulated by temperatures
below 15 or above 45°C.?
3. Chemosensitive pain receptors: Which are stimulated by chemicals like
P-factor, bradykinin, lactic acid, potassium ions ...etc?
All these receptors are naked free nerve endings.
I- CUTANEOUS PAIN
Cutaneous pain arises from the skin on application of a noxious stimulus. It is
conducted by somatic cutaneous nerves and is not referred to any other part. It is
usually accompanied by sympathetic reflexes (e.g. increase in heart rate and rise in
arterial blood pressure), but there is no reflex muscular rigidity.
Cutaneous pain could be of the fast "pricking" type or of the slow "burning" type.
Table 8-1: Differences between, fast and slow pain.
11 - DEEP PAIN
Deep pain is a slow type of pain which arises from deep structures; i.e. muscles,
tendons, ligaments and periosteum.
CHARACTERISTICS OF DEEP PAIN
1. It is dull, aching, diffuse and poorly localized.
2. Usually associated with nausea, sweating and hypotension.
3. Pain from tendons, ligaments and periosteum initiates reflex muscular
spasm in the nearby muscles.
4. It is conducted by the slowly conducting type-IV fibers.
5. It may be referred to the skin of the same dermatome.
2. Muscular spasm (cramp): In tetany or when one loses a lot of salt in sweating
(e.g. with muscular exercise in hot weather or miner's disease) muscle spasm
(cramp) occurs and stimulation of mechanosensitive pain receptors then pain
sensation. Ischemia also contributes to the production of pain in this condition.
Figure 8 -1: The areas from which pain is conducted by somatic and by autonomic nerves.
REFERRED PAIN
Referred pain is pain felt away from its site of origin.
Examples:
1. Ischemia of the heart causes pain that may be referred and felt in the left
shoulder and the inside of the left arm.
2. Pain from the gall bladder may be referred and felt in the right shoulder.
3. Pain of appendicitis may be referred to the umbilical area.
4. Pain from the ureter may be referred to the testis.
In this way, pain impulses from the viscera travel in the same central pathway as
pain impulses from the skin to reach the same final sensory neuron in the brain.
The final sensory neuron projects pain sensation to the skin as the skin is the place
from which it usually receives pain signals (fig. 5-2).
This means that the pain signals from the viscera converge to the same final
sensory neuron as the signals from the skin, the brain projects any pain sensation
from the viscera to the skin. This mechanism is known as "the convergence
projection mechanism".
Accordingly, if pain arises from a certain viscera from which impulses converge
with impulses coming from a certain area of skin, one would feel pain as if it is
coming from the skin not from the viscera.
Reference of pain occurs from viscera to deep structures or the skin and from
deep structures to the skin, but not the opposite way.
DERMATOMAL RULE OF REFERRED PAIN
Visceral or deep pain is referred to the dermatome which has the same nerve
supply as the site of pain. E,g. the heart, the left shoulder and the inside of the left
arm have the same nerve supply. So, pain from the heart is referred to the left
shoulder and the inside of the left arm (fig. 5-2).
Impulses from the injured area facilitate a central neuron. Impulses from the
hyperpathic area converge on the same central neuron. The convergence on a
central facilitated neuron explains the exaggerated pain sensibility. The
facilitator neuron which arises from the area of primary hyperalgesia exerts
lateral inhibition on the stimulator neuron which arises from the hyperpathic
area. This explains why the threshold of pain is increased in the hyperpathic area.
2. CAUSALGIA
Causalgia is a pathological condition in which there is hyperalgesia, allodynia
and spontaneous burning pain sensation long after a seemingly trivial skin injury.
It occurs if the skin injury was associated with nerve injury. The skin in the
affected area becomes thin and shiny with increased hair growth.
THE MECHANISM OF CAUSALGIA:
Nerve injury leads to sprouting of noradrenergic sympathetic nerve fibers into the
sensory nerve track up to the dorsal root ganglia of the sensory nerves of the
affected area. The dorsal root ganglia cells can be stimulated by sympathetic
activity. This stimulation may facilitate the sensory neuron leading to hyperalgesia
or allodynia, or it may excite it to discharge pain signals to the CNS leading to
spontaneous pain sensation.
2. THE HYPOTHALAMUS
B-endorphinergic fibers project from the periventricular nuclei and the medial
forebrain bundle of the hypothalamus to the periaquiductal gray matter of the
mesencephalon.
STRESS ANALGESIA
Stress analgesia is the suppression of pain sensation during stressful during stressful
conditions (fight or flight). In these conditions, pain impulses are blocked at two
levels:
A. At the first gate of pain transmission (the dorsal horn of the spinal gray
matter). The hypothalamus and other parts of the central analgesia system
activate the spinal PIC which blocks the transmission of pain signals at the
dorsal horn.
B. At the second gate of pain transmission (the thalamus). Corticofugal fibers
to the thalamus block by presynaptic inhibition the transmission of pain signals in
the thalamus before they reach the cerebral cortex.
IV) enter the spinal cord in the dorsal root of the spinal nerve then go up or down for
a few segments in the Lissaur s tract and terminate in laminae II, III and IV of
the dorsal horn of the spinal gray matter.
Fig. 6-3 ventral spinothalamic tract
SECOND ORDER NEURONS: are neurons in laminae II, III and IV of the dorsal horn.
Their fibers cross to the opposite side in front of the central canal then ascend in
the ventral column of the spinal white matter as the ventral spinothalamic tract up
to the brainstem and in the brainstem, they join the lateral spinothalamic tract to
form the spinal lemniscus (nervous tract made by union of more than one
tract) which ascend up to terminate in the ventral posterolateral nucleus of the
thalamus (VPLNT).
THIRD ORDER NEURONS: are neurons of the VPLNT. Their fibers project through
the central thalamic radiations to the final sensory neurons in the sensory cerebral
cortex.
THE LATERAL SPINOTHALAMIC PATHWAYS
There are two lateral spinothalamic pathways; the paleospinothalamic and the
neospinothalamic pathways.
1. THE PALEOSPINOTHALAMIC PATHWAY
enter the spinal cord in the dorsal root of the spinal nerve then go up or down for a
few segments in the Lissaur tract and terminate in the substantia gelatinosa of
Rolandi (laminae II, III) of the dorsal horn of the spinal gray matter.
SECOND ORDER NEURONS: are neurons in the substantia gelatenosa of Rolandi.
Their fibers cross in front of the central canal to the opposite side. Fibers ascend in
the anterolateral column of the spinal white matter as the lateral spinothalamic
tract. In the brainstem, the lateral spinothalamic tract. In the brainstem the
lateral spinothalamic tract joins the ventral spinothalamic tract to form the spinal
lemniscus. Fibers terminate in the nonspecific intralaminar nuclei of the
thalamus (ILNT).
During their course in the brainstem, some fibers deviate and make a separate tract
called "the spinoreticular tract". The fibers of this tract terminate in the reticular
formation of the brainstem. Multiple, short fiber neurons conduct the signals from
the reticular formation onto the intralaminar nuclei of the thalamus (ILNT).
THIRD ORDER NEURONS: are neurons of the ILNT. Their fibers project through the
anterior, central and posterior thalamic radiations to the final sensory neurons in all
parts of the cerebral cortex.
III) enter the spinal cord in the dorsal root of the spinal nerve and go up or down for
a few segments in the Lissaur tract then terminate in laminae II and V of the dorsal
horn of the spinal gray matter.
SECOND ORDER NEURONS: are neurons in laminae, II and V. Their fibers cross in
front of the central canal to the opposite side, and then ascend in the anterolateral
column of the spinal white matter as the lateral spinothalamic tract. In the
brainstem, the lateral spinothalamic tract joins the ventral spinothalamic tract to
form the spinal lemniscus. The fibers of the neospinothalamic tract terminate in
the ventral posterolateral nuclei of the thalamus (VPLNT).
Fig. 6-5 the neospinothalamic pathway
THIRD ORDER NEURONS: are the neurons of the VPLNT. Their fibers project through
the central thalamic radiations to the final sensory neurons in the sensory cerebral
cortex.
enter the spinal cord in the dorsal root of the spinal nerve then branch into medial
and lateral branches. The medial branches ascend without relay up in the ipsilateral
dorsal column of the spinal white matter where they are called "the dorsal column
tracts" or "the gracile and cuneate tracts". They terminate in the dorsal
column nuclei (the gracile and cuneate nuclei) in the medulla.
SECOND ORDER NEURONS: are the neurons of the dorsal column nuclei in the
medulla. Their fibers cross to the opposite side in the sensory decussation and
ascend in the brainstem as the medial lemniscus. They terminate in the ventral
posterolateral nucleus of the thalamus (VPLNT). .
THIRD ORDER NEURONS: are those of the VPLNT. Their fibers project through the
central thalamic radiations to the final sensory neurons in the sensory cortex.
* The gracile is the medial tract. It is formed in the lower part of the spinal cord and carries
sensations from the lower part of the body. The cuneate is the lateral tract. It is formed in
the upper part of the spinal cord at the level of the 6th thoracic spinal segment, and carries
sensations from the upper part of the body.
FIRST ORDER NEURONS: are the dorsal root neurons. Their afferent fibers (type I and
II) enter the spinal cord in the dorsal root of the spinal nerve and terminate in
lamina IV" of the dorsal horn of the spinal gray matter.
SECOND ORDER NEURONS: are neurons in lamina IV. Their fibers ascend in the
THIRD ORDER NEURONS: are those of the lateral cervical nucleus. Their fibers
cross to the opposite side and ascend in the brainstem as part of the medial
lemniscus to terminate in the VPLNT.
FOURTH ORDER NEURONS : are neurons of the VPLNT. Their fibers project
through the central thalamic radiations to the final sensory neurons in the sensory
cerebral cortex.
Fig. 6-7 the spinocervical pathway
Physiology
Dr. Basim Mohamad Alwan Lecture (7)
THE SOMATOSENSORY CONDUCTING SYSTEMS OF THE
SPINAL CORD
The ascending somatosensory tracts in the spinal cord are classified into
two conducting systems, i.e. the anterolateral and the dorsal
column-lemniscal systems. Each system has its own features and
characteristics.
The two thalami are large ovoid masses of gray matter situated at the
lateral walls of the third ventricle, one on each side. They are
interconnected by a short communicating bar of white matter (massa
intermedia) which traverses the third ventricle.
All the nervous signals which go to the cerebral cortex pass first
through and relay in the thalamus. That is why the thalamus is
sometimes called the "secretary of the cerebral cortex ".
SENSORY EFFECTS
First, there is complete hemi anesthesia at the onset of the disease. Few
weeks later protopathic sensation (primitive sensations which
include crude touch, pain and high or low temperatures) are
recovered. The threshold of pain is elevated but gives very unpleasant,
exaggerated central effect. Epicritic sensations (fine sensations, which
include fine touch, proprioceptive sensations and intermediate
grades of temperature) are permanently and irreversibly lost.
MOTOR EFFECTS
There is hemiparesis (weakness of the muscles), hemiataxia and
choreoathetoid movements.
SENSORY FUNCTIONS OF THE CEREBRAL CORTEX
The cerebral cortex is the highest center for conscious perception of
fine sensations. Crude sensations such as pain, temperature and crude
touch can be perceived at a lower level in the thalamus. Somatic
sensations are perceived in the parietal lobe, visual sensations are
perceived in the occipital lobe and auditory sensations in the temporal
lobe.
There are three somatic sensory areas in the cerebral cortex; the
primary somatic sensory area (SI), the secondary somatic sensory
area (SII) and the somatic sensory association area.
90
Figure 8 - 1: The lateral and medial surfaces of the left cerebral hemisphere showing the
primary motor cortex (M), the pre motor cortex (PM), the motor association area (MA)
and the supplementary motor area (SM).
[II] THE PREMOTOR AREA (Areas 6, 8 and 44)
The premotor area of the cerebral cortex (mainly area 6 of Brodmann
classification, but it also includes areas 8 and 44) lies immediately anterior to the
primary motor area. The topographic representation of the body is nearly the
same as in area 4. The premotor area includes some specialized areas with
specific functions (fig. 8-1):
1. Broca's area of speech (Word 44):
This area lies at the upper border of the lateral sulcus in front of the primary
motor cortex. It stores the motor programs for verbalization. Its damage leads to
inability to speak whole words except simple ones as "yes" or "no".
2. Eye field area (area 8):
It lies above Broca's area. It directs the eyes voluntarily towards any desired
object. It also controls the blinking movements of the eye lids. Damage of this
area leads to locking (fixation) of the eye on objects.
91
Figure 8-2: Body representation in the primary motor cortex
92
FUNCTIONS OF THE PREMOTOR AREA
1. Initiation of gross movements that involve groups of muscles to support and'
facilitate fine movement, e.g. fix the shoulders and arms at a certain position so
that the hands and fingers can do skilled movements (e.g. threading a needle).
2. Weak inhibition of the stretch reflex. It tends to decrease the skeletal muscle
tone.
3. A center for rotation of the head towards objects.
4. A center for skilled hand movements.
5. A center for verbalization of words (area 44).
6. A center for voluntary eye and lid movements (area 8),
7. Inhibition of the grasp reflex.
The premotor area acts by activating the corresponding nearby motor calls in me
primary motor area. This occurs in two ways:
First directly through direct projection fibers to area 4.
Second indirectly circuits starting from the premotor area to the corpus striatum
of the basal ganglia, to the thalamus, then back to terminate in area 4 of the
cerebral cortex.
93
background for finer hand or feet movements; e.g. the coordinated movement of
the trunk with the hand and feet during boxing.
This area is involved in preparation for movements before they start. It shows
electrical potentials shortly before the start of the movement (readiness
potential) and increase in metabolism and local blood flow on the mere intention
to move a muscle,
94
corresponding points on both sides.
B. FROM THE THALAMUS
• The ventrobasal complex (VPL and VPM nuclei); it receives specific sensory
signals.
• The intralaminar nuclei; it receives nonspecific signals to arouse the cortex.
• The ventral and medial nuclei; it receives impulses coming from the
cerebellum and basal ganglia.
EFFERENT CONNECTIONS
A. Pyramidal tract fibers to motor nuclei in the brainstem and spinal
cord.
B. To the basal ganglia (the caudate and putamen circuits).
C. To the red nucleus of the midbrain.
D. To the cerebellum through the middle cerebellar peduncle
(cortico-ponto-cerebellar fibers).
E. To adjacent cortical areas to inhibit any unwanted discharge (lateral
inhibition). These inhibitory fibers are collaterals from the axons of the giant
Betz cells. This helps to sharpen the outgoing signals.
95
THE MOTER TRACTS
Dr. Basim Mohamad Alwan Lecture 9
The motor tracts (also called the descending tracts) are divided into two groups of
tracts; the pyramidal and the extrapyramidal.
96
THE CORTICONUCLEAR TRACT
ORIGIN: From the eye field area in the frontal lobe (area 8) and the related areas in
the motor and the somatosensory areas.
COURSE AND DESTINATION: Fibers descend down through the genu of the
internal capsule to the brainstem. They terminate on the nuclei of cranial nerves III,
IV in the midbrain and VI in the pons on both sides.
FUNCTIONS
1. Voluntary conjugate movements of the eye to look at different objects.
2. Facilitate the stretch reflex of the external ocular muscles.
COURSE AND DESTINATION: Fibers descend down through the genu of the
internal capsule to the pons and medulla oblongata. They cross to the opposite side
to terminate on the nuclei of the cranial nerves V, VII, IX, XI and XII.
FUNCTIONS
1. Voluntary movement of muscles in the head and neck.
2. Facilitation of stretch reflex of these muscles
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Figure 9 -1: The origin, course, and destinations of the pyramidal tracts.
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THE CORTICOSPINAL TRACT
ORIGIN: From the motor, premotor, supplementary motor and somatic sensory
areas of the cerebral cortex.
COURSE AND DESTINATIONS: Fibers descend in the corona radiata, then
through the anterior two-thirds of the posterior limb of the internal capsule down
to the brainstem. In the medulla, fibers collect together to form the medullary
"pyramid". In the lower medulla, pyramidal fibers take one of three courses:
1. 90% of the fibers cross to the opposite side in the motor decussation and
descend in the posterolateral column of the spinal white matter as the "lateral
corticospinal tract". They terminate on the ventral horn cells mainly through
intemeurons, but some fibers terminate directly on ventral horn cells.
2. 8% of the fibers descend directly in the ventral column of the spinal white
matter of the same side as the "ventral corticospinal tract". They cross
gradually as they descend in the cervical and upper thoracic segments of the
spinal cord to terminate on the ventral horn cells of the opposite side.
FUNCTIONS
The crossed (lateral and ventral) corticospinal tracts have the following
functions:
1. Production of fine voluntary movements of the distal parts of the body e.g.
fingers and hands.
2. Facilitation of lower motor neurons and stretch reflex.
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The uncrossed corticospinal tract has the following functions:
1. Provide bilateral innervation of some muscles as the respiratory and abdominal
muscles.
2. Gross positioning movements controlled by the supplementary motor area.
3. Help partial recovery of movements after injury of the crossed
corticospinal tracts.
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cord very closely anterior to the lateral corticospinal tract. Fibers terminate on the
ventral horn cells either directly or through interneurons.
Lesions of the pyramidal tracts usually involve the corticorubrospinal pathway. If the
latter is spared, a good deal of gross movements is retained. Only the fine
movements of the fingers and hands are considerably impaired.
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Figure 9 - 2: A schematic diagram of the extrapyramidal system.
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THE TECTUM OF THE MIDBRAIN
It receives projection fibers from the globus pallidus of the basal ganglia, and
gives origin to two descending extrapyramidal tracts:
* The lateral tectospinal tract: Originates from the superior colliculus (the
center of visual reflexes), crosses to the opposite side and terminates in the cervical
segments of the spinal cord. It is concerned with directing the eye and turning the
head towards a light source (visuospinal reflexes).
* The ventral tectospinal tract: Originates from the inferior colliculus (the
center of auditory reflexes), crosses to the opposite side and terminates in the
cervical segments of the spinal cord. It is concerned with turning the head to direct
the ears towards a sound source (audiospinal reflexes).
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'nucleus, descends uncrossed to terminate on the alpha and gamma motor neurons.
• The ventral vestibulospinal tract: Originates from the vestibular
nucleus, descends on both sides of the spinal cord to terminate on
the alpha and gamma motor neurons.
The vestibulospinal tracts facilitate the stretch reflex and skeletal muscle tone.
They mediate some postural reflexes
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THE UPPER AND LOWER MOTOR NEURONS
To do a voluntary movement, signals start in the motor neurons of the cerebral
cortex and reach the skeletal muscles through two orders of neurons:
1. Upper motor neurons:
These are the neurons of the pyramidal and extrapyramidal tracts in the CNS. They
extend from the cerebral cortex and the extrapyramidal nuclei down to the motor
neuron pool of the brainstem and spinal cord. Neurons of the motor neuron pool
themselves are not included in the upper motor neurons.
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THE BASAL GANGLIA
Dr. Basim Mohamad Alwan Lecture 10
The basal ganglia (fig. 10-1) are sub cortical masses of gray matter found in the cerebral
hemispheres lateral to the thalamus that includes:
1. The caudate nucleus.
2. The lentiform (lenticular) nucleus. This consists of 2 parts:
a. An outer part called the putamen.
b. An inner part called the globus pallidus , which further divided into external
and internal segments.
Both caudate nucleus and putamen are called the corpus striatum (striate body or
striatum).
3. The subthalamic nucleus (subthalamus or body of LUYS).
4. The substantia nigra in the midbrain.
The afferent connections to the basal ganglia terminate mainly in the corpus
striatum, whilst the efferent connections originate mainly from the globus pallidas.
Figure 10-1 Transverse section in the cerebrum showing the basal ganglia
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NEURAL CONNECTIONS OF THE BASAL GANGLIA
There are numerous free interconnections between various nuclei of the basal
ganglia. This is in addition to the connections with the cerebral cortex, thalamus
and brainstem.
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THE PUTAMEN CIRCUlT
The putamen circuit (fig.10-3) starts at the motor association and sensory
association areas → to the putamen → the globus pallidus → the ventrolateral
(VL) nucleus of the thalamus → premotor and primary motor areas of the cortex.
There are other circuits which are closely associated with the putamen circuit.
They connect the basal to the subthalamus, substantia nigra:
(a) Putamen → globus pallidus → subthalamus → thalamus → motor cortex.
(b) Putamen → globus pallidus → substantia nigra→thalamus→ motor cortex
Through these circuits the basal ganglia receive thoughts and ideas from the
cerebral cortex and feedback plans and programs for motor actions to the motor
and premotor areas.
CONNECTIONS WITH THE BRAINSTEM
The basal ganglia are connected with some centers in the brainstem, from which
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fibers descend in the extrapyramidal tracts down to the spinal cord. Fibers project
from the globus pallidas to:
1. The reticular formation, from which the reticulospinal tracts originate.
2. The red nucleus, from which the rubrospinal tract originates.
3. The vestibular nucleus, from which the vestibulospinal tracts originate.
4. The inferior olive, from which the olivospinal tract originates.
This is in addition to fibers to the subthalamic, substantia nigra, and tectum.
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protein made in the liver called ceruloplasmin until it is excreted in bile.
In Wilson disease, there is failure, of ceraloplasmin formation and inability to
excrete copper in bile. Serum copper level rises which leads to copper
intoxication. Large amounts of copper accumulate in the cells of the liver and the
lentiform nucleus of the basal ganglia which lead finally to hepatolenticular
degeneration.
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ROLE OF THE CAUDATE CIRCUIT
1. Design of plans which convert thoughts and ideas into motor actions: The
caudate circuit directs the motor activity according to the thoughts of mind; i.e.
converts thoughts into motor plans. It determines what patterns of movements
will be used and in what sequence to achieve a complex goal; e.g. when dressing,
one puts on the shirt then the necktie before the jacket.
2. Determining the timing and scale of movement; The basal ganglia
determine:
(a) To what extent the movement will be fast.
(b) For how long the movement will last.
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Figure 10 - 4: A typical drawing made' by patient with a lesion in the left
basal ganglia or the left parietal lobe of the cerebral cortex.
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sleep but increase with nervous excitement.
2. Change in muscle tone; either hyper or hypotonia.
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(C) HEMIBALL1SMUS (Gr.: ballismus means jumping)
CAUSE: Lesion in the subthalamus.
FEATURES:
• Sudden, involuntary, strong, spasmodic movements that involve
one limb or a whole one side of the body. It might occur in one
leg during walking leading to stumbling of the body.
FEATURES:
Three features characterize parkinsonism; tremor, rigidity and akinesia.
1. TREMOR
Tremor is an involuntary, rhythmic, oscillating movement due to rhythmic short
contractions of muscles. The tremor of Parkinsonism occurs at a frequency of 4-8
Hz. At the hands, it usually takes the form of pill-rolling movement. The tremor
might occur in the muscles of mastication leading to an up and down movement
of the mandible (mandibular tremor). The tremor occurs in the waking time
during rest. It markedly diminishes or disappears during voluntary movement.
That is why it is called a "static tremor". It disappears also during sleep.
The parkinsonian tremor is caused by activation of negative feedback circuits
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between the basal ganglia and the motor cortex → rapid on-off inhibition of the
motor cortex → alternating activation inactivation of the muscles → tremor.
2. RIGIDITY
Parkinsonian rigidity occurs in both flexor and extensor muscles but is more in the
flexors leading to a flexor attitude of the patient (fig. 10-5). When bending a limb
of a parkinsonian patient, the muscle rigidity resists the bending all the way
during bending, making the limb appearing as a pipe of lead (lead pipe rigidity),
or it may give a series of "catches" or "clicks' during the bending (cog-wheel
rigidity).
Parkinsonian rigidity is caused by:
(a) Facilitation of the gamma motor neurons due to lo SS of the supraspinal
inhibitory effect of the lentiform nucleus.
(b) Facilitation of the alpha motor neurons due to lack of dopamine. The caudate
nucleus becomes hyperactive. It sends facilitatory discharge via the
extrapyramidal tracts down to the alpha motor neurons of the motor neuron pool.
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3. AKINESIA
Akinesia means lack of movement. Each movement is carried out as a "sequence"
of phases of excitation and inhibition. Due to lack of dopamine, the basal ganglia
is "locked" at a state of excitation. So, it cannot make a plan or activate a program
of a movement. The patient avoids voluntary movements because he finds great
difficulty in initiating this movement due to the absence of the planning and
programming function of the basal ganglia.
Parkinsonian akinesia is manifested by:
(a) Lack of voluntary movement due to difficulty to initiate this movement.
The patient appears as if he is paralyzed although he is not. That is why
Parkinson disease is also called "paralysis agitans".
(b) Refraining from habitual movements, e.g. rolling of beads, or
manipulating one's hairs during reading.
(c) Absence of associating habitual movements, e.g. swinging of arms during
walking.
(d) Mask face; due to lack of movement of facial muscles of expression,
(e) Slow, monotonous, low-volume speech.
(f) The gait (the way of walking) is shuffling; the patient walks in short steps
without lifting his feet off the ground.
TREATMENT OF PARKINSONISM
Medical: As Parkinsonism is caused by an imbalance between dopamine and
acetylcholine in the basal ganglia, it is treated by either reducing acetylcholine
activity or increasing dopaminergic activity. Reducing Ach activity is done by
giving atropine (a muscarinic cholinergic blocker). Increasing dopaminergic
activity is done by giving L-dopa. L-dopa is preferred over dopamine because
L-dopa crosses the blood-brain barrier much easier.
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Surgical: Destruction of the ventrolateral nuclei of the thalamus by
electrocoagulation disrupts the feedback circuits between the basal ganglia and
the motor cortex. This abolishes the tremor.
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Dr. Basim Mohamad Alwan Lecture 11
THE CEREBELLUM
The cerebellum receives direct or indirect input signals from all the
sensory pathways. This sensory information does not reach conscious
perception. The cerebellum functions as a special kind of computer
which automatically integrates the sensory inputs to provide rapid
responses of smooth coordinated motor actions.
FUNCTIONAL ANATOMY
Cerebellum (fig. 11-1, 11-2) consists of a midline structure called the vermis,
two cerebellar hemispheres on both sides, and a separate lobe called the
flocculonodular lobe on the inferior surface.
Three pairs of cerebellar peduncles connect the cerebellum with the brainstem.
The superior cerebellar peduncle (SCP) connects the cerebellum with "the
midbrain, the middle peduncle (MCP) with the pons and the inferior peduncle
(ICP) with the medulla.
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Figure 11 - 1: The anatomical (right) and functional (left) divisions of the
cerebellum.
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Fig. 11-2 Functional parts of the cerebellum
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Figure 16-3: Cellular layers of the cerebellum. The climbing and Mossy
fibers
All the afferent fibers to the cerebellum are one of two types (fig. 11-3):
(A) CLIMBING FIBERS: Which originate from the inferior olive. They enter
the cerebellum, give off collaterals to the nuclear cells and proceed to terminate
on the dendritic branches of the Purkinje cells in the molecular layer of the cortex.
(B) MOSSY FIBERS: Which originate from all parts of the CNS including me
inferior olive. They give off collaterals to the nuclear cells and terminate on the
granule cells of the cerebellar cortex. The granule cells then relay on the dendritic
branches of the Purkinje cells in the molecular layer of the cortex.
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All the afferent fibers to the cerebellum terminate in the cortex. All parts of the
cerebellar cortex send inhibitory projection fibers from the Purkinje cells to the
deep nuclear cells. These fibers are the only projection fibers from the cortex.
Some parts of the cortex of the flocculonodular lobe send direct projection fibers
to the vestibular nucleus in the medulla oblongata. In this respect, the vestibular
nucleus functions as a cerebellar nucleus.
The efferent fibers from the cerebellum are the axons of the nuclear cells. The
nuclear cells receive continuous excitatory input from the mossy fibers and
inhibitory input from the Purkinje cells. The net effect is moderate continuous
facilitation leading to continuous tonic facilitatory discharge from deep nuclear
cells during rest. Stimulation of nuclear cells excitatory output signal (i.e.
increase in the frequency of discharge in the efferent fibers). Inhibition of nuclear
cells inhibitory output signal (i.e. decrease in the frequency of discharge in
the efferent fibers).
CEREBELLAR CONNECTIONS
AFFERENT CONNECTIONS (fig. 11 - 3)
[I] FROM THE BRAIN
2. CORTICO PONTO CEREBELLAR FIBERS: They originate from the premotor area
of the cerebral cortex pontine relay nuclei Mid. cer. ped. contralateral
cerebrocerebellum. They transmit signals from the cortex giving an "efference
copy" of the plan of the intended movement.
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3. OLIVO CEREBELLAR FIBERS: They originate in the inferior olive inf. cer.
ped. all parts of the ipsilateral cerebellum. Inferior olive receives fibers from the
motor cortex, basal ganglia, reticular formation and spinal cord. The inferior olive
compares the signals from the brain with those from the spinal cord and feed the result to
the cerebellum.
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Figure 11-4: The afferent cerebellar connections.
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FIRST ORDER NEURONS: are the dorsal root neurons. Their afferent type-II
fibers enter the spinal cord in the dorsal root terminate in the Clarke nucleus
(lamina VI of the spinal gray matter).
SECOND ORDER NEURONS: are those of Clarke nucleus at the base of the
dorsal horn. Their fibers ascend in the same side up in the posterolateral column
of the spinal white matter as the dorsal spinocerebellar tract up to the medulla
oblongata. In the medulla fibers pass through the inferior cerebellar peduncle to
terminate in the cortex of the spinocerebellum.
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2. THE VENTRAL SPINOCEREBELLAR PATHWAY
The ventral spinocerebellar pathway (fig. 11-5) consists of two orders of neurons.
FIRST ORDER NEURONS: are the dorsal root neurons. Their afferent type-II
fibers enter the spinal cord in the dorsal root and then terminate in lamina VII of
the spinal gray matter.
SECOND ORDER NEURONS: are neurons of lamina VII of the spinal gray
matter. Some of the fibers cross to the opposite side, the others ascend in the same
side up in the anterolateral column of the spinal white matter as the ventral
spinocerebellar tracts up to the midbrain. In the midbrain, fibers of the ventral
spinocerebellar tracts of both sides turn to pass through the superior cerebellar
peduncle to terminate in the cortex of the spinocerebellum.
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FUNCTIONS: Neurons of the ventral spinocerebellar tract are stimulated by
signals reaching the ventral horn cells of the spinal cord in the motor tracts. It
informs the cerebellum about the motor signals reaching the ventral horn cells.
So, it gives the cerebellum an "afference copy" of the final motor orders which
will be executed. The pathway also conducts some proprioceptive information
from the periphery to the cerebellum. But in that respect it is less important than
the dorsal pathway.
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Figure 11 - 7: The efferent cerebellar connections
Fibers originate in the dentate nucleus in the cerebellar hemisphere sup. cer. ped.
then cross to the opposite side in the brainstem ventrolateral nucleus of the
thalamus cerebral sensorimotor cortex.
The cerebellum is connected to the cerebral cortex by afferent and efferent fibers.
These form a neuronal circuit that start and end in the cerebral cortex. This circuit is
called the cortieo ponto cerebello dentate thalamo cortical circuit.
128
Physiology
FUNCTIONS OF THE CEREBELLUM
Dr. Basim Mohamad Alwan Lecture 12
129
THE CEREBELLAR STRETCH REFLEX: This reflex operates when a contracting
muscle meets an unexpected load. Signals from muscle spindles are transmitted
to the spinocerehellum via the spinocerebellar tracts. The spinocerebellum
responds by output signals to the alpha and gamma motor neurons of the spinal
cord to increase the muscle tone to the appropriate required level (the load
reflex).
130
4. SERVOCOMPARATOR (force regulator):
The cerebellum (fig. 12-1) receives input signals from:
(i)The premotor cortex and inferior olive, before the start of movement. An
"efference copy" of the plan of movement informs the. cerebellum of the
"intention" to make a movement.
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signals in the climbing and mossy fibers.
The absence of this function leads to overshooting of movements and when the
motor cortex corrects the overshooting, the correction overshoots again. This
process of "correction of the overshooting and overshooting of the correction" is
repeated several times before the movement reaches its target. In this way, a
hand or a finger oscillates back and forth past its target before it finally settles on
it. This feature is called "intention tremor" or "kinetic tremor".
6. PREDICTTVE FUNCTION:
As the cerebellum receives sensory input from all sensory organs, it is informed
about the rate and direction of movement. The cerebellum uses this information
to compute and change the rate and direction of movement to reach a certain
target at a certain time; e.g. the thrust of a goal-keeper to catch a kicked football,
or the thrust of a tennis player to meet a coming ball with his racket. In these
cases, visual signals inform the cerebellum about the speed and direction of the
ball movement. Proprioceptive signals inform the cerebellum about the speed and
direction of body movement. The cerebellum adjusts the movement of the body
to meet the ball at a certain time in a certain location.
When a person runs towards a wall, this function enables him to stop just before
the wall without hitting it.
132
movement abruptly without overshooting.
Potentiation of the starting is achieved by the initial excitatory output signals of
the mossy fiber circuit. The abrupt termination is achieved by the inhibitory
output signals which follow the excitatory signals.
133
The cerebellar kinetic tremor results from a series of "correction of overshooting
and overshooting of the correction". This disability is tested by the finger to-nose
test (fig. 12-3).
Figure 12 - 3: Finger to nose test in a normal person (A) and in a person with
cerebellar syndrome (B).
Figure 1 2 -4 : Adiadokokinesia.
134
respiratory movements. This results in jumbled speech in which some syllables are too
long, others are too short. The volume of sound is poorly controlled; it oscillates
between loud and faint. Sometimes, speech becomes scanning or staccato speech,
where speech is cut off into short syllables separated by regular intervals, e.g. I
re-cei-ved an in-vi-ta-tion.
(f) Rebounding: This is manifested by an overshooting of a limb when
a resistance to its movement is suddenly withdrawn. This disability is
tested by the "arm flexion test" (fig 12-5)
135
PHYSIOLOGY
Dr. Basim Mohamad Alwan Lecture 13
REFLEXES
REFLEX ARC
136
ORGANIZATION OF THE SPINAL CORD FOR MOTOR FUNCTIONS (fig. 14-2)
Each segment of the spinal cord between one spinal nerve and the next has
several million neurons in the gray matter.
These neurons are:
Anterior Motor Neurons
Several thousand neurons are located in each segment of the anterior horn of
spinal cord.
They are 50-100% larger than most of others.
They give rise to the nerve fibers that leaves the spinal cord by way of the
ventral roots and innervates the skeletal muscle fibers.
They are of 2 types:
Alpha Motor Neurons
They give rise to type A alpha nerve fibers that innervate the large skeletal
muscle fibers.
Stimulation of a single nerve fiber excites from as few as 3 to as many as
hundred skeletal muscle fibers.
Gamma Motor Neurons
These neurons transmit impulse through type A gamma fibers.
They are much smaller and reach special skeletal fibers called "intrafusal
fibers", which is part of the muscle spindle.
Interneuron
These present in all areas of the gray matter.
They are numerous about 30 times as the anterior motor neurons.
They are small, highly excitable, and capable of firing as rapidly as 1,500
times / second.
They have many interconnections one with the other and many of them
directly innervate the anterior motor neurons.
137
Fig. 13-2 Spinal cord organization for sensory, motor and autonomic functions
138
MUSCLE SENSORY RECEPTORS (fig.13-3, 13-4)
Proper control of muscle function requires not only excitation of the muscle by
the anterior motor neurons but also continuous sensory feedback information
from each muscle to the spinal cord giving the status of the muscle at each
instant, that is:
To provide this information, the muscle and its tendon are supplied
abundantly with 2 special types of sensory receptors "muscle spindles and
Golgi tendon organs".
I. One respond best to how much the muscle has been stretched.
II. Other responds to both the magnitude of the stretch and the speed with
which it occurs.
These receptors consist of afferent nerve fiber endings that are wrapped
around modified muscle fibers. Several of which are enclosed in a connective
tissue capsule. The entire structure is called "muscle spindle".
Each spindle is 3-10 mm long.
It is build around 3-12 very small modified intrafusal fibers that are pointed at
their ends and attached to glycocalyx of the surrounding large "extrafusal
fiber".
Nuclear-bag fibers
a. They are 1-3 in each spindle.
b. There is large number of nuclei congregated in an expanded bag in the
central portion of the receptors.
c. They are innervated by primary nerve endings
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Nuclear-chain fibers
a. They are 3-9 in each spindle.
b. They are about 1/2 in diameter and 1/2 as long as the nuclear-bag fibers.
c. Their nuclei aligned in a chain throughout the receptor area.
d. They are innervated by primary and secondary nerve endings.
e. Their ends are connected to the nuclear-bag fibers.
The sensory fibers which originate in the central portion and stimulated by
stretching of this mid portion of the spindle are of 2 types:
140
Fig. 13-4 muscle spindle
The muscle spindles are parallel to the extrafusal fibers, such that stretch of
the muscle by external force pulls on the intrafusal fibers, stretching them and
activating their receptor endings with reflex contraction of the extrafusal fibers
of the muscle.
The more the muscle is stretched or the faster it stretched, the greater the
rate of the receptor firing.
In contrast, contraction of the extrafusal fibers and the resultant shortening of
the muscle remove tension on the spindle and slow the rate of firing of the
stretch receptor.
When the afferent fibers form the muscle spindle enter the CNS, they divide
into branches that take several different paths:
First Path:
Directly stimulates motor neuron going back to the muscle that was stretched,
thereby completing a reflex arc known as the "stretch reflex".
This reflex is probably the most familiar in the form of the knee jerk.
1. The examiner taps the pattelar tendon which passes over the knee and
connects extensor muscles in the thigh to the tibia in the lower leg.
2. As the tendon is pushed in, and thereby stretched by tapping.
3. The thigh muscles to which it attached are stretched and all the stretched
receptors within these muscles are activated.
4. More action potentials are generated in the afferent nerve fibers from the
stretched receptors.
5. They are transmitted to the motor neurons that control these muscles.
6. The motor units are stimulated
7. The thigh muscles are shortens
8. The patient's lower leg is extended to give the knee jerk.
141
Note: In contrast to the knee jerk, during normal movement, stretch receptors are
rarely all activated at the same time, nor are they activated so strongly.
Moreover, movement occurs in response to the integration of many types of
local descending controls.
Second Path
1. The afferent nerve fibers from stretch receptors end on interneuron.
2. When activated, inhibit the motor neuron controlling the antagonistic muscles
(in the knee jerk, the flexor muscles of the knee are inhibited).
Third Path
1. Afferent nerve fibers activate motor neurons of synergistic muscles, that is,
muscles whose contraction assists the intended motion (in the knee jerk,
other extensor muscles).
2. The muscles activated are on the same side of the body as the receptors and
the response therefore is ipsilateral.
Fourth Path
1. Afferent nerve fibers continue to the brain stem.
2. They synapse there with interneuron which forms the next link in the pathway
that conveys information about the muscle length to areas of the brain dealing
with motor control.
ALPHA-GAMMA COACTIVATION
When the muscle shortens, stretch of the intrafusal fibers decreased, and at this
time, the spindle stretch receptors go completely slack, and they no stop firing action
potentials.
But:
In this situation, there can be no indication of any further changes in the muscle
length.
Physiologically:
To prevent this loss of information, the two ends of each intrafusal muscle fiber are
also stimulated to contract during the shortening of the extrafusal muscle fibers.
Thus, maintaining tension in the central region of the intrafusal fibers, where the
stretch receptors are located.
Note: The intrafusal muscle fibers are not large enough or strong enough to shorten
a whole muscle and move joints; their sole job is to maintain tension on the
spindle stretch receptors.
Note: Both alpha and gamma motor neurons are activated by interneurons in their
immediate vicinity and by neurons of the descending pathways. In other
words, they are coactivated, that is, excited at almost the same time during
many voluntary and involuntary movements.
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TENSION-MONITORING SYSTEM AND GOLGI TENDON REFLEX
Any given set of inputs to a given set of motor neurons can lead to various
degrees of tension in the muscles they innervate depending on:
a. Muscle length
b. Load on the muscle
c. Degree of muscle fatigue
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vii. Branches of the afferent neurons cause widespread inhibition via
interneurons, of the motor neurons to the contracting muscle and its
synergists.
viii. They also stimulate the motor neurons of the antagonistic muscles.
Importance
1. Prevent tearing of the muscle or avulsion of the tendon from its attachments
to the bone.
2. Equalize the contractile forces of the separate muscle fibers (that is fibers
which exert excess tension become inhibited by the reflex and the reverse is
true. This will spread the muscle load over all fibers and would prevent
damage in isolated areas of a muscle where small numbers of fibers might be
overloaded.
Cutaneous sensory stimuli on a limb are likely to cause the flexor muscles of the limb
to contract, thereby stimulating withdrawing the limb from the stimulating object. This
is called "flexor reflex" or the "nociceptive reflex" or simply "pain reflex".
It is polysynaptic reflex
The response includes flexor muscles contraction and inhibition of the
extensor muscles, so that the part stimulated is flexed and withdrawn from the
stimulus.
When a strong stimulus is applied to a limb, the response includes not only
flexion and withdrawal of that limb but also extension of the opposite limb.
This is called "crossed extensor reflex".
144
PHYSIOLOGY
Dr. Basim Mohamad Alwan Lecture 14
SPINAL CORD
a) All motor functions are blocked in all segments below the level of transaction.
b) Only some of sensory modalities are lost on the transected side and others
are lost on the other side.
c) Pain, heat, and cold sensations (served by spinothalamic tract) are lost on the
opposite side of the body in all dermatomes 2-6 segments below the level of
transaction.
d) Kinesthetic position, vibration, discrete localization and the two-point
discrimination sensations (served by dorsal and dorsolateral columns) are lost
on side of transaction in all dermatomes below the level of transaction.
e) Discrete light touch sensation is impaired on the side of transaction.
f) Crude touch sensation which is poorly localized still persist because of
transmission in the opposite spinothalamic tract.
145
Fig. 14-1 Brown sequard syndrom
When the spinal cord is transected in the upper neck, all cord functions including
cord reflexes become depressed and lost. This reaction is called "spinal shock".
Mechanism:
The normal activity of spinal cord neurons depends to a great extent on the
continual tonic excitation by discharges of nerve fibers entering the cord from
higher centers (particularly discharges transmitted through reticulospinal,
vestibulospinal, and corticospinal tracts).
After few hours to few weeks, the spinal neurons gradually regain their
excitability (this is a natural characteristic of the neurons anywhere in the
CNS).
In most non-primates, excitability of cord centers returns essentially to normal
within a few hours to day or so.
In human being, return is delayed fro several weeks and occasionally never
complete. Sometimes, recovery is excessive with resultant hyper excitability
of some or all cord functions.
The following are some of spinal functions specifically affected during or after
spinal shock:
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(2) All skeletal muscle reflexes integrated in spinal cord are blocked during initial
stage of shock. Two weeks to several months are needed by those reflexes
to return to normal.
Note: Sometimes, the reflexes become hyper excitable (especially if few facilitatory
pathways remain intact between the brain and the cord whiles the remainder
of the spinal cord is transected.
Note: The first reflex to return normal are stretch reflexes and remnants of steeping
reflexes. In some patients, the knee jerk is returned first and in other patients,
slight contraction of leg reflexes and adductors in response to noxious stimuli.
(3) Sacral reflexes for control of UB and colon evaluation are suppressed for the
first few weeks after cord transaction but then eventually return.
A. Threshold of withdrawal reflex is low (minor noxious stimuli may cause not
only prolonged withdrawal of one extremity but marked flexion-extension
patterns in the other 3 limbs).
B. Repeated flexion movements occur for prolonged periods and contractures of
flexor muscles develop.
C. Stretch reflexes are hyperactive.
D. Reflex contractions of the full UB and rectum occur. The hyperactive UB
reflexes keep it in a shrunken state leading to hypertrophy and fibrosis of its
wall.
E. Blood pressure is generally normal at rest, but wide swings in the pressure
are common as the feedback regulation by baroreceptor reflexes is absent.
F. Bouts of sweating and blanching of the skin.
G. Genital manipulation in males produces erection and even ejaculation.
H. The Mass reflex (strong nociceptive stimulus to skin or excessive filling of a
viscous (over distention of the UB or gut) can cause massive discharge of
large portions of the cord. The effects are:
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The colon and UB are likely to evacuate
The blood pressure rises to a systolic pressure of > 200 mmHg
Profuse sweating of large areas of the body.
DECEREBRATE RIGIDITY
Mechanism
Blocking of normal strong excitatory input to medullary reticular nuclei from cerebral
cortex, red nucleus and basal ganglia → causing the medullary reticular inhibitory
system become nonfunctional → allowing full activity of the pontine excitatory
system and development of rigidity.
The antigravity muscles exhibit phenomenon called spaticity as well as rigidity (this
means any attempt to change position of a limb or other parts of the body, especially
attempts to stretch the muscles suddenly, is resisted by powerful stretch reflex).
This is because:
The pontine and vestibular antigravity signals to the cord selectively excite gamma
moor neurons in the spinal cord much more than they excite α motor neurons. This is
tightens the intrafusal muscle fibers if the muscle spindles which in turn strongly
sensitizes the stretch reflex feedback loop.
1. Placing the animal on its back causes maximal extension of the four limbs.
2. Turning the animal to one side causes the rigidity to decreases
3. Putting the animal in prone position causes minimal rigidity
These changes in rigidity are initiated by the action of gravity on otolith organs
and affected via vestibulospinal tracts.
Moving the head of decerebrate animal relative to the body produces changes
in the pattern of gravity.
1. Turning the head to one side causes the limbs on that side become rigidly
extended while contralateral limbs become less so.
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2. Flexion of the head causes flexion of the forelimbs and continued extension of
hindlimbs.
3. Extension of the head causes flexion of the hindlimbs and extension of the
forelimbs.
(1) Lesions of the lower motor neurons (spinal and cranial motor neurons that
directly innervate the muscles) are associated with flaccid paralysis muscular
atrophy and absence of the reflex responses.
(2) Upper motor neuron lesions (the neurons in the brain and spinal cord that
activate the motor neurons are destroyed) are associated with spastic
paralysis and hyperactive stretch reflexes in the absence of the muscle
atrophy. It is of 3 types:
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Physiology
Dr. Basim Mohamad Alwan Lecture 15
THE HYPOTHALAMUS
The hypothalamus (fig. 15-1) is the part of the diencephalon which forms the
floor and part of the lateral wall of the third ventricle. It is a small structure that
weighs about 5 gm, but is the most important part of the brain in controlling
homeostasis. It is connected to the pituitary gland by the pituitary stalk
(hypophysial stalk). The hypothalamus is a major central component of the
limbic system.
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THE HYPOTHALAMIC NUCLEI
The hypothalamic nuclei (fig. 15-l & 15-2) are classified into five groups; anterior,
middle, posterior, lateral and periventricular.
1. The anterior group: Which includes the anterior, the preoptic, the supraoptic,
the paraventricular, and the suprachiasmaric nuclei?
2. The middle group: Which includes the arcuate, the ventromedial and dorsal
nuclei.
3. The posterior group: Which includes the posterior nucleus, the premamillary
nucleus, and medial and lateral mamillary nuclei?
4. The lateral nucleus: Which forms one large nuclear mass?
5. The periventricular nucleus: Which is a thin sheet of gray matter adjacent to the
third ventricle?
Figure 15-2: Coronal (frontal plane) section in the hypothalamus showing the
lateral, periventricular, and paraventricular nuclei.
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NERVOUS CONNECTIONS OF THE HYPOTHALAMUS
The hypothalamus receives input signals from:
1. The limbic system; the limbic lobe of the cerebral cortex (through the medial
forebrain bundle), the amygdala and the hippocampus.
2. The reticular formation of the brainstem; the sensory reticular formation,
the nucleus ceruleus, the raphe nuclei, and the nucleus of the tractus solitarius.
3. The retina, through fibers in the optic nerve which terminate in the
suprachiasmatic nucleus.
4. The thalamus.
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effects; e.g. micturition. But the control of the parasympathetic functions by the
hypothalamus is very limited and there is "no parasympathetic center' as such in
the hypothalamus.
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Table 15 -1: The hypothalamic releasing and inhibiting hormones.
Hypothalamic hormone Main site of formation The affected ant. Pit. hormone
The supraoptic and paraventricular nuclei of the -hypothalamus are connected to the
posterior pituitary through the hypothalamo-hypophysial tract. Two types of
specific neurosecretory cells in these nuclei synthesize the hormones oxytocin and
antidiuretic hormone (ADH). These hormones flow down in the axoplasm of the
neurosecretory cells to the axon terminals in the posterior pituitary where they
remain stored in secretary vesicles inside the nerve terminals. The hormones are
released on the arrival of the proper nerve signals from the supraoptic and
paraventricular nuclei. The hormones then diffuse through the walls of the
capillaries of the posterior pituitary into the blood stream.
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[III] THERMOREGULATION
The hypothalamic thermostat consists of a "heat loss center" in the anterior
"hypothalamus and a "heat gain center" in the posterior hypothalamus. Both
centers are interconnected and work in a reciprocal manner.
Stimulation of the heat loss center leads to cutaneous vasodilation and profuse
sweating. Its damage leads to high liability to hyperthermia. Stimulation of the heat
gain center leads to cutaneous vasoconstriction, increased muscle tone, shivering
and stimulation of catecholamine secretion. Its damage leads to high liability to
hypothermia.
The heat loss center contains thermosensitive cells. These cells are sensitive to any
change in blood temperature (± 0.02°C) which is an indicator of the body core
temperature. It responds mainly to any increase in core temperature to prevent
hyperthermia.
The heat gain center contains "thermoresponsive" cells which are not
thermosensitive. These cells respond to input signals coming from
cutaneous thermoreceptors which monitor the surface temperature. It responds
mainly to cooling of the skin to prevent hypothermia.
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weight for each individual. If a person is starved for some time, then left free to eat
afterwards, he eats only enough to restore his prestarvation weight. Also if a
person is overfed for some time and left free to eat afterwards, he eats too little until
he regains his previous weight.
The amygdaloid nucleus is closely associated with feeding. It is concerned with
"sorting out" of food into edible or inedible. Lesion in the amygdaloid nuclei leads
to hyperphagia, but unlike animals with lesions in the hypothalamic satiety center,
the animals with amygdaloid lesions try to eat any available object
(omniphagia). They eat some of any available object before they discover if it is
edible or not (oral exploration).
Figure 15-3: The effects of a lesion in the hypothalamic satiety center (left)
and in the feeding center (right).
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4. From subfornical organ (SFO) and organum vasculosum of lamina
terminalis (OVLT). These organs are circumventricular organs found at the
anteroventral border of the third ventricle (AV3V) outside the blood-brain barrier.
They are stimulated by angiotensin II (AH) which is released in cases of
hypovolemia
5. From the limbic system and cerebral cortex;. Psychic and emotional stimuli
can produce or modify thirst sensation.
6. From the mouth and pharynx.
Hypertonicity of the plasma or hypovolemia stimulate thirst center and ADH release
(i.e.: stimulate water intake and" inhibit water loss). Hypotonicity or hypervolemia
has the opposite effect.
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First, is the suprachiasmatic nucleus (SCN) which is connected to the retina by
the retinohypothalamic tract. This tract synchronizes the activity of the SCN to the
circadian light/dark cycle. This nucleus is responsible mainly for regulating the
circadian waking/sleeping rhythm.
Second, is the ventromedial nucleus of the hypothalamus (VMNH) which is
connected with the SCN? It is responsible mainly for temperature, endocrinal and
feeding rhythms.
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FEAR
Fear is an unpleasant emotional state which involves a sense of insecurity because
of impending danger or evil. It is produced by stimulation of the fear center in the
periventricular nuclei. Reactions to fear include cowering, avoidance, and sweating,
pupillary dilation, turning the head from side to side to seek escape and flee.
Amygdaloid nuclei in the temporal lobes activate the fear center in the
hypothalamus.
Bilateral temporal lobectomy abolishes fear sensation. In this case, the subject cannot
evaluate dangers and proceeds towards them without precautions; e.g. handling
dangerous animals as scorpions or snakes, or crossing roads full of rapidly going
vehicles.
RAGE
Rage is violent anger. It is produced by stimulation of a certain area of the lateral
hypothalamus (rage area). This area is tonically inhibited by the ventromedial
nucleus (placidity area), and the limbic association area of the cerebral cortex.
Lesions in the placidity area or the limbic association area produce rage.
Reactions in rage include taking the attack position, generalized sympathetic
stimulation and fighting. In cats there is hissing, spitting, growling and well
directed biting and clawing.
PLACIDITY
Placidity means calmness with little or no response to provocation. It is produced by
stimulation of the ventromedial nucleus of the hypothalamus (the placidity area),
or bilateral damage of the amygdaloid nuclei.
The amygdaloid nuclei facilitate the rage area and inhibit the placidity area or
bilateral amygdaloid damage of the amygdaloid nuclei. The amygdaloid facilitates
the rage area and inhibits the placidity area. Bilateral amygdaloid lesions would then
inhibit the rage area and facilitate the placidity area. If the placidity area is
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subsequently damaged, placidity changes into rage because the rage area would be
released from the inhibitory influence of the placidity area.
Bilateral destruction of the amygdaloid nuclei was made in Japan on agitated,
violent, aggressive mental patients. The patients turned placid and manageable,
without any sign of hyper sexuality.
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EFFECTS OF LESIONS IN THE HYPOTHALAMUS
Lesions in the hypothalamus produce widely variable effects depending on the
locality, the extent and the mode of onset; i.e. rapid (acute) or gradual (chronic). A
lesion may produce one or more of the following manifestations.
1. Endocrinal disturbances:
The most common endocrinal disturbance of hypothalamic origin is diabetes
insipidus which is produced by lesions in the supraoptic "or paraventricular nuclei.
There is lack of ADH secretion from the posterior pituitary. This leads to marked
polyuria and polydipsia.
Another form of endocrinal disturbance is precocious puberty i.e. very early
onset of puberty.
Irregularities of the menstrual cycle occur with lesions in the preoptic area or with
psychic disturbances.
Hyper or hypo function of other glands due to hypothalamic causes are possible but
very rare.
2. Hyperthermia or hypothermia:
Produced by lesions in the hypothalamic thermostat.
3. Hyperphagia or anorexia:
Produced by lesions in the hypothalamic appestat. This leads to either
hypothalamic obesity or severe emaciation.
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5. Disturbances in memory and learning ability:
This is due to interruption of the Papez circuits of the limbic system which are
concerned with short term memory. Lesions in the punishment or reward centers
depress the ability to develop long term memory for important events.
6. Autonomic disturbances:
E.g. Lack of response to emergency situations. Increase or decrease in
catecholamine release, excessive sweating, spontaneous vasodilation (hot flushes) or
vasoconstriction.
7. Emotional disturbances:
E.g. fear, rage, or placidity due to irritation or damage of different hypothalamic
regions.
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PHYSIOLOGY
Dr. Basim Mohamad Alwan Lecture 16
RETICULAR FORMATION
This is a network of neurons located in the brain stem, extending upwards to the
diencephalon (thalamus, hypothalamus and sub thalamus) and downwards to the
upper part of the spinal cord, where it merges with its interneuron's (fig 16-1).
Many nuclei and centers are present within its meshes (respiratory & cardiac
centers, the substantia nigra, the red, vestibular and raphe muclei). It is divided
into sensory and motor parts.
This part consists of a large number of small neurons that have multiple
interconnection with each other (which allows marked convergence, divergence
and after discharge).
It receives a rich polysensory input (afferent fibers) from
A. All ascending lemnisci.
B. The visual, auditory and olfactory nervous pathways.
C. The basal ganglia.
D. The cerebellum.
E. The cerebral cortex (corticofugal fibres )
F. The hypothalamus.
G. The vestibular apparatus.
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(B) THE MOTOR PART
This part consists of large neurons, which receive signals from the sensory
part, and their axons constitute the output (efferent) fibres from the
reticular formation , it contains facilitatory and inhibitory parts .
1. Facilitatory (excitatory) reticular formation: This is located in the
pons and midbrain (specially the former). it has an inherent activity and
the axons of its neurons divide into 2 branches :
a. An ascending branch, which excites the cerebral cortex, and is
called the ascending reticular activating system or ARAS.
b. An descending branch (ventral reticulospinal tract) which
facilitates the spinal centers.
2. Inhibitory reticular formation: this is located mainly in the medulla
oblongata, it has no inherent activity, and its axons descend as the
lateral reticulospinal tract, which inhibits the spinal centers.
The ARAS controls the electric activity of the cerebral cortex, and is concerned
with consciousness and production of the alert response, so reduction of its
activity leads to sleep.
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FACTORS THAT AFFECT THE ACTIVITY OF
THE ARAS
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Physiology
Dr. Basim Mohamad Alwan Lecture 17
THE LIMBIC SYSTEM
COMPONENTS OF THE LIMBIC SYSTEM
The limbic system is the area of the brain that regulates emotion and
memory. This system consists of a group of structures that make the border
between the neocortex and the brainstem (limbus = border). It has two
components:
1. The limbic lobe (archicortex and paleocortex) (fig. 17-1). It is the oldest part
of the cortex. It includes the subcallosal gyrus, the cingulate gyrus, the
retrosplenial cortex, the hippocampus, the parahippocarnpal gyrus and the uncus.
It also includes the piriform cortex and the entorhinal cortex which are connected
to the olfactory bulb and tubercle.
2. A group of deep structures intimately related to the limbic lobe.
Figure 17-1: A view of the medial surface of the right cerebral hemisphere showing the
components of the limbic system
They include the hypothalamus, the amygdale, and the anterior nuclei of the
thalamus, the septal nuclei and the upper part of the midbrain (the limbic
midbrain area - LMA) (fig. 17-2).
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Figure 17 – 2: The limbic system.
M.Str and, LStr; medial and lateral olfactory striae; Str med; stria medullaris; Tub; olfactory
tubercle; DB; diagonal band of Broca; Sep; septum; AT; anterior nucleus of the thalamu; M;
mamillary body; H; Habenula; P; interpeduncular nucleus; MFB medial forebrain bundle;
CONNECTIONS (fig.17-3)
Besides the extensive interconnections between different parts of the limbic system,
it is also connected to higher and lower centers.
The temporal cortex mediates information from the visual, auditory, and somatosensory
cortices to the amygdala and the hippocampus. The orbitofrontal cortex is connected to
the hypothalamus. It is the only neocortical region with direct connection to the
hypothalamus and the most important neocortical control element on the limbic
functions.
The medial forebrain bundle connects the thalamus and hypothalamus with the
orbitofrontal cortex upwards and with the limbic midbrain area (LMA) downwards.
PAPEZ CIRCUIT: The Papez circuit of the brain is one of the major pathways
of the limbic system and is chiefly involved in the cortical control of emotion.
The Papez circuit plays a role in storing memory. Described by James Papez in
1937, Papez discovered the circuit after injecting rabies virus into a cat's
hippocampus and monitoring its progression through the brain.
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Fig. 17-3 Papez circuit
Fig. 17-4 the brain structures associated with the limbic system
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• Its functions are closely associated with hypothalamic functions.
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2. MOTIVATION
Motivation is the feeling which activates a certain behavior to achieve a certain goal.
Motivation is controlled by the limbic association area. The reward and punishment
systems help the limbic association area to decide whether to approach or avert a
certain experience.
3. EMOTIONS
Emotions are states of strong feelings, associated with autonomic, and endocrinal
changes, and a strong affect. An emotional state starts by stimulation of the reward
or the punishment systems. This activates the excitatory reverberating circuits of
the limbic system which set other structures into action:
1. The thalamus which activates the cerebral cortex and increases
the level of alertness.
2. The hypothalamus which starts autonomic and endocrinal reactions; e.g.
tachycardia, hypertension and adrenaline secretion.
3 The amygdaloid nuclei which adjust the hypothalamic sensitivity
4. The orbitofrontal cortex which decides the behavioral motor response to the
incoming signal.
5. The hippocampus which sorts out the input signals and decides whether they
will be stored in memory or ignored and discarded.
Emotions outlast the provoking stimuli because they depend on the activity of the
excitatory reverberating circuits of the limbic system which have a long
afterdischarge. Emotions also cannot be turned on or off voluntarily because the motor
cortex has no efferent connections that can interfere with these circuits.
Stimulation of the medial, forebrain bundle or the septal nuclei produces a sense
of joy and happiness.
4. MEMORY
The limbic system plays an important role in sorting out the sensory signals into
significant ones which are stored in memory and insignificant ones which are
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ignored. It is also important for encoding and consolidation of memory.
5. LEARNING
The hippocampus and amygdala are quite important for operant conditioning and
intelligence.
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rate and arterial blood pressure. The response produced from wide areas in the
limbic system. It is part of response to emotions.
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PHYSIOLOGY
Dr. Basim Mohamad Alwan Lecture 18
SLEEP
Sleep is a state of unconsciousness from which the person can be aroused by
sensory stimuli. A normal adult person sleeps 7-8 hr/day.
A newly-born infant sleeps much longer time (16-18 hi/day), whilst an old person
sleeps less (5-6 hr/day).
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TYPES OF SLEEP
There are two types of sleep which follow each other in a cyclic manner during
the sleep period; these types are:
1. NON-REM SLEEP
Non-REM sleep is also called slow wave sleep, or NREM sleep. It is a quiet sleep
during which there is no REM (Rapid Eye Movement). There are no dreams, but
other signs of mental activity might show up; as sleep-talking or sleep walking
(somnambulism) and night terror of children. Muscles are relaxed.
There are four stages of the non-REM sleep which can be identified by the EEG
recording as follows.
(a) STAGE I (very light steep)
This stage is characterized by slowing of the EEG rhythm and the appearance of
small theta waves. If a person is awakened during this stage, he asserts that he
was not asleep, but just closing his eyes. This stage occurs only at the onset and at
the waking up from sleep.
(b) STAGE II (light sleep)
This stage is characterized by the appearance in the EEG of sleep spindles on a
background of theta waves. Sleep spindles are bursts of large waves with a
frequency of 14-15 Hz which last for 1-2 seconds.
(c) STAGE III (intermediate sleep)
This stage is characterized by the appearance in the EEG of rapid delta waves
(frequency 3-3.5 Hz). Breathing is slow and even, pulse rate is about 65 beats
/min, temperature and arterial blood pressure continue to decline.
(d) STAGE IV (deep sleep)
This stage is characterized by the appearance in the EEG of delta-max waves
(delta waves with maximum slowing; frequency 0.5 - 1.2Hz). This stage occurs
only in the early sleep cycles. There is maximum slowing of breathing and heart
rate (about 60 beats/min). Cheyne-Stoke breathing may occur.
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2. REM SLEEP
During REM {Rapid Eye Movement) sleep, there is rapid roving movement of the
eye. Dreams occur during this type of sleep. The EEG shows the desynchronized
β-rhythm. Although the EEG pattern is indicative of an activated brain, the
awakening threshold is as high as in deep sleep. That is why REM sleep is also called
"paradoxical sleep". There is marked decrease in muscle tone except for occasional
twitches of the facial and finger muscles. During REM sleep, dreams with sexual
elements are associated with erection of the penis and possible ejaculation.
SLEEP CYCLES
Normal sleep starts by non-REM sleep for about 80 min (70- 100) followed by
REM sleep for about 20 min (10-40). The cycle is then repeated but with shorter
NREM and longer REM periods. Four to five sleep cycles occur in a normal one
night sleep. In the later cycles, sleep becomes lighter with no NREM stage IV
(deep sleep) phases. The duration of deep sleep periods shortens with the advance
of age.
MECHANISM OF SLEEP
There are three theories to explain how sleep is induced. All of them are valid and
operating for induction of sleep and controlling the waking/sleeping rhythm.
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urine of subjects during deep sleep.
Table 18 -1: A comparison between NJREM and REM sleep.
Criteria NREM sleep REM sleep
The concentration of factor-S in the brain declines steadily during sleep leading
finally to termination of sleep and start of wakefulness. According to the
metabolic theory of sleep, the important factor in determining the
waking/sleeping rhythm.
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relaxation in a comfortable bed in a quiet, dark room at comfortable temperature.
Under these conditions, all sensory signals are reduced to minimal (functional
sensory deafferentation) and the ARAS activity is markedly reduced. Mental
relaxation eliminates any excitatory corticofugal signals and helps the onset of
sleep.
After a long period of wakefulness ARAS activity is depressed by fatigue. This
reduces the excitability of the cortical neurons leading to sleep.
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(c) WAKING/SLEEPING OSCILLATOR CENTER
The suprachiasmatic nucleus of the anterior hypothalamus is responsible for
synchronizing the waking/sleeping rhythm with the 24-hr light/dark cycle. It is
considered as the waking/sleeping oscillator center. The suprachiasmatic nucleus acts
by stimulating the raphe nuclei which in turn induce sleep. Damage of this nucleus
leads to intense wakefulness. This eventually leads to severe exhaustion which could
be fatal.
JET LAG
Jet lag is the delay of synchronization of sleep and other biological functions of
the body to a shift in the light-dark cycle.
Flying by modem fast jet planes causes shift of the light dark cycles; the day of
the flight is shortened by flying eastwards and is lengthened by flying westwards.
The circadian rhythm of sleep and other biological functions take one day per
time zone (one-hour shift) for readjustment to synchronize with the new
light-dark cycles. Readjustment is easier after flight to the west than to the east.
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pressure. Also, there is general slowing of the circulation with prolongation of the
circulation time.
RESPIRATORY SYSTEM
There is decrease in the rate and depth of breathing which decreases pulmonary
ventilation, Cheyne-Stoke's breathing may occur due to slow circulation and
prolonged lung-to-brain circulation time. Airway resistance increases because of
the increased vagal tone.
BLOOD
PCO2 rises up with a tendency to acidosis due to decreased pulmonary ventilation.
The hematocrit value increases because of the chloride shift.
DIGESTIVE SYSTEM
There is enhanced secretory and motor activity. Splanchnic blood flow increases
and absorption is enhanced.
METABOLISM
Metabolic rate decreases by 10-30 %. Body temperature drops by 0.5- 1°C. The
circadian metabolic and temperature cycles are synchronized with
waking/sleeping cycles, but are not dependent on sleep; i.e. they occur even
without sleep.
ENDOCRINE GLANDS
Secretion of most hormones show a variable degree of circadian rhythmicity
which is synchronized with the waking/sleeping rhythm but again it is mostly
independent of sleep. ACTH and Cortisol secretion decreases to a minimal level
at midnight and reaches a maximum level at about 8 AM.
Secretion of growth hormone, however, is directly related to sleep. It is stimulated
by NREM sleep and inhibited by REM sleep.
SKELETAL MUSCLE TONE
Skeletal muscle tone decreases during sleep, it decreases during REM more than
during NREM sleep. The decrease in muscle tone occurs by inhibition of the
facilitatory reticular formation.
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KIDNEYS
The rate of urine formation increases due to the decrease in sympathetic tone and
the increase in the renal blood flow.
PUPILS
Pupils are constricted despite lid closure. The oculomotor nucleus is released from
cortical inhibition. The parasympathetic tone is higher
during sleep.
SLEEP DISORDERS
INSOMNIA
Insomnia means lack of sleep despite convenient surroundings. A normal adult
can manage with 5.5 hr of sleep/day for long periods without ill effects. Insomnia
may he caused by psychological factors as anxiety, fear, or depression; or the
intake of analeptic substances as tea, coffee, or cola; or lesions in the sleep centers
in the brainstem or the suprachiasmatic nucleus of the hypothalamus, or an
irritative lesion in the dorsal hypothalamus.
Prolonged insomnia leads to bizarre behavior, temporary neurosis and psychosis.
Mental brightness and memory fail with lack of attention. After 4-5 days of sleep
deprivation, hallucinogenic substance similar to LSD (lysergic acid diethylamide)
appears in blood leading to hallucinations.
SNORING
It is the production of sound by a sleeping person during breathing. The person is
usually in the supine position with the mouth open. The tongue sinks back into the
throat. Snoring is occasionally followed by sleep apnea which could be fatal.
SLEEPTALKING
This is not an abnormality. It is just a sign of mental activity which occurs during
NREM sleep.
SLEEPWALKING (Somnambulism)
This is neither pathological nor harmful symptom. It happens to people at any age
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but is most common in children and young adults.
The eyes of the sleepwalker are open, gazing straight ahead to nothing. He avoids
obstacles in his way but pays no attention to the surroundings. Sleepwalking
occurs during deep NREM sleep and is not accompanied by dreaming. It is a
special form of walking guided by sensory stimuli but without consciousness.
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PHYSIOLOGY
Dr. Basim Mohamad Alwan Lecture 19
LEARNING
Learning is the ability of the brain to use previous experience to modify
the inborn reactions or create new ones. There are two types of
learning; non-associative and associative.
1. NON-ASSOCIATIVE LEARNING
In this type of learning, the subject learns whether to ignore or to respond to a
certain stimulus. This occurs through two mechanisms; habituation and
sensitization.
(a) HABITUATION
This is the gradual decrease in response when the stimulus is frequently repeated.
For example, a loud and unexpected sound produces several reflexes, i.e. looking
towards the sound source, change in heart rate and blood pressure. If the sound
turns out to be insignificant to the subject, subsequent repetition of the sound
produces little or no response at all.
Habituation is stimulus specific. If one is habituated to traffic noise, he will be
able to sleep in this noise. Then, on a background of traffic noise, either an
unusual sound or unusual silence will wake him up. Also, a mother who sleeps
through many kinds of noise, wakes up promptly when her baby cries.
Habituation is the simplest and most widespread form of learning. Through
habituation, one learns to ignore a huge number of insignificant stimuli.
(b) SENSITIZATION
This is the potentiation of a response to a certain stimulus by coupling it with
another intense or noxious stimulus. For example, one normally ignores stray
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dogs (by habituation), but if one is bitten by a stray dog, he becomes very attentive
to avert dogs for a long time (the aversion reaction).
Sensitization is stimulus specific. A person who was bitten by a dog will not be
afraid of a caw.
Habituation and sensitization are simple but very important learning processes.
Through them, one learns to direct his attention to significant stimuli and ignore the
much more numerous insignificant ones.
2. ASSOCIATIVE LEARNING
In this type of learning, the subject learns the correlation between one stimulus
and another. Associative learning occurs by conditioning of body reactions.
There are two types of conditioning; classical and operant conditioning.
(a) CLASSSCAL CONDITIONING
Classical conditioned reflexes are reflexes in which a nonspecific stimulus is
made to produce the same response as the specific stimulus of a certain reflex.
They are produced by applying the nonspecific stimulus (conditioned stimulus -
CS) before the specific stimulus (unconditioned stimulus - US) for several times.
When conditioning is established, the application of the CS produces the same
response as the US.
For example, salivation is a normal response to food intake. If a person gets used
to taking tasty meals in a certain restaurant, when conditioning is established, the
entry into this restaurant would reflexly stimulate salivary secretion even without
taking food. In this case, the entry into the place which is the conditioned stimulus
(CS) becomes linked to food intake which is the unconditioned stimulus (US).
To establish a conditioned reflex, the CS must be applied before the US not after it.
The two stimuli must not be separated by a long interval or by any distracting
stimulus. The pairing of the CS and US must occur for several times until new
facilitated pathways for the new conditioned reflex are formed.
The center of classical conditioning is the cerebral cortex. Most of the classical
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conditioned reflexes are integrated in the orbitofrontal cortex.
(b) OPERANT CONDITIONING
Operant conditional reflexes are "reflexes in which the subject learns to take an
action in response to a stimulus to get a reward or avert a punishment"; i.e. the
subject "operates" on his surroundings. For example, a car driver would slow
down and stop the car on seeing the red traffic light, and drives on when seeing the
green light.
Operant conditioning cannot be established in the absence of the cerebral cortex,
especially the orbitofrontal cortex. The hippocampus and the amygdala are
important in linking the stimulus to the operation.
INTELLIGENCE
Intelligence is the efficient employment of past and present experience to get the
best solution for a problem. It is a mental faculty which requires three brain
capabilities:
1. Rapid grasping of significant signals, their coding and storage in the
appropriate memory stores.
2. Rapid retrieval of the appropriate, sufficient information related to current
experience.
3. Efficient linking of information from past experience to information from the
current one to reach accurate evaluation of the situation and formulating or
creating ideas of the best way to handle it.
Although man-made computers grasp, store, retrieve and link data fed to them,
they differ from the brain in that they cannot create new ideas although they can
formulate solutions to problems based on the stored data.
Intelligence is a combined function of the cortical association areas together with
the limbic system. It is the basis for professional efficiency particularly in
intellectual professions as scientists and physicians. High intelligence requires
rich, well coded memory stores.
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Intelligence is not inherited. It is an inborn brain capability which is influenced by
social and environmental conditions. It can be improved by appropriate training.
Trials to improve intelligence by drugs have all failed.
The intelligence quotient (IQ) is a number indicating the ratio of a person's
intelligence relative to the average.
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PHYSIOLOGY
Dr. Basim Mohamad Awan Lecture 20
MEMORY
Memory is the ability of the brain to store information and retrieve it at a later
time. The storage capacity of the human brain is limited. So, the information that
flow into the brain is classified. The most important ones (less than 1%) are
selected and stored, but all the rest are neglected and forgotten.
STORAGE CAPACITY OF THE BRAIN
The information unit is the "bit", A bit is the simplest form of sensory experience;
i.e. a letter, a line, a color, a tone, a smell...etc. The capacity of all the sensory system
to send information to the brain is less than 50 bits/s. E.g. during quiet reading, the
rate of information flow to the brain is 40 bits/s, during mental calculation it is 12
bits/s and during counting it is 3 bits/s. An average rate of information flow is about
20 bits/s. For learning a language, 40-50 million bits should be stored in memory.
Ten neurons are required to store one bit of information. The total storage capacity
of the human brain is about 3x 108 bits.
TYPES OF MEMORY
There are four different types of memory:
[I] SENSORY MEMORY (Immediate memory).
[II] PRIMARY MEMORY (Short-term memory)
[III] SECONDARY MEMORY (Long-term memory)
[IV] TERTIARY MEMORY (permanent memory)
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immediately after the information is acquired. The spontaneous gradual decline in
the amount of stored information is called "fading" of information. The
spontaneous disappearance of information from the memory is called
"extinction" of information. The information in sensory memory can be
transferred to the secondary memory.
[II] PRIMARY MEMORY (Short-term memory)
This is a memory that lasts for few minutes to few hours. The information enters
this memory by verbalization; i.e. through spoken or written words. The primary
memory is not found in young infants or animals as they would not understand the
meaning of spoken or written words.
The capacity of primary memory is small. Bits of information are introduced into
it in chronological order, one after the other. The new information replaces the old
ones. The latter are then forgotten.
The access to the primary memory stores is rapid; one can retrieve the information
rapidly.
[III] SECONDARY MEMORY (Long-term memory)
This is a memory that lasts for several hours up to several years. The information
is introduced into this memory from the sensory and primary memories by two
mechanisms:
L Stimulation of the reward or punishment systems.
2. Repeated practice or rehearsal of the experience.
The capacity of the secondary memory is large. The information is stored
according to its significance. The bits of information of related significance are
stored together. The access to the secondary memory stores is slow; it takes some
time to remember the wanted information.
Forgetting of information in the secondary memory occurs when a new
information conflicts with an old stored one. In this case, one information cancels
the other either by repulsion or by replacement If the 'old information repels the
new one; the process is called "proactive inhibition". If the new information
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replaces the old one, the process is called "retroactive inhibition".
In this way. the more we have learned, the greater the liability to forget the new
information by proactive inhibition. The old information inhibits the acquisition
of new ones. Therefore, the blame for most of our forgetting must be placed on
what we have learned before.
[IV] TERTIARY MEMORY (Permanent memory)
This is the permanent memory. The information stored in this memory are never
forgotten; e.g. one's name or the ability to read and write. Information in the
tertiary memory comes from the secondary memory by years of practice, which
strongly consolidates the memory. The stored information in the tertiary memory
remains available for retrieval even if information in other memories are erased
by brain injury or disease. This is because information in the tertiary memory
occupy large areas of the brain and more than one "copy" of the information are
stored in different regions of the brain.
The access to the ternary memory is very rapid, e.g. one immediately remembers
his name if he is asked about it.
MECHANISMS OF MEMORY
[I] SENSORY MEMORY
Sensory memory is made by prolonged after discharge in the neuronal circuits.
Three mechanisms are involved:
(a) Activation of reverberating circuits leading to repeated reactivation of
neurons.
(b) Short term synaptic potentiation by multiple successive stimulation of input
neurons.
(C) Synaptic sensitization by coupling the sensory experience with intense or
noxious stimulus.
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[II] PRIMARY MEMORY
The primary memory is made by the formation of temporary memory traces. A
memory trace is a newly developed pathway for signal transmission resulting
from facilitation of new synapses. This leads to the creation of new circuits in the
brain that keeps the memory of the experience. Activation of these circuits brings
the memory up to one's mind. There are two possible mechanisms for the
formation of the new memory traces:
(a) Long term potentiation of synapses. During verbalization the brain catches
the new interesting information and rehearses it several times.
(b) Changes in the physical properties of the postsynaptic membrane
leading to enhanced sensitivity to the chemical transmitter.
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[IV] TERTIARY MEMORY
Tertiary memory is made by the formation of permanent memory traces
(permanent engrams). These permanent engrams are made by structural
changes in the neurons. The changes are similar to those in secondary memory.
Tertiary memory may be considered as an advanced stage of secondary memory.
Table 26-1 compares and contrasts the different types of memory
Entry into storage Automatic during Verbalization Practice or stim. Repeated practice
perception of reward or for long time
punish, systems
Speed of retrieval Very rapid Rapid Slow Very rapid
CONSOLIDATION OF MEMORY
Consolidation of memory means the transfer of information from the Sensory and
primary short-term memories to the secondary long-term memory. This process takes
from 5 minutes for minimal consolidation to two hours for maximal consolidation.
Consolidation of memory could be interrupted by deep anesthesia, brain
concussion or electroconvulsive therapy (ECT). Accordingly, if a sensory
impression is made, then followed within 5 minutes by brain concussion or ECT or
anesthesia, the experience gets extinct. This explains why patients who had brain
concussion in accidents cannot remember what happened at the time of the
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accident. If the concussion occurs 2 hours after" the sensory experience, the
information remains unaffected. If it occurs within two hours, the memory is
affected proportionately.
Consolidation occurs to the information which attracts the attention of the mind.
The brain automatically rehearses this information.
A wide awake person consolidates memories far better than a person with mental
fatigue. This is because the wide awake brain is more attracted by the new
information and is capable of making rapid and more frequent rehearsals that
would consolidate memory more effectively.
Normal quiet sleep consolidates the memory of information received before the
onset of sleep.
ENCODING OF MEMORY
Encoding of memory is the classification, then placing each memory item with other
related items in the proper memory store; i.e. memory archiving. It is part of the
consolidation process. The hippocampus plays a central role in this function. All bits
of information go first to the hippocampus where they are sorted out as significant or
insignificant. If the information is classified as significant, single are sent to the
mamillary bodies of the hypothalamus. From the hypothalamus signals proceed on
to the orbitofrontal cortex, then to the basal forebrain (fig. 19-1). From the basal
forebrain (nucleus basalis of Meynert) there are diffuse cholinergic projections to
the memory stores which are found in all parts of the neocortex, the amygdala and
the hippocampus.
The amygdala associates the memories formed through different senses, then
through its connections with the hypothalamus (the amygdalohypothalamic
pathways) it is responsible for the emotional and autonomic responses to
memories.
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Figure 19-1: brain areas concerned with encoding of long term memory.
Long-term memories are stored in the form of engrams in different regions of the
brain. To retrieve a certain memory item, one should get an access to the specific
engrams of this item and activates them. This can be done by different
associations. For example the word "Egypt" could be accessed and activated by
other words as "the pyramids", "the sphinx", "the Nile" or hearing part of the
opera "Aida" or seeing a photo of a pharaoh with his characteristic features and
head dress. Each of these methods of access is considered as a specific "key"
which "unlocks " and activates the specific engrams of the stored item.
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their voices. A prosopagnostic patient develops emotional and autonomic
reactions on seeing a familiar face, but he wouldn't identify the person until he
hears him speaking.
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AMNESIA
Amnesia (Gr. = forgetfulness) means the inability to remember past experience.
There are several types of amnesia:
1. RETROGRADE AMNESIA
It is the inability to recall events that occurred shortly before the onset of brain
malfunction without affecting memories of the remote past. Retrograde amnesia
occurs with brain concussion (post-traumatic
amnesia), anesthesia, electric shock (therapeutic ECT or accidentally). In these
conditions, a transient brain malfunctioning erases the memories of events over a
long period before the onset of malfunctioning. During recovery, the length of the
period of amnesia shrinks progressively till it involves only several minutes.
2. ANTEROGRADE AMNESIA
It is the inability to form new memories. The memories consolidated before the
onset of amnesia are retained. The sensory and primary memories are functional
but cannot be consolidated.
Anterograde amnesia occurs with bilateral lesions in the hippocampus or other
structures involved in the encoding of memory.
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family, his friends or his personal effects.
(iii) The inability to remember past events persists although the patient
can make new memories.
Complete recovery of memory almost always occurs.
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PHYSIOLOGY
Dr. Basim Mohamad Alwan Lecture 21
SPEECH
Speech is the expression of ideas by spoken words. It is a sophisticated function
which is a characteristic of the human brain.
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HEARING AND SPEECH
The development of the faculty of speech depends first on the ability to hear
spoken words. A young baby starts first to learn the meaning of the heard words
then tries to imitate them by vocalization (uttering simple sounds) then by
verbalization (uttering words). So, speech is learned basically through hearing. If
a person is born deaf, he cannot develop the faculty of speech and is destined to
be dump.
Perception of spoken words is the function of the primary auditory area (area. 41)
in the temporal lobe at the floor of the lateral sulcus. Signals are then conveyed to
the adjacent auditory interpretative area (area 42). This area understands the
meaning of the heard words. It feeds the message of the heard words to the
angular gyrus (general interpretative area - area 39) which correlates them with
other related items stored in memory in the process of thinking.
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center) in the premotor cortex via the "arcuate fasciculus.
Figure 20-1: Wernicke's area, angular gyrus , the arcuate fasciculus, and
Broca's area.
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This is the function of Wernicke's area which receives input signals from the
angular gyrus and sends output signals to Broca's area.
3. Word formation: This is the function of Broca's area which receives input
signals from Wernicke's area and sends programmed impulses to the primary motor
cortex to move the muscles of speech in a specific sequence to produce different
words.
4, Verbalization: It is the coordinated contraction of muscles of speech in a
certain sequence to produce spoken words. This is the function of the motor
cortex, the motor nerves and the muscles of speech.
Ideas may be expressed in writing. In this case, Wernicke's area feeds the
signals to Exner's center to write the desired words.
SPEECH DEFECTS
Speech defects are divided into two main categories"
(I) Aphasia
(II) Dysarthria
(I) Aphasia
It is a speech defect in a patient who can see, hear and move the muscles of
speech.
TYPES OF APHASIA
1-Sensory (receptive) aphasia.
2. Motor aphasia.
3. Wernicke's aphasia.
4. Global aphasia.
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Sensory aphasia is found in two forms:
(a) Sensory auditory aphasia (word deafness): This is due to a lesion in the
auditory interpretative area. The patient can hear the spoken words, but is unable
to understand the message.
(b) Sensory visual aphasia (word blindness or dyslexia): This is due to a
lesion in the visual interpretative area. The patient can see the written words but
is unable to understand the message.
3. WERNICKE'S APHASIA
This aphasia is caused by lesions in Wernicke's area of the categorical
hemisphere. The patient comprehends ideas expressed by spoken or written
words. He formulates thoughts and ideas but doesn't know how to express them.
The process of verbalization is normal, so the patient can talk and sometimes he
talks too much (fluent aphasia). However, his speech is full of jargon (speech
full of too much unnecessary words) and neologism (new words invented by
the patient) that make little sense.
Very rarely, when the lesion is in the arcuate fasciculus, the Wernicke's, area is
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disconnected from Broca's area. The patient knows what he wants to say, but
cannot produce the required speech. This condition is called "conduction
aphasia".
4. GLOBAL APHASIA
This aphasia is caused by extensive lesions in the categorical hemisphere
involving both frontal and temporal lobes. The aphasia is general; it involves the
receptive and expressive functions.
[II] DYSARTHRIA
Dysarthria means difficulty in producing clear, normal speech due to a defect in
the motor system of verbalization. There is either weakness, incoordination,
hyper or hypotonia, or paralysis of the muscles of speech.
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