Neurophysiology lectures pdf - The Nervous System

Physiology

Dr. Basim Mohamad Alwan Lecture (1)

INTRODUCTION

The nervous system is unique in the vast complexity of thought

processes and control actions it can perform. It receives each minute

literally millions of bits of information from the different sensory

nerves and sensory organs and then integrates all these to determine

responses to be made by the body. The nervous system contains more

than 100 billion neurons and consists of the central nervous system

(CNS) and the peripheral nerves (fig. 1-1).

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.

DIVISIONS OF THE NERVOUS SYSTEM

The nervous system comprises three major systems;

I. THE AUTONOMIC NERVOUS SYSTEM

: Is the part of the nervous

system which is concerned with the involuntary control of the visceral

activity. It includes sympathetic, parasympathetic and enteric

divisions.

II. THE SOMATIC NERVOUS SYSTEM:

Is the part of the nervous

system which is concerned with conscious perception of different

sensations, and voluntary control of the muscular activity.

This system is divided into two divisions;

(i) SENSORY DIVISION:

Which is concerned with conscious

perception of somatic sensations? It includes the sensory (afferent)

nerves, the sensory (ascending) tracts inside the CNS, the sensory

reticular formation, the thalamus and the sensory cerebral cortex.

(ii) MOTOR DIVISION:

Which is concerned with voluntary control of

muscular activity? It includes the motor cerebral cortex, the basal

ganglia, the cerebellum, the motor reticular formation, the motor

(descending) tracts inside the CNS and the motor (efferent) nerves.

(iii). THE INTEGRATIVE NERVOUS SYSTEM: Is the part of the

nervous system which is concerned with the sophisticated functions of

the brain. These functions include memory, thinking, learning,

language, speech, emotions and general behavior. The main parts of the

integrative division are the cortical association areas and the limbic

system.

All these three systems and divisions are interconnected and their

functions are integrated together and with other systems in the body.

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:

Figure 1-2: The five basic components of a reflex arc

1. Receptor: A sensor which is excited by the stimulus.

2. Afferent nerve: Which conveys input signals to the CNS? The

afferent nerve is also called the sensory nerve,

3. Center: A collection of neurons that receive the sensory

information and issue the order for proper response.

4. Efferent nerve: A nerve that conveys output signals from the CNS

to the effector organ. The efferent nerve is either a motor nerve to a

muscle or a secretary nerve to a gland.

5. Effector organ: A muscular or glandular structure which receives

the final order and executes the reflex response.

NEURAL SYNAPSES

A synapse is the junctional area between a nerve terminal and another

cell. If the second cell is a neuron the synapse is then called a "neural

or neuronal synapse".

The axon of a neuron conducts impulses away from the cell body to

relay onto another cell at the synapses (fig. 1.3). The axon branches

extensively near its end, giving off 1000 branches on the average. Each

branch ends in a nerve terminal. This terminal is a disc-like expansion

called the synaptic knob (the terminal button or the end foot). There

is a gap between the nerve terminal and the adjacent neuron 3 0 - 50 nm

wide called the synaptic cleft. So, at the neural synapse there is

contiguity but no continuity of the two adjacent neurons.

The neuron which conducts impulses to the synapse is called the

"presynaptic neuron'' or "input neuron" and that which conducts

impulses away from the synapse is called the "postsynaptic neuron"

or "output neuron". The synaptic knobs of the presynaptic neuron

contain vesicles called synaptic or transmitter vesicles which contain

the chemical transmitter of the neuron. A polypeptide called synapsin

is found in the walls of the vesicles which bind the transmitter vesicles

to the cytoskeleton keeping them in the cytoplasm away from the release

sites on the presynaptic membrane.

Figure 1-3: Neural synapse

THE IMPORTANCE OF SYNAPSES IN THE NERVOUS SYSTEM

Synapses act as "unidirectional valves" in the nervous pathways, i.e.

they allow the flow of impulses from the pre to the postsynaptic

neurons only. This ensures the flow of impulses in the nervous

pathways in the forward "orthodromic" direction only. Any impulse

that travels along a neuron in the opposite "antidromic" direction

cannot be transmitted to the next neuron because it dies off at the first

set of synapses it meets.

Also, synapses are the sites in the nervous pathways at which

transmission of impulses can be most easily influenced. At the synapse,

transmission of impulses can be accelerated, slowed down, or blocked

by physiological, pathological or pharmacological influences.

CLASSIFICATION OF SYNAPSES

Synapses could be classified according to either their location between

the pre and postsynaptic neurons (histological classification), or the

mechanism of transmission of impulses across them (physiological

classification),

HISTOLOGICAL CLASSIFICATION

According to this classification, synapses are classified into three types

(fig.1-4):

1. Axodendritic synapses: These are synapses between the axon

terminals of the presynaptic neuron and the dendrites of the

postsynaptic neuron.

2. Axosomatic synapses: These are synapses between the axon

terminals of the presynaptic neuron and the soma of the postsynaptic

neuron

Figure 1-4: histological classification of synapses

3. Axoaxonic synapses: These are synapses between the axon

terminals of the presynaptic neuron and the axon of the postsynaptic

neuron.

PHYSIOLOGICAL CLASSIFICATION

According to this classification, synapses are classified into three

types:

1. CHEMICAL SYNAPSES:

In these synapses, transmission of signals

occurs by releasing a ''chemical transmitter" from the presynaptic

terminal into the synaptic cleft. The transmitter then acts on specific

receptors on the postsynaptic membrane to generate postsynaptic

potential. There are more than 40 different synaptic transmitters in the

CNS which are either small molecule rapidly acting (acetylcholine) or

large molecule slowly acting (substance P).

Chemical synapses are the only type of synapses found in the

human nervous system.

2. ELECTRICAL SYNAPSES:

In these synapses, there are gap

junctions between the pre and postsynaptic membranes which allow

the transmission of the depolarization wave directly from the pre to the

postsynaptic membrane.

CONJOINT SYNAPSES (ELECTROCHEMICAL):

In these synapses,

transmission of impulses occurs by both mechanisms electrical and

chemical. They are found in some fish and invertebrates.

THE MECHANISM OF RELEASE OF TRANSMITTER AT THE

CHEMICAL SYNAPSES

When the action potential reaches the nerve terminal, it opens the calcium

gates allowing Ca

influx from the extracellular fluid into the cytoplasm.

induces the phosphorylation of synapsin. This detaches the

synaptic vesicles from their binding to the cytoskeleton. The vesicles get

attached and fused to specific release sites on the presynaptic membrane.

The release sites then rupture and the chemical transmitter is released

into the synaptic cleft. This process is a passive process.

THE MECHANISM OF ACTION OF THE CHEMICAL TRANSMITTER

The transmitter moves in the fluid in the synaptic cleft by simple

diffusion to the receptors on the postsynaptic membrane. It activates these

receptors to generate postsynaptic potential (PSP). There are two types

of PSPs; excitatory and inhibitory:

1. THE EXCITATORY POSTSYNAPTIC POTENTIALS (EPSPs)

EPSPs are produced by depolarization of the postsynaptic membrane

due to sodium influx. The action of the chemical transmitter is to open

the gated sodium channels leading to sodium influx. Some transmitters

produce EPSPs by closing K

channels (membrane depolarization).

2. THE INHIBITORY POSTSYNAPTIC POTENTIALS (IPSPs

)

IPSPs are produced by hyperpolarization of the postsynaptic membrane

due to C1

influx and / or K

efflux. The action of the transmitter in this

case is to open the gated chloride and / or potassium channels. The IPSPs

decrease the excitability of the postsynaptic neuron and resist the

development of any action potential in it.

The excitatory and inhibitory postsynaptic potentials do not obey the

all or none rule. They can be summated either temporally or spatially.

SUMMATION OF THE POSTSYNAPTIC POTENTIALS

There are two ways of summation of the postsynaptic potentials;

temporal and spatial summation.

1. TEMPORAL SUMMATION

This is summation of the postsynaptic potentials produced by a train of

impulses on one presynaptic terminal, reaching the same synapse one

shortly after the other (fig. 1-5). Each time an impulse reaches the

synapse it creates a PSP which is summated with other PSPs in its

magnitude.

Figure 1-5: The mechanism of temporal summation.

Temporal summation is possible because the opening of a ligand-gated

channel lasts for about one ms (millisecond) whilst the PSP produced

by this opening lasts for about 15 ms. In this way any other opening of

the same channel within 15 ms would produce another PSP that will

potentiate the previous one.

2. SPATIAL SUMMATION

This is summation of postsynaptic potentials produced by multiple impulses

in several presynaptic terminals which reach several synapses at the same

moment (fig. 1-6). A large number of postsynaptic spots are stimulated

simultaneously. This increases the stimulated surface area of the

postsynaptic neuron. The simultaneously generated postsynaptic potentials

potentiate each other. In most cases in vivo, both types of summation

occur at the same time (temporospatial summation) where multiple

impulses arrive one shortly after another at several presynaptic terminals.

Figure 1-6: The mechanism of spatial summation

THE RESULT OF SUMMATION OF PSPs

An average neuron in the CNS receives about 1000 terminals from

different presynaptic neurons. Some of these terminals are excitatory and

some are inhibitory. Excitatory and inhibitory postsynaptic potentials

may occur at the same time. Summation of PSPs results in one of two

conditions in the postsynaptic neuron:

1. INHIBITORY STATE

This occurs when the inhibitory input is greater than the excitatory input

so IPSPs are produced and the cell membrane becomes hyperpolarized

and its excitability decreases.

2. EXCITATORY STATE

This occurs when the excitatory input is greater than the inhibitory input so

more EPSPs are produced and the cell membrane becomes depolarized.

When depolarization reaches a critical threshold level (the firing level) a

propagated action potential (nerve impulse) is produced.

The propagated action potential starts at the initial segment of the

neuronal axon not at the soma of the neuron because:

i. The density of the voltage-gated Na

channels at the initial

segment is seven times as much as those at the membrane of the

soma. This allows greater and faster Na

influx which creates more

rapid depolarization up to the firing level.

ii. The depolarization required to open the voltage gated Na

channels at "the initial segment is only +15 mV, whilst the required

depolarization at the soma is +30 mV.

This explains why the axoaxonic synapses are the most effective in

exciting the postsynaptic neuron. This is because they are the nearest

to the initial segment. The least effective synapses are the

axodendretic synapses.

THE EXCITATORY AND INHIB ITORY NEURONS

The presynaptic neuron is either excitatory or inhibitory to the

postsynaptic neurons. This is because neurons can release only one type

of transmitter which is either excitatory or inhibitory to the postsynaptic

neuron. A cotransmitter may be released with the primary

transmitter. It is, however, always a potentiator of the primary

one.

PRESYNAPTIC AND POSTSYNAPTIC INHIBITION

Transmission of impulses across the synapse can be inhibited or

blocked in two ways (fig. 1-6):

1. PRESYNAPTIC INHIBITION

Presynaptic inhibition is the inhibition of synaptic transmission by

inhibiting the release of the transmitter from the presynaptic nerve

terminal. It can be induced by certain drugs (botulinum, toxin) or by

certain inhibitory neurons (attenuators) which synapse on presynaptic

terminals. The attenuator neuron inhibits the synapsin phosphorylase

enzyme of the excitatory neuron so the transmitter vesicles remain

attached to the cytoskeleton and no release of the transmitter.

Figure 1-7: Presynaptic and postsynaptic inhibition.

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)

PROPERTIES OF SYNAPTIC TRANSMISSION

Transmission of signals across the synapses is characterized by:

1. FORWARD DIRECTION

Transmission in synapses is unidirectional, i.e. from the presynaptic to

the postsynaptic neuron, not the reverse. This is because the postsynaptic

neuron cannot release a chemical transmitter at the synapse. So, the

synapse acts as a unidirectional "valve" to keep the flow of signals

between neurons always in the right direction.

2. SYNAPTIC DELAY

When an impulse reaches a nerve terminal, it takes a delay time of

0.5-1.0 ms to pass across the synapse to the postsynaptic neuron. This

time is taken for the release of the chemical transmitter, its diffusion in

the synaptic extracellular fluid, activation of receptors, induction and

summation of postsynaptic potentials.

3. SYNAPTIC AFTERDISCHARGE

After discharge is the persistence of output signals after stoppage of

the input signals. Synaptic afterdischarge occurs at some synapses

because of the delay of inactivation of the chemical transmitter. So, an

impulse conducted by a presynaptic neuron may produce more than,

one impulse in the postsynaptic neuron. The duration of the synaptic

afterdischarge is longer if the chemical transmitter released by the

presynaptic neuron is a long acting one (substance P).

4. FATIGUE

Fatigue is the decline in response caused by prolonged activity. For a

synapse, fatigue is the decline in the response of the postsynaptic neuron

after a long period of high frequency stimulation of the synapse (> 60

Hz). It is manifested by prolongation of the synaptic delay, then failure to

transmit some or all of the impulses across the synapse.

The synapse is an early site of fatigue in the reflex arc and the fatigue of

the neural synapses is caused by:

i. Exhaustion of the chemical transmitter in the presynaptic terminals

which is the main cause.

ii. Inactivation of some postsynaptic receptors due to accumulation of

metabolites.

iii. Marked increase of the intracellular Ca

in the postsynaptic

neuron. This high Ca

level opens K

channels so K

efflux and

hyperpolarization of the postsynaptic membrane decreasing the

excitability of postsynaptic neuron.

Fatigue is a protective mechanism against excess neuronal activity;

e.g. fatigue is the most important means by which the excess

excitability of an epileptic circuit is cut off and stopped. This leads to

spontaneous ending of the epileptic fit (normal protective mechanism).

5. SYNAPTIC POTENTIATION (FACILITATION)

This is an increase in the postsynaptic response caused by previous

presynaptic stimulation.

It may be a short-term or a long-term potentiation.

A. SHORT TERM (POST TETANIC) POTENTIATION

This occurs after a short period of low frequency stimulation of the

synapse (< 60 Hz). It is caused by an increase in the intracellular Ca

level in the presynaptic neuron, which increases the release of the

transmitter. Short-term potentiation lasts for few seconds up to few

minutes.

B. LONG TERM POTENTIATION (LTP)

This occurs after a short period of high frequency stimulation (>60 Hz).

LTP is caused by the release of arachidonic acid from the postsynaptic

neuron which acts on the presynaptic neuron to release more of the

transmitter (Glutamate).

Long-term potentiation occurs in several parts of the CNS, particularly

in the hippocampus and it plays an important role in memory and

learning.

6. SYNAPTIC DEPRESSION (HABITUATION)

Habituation is the gradual decrease in the postsynaptic response when

stimulation of the presynaptic neuron is frequently repeated. With

complete habituation, the postsynaptic response may disappear

altogether.

Habituation is due to inactivation of Ca

channels in the presynaptic

neuron which decrease in intracellular Ca

so release of smaller

amount of transmitter from the presynaptic terminals. The cause of

this, inactivation is unknown.

Habituation could be short-term or long-term depending on how many

times the stimulus is applied. It is an important mechanism of learning,

as it enables the subject to ignore insignificant stimuli.

Habituation of synapses is different from adaptation which occurs in

excitable tissues. Adaptation is the decline in response to a constant

maintained stimulus.

7. SENSITIZATION

Sensitization of a synapse is the potentiation of the postsynaptic

response to a certain stimulus by coupling the stimulus to another

intense (usually painful) stimulus (fig.2-1).

The terminal which conducts the intense or painful stimulus is called

a facilitator terminal. It relays on the presynaptic sensory terminal.

The facilitator terminal stimulates the presynaptic sensory terminal

lead to prolonged action potential in the sensory terminal and more

influx into the sensory terminal so release of more transmitter and

potentiated postsynaptic response result.

Sensitization is an important mechanism in memory and learning.

Figure 2-2: The mechanism of synaptic sensitization.

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

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.

10. EFFECT OF DRUGS

Caffeine, theophylline and theobromine which are found in coffee,

tea enhance synaptic transmission. They increase neuronal excitability

by lowering the threshold of excitation.

Strychnine enhances synaptic transmission by blocking the action of

central inhibitory transmitters (e.g. glycine).

Hypnotics and anesthetics depress synaptic transmission by

decreasing neuronal excitability. They stabilize the cell membrane by

increasing the resting membrane potential (hyperpolarization).

PROCESSING OF SIGNALS IN THE CNS

Nerve signals (impulses) enter the CNS to be directed to various

neuronal pools

(collection of neurons). In the neuronal pools, input

signals are processed, and output signals emerge out to proceed to

specific destinations.

THE DISCHARGE ZONE AND THE FACILITATED FRINGE

(THE LIMINAL ZONE AND THE SUBLIMINAL FRINGE)

When an impulse in an excitatory input neuron reaches the neuronal pool, it

stimulates a group of neurons which form the "stimulatory field'' of this

neuron (fig.2-3).

Figure 2-3: The stimulatory field of an input neuron.

At the middle of the field, stimulation reaches a liminal level

(threshold) and the neurons in this zone discharge impulse. The zone

where neurons discharge impulse is called the discharge zone or the

liminal zone of the input neuron.

Around the discharge zone, there is a circular zone (a fringe) in which

the neurons are only facilitated without reaching the

liminal

firing

level. This zone is called "the facilitated fringe" or "the subliminal

fringe" of the input neuron.

An impulse in an inhibitory input neuron produces an "inhibitory

field'' with maximum inhibition at its center.

FORMS OF SIGNAL PROCESSING IN THE NEURONAL POOLS

Signal processing in the neuronal pools takes one of the following

forms:

[I] Convergence.

[II] Divergence.

[III] Prolongation.

[IV] Shortening.

[V] Sharpening.

[I] CONVERGENCE OF SIGNALS

Convergence is the direction of signals from several input neurons to

excite a single output neuron. There are two main types of convergence

in the neuronal pools.

1. CONVERGENCE FROM A SINGLE SOURCE

This is important because no neuron can be excited by a single input

terminal. So, convergence must occur on neurons to excite those

neurons (fig.2-4). The spatial summation of postsynaptic potentials

from the multiple input terminals builds up a threshold membrane

potential to excite the neuron.

Figure 2-4: convergence from single

source

2. CONVERGENCE FROM .MULTIPLE SOURCES

This is important because it enables neurons of the neuronal pool to

receive signals from different sources (fig. 2-5).

The effect produced will be the resultant of all the inputs whether

excitatory or inhibitory; e.g. motor neurons of the ventral horn of the

spinal gray matter receive inputs from the pyramidal and extra

pyramidal tracts and from the afferent fibers of the stretch reflex and

several intermediate neurons. All these input neurons influence the

contraction and relaxation of the skeletal muscles.

Figure 2-5: Convergence from multiple sources.

[II] DIVERGENCE OF SIGNALS

Divergence is the spread of a signal from one input neuron into more

than one output neuron. There are two main types of divergence in the

neuronal pools:

1. DIVERGENCE IN THE SAME BATHWAY

This leads to spread of the signal into an increasing number of neurons

as it passes from one order of neurons into another (fig. 2-6). It may be

called an "amplifying divergence". It occurs, for example, in the

pyramidal tract where a single pyramidal neuron in the motor cerebral

cortex can excite up to 10,000 muscle fibers.

Figure 2 - 6: Amplifying divergence.

2. DIVERGENCE INTO MULTIPLE PATHWAYS

This leads to spread of the signal into two or more separate directions

from the pool (fig .2-7). It may be called a "diversifying divergence".

It occurs, for example, in the paleospinothalamic tract where

some signals proceed directly to the thalamus and others enter the

spinoreticular tract.

Figure 2-7: Diversifying divergence.

[III] PROLONGATION OF SIGNALS (AFTERDISCHARGE)

Afterdischarge is the persistence of output signals after stoppage of the

input signals. This is possible through the following mechanisms:

1. SYNAPTIC AFTERDISCHARGE:

2. OPEN-OHAIN CIRCUITS

These are circuits in which several interneuron's are arranged to form

an open circuit (fig. 2-7). When interneuron (1) is excited, it sends a

signal to the output neuron and collateral to excite interneuron (2).

Interneuron (2) then sends a signal to the output neuron and collateral

to excite interneuron (3) and so on. The result will be a barrage

(train of

impulses follows each other)

of impulses in the output neuron. The

interneurons of the open-chain circuits are called "the interneuronal

barrages.

Figure 2 - 8: An open chain circuit with interneuronal barrages

3. CLOSED {REVERBERATING} CIRCUITS

These are circuits in which the output neuron is repeatedly activated

through a closed circuit of interneurons (fig.2-8). When interneuron (1)

is excited, it sends an impulse to the output neuron and collateral to

excite interneuron (2). Interneuron (2) then re-excites interneuron (1),

and so on.

Figure 2 - 8: A closed chain (reverberating) circuit of neurons.

Reverberating circuits can be facilitated or inhibited by other input fibers.

When facilitated the frequency and duration of discharge in output fibers

increase. When inhibited, the frequency and duration decrease.

The cycle of reverberation stops by either fatigue of synapses or

inhibition by other input fibers. The frequency and duration of

discharge from a reverberating circuit depends on the number of

neurons (i.e. the number of synapses) in the circuit. The larger the

number the lower is the frequency and the longer is the duration.

RHYTHMIC SIGNAL OUTPUT

Certain centers in the CNS produce rhythmic signals, e.g. the

respiratory center in the brainstem. This rhythmic signal output is

caused by reverberating circuits involving a large number of

interneurons. The large number of synapses slows down the frequency

of output discharge and delays fatigue of synapses.

[IV] SHORTENING OF SIGNALS

Shortening of signals means suppression of afterdischarge in the output

neurons. This is done by either feedback or feed forward inhibition.

1. FEEDBACK INHIBITION

This occurs when an excitatory neuron stimulates an inhibitory neuron

then the inhibitory neuron turns back to inhibit the initial excitatory

neuron. In this case, stimulation of a neuron results in feedback

inhibition of the same neuron to shorten the duration of discharge and

prevent any afterdischarge. This occurs, for example, with the spinal

motor neurons (the ventral horn cells). Each spinal motor neuron

regularly gives off a collateral branch which synapses with an inhibitory

interneuron called "Renshaw cell".

Renshaw cell sends inhibitory signals to the cell body of the original

spinal motor neuron (feedback inhibition). The inhibition of the original

motor neuron suppresses any synaptic afterdischarge to prevent

undesired prolonged activity of the motor nerve.

2. FEEDFORWARD INHIBITION

This occurs when an input neuron stimulates an output neuron plus an

inhibitory interneuron then the inhibitory interneuron inhibits the output

neuron (fig. 2-9). In this case, stimulation of an input neuron results in

stimulation then rapid inhibition of the output neuron. This prevents any

undesired prolonged discharge from the output neuron.

Feed forward inhibition occurs in the cerebellum where a single input

neuron stimulates an output neuron and a Purkinje cell.

The Purkinje cell then inhibits the output neuron, cutting short any

undesired afterdischarge.

Figure 2 - 9: Feedforward inhibition.

[V] SHARPENING OF SIGNALS

Sharpening of signals means the limitation of signals to the target

neurons only. This requires the inhibition of any undesired activity in

the nearby neurons. This is achieved by either lateral or reciprocal

inhibition mechanisms.

1. LATERAL INHIBITION

Lateral inhibition occurs when a neuron sends collaterals to inhibit the

nearby neurons through intermediate inhibitory neurons. This helps to

focus the activity to the original neuron and eliminate any undesired

discharge from the nearby neurons. The function of Renshaw" cell

shows an example of both feedback inhibition (of the original motor

neuron) and lateral inhibition (of the nearby neurons).

Lateral inhibition occurs also in sensory neurons. Sensory fibers

conducting touch (scratching) laterally inhibit itch and pain conducting

fibers at the dorsal horn of the spinal gray matter. In this way scratching

relieves itch and pain sensations.

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".

RECEPTIVE FIELD: the spatial region where application of a stimulus causes a
sensory neuron to respond.



receptive fields can overlap



definition applies to higher order neurons, as well as to primary

afferents

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

THE DORSAL HORN OF THE SPINAL GRAY MATTER

The

dorsal horn of the spinal gray matter is the site of relay of most of

the afferent sensory fibers. A cross section in the spinal cord shows

several anatomical laminae of the gray matter. Each type of sensory

fibers relays in certain specific laminae as shown in fig. 4-2.

Fig.3-2 the dorsal and ventral horn of SC

THE COURSE OF THE AFFERENT SPINAL NERVE AFTER ENTERING

THE SPINAL CORD

As the afferent spinal nerve fiber enters the spinal cord, it takes one of

the following courses:

1. Ascends or descends for few segments at the tip of the dorsal horn

forming the Lissaur tract before entering into the dorsal horn.

2. Enter the dorsal horn to relay on neurons in different laminae of the

dorsal horn. These neurons are either interneurons (intermediate

neurons) or second order neurons of their sensory pathway.

3. Proceeds in the spinal gray matter to relay on motor neurons in the

ventral horn (the reflex arc of the stretch reflex).

4. Ascends without relay in the dorsal column of the spinal white

matter forming the dorsal column tracts (gracile and cuneate tracts)

terminate in the dorsal column nuclei (graclle and cuneate nuclei) in

the medulla oblongata.

SENSORY RECEP TORS

A sensory receptor is a specialized nerve ending which is sensitive to a

specific type of stimulus and produces a specific type of sensation.

FUNCTIONS OF RECEPTORS

1. Detectors of the type of the stimulus. Each receptor is specialized to

detect a certain type of stimulus, e.g. touch, heat, pain etc.

2. Sensitizers, which lower the threshold of stimulation of nerve

endings.

3. Transducers, which convert the energy of the stimulus into an

electric response, i.e. a membrane potential which generates an action

potential in the afferent nerve.

4. Gauges, which measure the intensity of the stimulus.

Accordingly, it can be concluded that without receptors, the CNS

becomes almost useless.

PROPERTIES OF THE SENSORY RECEPTORS

(A) SPECIFICITY

Each receptor is highly sensitive to a certain type of stimulus which is

called the "adequate stimulus" for this receptor. When the adequate

stimulus is used, the receptor is stimulated by the least amount of

energy. If the receptor is stimulated by a stimulus other than its

adequate stimulus, it needs high energy and still gives its specific type of

sensation; e.g. light receptors in the eye could be stimulated by a strong

mechanical blow on the eye, these results in seeing flashes and stars.

(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 - 3: The generator potentials produced by 4 increasing intensities of stimuli

(1,2,3,4). When the generator potential reaches the firing level, a full action potential

is produced in the afferent nerve.

The generator potential is characterized by:

1. It does not obey the all or none rule. Its magnitude increases

proportionately with the intensity of the stimulus.

2. It is not followed by a refractory period.

3. It has a long duration (more than 5 ms). So, it can be temporally

summated.

4. When it reaches a threshold value, it activates the first node of

Ranvier of the afferent nerve to generate an action potential in the

afferent nerve.

Figure 3 - 4: The relationship between the magnitude of the generator potential and

the frequency of discharge of impulses in its afferent nerve.

5. It is not blocked by local anesthetics. Local anesthetics prevent the

development of the action potential at the first node of Ranvier but do

not prevent the development of the generator potential.

When the generator potential exceeds the threshold value, the

frequency of discharge of impulses in the sensory nerve becomes

directly proportionate with the amplitude of the generator potential

(fig. 3-3).

(C) DISCHARGE OF IMPULSE

The response of a receptor to a change in the intensity of the stimulus is

by changing the "frequency" of impulses generated in the afferent

nerve. That is why the response of receptors: to a change in stimulus

intensity is called a "frequency modulated response" or "FM

response". Weber-Fechner law states that "The frequency of discharge

of impulses from a receptor is directly proportionate with the log

intensity of stimulus.

Figure 3 - 5: The compression function of receptors

For example, a hundred-fold increase in the intensity of the stimulus

leads to only twofold increase in the frequency of discharge of impulses

from the receptor. The modulation of large changes in the intensity of the

stimulus to small changes in the frequency of impulses is referred to as

"the compression function" of the receptor (fig.3-5). This function

enables the receptor to respond to, and discriminate, a wide range of

stimulus intensity, e.g. sound receptors can inform the CNS of sound

intensity range of one to ten billion-folds.

(D) ADAPTATION OF RECEPTORS

Adaptation is the decline in response to a constant maintained stimulus.

If a constant maintained stimulus is applied to a receptor, the frequency

of discharge of impulses in its afferent nerve declines with time. The

rate of decline depends on the type of receptor (fig. 3-6).

The sensory receptors are classified according to their rate of

adaptation, into three types:

Figure 3-6: Adaptation of receptors

1. Rapidly adapting receptors (phasic receptors), e.g. touch and hair touch

receptors.

2. Moderately adapting receptors e.g. thermoreceptors in the

temperature rangebetween 20-40°C.

3. Slowly adapting receptors (tonic receptors), e.g. muscle spindles

and Golgi tendon organs.

The rate of adaptation of each type of receptors fits its function. E.g.

touch receptors adapt rapidly, so after putting clothes on; it would be

irritating to feel the touch of clothes all the time. So, touch receptors

adapt rapidly and stop discharging. On the other hand, muscle spindles

send continuous proprioceptive signals to the CNS which maintain

body posture and equilibrium which are needed all the time, so they

adapt very slowly.

Figure 3 - 7: rate of adaptation of different types of receptors.

MECHANISM OF ADAPTATION OF RECEPTORS

The following factors contribute to the process of adaptation of

receptors:

1. Gradual inactivation (closure) of some Na

channels in the

membrane of the nerve ending so membrane depolarization becomes

difficult.

2. Dissipation of some of the stimulus energy to the surrounding tissues

i.e. redistribution of the energy of the stimulus.

3. Decreased sensitivity of the node of Ranvier.

CLASSIFICATION OF RECEPTORS ACCORDING TO THEIR ADEQUATE

STIMULUS

According to the type of their adequate stimulus, receptors are

classified into 5 main categories as shown in fig. 3-8.

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.

1. CODING OF THE MODALITY OF THE STIMULUS

Each sensory pathway from the receptor up to the final sensory neuron in

the brain is specialized to serve a specific sensory modality.

Stimulation of any point along the course of any sensory pathway

produces its specific sensation. The reservation of a specific sensory

pathway to serve a specific type of stimulus is referred to as "the

labeled line principle"; i.e., the whole line from the receptor to the

final sensory neuron in the brain is "labeled" for conducting impulses of

a specific sensation.

So, the coding of a stimulus modality is by sending the impulses

through its specific sensory pathway (i.e. its labeled line).

LABELED LINE PRINCIPLE

(MULLER'S LAW OF SPECIFIC NERVOUS ENERGY)

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 LOCALITY OF 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.

3. CODING OF THE INTENSITY OF THE STIMULUS

The intensity of the stimulus is coded by two factors:

The frequency of discharge from the sensory receptor. The

frequency is proportionate with the log intensity of the stimulus

(Weber Feschner law)

The number of activated receptors. A stronger stimulus activates

more receptors. The activation of more receptors by stronger stimuli is

called "recruitment of receptors".

Physiology

Dr. Basim Mohamad Alwan Lecture (4)

SOMATIC SENSATIONS

Somatic sensations are sensations which are conducted by the somatic nerves and

come to conscious perception. They are classified into three categories;

[I] MECHANORECEPT1VE SENSATIONS

These are sensations produced by mechanical stimuli. They include senses of

touch (crude and fine), tickle and itch, texture of material, vibration, pressure,

stereognosis, muscle tension and proprioception.

[II] THERMORECEPTIVE SENSATIONS

These are sensations produced by thermal stimuli. They include warmth and cold

sensations.

[III] PAIN SENSATION

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.

Figure 4 - 1: Cutaneous mechanoreceptors. A: free nerve endings, B: Basket endings

around hair follicle, C: Merkel discs, D: Ruffini ending, E: Pacinian corpuscle, E: Meissner

corpuscle.

These receptors differ in their excitability, rate of adaptation, and the ability to

respond to repetitive stimuli. They are present in the skin all over the body, but

highly condensed in the finger tips and lips which are highly sensitive to touch.

[II] DEEP MECHANORSCEPTORS

These receptors are of two types:

i. Muscle spindles: which are stretch receptors found in the fleshy part of skeletal

muscles?

ii. Golgi tendon organs: which are tension receptors found in the tendons of the

skeletal muscles.

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) FINE TOUCH

This is touch sensation with accurate identification of the locality and the number

of stimuli. Fine touch sensation is classified into senses of tactile localization

and tactile discrimination.

(a). TACTILE LOCALIZATION

It is the ability to identify the point where the stimulus is applied. It is tested by

touching the skin of blind-folded subject by the tip of a blunt-pointed object, then

asking the subject to open his eyes and point out the site where he was touched.

The acuity of this sense is inversely proportionate to the distance of error in

localizing the stimulus.

(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.

TEXTURE OF MATERIAL SENSATION

This is the ability to identify the substance from which a textile is made; e.g. silk,

wool, cotton, synthetic material ...etc., by touching and without seeing it. It is a

special type of fine touch sensation which is conducted by the gracile and cuneaie

pathway.

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.

4. PROPRIOCEPTIVE SENSATIONS (PROPRIOCEPTION)

Proprioception is the sensation of the position of different parts of the body

relative to each other and the position of the body in space.

Proprioception is divided into two types:

(A) STATIC PROPRIOCEPTION (SENSE OF POSITION)

Static proprioception is the sense of the position of different parts of the body

relative to each other. The receptors are the deep mechanoreceptors (muscle

spindles and Golgi tendon organs. It is tested by putting a limb in an unusual

position and asking the blind-folded subject to put the other limb in a similar

position.

(B) DYNAMIC PROPRIOCEPTION

(SENSE OF MOVEMENT, KINESTHETIC SENSATION OR KINESTHESIA)

Dynamic proprioception is the sense of movement of joints. The receptors are the

Pacinian corpuscles and Golgi tendon organs in ligaments and synovial

membranes of joints. This sense is tested by moving a joint and the blind-folded

subject is asked to tell when the movement begins and when it stops or when the

rate of movement changes.

THERMORECEPTIVE SENSATIONS

Thermoreceptive sensations are those of warmth and cold. There are two types

of specialized thermoreceptors, one is sensitive to warmth and the other is

sensitive to cold. Thermoreceptors are found in the base of the epidermal layer of

the skin. There are warmth sensitive spots on the skin where there are warmth

receptors only and cold sensitive spots where there are cold receptors only. The

number of cold spots on the skin is 4-10 times as many as those of the warmth

spots. The highest density of thermoreceptors is found in the skin of the face and

hands.

Thermoreceptors are also found in the abdominal viscera, the spinal cord and

around great veins. These receptors are concerned mainly with informing the

hypothalamic thermostat of any increase in the body core temperature. They do

not give rise to warmth or cold sensations.

Cutaneous thermoreceptors monitor the temperature of the skin, not that of the

body. An alcoholic drink in cold weather gives a sense of warmth mainly because

it causes cutaneous vasodilation leading to warming of the skin. In this case, the

sense of warmth reflects an increase in the temperature of the skin, not that of the

body. The body temperature might even decrease because of the excessive heat

loss from the skin.

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

C with maximum frequency of discharge at about

40°C (fig. 4-3). At temperatures lower than 40

C 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).

Figure 4 - 4: Krause end bulb.

At temperatures higher than 25°C, the frequency of discharge decreases and the

discharged impulses take the ungrouped pattern. Cold sensation is transmitted

by type III nerve fibers.

Figure 4-5: The change in

frequency and pattern of discharge from thermoreceptors with the

change of temperature

Thermoreceptors adapt at temperatures between 20-40°C, giving a feeling of

thermeneutrality, but no adaptation occurs outside this range. At temperatures

below 15

C or above 45°C, thermosensitive pain receptors are activated giving

rise to pain sensation (cold pain and heat pain). Pain sensation at temperature

ranges of 10-15 and 45-50 is very mild and masked by the senses of extreme cold

or extreme warmth respectively. The sense of thermal pain is clearly perceived at

temperatures below 10 or above 50 °C.

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.

PARADOXICAL COLD SENSATION

Rapid warming of the skin to temperatures between 45-50

C gives a transient

false sense of cold (paradoxical cold sensation). This is because at this

temperature range, cold receptors are transiently stimulated (fig. 4-3).

Paradoxical cold, like any cold sensation, produces reflex vasoconstriction and

rise in arterial blood pressure (the cold pressor effect).

Hot water showers are not recommended for cardiac patients because they may

give a sense of cold and then cold pressor effect which lead to rise in arterial blood

pressure and increase in the work load on the heart and heart failure.

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.

CHARACTERISTICS OF PAIN SENSATION

Pain has the following characteristic properties

1. Widespread distribution: Pain receptors are present almost everywhere in the

body. It is most abundant in the skin.

2. High threshold of stimulation: The stimuli used to produce pain sensation

(noxious stimuli) are of high energy that causes damage of the tissues.

3. It is produced by a variety of stimuli; mechanical, thermal or chemical.

4. It is a nonadapting sensation; pain sensation persists so long as the noxious

stimulus is applied, the sensation of pain might even increase.

5. It produces prepotent withdrawal reflexes; a prepotent reflex is a reflex that

takes priority over any other reflex occurring at the same time. E.g. swinging of

the arms is an automatic reflex that occurs during walking. If during walking a

noxious stimulus is applied to the arm, swinging stops and the arm is rapidly

withdrawn away from the stimulus.

6. It is the only sensation which produces an unpleasant "affect" without

any previous learning or experience. The pleasantness or unpleasantness of

other sensations are conditioned and depend on previous learning and experience.

Only pain has a "built-in" unpleasant affect. Prefrontal lobotomy (an operation to

cut the deep connections of the frontal lobes with the rest of the brain) abolishes

this affect. After this operation, the patient feels the pain, but it does not bother

him.

7. It can be perceived at the thalamus. The cerebral cortex is not essential for

the perception of the slow type of 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.

TYPES OF PAIN ACCORDING TO ITS SITE OF ORIGIN

According to the site of its origin, pain is classified into three types:

I. CUTANEOUS PAIN: Which arises from the skin and is transmitted by

cutaneous somatic nerves?

II. DEEP PAIN: Which arises from deep structures like muscles, tendons,

ligaments, periosteum, and is transmitted by deep somatic nerves?

III. VISCERAL PAIN: Which arises from viscera like the heart, the kidney and

the intestine, and is transmitted by the visceral afferent fibers in the autonomic

nerves?

TYPES OF PAIN ACCORDING TO THE SPEED OF ITS CONDUCTION

Pain is conducted by either type III or type IV sensory nerve fibers.

Accordingly, there are two types of pain; fast pain which is conducted by type III

fibers, and slow pain which is conducted by type IV fibers. They differ widely in

their properties and characteristics.

On application of a noxious mechanical stimulus to the skin (e.g. a pinprick on

the foot), one first feels a bright, sharp, localized pain of very short duration (less

than one second). This is the fast pain, which is also called "pricking pain". This

pain is produced by stimulation of the mechanosensitive pain receptors. Shortly

after feeling the pricking pain, one feels a dull, intense, burning, diffuse pain of

longer duration (few sec. to few min.). This is the slow pain, which is also called

"burning pain" or "aching pain". This pain is produced by stimulation of the

chemosensitive pain receptors.

CHARACTERISTICS OF FAST PAIN

1. It is only cutaneous.

2. It is conducted by type-Ill fibers (speed: 6-30 m/s)

3. It is felt immediately after application of the stimulus (0.1 second after

application of the stimulus).

4. It is of very short duration.

5. It is bright and sharp.

6. It is well localized.

7. It is perceived only by the sensory cerebral cortex.

8. It is conducted by the necspinothalamic sensory pathway.

CHARACTERISTICS OF SLOW PAIN

1. It can be cutaneous, deep or visceral.

2. It is transmitted by the slowly conducting type-IV fibers (speed: 0.5-2 m/s).

3. It starts about one second after application of the stimulus.

4. It lasts for a long time.

5. It is dull, aching (or burning).

6. It is diffuse and poorly localized.

7. It can be perceived at the level of the thalamus; the cerebral cortex is not

essential for its perception.

8. It is conducted by the paleospinothalamic sensory pathway.

DISSOCIATION OF FAST AND SLOW PAIN

One type of pain may disappear leaving the other intact, as in the following

conditions:

1. Compression or hypoxia of a nerve abolishes the conduction of fast pain but

leaves slow pain. This is because hypoxia affects the thick type-Ill nerve fibers first

2. Mild local anesthesia (e.g. local low dose of cocaine) abolishes the conduction

of slow pain but leaves fast pain. This is because mild anesthesia affects the thin

type-IV nerve fibers first

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.

CRITERION

FAST PAIN

SLOW PAIN

1. Site of origin

only cutaneous

cutaneous, deep or

visceral

2. Time of perception

0.1 sec. after the stimulus

1 sec. after the stimulus

3. Characteristics

bright, sharp & localized

dull, intense and diffuse

4. Duration

very short (less than 1

sec.)

longer (few sec. - few

min.)

5. Conducting nerves

type-HI fibers

type-IV fibers

6. Sensory pathway

neospinothalamic

pathway

paieospinothalamic

pathway

7. Associated reflexes

rapid,

protective withdrawal

reflexes

slower

autonomic reflexes (e.g.

increase in heart rate &

ABP)

8. Abolished by

hypoxia or pressure on

the nerve

mild local

anesthesia (low dose

of local cocaine)

9. Center of perception

cerebral cortex

thalamus

10. Relay in dorsal horn

laminae II & V

laminae II & III

11.Relay nuclei in the

thalamus

VPLN

ELN

12.Relay in

reticular

formation

no relay

relay

13.Final destination in

CNS

sensory cerebral cortex

all areas of the cerebral

cortex.

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.

CAUSES OF DEEP PAIN

1. Ischemia of skeletal muscles: This leads to the release and accumulation of

P-factor (Lewis pain-producing factor). The nature of this factor is not exactly

known, but it could be bradykinin, histamine, proteolytic enzymes, lactic acid or

potassium ions or a collection of all these substances.

P-factor directly stimulates the chemosensitive pain receptors, but it also

facilitates the mechanosensitive and thermosensitive pain receptors.

Prostaglandins are released from damaged and inflamed tissues. They facilitate

but do not stimulate pain receptors. So they produce tenderness of the affected

area.

INTERMITTENT CLAUDICATIONS (LAMENESS OR LIMPING):

This disease is an example where there is severe ischemic pain in the muscles of the

lower limb. In this condition, there is narrowing of blood vessels of the lower limbs

(following vascular inflammation or severe atherosclerosis). The slightest exercise

leads to accumulation of the P-factor and pain sensation then limping. . During rest", there

is no. pain as there is no accumulation of the P-factor.

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.

3. Bone injury: It is painful because of the chemical and mechanical irritation of

the overlying periosteum. Bone itself is insensitive to pain.

4. Inflammation of joints: It is painful due to chemical and mechanical irritation

of the surrounding tendons and ligaments.

III - VISCERAL PAIN

Visceral pain is a slow type of pain that arises from the viscera (abdominal and

thoracic contents). It is carried by the visceral afferent type-IV slow conducting nerve

fibers. Some regions are insensitive to pain as the liver parenchyma and lung

alveoli.

CHARACTERISTICS OF VISCERAL PAIN

1. It is diffuse, dull or colicky.

2. It is a slow pain, carried by the slowly conducting type-IV fibers.

3. It is poorly localized.

4. It may be referred to the skin or other deep structures.

5. It is associated with:

(a) Autonomic reflexes: Nausea; vomiting, sweating, bradycardia. That is why

visceral pain is said to be "sickening".

(b) Somatic reflexes: Rigidity of the overlying skeletal muscles; e.g. the rigidity

of muscles over the inflamed appendix (guarding rigidity).

dermatome.

(d) Strong emotional affect: With depression, malaise and bad mood.

NERVES CONDUCTING VISCERAL PAIN

Visceral pain is conducted via afferent visceral fibers in the autonomic nerves (fig.

8-1). Somatic nerves conduct pain from some parts of the viscera.

VISCERAL PAIN CONDUCTED BY SYMPATHETIC NERVES

Afferent fibers that run with sympathetic nerves conduct pain from the thoracic and

abdominal viscera, the urinary bladder, uterus and uterine tubes.

VISCERAL PAIN CONDUCTED BY PARASYMPATHETIC NERVES

• With glossopharyngeal and vagus nerves (Cr. IX and X nerves):

Pain from pharynx, trachea and upper part of the esophagus

• With the pelvic nerve (S 2, 3 & 4): Pain from sigmoid colon,

rectum, the trigone of the bladder and the genital organs.

Figure 8 -1: The areas from which pain is conducted by somatic and by autonomic nerves.

VISCERAL PAIN CONDUCTED BY SOMATIC NERVES

Thoracic intercostal nerves carry pain sensations from parietal pleura, parietal

pericardium and parietal peritoneum. This pain is called "parietal pain". It is

well localized.

CAUSES OF VISCERAL PAIN

1. Ischemia: Ischemic pain is due to accumulation of the P-factor which

stimulates the chemosensitive pain receptors. E.g. anginal pain of myocardial

ischemia.

2. Spasm of a hollow viscus: Spasmodic pain is colicky pain caused mainly by

stimulation of the mechanosensitive pain receptors. Ischemia due to squeezing of

blood vessels may contribute to pain production. E.g. intestinal, renal or biliary

colic.

3. Overdistention of a hollow viscus: Overstretch of the tissues stimulates

mechanosensitive pain receptors. Ischemia may contribute. E.g. overdistention of

the intestine by large volumes of gases.

4. Chemical irritation: Chemical irritants produce pain by stimulating

chemosensitive pain receptors. E.g. Rupture of a peptic ulcer could lead to leak of

the highly acidic gastric juice into the peritoneum leading to severe abdominal

pain. Inflammations produce pain by producing chemical irritants (pain

producing substances).

5. Traction on the mesentery: E.g. by an abdominal tumor. This cause is rare

and of little clinical significance.

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.

MECHANISM OF REFERRED PAIN (convergence projection mechanism):

Afferent pain-conducting fibers from the viscera converge with afferent

pain-conducting afferent pain-conducting fibers from the skin on one central

neuron of the paleospinothalamic tract.

Figure 5-2: An example of the convergence projection mechanism of referred pain.

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).

THE GATE THEORY OF PAIN TRANSMISSION

The dorsal hom of the spinal gray matter is the site of first relay in the sensory

pathway of pain. At this level, there is a group of inhibitory, enkephalinergic

intemeurons which form the "Pain. Inhibitory Complex, PIC. When

stimulated, these interneuron's block the transmission of pain sensation by

presynaptic inhibition of the primary pain-conducting fibers. At the dorsal horn

also, transmission of pain sensation could be facilitated in cases of secondary

hyperalgesia. In this way, the dorsal horn acts as a "gate" that may pass, facilitate

or block pain transmission. Accordingly, the dorsal horn of the spinal gray matter

is sometimes referred to as the "gate" for pain transmission.

The same "gating" mechanism for pain is found also at the thalamus where pain

signals could be blocked by corticofugal fibers or facilitated by intralaminar

thalamic nuclei. In this way, the thalamus acts as a secondary gate for pain

transmission.

Physiology

Dr. Basim Mohamad Alwan Lecture (6)

INTERINSIC MODIFICATION

F PAIN SENSIBILITY

Intrinsic mechanisms can modify pain sensation leading to exaggerated or

suppressed pain sensibility.

I. EXAGGERATED PAIN SENSIBILITY

1. CUTANEOUS HYPERALGESIA

This is a pathological condition where pain sensibility from the skin is exaggerated.

It usually follows a skin injury or inflammation. There are two types of cutaneous

hyperalgesia:

A. PRIMARY HYPERALGESIA

In this case, the threshold of pain sensation from the affected area is lowered. A

stimulus which normally produces mild pain causes severe, prolonged pain.

Primary hyperalgesia occurs in conditions like sunburns. It is restricted to the

affected area of skin and the area of hyperemia around it (the area of the spreading

flare). This type of hyperalgesia is caused by facilitation of pain receptors by

substances released from the damaged or inflamed tissues, e.g. histamine,

bradykinins, substance-P, Prostaglandins ...etc.

ALLODYNIA

is a severe type of primary hyperalgesia in which a gentle stimulus like

a breeze or the touch of clothes produces severe pain.

B. SECONDARY HYPERALGESIA (HYPERPATHIA)

In this case, the threshold of pain is increased, but when the threshold is reached it

produces severe burning pain. It occurs in a normal skin area that extends beyond the

spreading flare of the injured skin. Secondary hyperalgesia is produced by

convergence-facilitation mechanism (fig. 6-1).

Figure 6-1: The convergence facilitation mechanism of secondary hyperalgesia.

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.

3. THE THALAMIC SYNDROME

Thalamic syndrome is caused by thrombosis of the thalamogeniculate artery, a

branch of the posterior cerebral artery. At first, all sensations are lost on the

opposite side. Few weeks later, pain sensibility is regained. A noxious stimulus

produces very severe, stabbing and extremely unpleasant pain. This is due to the

facilitation of the medial and laminar nuclei of the thalamus which do not degenerate

in this syndrome. They potentiate pain conducted by the reticular activating system of

the brainstem.

II. SUPPRESSED PAIN SENSIBILITY

ANALGESIA

Analgesia means suppression of pain sensation. There is an analgesia system in

the body which can suppress pain sensibility by activating the spinal pain

inhibitory complex. The analgesia system of the body is divided into peripheral

and central analgesia systems.

THE PERIPHERAL ANALGESIA SYSTEM

The peripheral anesthesia system consists of the type-II sensory nerve fibers which

conduct mechanoreceptive sensations.

Immediately after they enter into the spinal cord, type-H fibers divide into medial

and lateral branches. The medial branch ascends to form the gracile and cuneate

tracts, and the lateral branch stimulates the PIC to inhibit pain transmission. In

this way, pain sensation can be suppressed by scratching or rubbing of the skin.

Counterirritants which are applied to the skin to suppress pain (mustard plaster

or liniments) work on this principle. They stimulate the cutaneous receptors

which send impulses through type-II fibers that stimulate the PIC. This is also the

basis for acupuncture.

On the same principle, electrodes surgically implanted in the dorsal column

activate the PIC and suppress pain sensibility. They are sometimes used for

treatment of intractable pain.

THE CENTRAL ANALGESIA SYSTEM

This system consists of five components (fig. 6-2)

1. THE CEREBRAL CORTEX

Many areas of the cerebral cortex, especially the limbic association area, project

corticofugal fibers to:

a. The thalamus; these fibers block pain signals at the level of the thalamus (the

second gate for pain transmission).

b. The periaquiductal gray matter of the mesencephalon.

The corticofugal fibers are B-endorphinergic.

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.

THE PERIAQUEDUCTAL GRAY MATTER OF THE MIDBRAIN

Neurons from this area project enkephalinergic fibers to the reticular formation of the

brainstem and fee raphe magnus nucleus.

4. THE RETICULAR FORMATION OF THE BRAINSTEM

This structure sends serotonergic descending fibers in the lateral reticulospinal

tract to activate the spinal PIC. It also projects fibers to the raphe magnus nucleus.

Fig.6-2 the central analgesia system

5. THE RAPHE MAGNUS NUCLEUS

The raphe magnus nucleus is found in the lower pons and upper medulla.

Serotonergic nerve fibers descend from this nucleus down in the lateral reticulospinal

tract to activate the spinal PIC.

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.

THE NERVOUS PATHWAYS OF SOMATIC SENSATIONS

A tract is a bundle of nerve fibers in the spinal cord with common origin, common

destination and a common function. An ascending tract is a sensory tract which

conducts sensory signals up to the higher brain centers. A descending tract is a

motor tract which conducts motor signals from the higher brain centers down to the

motor neurons in the motor neuron pool.

The nervous pathway of a sensation starts from its sensory receptors up to the

final sensory neurons in the brain. It involves 2 - 4 orders of neurons. The first

order neurons of all sensory pathways are the afferent sensory nerves which have

their cell bodies in the dorsal root ganglia or equivalent ganglia of the cranial

nerves. An ascending tract is the part of the sensory pathway which is found in

the spinal cord.

THE VENTRAL SPINOTHALAMIC PATHWAY

The ventral spinothalamic pathway (fig. 6-3) is the sensory pathway for crude

touch, tickle and itch sensations. It has three orders of neurons:

FIRST ORDER NEURONS:

are the dorsal root neurons. Their afferent fibers (type III and

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

Fig. 6-4 the paleospinothalamic pathway

The paleospinothalamic pathway (fig. 6-4 is the sensory pathway for slow pain,

and temperature sensations.

FIRST ORDER NEURONS:

are the dorsal root neurons. Their afferent fibers (type 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 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.

2. THE NEOSPINOTHALAMlC PATHWAY

The neospinothalamic pathway (fig. 6-5) is the sensory pathway for fast pain.

FIRST ORDER NEURONS:

are the dorsal root neurons. Their afferent fibers (type

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.

THE DORSAL COLUMN PATHWAY

The dorsal column pathway (also called the graeile and cuneate pathway) (fig. 6-6) is

the sensory pathway for fine touch, fine pressure, vibration, stereognosis, muscle

tension and proprioceptive sensations.

FIRST ORDER NEURONS:

are the dorsal root neurons. Their afferent fibers (type II)

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.

Fig. 6-6 the dorsal column pathway

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.

THE SPINOCERVICAL PATHWAY

The spinocervical pathway (fig. 6-7) is an accessory pathway for the dorsal column

pathway. It conducts impulses at a faster rate. So, impulses in this pathway reach the

cerebral cortex before those conducted by the dorsal column pathway.

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

ipsilateral posterolateral column of the spinal white matter as the spinocervical

tract. The fibers terminate in the lateral cervical nucleus

(a longitudinal cell column

lateral to the tip of the dorsal horn of the upper 2-3 cervical segments)

of the same side.

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 ANTEROLATERAL SYSTEM

The anterolateral system has two components; the ventral and the lateral

spinothalamic tracts. The fibers of the first order neurons which serve

this system are the slow, thin, myelinated type-III and the

nonmyelinated type-IV fibers.

CHARACTERISTICS OF THE ANTEROLATERAL SYSTEM

1. It is a slowly conducting system made up of thin type-III and IV

fibers.

2. It has moderate degree of somatotopic lamination. This allows only

moderate degree of localization and discrimination of its sensations.

3. The intensity discrimination of its sensations is poor. Sensations of this

system can be identified in only 10-20 grades of intensity.

4. It cannot transmit rapidly repetitive signals.

5. It conducts sensations from the contralateral side of the body.

THE DORSAL COLUMN-LEMNISCAL SYSTEM

The dorsal column-lemniscal system has three components; the dorsal

column tracts (gracile and cuneate), the spinocervical tract, and the medial

lemniscus. The fibers of the first order neurons which serve this system are

the rapidly conducting, thick, myelinated, type-I and II fibers.

CHARACTERISTICS OF THE DORSAL COLUMN LEMNlSCAL SYSTEM

1. It is a rapidly conducting system made up of the thick type-I and II

fibers.

2. It has a high degree of somatotopic lamination; i.e. it is arranged in

many laminae, each lamina serves a specific topic on the body

surface. This allows a high degree of localization and discrimination of

its sensations.

3. The intensity discrimination of its sensations is high. Most sensations

in this system can be identified in up to 100 grades (100 separate

degrees of intensities).

4. It can conduct rapidly repetitive signals. This enables this system to

conduct vibration sense.

5. It conducts sensations from the ipsilateral side of the body.

THE THALAMUS

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 ".

ANATOMICAL DIVISIONS OF THE THALAMUS

In each thalamus there are 5 groups of nuclei:

1. Anterior group: This is connected to the cingulate gyrus and

forms part of the limbic circuit concerned with recent memory.

2. Medial group: This includes the dorsomedial nucleus, the

intralaminar and middle nuclei.

3. Lateral group: This includes the dorsolateral and posterolateral

nuclei.

4. Ventral group: Which includes?

(a) The ventroanterior (VA) nucleus.

(b) The ventrolateral (VL) nucleus.

includes:

(i) Ventral posterolateral (VPL) nucleus.

(ii) Ventral posteromedial (VPM) nucleus.

5. Posterior group (metathalamus): Which includes the medial and

lateral geniculate bodies.

Various nuclear groups of the thalamus are freely interconnected by

short intermediary neurons.

FUNCTIONAL DIVISIONS OF THE THALAMUS

Functionally, the thalamic nuclei could be classified into four

categories:

[I] Specific projection nuclei (cortical relay nuclei):

a. Ventral posterolateral nucleus (VPL) nucleus, which is the site of

relay of the somatic sensory pathways from the trunk and limbs

b. Ventral posteromedial nucleus (VPM) nucleus, which is the site

of relay of the trigeminal sensory pathway from the head.

c. Medial geniculate body (MGB); site of relay of the auditory

pathway.

d. Lateral geniculate body (LGB): site of relay of the visual pathway.

e. Dorsomedial nucleus; site of relay for the olfactory pathway.

AFFERENT CONNECTIONS:

From the medial, spinal and trigeminal

lemnisci, optic tract, hearing and olfactory pathways.

EFFERENT CONNECTIONS:

Specific thalamic projection system to

specific points in the somatic audio and visual sensory areas of the

cerebral cortex.

[II] Nonspecific projection nuclei:

a. Intralaminar and midline nuclei.

b. Ventroanterior nucleus.

c. Anterior nuclei.

AFFERENT CONNECTIONS:

From the ascending reticular activating

system (ARAS), and the paleospinothalamic tracts.

EFFERENT CONNECTIONS:

Nonspecific thalamic projection fibers to

all parts of the cerebral cortex. The anterior nuclei are connected to the

hypothalamus and limbic system.

[III] Association nuclei:

a. Dorsolateral nucleus.

b. Posterolateral nucleus.

AFFERENT CONNECTIONS:

From other thalamic nuclei

EFFERENT CONNECTIONS:

To prefrontal, parietal and occipital

cortical association areas. No subcortical connections.

[IV] Motor nuclei:

The most important of these is the ventrolateral (VL) nucleus.

AFFERENT

CONNECTIONS: From the basal ganglia and cerebellum.

EFFERENT CONNECTIONS:

The motor cortex.

FUNCTIONS OF THE THALAMUS

1. It is a relay station for all the sensory pathways in their way to the

cerebral cortex. Sensory signals are processed in the thalamus before

reaching the cortex (thalamus is the secretary of the cortex).

2. It acts as a final sensory center for conscious perception of some

sensations: i.e. slow pain, high or low grades of temperature and crude

touch.

3. Facilitation of the cerebral cortex, raising its excitability up to the

level necessary to do all cerebral functions. Without the thalamus, the

cerebral cortical functions are markedly depressed. The cerebral cortex

and thalamus are sometimes considered as one unit called "the

thalamocortical system".

4. Identification of the stimulus affect (pleasant or unpleasant), and

controlling the emotional and motor reactions to it. This is done in

collaboration with the cerebral cortex, the limbic system and

hypothalamus

5. It is part of the limbic circuit which is concerned with recent memory

and memory search.

6. It is part of the caudate and putamen circuits which control the

motor activity

THE THALAMIC SYNDROME (The thalamic hypersthetic anesthesia)

The most common cause of this syndrome is thrombosis of the

thalamogeniculate artery which is a branch of the posterior cerebral

artery. This leads to degeneration of the posterior and ventral parts of the

thalamus. The manifestations which appear on the contralateral side of

the lesion include:

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.

THE PRIMARY SOMATIC SENSORY AREA (SI):

LOCATION;

In the postcentral gyrus of the parietal lobe (Bro dmann

areas 3, 1 and 2) (fig. 7-1). It receives projection fibers from the

ventrobasal complex of the thalamus (VPLNT and VPMNT). In this

area, there are the final sensory neurons of the somatic sensory

pathways of fine sensations.

BODY REPRESENTATION

: It is crossed and inverted representation

(fig. 7-2). The upper half of the face is bilaterally represented.

Crossed representation means that each half of the body is represented on

the contralateral cerebral hemisphere.

Inverted representation means that upper parts of the body are represented

in the lower part of the cortex and lower parts of the body in upper part of the

cortex.

Figure 7-1: Map of Brodmann areas of the cerebral cortex. It is based on

histological typing of cortical cells (first published in 1909).

The area of representation of each part is proportional to the number of

receptors in this part, not to its size, e.g. the lips and thumb are

represented by relatively large areas, whilst the trunk is represented by

relatively small area.

Figure 7 - 2: Body representation in the postcentral sensory gyrus

Cells in the sensory cortex are arranged in columns projecting inwards

from the surface. Points in the cortex that represent a certain area of the

body contain several columns each column is specialized in perception

of a specific sensory modality. So, modality representation is

included within the topographic representation.

Topographic areas of representation are not permanent or unchan-

geable, but can be changed and modified. E.g., if a finger is amputated,

the cortical representation of the neighboring fingers creep into the area

of the amputated finger.

FUNCTIONS:

The primary somatic sensory area is essential for the

perception of:

1. Fine touch sensation, i.e. tactile localization and discrirnination.

2. Localization of pain and temperature sensations, SI is not essential

for the perception of pain and temperature sensations, it is only needed for

their accurate localization.

3. Intensity discrimination of different stimuli.

4. Texture of material.

5. Proprioception; static and dynamic.

SI area project connection fibers to the secondary somatic sensory area (SII)

and the somatic sensory association area for interpreting the meaning and

significance of the sensory information; E.g. stereognosis.

THE SECONDARY SOMATIC SENSORY AREA (SII)

LOCATION:

In the supramarginal gyrus (Brodmann area 40), behind

mellower part of SI.

BODY

REPRESENTATION:

Bilateral representation with poor

topographic representation. The head area is generally in the anterior part

and the leg area in the posterior part.

SII receives connection fibers which convey input signals from SI, the

visual and auditory cortical sensory areas, and the thalamic nuclei on both

sides of the body.

FUNCTIONS:

SII is a potentiator of SI. It cannot work independent of SI.

SI, however, can carry out its functions without SII. So, SI can work

without SII, but the opposite is not true.

SOMATIC SENSORY ASSOCIATION AREA

(SOMATIC INTERPRETATIVE AREA)

LOCATION:

In the posterior parietal cortex (Brodmann areas 5 and 7),

behind SI and above SII.

CONNECTIONS:

It receives sensory signals from SI, SII, and the thalamus.

FUNCTIONS:

1. It combines all sensory signals to give meaning to the complex

sensory input.

2. Stereognosis. This area is the center of stereognosis.

3. Spatial orientation of the body with its surroundings. The person

recognizes the position of each part of the body relative to other

parts and to the surrounding objects.

4. Memory. This area is the memory store of previous sensory

experience. Stimulation of this area produces sensory hallucinations.

EFFECT OF

LESION

: A lesion in the somatic sensory association area

results in:

1. Astereognosis, i.e. inability to identify objects by their touch, shape,

weight and texture.

L .Autotopagnosia, i.e. loss of recognition of part or whole

contralateral side of the body. The patient does not acknowledge the

existence of the affected part and fails to include it in planning of

voluntary movement. E.g. he does not swing the arm of the affected side

during walking, he puts clothes on one side of the body and ignores the

other or he shaves only one side of his beard.

3. Impaired memory and decreased intelligence.

CELLS AND LAMINAE OF THE CEREBRAL CORTEX

The cerebral cortex is arranged in six distinct laminae according to the

histological architecture of each laminae (fig. 7-3). These laminae are

labeled from outside inwards as lamina I to lamina VI. There are

generally two types of cells in the cerebral cortex (fig. 7-4).

1. The pyramidal cells; which have a pyramidal shape and are found

in layers II, III, V and VI. The special feature of these cells is that their

axons leave the cortex. These axons terminate in one of the following

destinations:

a. Association fibers: which originate from lamina II and terminate

in other cortical areas on the sat

b. Commissural fibers; which originate from lamina III and

terminate in cortical areas on the opposite side.

c. Pyramidal tracts; which originate from lamina V and terminate in

motor nuclei in the brainstem and spinal cord.

d. Cortical projection fibers; which originate from lamina VI and

terminate in subcortical structures; e.g. corticothalamic projections.

2. The stellate cells: which have a star-like shape and are found mainly

in layer IV? Their axons terminate within the cortex. They are the final

cortical sensory neurons which are responsible for conscious

perception of different sensations.

Figure 7-3: The types of cells in different layers of the cerebral cortex and

their connection.

FUNCTIONS OF THE DIFFERENT CORTICAL LAMINAE

Lamina I: It consists of interconnecting nerve fibers which connect

different areas of the cortex. These fibers arise from all other laminae in

the cortex. It also contains fibers from the nonspecific thalamic

nuclei.

Lamina II: Contains pyramidal cells which send association fibers to

other areas of the cortex on the same side.

Lamina III: Contains pyramidal cells which send commissural fibers to

the cortex on the opposite side.

Lamina IV: Consists of stellate cells which receive input fibers from the

specific sensory nuclei of the thalamus. These cells are the final sensory

neurons which are responsible for the conscious perception of different

sensations.

Lamina V: Consists of pyramidal cells whose axons descend as the

motor pyramidal tracts.

Lamina VI: Consists of pyramidal cells whose axons form

corticofugal fibers that project to subcortical structures (e.g.

corticothalamic projections).

PHYSIOLOGY

Dr. Basim Mohamad Awan Lecture 8

MOTOR FUNCTIONS OF THE CEREBRAL CORTEX

All voluntary movements involve the conscious activity of the "motor cerebral

cortex of the brain. The motor cortex lies in front of the central sulcus and

occupies most of the frontal lobe (fig. 13-1). It is divided into 4 separate areas:

[I] THE PRIMARY MOTOR AREA

[II] THE PREMOTOR AREA

[III] THE SUPPLEMENTARY MOTOR AREA

[IV] THE MOTOR ASSOCIATION AREA

[I] THE PRIMARY MOTOR AREA (Area 4)

The primary motor area of the cerebral cortex (area 4 in Brodmann classification)

occupies the precentral gyrus in the frontal lobe. The body is topographically

represented in an inverted and crossed manner (fig. 8-1). The upper part of the

face is bilaterally represented and the area of representation of each part is

proportionate to the degree of fine movements in this part, e.g. hands and muscles

of speech are represented by large areas, whilst the trunk is represented by a small

area. The primary motor area contains two types of neurons:

1. Dynamic neurons: Which discharge at high frequency for a short time at the

beginning of contraction causing the initial development of force?

2. Static neurons: Which discharge at a much slower frequency but for much

longer time to maintain contraction for as long as required.

FUNCTIONS OF THE PRIMARY MOTOR AREA

1. Initiation of voluntary, fine, discrete (separate) movements of the distal parts of

the body e.g. hands and fingers.

2. Facilitation of stretch reflex; i.e. facilitation of skeletal muscle tone and tendon

jerks.

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.

Figure 8-2: Body representation in the primary motor cortex

3. Head rotation area (part of area 6):

Lies immediately above area 8 and works in close association with it. It directs

the head towards different objects.

4. Hand skills area (part of area 6):

Lies immediately anterior to the primary motor area for hands and fingers. It

stores the motor programs for skilled hand movements; e.g. sharpening a pencil

or peeling a potato. Damage of this area leads to "motor apraxia"; i.e. inability

to do skilled hand movements. This area includes the "Exner center" for writing

skill.

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 MECHANISM OF ACTION OF THE PREMOTOR AREA

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.

[III] THE SUPPLEMENTARY MOTOR AREA

The supplementary motor area (fig. 8-1) is an extension of area 6 in the medial

surface of the cerebral hemisphere. Accordingly, it is also called "the medial

area 6". Topographic representation of the body is bilateral and in a horizontal

position; head anteriorly and legs posteriorly. This area is connected by

projection fibers to the premotor and the primary motor areas.

The supplementary motor area supplements the functions of the premotor area in

producing positioning and fixation of the different parts of the body as a

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 s hows

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,

[IV] THE MOTOR ASSOCIATION AREA

This area occupies the frontal lobe in front of the premotor area (fig. 8-1). It

receives input signals from the parieto-tempqro-occipital association area and

projects output' signals to the motor and premotor areas through the caudate and

putamen circuits.

FUNCTIONS OF THE MOTOR ASSOCIATION AREA

1. Setting off goals and aims of movement and then taking the decision to

start the movement. Once the decision is taken, signals are sent to the basal

ganglia (the motor consultant of the cerebral cortex) to activate programs or set

plans for the movement. The motor plans and programs are then fed to the motor

and premotor areas.

2. Elaboration of thoughts; i.e. carrying out prolonged thought processes

which involve setting of plans and developing new constructive ideas. This is the

area of the brain which is concerned with deep quiet thinking during rest. A

lesion in this area abolishes creativity and planning for the future.

CONNECTIONS OF THE MOTOR CORTEX

AFFERENT CONNECTIONS

A. FROM OTHER CORTICAL AREAS

• Of the same side: from somatic sensory areas, visual and auditory areas.

• Of the opposite side: from the contralateral motor cortex to connect

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 gi

ant

Betz cells. This helps to sharpen the outgoing signals.

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.

THE PYRAMIDAL TRACTS

The pyramidal tracts are three tracts of common origin but separate destinations

(fig. 9-1). These tracts are:

1. The corticonuclear tract; which originates in the cerebral cortex and terminates

on motor nuclei in the midbrain and pons.

2. The corticobulbar tract; which originates in the cerebral cortex and terminates

on motor nuclei in the pons and medulla.

3. The corticospinal tract; which originates in the cerebral cortex and terminates

on the motor neurons of the spinal cord.

THE ORIGIN OF THE PYRAMIDAL TRACTS

The pyramidal tracts originate from:

1. The primary motor area: 30% of the fibers.

2. The premotor and supplementary motor areas: 30% of the fibers.

3. The somatic sensory areas: 40% of the fibers.

The pyramidal tracts arise from lamina V of the cerebral cortex which contains

the pyramidal cells. There are two types of fibers in the pyramidal tracts:

a. Thick fibers (16 um in diameter). These arise from the giant pyramidal cells

(Betz cells) found only in the primary motor area. They constitute only 3% of the

total number of fibers.

b. Thin fibers (less than 4 um in diameter). These arise from small pyramidal

cells found in different parts of the cortex. They constitute the remaining 97% of

the fibers.

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.

THE CORT1COBULBAR TRACT

ORIGIN

From the lower part of the motor and sensory" areas of the cerebral cortex.

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

Figure 9 -1: The origin, course, and destinations of the pyramidal tracts.

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.

3. 2% of the fibers descend directly in the posterolateral column of the spinal

white matter as the "uncrossed corticospinal tract". They terminate on the

ventral horn cells of the same 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.

THE EXTRA PYRAMIDAL SYSTEM

The extrapyramidal system (fig. 9-2) includes all parts of the nervous system other

than the pyramidal tracts that contribute to the control of skeletal muscle activity.

These parts include the basal ganglia, the red nucleus, the reticular formation of the

brainstem, the vestibular nuclei, and the tectum of the midbrain and the inferior olive

of the medulla. All these parts send signals down to the spinal motor nuclei in the

descending extrapyramidal tracts.

THE BASAL GANGLIA

It receives projection fibers from the motor cortex to corpus striatum and then to globus

pallidus then to several nuclei in the brainstem. These nuclei include the subthalamus,

substantia nigra, red nucleus, tectum of the midbrain, reticular formation, vestibular

nucleus and inferior olive.

THE RED NUCLEUS

It is located in the midbrain and receives projection fibers from the motor cortex (the

corticorubral tract) and collaterals from the corticospinal tract as it passes through

the midbrain. It also receives projection fibers from the globus pallidus of the basal

ganglia. All these fibers synapse in the lower part of the red nucleus which

contains giant pyramidal neurons similar to Betz cells. Rubrospinal tract

originates from these neurons, cross to the opposite side and descend in the spinal

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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.

FUNCTIONS OF THE RED NUCLEUS

1. It is a relay station in the corticorubrospinal pathway which acts as an accessory

pathway for the corticospinal tracts. This pathway can initiate gross movements.

2. It is inhibitory to the motor neurons and stretch reflex through stimulation of

the inhibitory reticular formation of the brainstem.

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.

102

Figure 9 - 2: A schematic diagram of the extrapyramidal system.

103

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).

THE RETICULAR FORMATION OF THE BRAINSTEM

It receives projection fibers from the globus pallidus of the basal ganglia, and

gives origin to two descending extrapyramidal tracts:

* The lateral reticulospinal tract: Originates from the inhibitory reticular

formation of the medulla. Some fibers cross to the opposite side, but most fibers

descend in the same side of the spinal cord. It inhibits the gamma motor neurons,

thus inhibiting the stretch reflex and skeletal muscle tone.

• The-ventral reticulospinal tract: Originates from the facilitatory reticular

formation of the pons. Fibers descend without crossing to terminate on the gamma

motor neurons of the ipsilateral side of the spinal cord. It facilitates the gamma motor

neurons, thus facilitating the stretch reflex and the skeletal muscle tone.

THE VESTIBULAR NUCLEUS OF THE MEDULLA

It receives projection fibers from the globus pallidus of the basal ganglia, and

gives origin to two descending extrapyramidal tracts;

• The lateral vestibulospinal tract: Originates from the vestibular

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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

THE INFERIOR OLIVE OF THE MEDULLA

The inferior olive receives input fibers from the motor cortex, the globus pallidus

of the basal ganglia and the spinal cord. It sends output fibers to the cerebellum. It

projects the fibers of the olivospinal tract which descend in the spinal cord to

terminate on the ventral horn cells of the same side. The olivospinal tract is

facilitatory to the stretch reflex and the skeletal muscle tone.

The inferior olive works in close association with the cerebellum to correct any

deviation of the muscle contraction from the preset plan of movement (the

servocomparator function of the cerebellum).

GENERAL FUNCTIONS OF THE EXTRAPYRAMIDAL SYSTEM

1. Mediation of gross movements which involve a group of large muscles.

2. Provides a weaker alternative to the pyramidal system for mediation of some

discrete movements.

3. Mediation of fixation and positioning movements which accompany other fine

movements.

4. Adjustment of the skeletal muscle tone through facilitation or inhibition.

5. Adjustment of muscle movements to match preset plans to reach a certain target.

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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.

2. Lower motor neurons:

These are the neurons of the motor neuron pool and their axons which form the

motor nerves to the skeletal muscles.

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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.

CONNECTIONS WITH THE CEREBRAL CORTEX

The basal ganglia are connected to the cerebral cortex through two main circuits,

the caudate and putamen circuits.

THE CAUDATE CIRCUIT

The caudate circuit (fig.10-2) starts at the motor association and sensory

association areas of the cerebral cortex → to the caudate nucleus → the globus

pallidas → ventrolateral (VL) nucleus of the thalamus → premotor and primary

motor areas of the cortex.

Figure 10-2: The caudate circuit

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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

Figure 10- 3: The putamen circuit.

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.

NEUROTRANSMITTERS IN THE BASAL GANGLIA

• Fibers from the cerebral cortex to the corpus striatum release

glutamate, Intrastriatal intemeurons release acetylcholine when

stimulated by glutamate.

• Fibers from the substantia nigra to the corpus striatum release dopamine.

• Fibers from the corpus striatum to the globus pallidus and substantia nigra

release gamma-aminobutyric acid (GABA).

• Fibers from the brainstem to the basal ganglia release noradrenaline,

serotonin and enkephalin.

Glutamate, acetylcholine and noradrenaline are excitatory transmitters to the

basal ganglia, whilst dopamine, GABA, serotonin and enkephalin are inhibitory.

A delicate balance between the excitatory and inhibitory transmitters is essential

for proper functioning of the basal ganglia.

METABOLIC CHARACTERISTICS OF THE BASAL GANGLIA

The basal ganglia are characterized metabolically by the following:

1. High metabolic rate, with high rate of O

consumption. They suffer rapidly

from hypoxia or ischemia.

2. High ability to concentrate copper. Excess copper in the plasma is bound to a

110

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.

FUNCTIONS OF THE BASAL GANGLIA

The functions of basal ganglia are purely motor. In lower animals and birds in

which the cerebral cortex is poorly developed, the basal ganglia act as the primary

motor cortex. In humans, they play an important role in controlling the muscle

tone and voluntary movements'.

[A] ROLE IN CONTROLLING THE MUSCLE TONE

The caudate nucleus stimulates muscle tone through stimulation of the vestibular

nucleus and inferior olive.

The lentiform nucleus inhibits the muscle tone through inhibition of the primary

motor cortex and stimulation of the inhibitory reticular formation and red nucleus

of the brainstem.

The inhibitory influence of the basal ganglia on the muscle tone is stronger than

the stimulatory influence.

[B] ROLE IN CONTROLLING VOLUNTARY MOVEMENT

Planning and programming of movements start in the basal ganglia. Neurons of

the basal ganglia discharge before the movement begins. The basal ganglia works

in collaboration with the cerebral cortex through the caudate and putamen circuits

to produce a coordinated, organized and purposeful movement.

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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.

Damage of the caudate circuit leads to:

• Inability to organize movements to achieve a complex goal; e.g. one wears the

necktie before the shirt.

• Inability to write or draw figures with a fixed scale; e.g. if a patient

with a lesion in the left caudate circuit draws a face of a human

being, he draws the left side of the face (which is in the right field of

vision) to a much smaller scale than the right side (fig. 10-4).

• Excluding the contralateral side of the body from any motor plans.

The patient avoids using the contralateral side of his body and ignores it as if it

does not exist.

E.g. when the patient walks he swings the arm of the healthy side

but not that of the ignored side.

112

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.

ROLE OF THE FUTAMEN CIRCUIT

Storage of motor programs of familiar motor actions: e.g. writing

one's name or signature, lighting a candle or a kerosene lamp.

Damage of this circuit leads to motor apraxia ; i.e. loss of ability to

carry out familiar movements in the absence, of muscle paralysis. E.g.,

one finds difficulty to write as if he is learning to write for the first time.

MANIFESTATIONS OF LESIONS IN THE BASAL GANGLIA

Lesions in the basal ganglia produce two characteristic features which appear on

the contralateral side of the lesion:

1. Involuntary movements during rest. These movements are in the form of

chorea, athetosis, hcmiballismus or static tremor. The movements disappear during

113

sleep but increase with nervous excitement.

2. Change in muscle tone; either hyper or hypotonia.

(A) CHOREA (Gr.: choreia means dance)

CAUSE: Lesion in the caudate nucleus.

FEATURES:

• Involuntary, rapid, purposeless "dancing" movements during rest. They might

be superimposed on voluntary movements leading to their disruption.

• Hypotonia (caudate nucleus is normally facilitatory to the stretch reflex).

• Chorea is accompanied by loss of the caudate circuit functions (see above).

TYPES OF CHOREA

1. Sydenham chorea: Which occurs in young children (5-15 years) as a

complication of rheumatic fever? It is more common in females than in males.

2. Huntington chorea: Which is a hereditary disease that appears usually at the

fourth decade of life? It is accompanied with, dementia and block of much of the

thinking processes.

3, Chorea gravidarum: which occurs during pregnancy and chorea of the

contraceptive pills?

(B) ATHETOSIS (Gr.: athetos means not fixed)

CAUSE: Lesion in the putamen.

FEATURES:



Involuntary, spasmodic, slow, writhing (snake-like) movements of one or

more limbs, particularly the hands. It is also called "mobile spasm"

because the limbs cannot be kept at a fixed position.

• Hypertonia (putamen is normally inhibitory to the stretch reflex).

• Athetosis is associated with loss of putamen circuit functions.

114

(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.

(D) PARKINSONISM (Parkinson disease, or Paralysis agitans)

CAUSE: Lesion in the substantia nigra leading to degeneration of the

dopaminergic neurons that project to the corpus striatum.

Normally, there is a steady loss of dopaminergic neurons and receptors with age.

This process is accelerated by atherosclerosis or phenothiazine tranquilizers

which block dopamine receptors. In this case, an imbalance occurs between

dopamine (from the nigral projection fibers) and acetylcholine (from the cortical

projection fibers) in the corpus striatum.

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

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.

Figure 10-5: The change in posture in case of Parkinsonism.

116

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.

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.

117

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.

118

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.

PHYSIOLOGICAL DIVISIONS OF THE CEREBELLUM

Physiologically, the cerebellum is divided into three functional divisions (fig.

16-1):

1. THE ARCHICEREBELLUM (vestibulocerebellum); is the oldest part of the

cerebellum. It consists of the flocculonodular lobe. It is connected to the

vestibular apparatus through the vestibular nuclei in the medulla. It is concerned

with maintenance of equilibrium.

119

Figure 11 - 1: The anatomical (right) and functional (left) divisions of the

cerebellum.

2. THE PALEOCEREBELLUM (spinocerebellum); which consists of the vermis and

the medial paravermal parts of the cerebellar hemispheres. It receives signals from

the peripheral proprioceptors. It is concerned with the control of muscle tone and

gross movement.

3. THE NEOCEREBELLUM (cerebrocerebellum or the pontocerebelium); which

consists of the lateral parts of the cerebellar hemispheres. It is connected to the

cerebral cortex. It is concerned with the control of skilled voluntary movements

initiated by the cerebral cortex.

All these three divisions are interconnected by interneurons.

120

Fig. 11-2 Functional parts of the cerebellum

THE STRUCTURE OF THE CEREBELLUM

A section in the cerebellum shows an outer layer of gray matter which forms the

cerebellar cortex and an inner core of cerebellar white matter. The cerebellar cortex

is made up of three layers (fig. 11-3):

1. An outer molecular layer containing mainly interconnecting fibers.

2. An intermediate Purkinje cell layer containing mainly the giant Purkinje

cells.

3. An inner granule cell layer containing mainly granule cells.

The cortices of the various parts of the cerebellum are freely interconnected by

interneurons.

The deep white matter contains four cerebellar nuclei (fig. 11-6).

121

Figure 16-3: Cellular layers of the cerebellum. The climbing and Mossy

fibers

AFFERENT FIBERS TO THE CEREBELLUM

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.

122

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

1. TECTO-CEREBELLAR FIBERS: They originate from the superior and inferior

colliculi in the tectum of the midbrain



Sup. cer. ped.



different parts of the

ipsilateral cerebellum.

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.

123

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.

4. VESTIRULO CEREBELLAR FIBERS: They originate from the vestibular nucleus



inf. cer. ped.



the ipsilateral vestibule cerebellum. They

transmit signals about body posture and equilibrium.

5. RETICULO CEREBELLAR FIBERS: They originate from the

reticular formation



mid. and inf. cer. ped.



the ipsilateral

spinocerebellum. They transmit signals of various sensations.

124

Figure 11-4: The afferent cerebellar connections.

[II]FROM THE PERIPHERY

The cerebellum receives input signals from all sensations. Most of the sensory

input comes through collaterals from the sensory pathways to the sensory

reticular formation and from there on to the cerebellum via the reticulocerebellar

fibers.

Proprioceptive informations are continuously carried to the cerebellum via the

dorsal and ventral spinocerebellar pathways.

1. THE DORSAL SPINOCEREBELLAR PATHWAY

This pathway (fig. 11-5) consists of two orders of neurons.

125

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.

Figure 11 - 5: The dorsal spinocerebellar pathway.

FUNCTIONS: It transmits static and dynamic proprioceptive signals from the

muscles, tendons and ligaments to the cerebellum.

126

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.

Figure 11- 6: The ventral spinocerebellar pathway.

127

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.

EFFERENT CONNECTIONS (fig. 11-6)

All the efferent (output) fibers from the cerebellum arise from the deep cerebellar

nuclei. They are axons of the deep nuclear cells.

[I] FROM THE ARCHICEREBELLUM

Fibers originate in the fastigial nucleus in the flocculonodular lobe



inf. cer.

ped.



vestibular nucleus. Some fibers arise from the cortex of the

flocculonodular lobe and project directly to the vestibular nucleus. Others

originate in the fastigial nucleus and descend to the spinal cord (fastigiospinal

tract).

[II] FROM THE PALEOCEREBELLUM

Fibers originate in two nuclei:

1. Fastigial nucleus in "the vermis.



inf. cer. ped.



reticular formation.

2. Nucleus interpositus in the paravermal portion:

•



Sup. Cer. Ped.



ventral thalamic nuclei -» motor cortex

•



Sup. Cer. Ped.



medial thalamic nuclei -» basal ganglia.

•



- Sup. Cer. Ped.



red nucleus.

•



Sup. Cer. ped.



culomotor nucleus

•



Inf. Cer. Ped.



vestibular nucleus.

128

Figure 11 - 7: The efferent cerebellar connections

[II] FROM THE NEOCEREBELLUM

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.

129

Physiology

FUNCTIONS OF THE CEREBELLUM

Dr. Basim Mohamad Alwan Lecture 12

[1] CONTROL OF POSTURE AND EQUILIBRIUM

This is mainly the function of the archicerebellum and some portions of the

vermis. The cerebellum plays a minor role in maintaining posture through a

servocomparator function. It compares signals from the vestibular apparatus (i.e.

the nonauditory labyrinth) with proprioceptive signals from different parts of the

body then sends corrective signals to adjust muscle tone to maintain posture. The

same mechanism occurs to maintain equilibrium during slow movement.

The cerebellum plays a major role in maintaining equilibrium during rapid

motions and motions with rapidly changing direction through a predictive

function. In this case the cerebellum doesn't wait for proprioceptive signals from

the body as they might be too late. Instead, it uses the proprioceptive signals

from the vestibular apparatus and the periphery to compute the speed and

direction of the present movement, then, it predicts the direction and speed of the

coming movement and responds to correct any disturbance in equilibrium during

this movement.

[II]CONTROL OF MUSCLE TONE

The neocerebellum and paleocerebellum facilitate the muscle tone, whilst the

archicerebellum inhibits it. During rest, the fac ilitatory influence predominates.

Although the facilitatory output originate from the cerebrocerebllum and

spinocerebellum, the spinocerebeilum is the main part of the cerebellum

concerned with controlling the muscle tone through increasing or decreasing the

facilitatory output.

130

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).

[III] CONTROL OF VOLUNTARY MOVEMENT

The cerebrocerebellum influences voluntary movement through the

following functions:

1. PLANNING: The cerebrocerebellum receives input signals from the premotor

cortex and inferior olive before the start of movement to give the cerebellum an

"efferenee copy" of the motor plan. This informs the cerebellum about the

"intention

to do a movement.

Through connections with the motor cortex the cerebellum "monitors" the flow

of signals from the motor cortex and corrects any deviation from the planned

sequential order.

2. TIMING OF MOVEMENT: The; cerebellum determines the start and

termination of each of the sequential movement which form a complex movement.

Without this function, the person becomes unable to determine when the next

movement should begin. The succeeding movement begins too early or, more

likely, too late leading to decomposition of movement.

3. JOINING OF MOVEMENT: The dentate nucleus shows the "activity pattern

of the next movement at the same time the present movement is occurring. The

cerebrocerebellum is not concerned with what is happening at a given moment

but with what will happen at the next. This leads to rapid succession of the

sequential movements' one after the other to produce a smooth, joined complex

movement.

131

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.

Figure 12-1: The servocomparator function of the cerebellum

(ii) The spinocerebellar tracts, during the movement. An "afference copy" of

the signals reaching the ventral horn cells and proprioceptive signals from the

moving muscles and joints inform the cerebellum about the "performance" of

the movement.

The spinocerebellum then compares the afference with the efference copy; i.e.

the performance with the intention. If there is any error in the performance, the

cerebellum sends correction signals via the descending motor tracts to adjust the

movement to match the intention.

5. DAMPING OF MOVEMENT:

Damping of movement means ending of movement abruptly without oscillation.

The cerebellum acts as a "break" which terminates the movements exactly at the

right time when the desired movement is completed. This is achieved through the

inhibitory output signals from the nuclear cells which occurs in response to input

132

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.

INITIATION AND TERMINATION OF BALLISTIC MOVEMENT:

A ballistic movement is a short movement whose direction and speed is

determined by the initial thrust; e.g. movements of the finger of a typist during typing.

After starting a ballistic movement, its direction and speed cannot be changed.

The rapidity and shortness of movement do not allow the cerebellum to carry out

its servocomparator adjustive function. The role of the cerebellum here is to

potentiate the starting of the movement to allow a rapid onset and to terminate the

133

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.

THE CEREBELLAR SYNDROME

The cerebellar syndrome results from lesions that involve the cerebellar nuclei.

Removal of large parts of the cerebellar cortex without injuring the deep nuclei

leaves little long term effects. That is why neurosurgeons take great care not to

injure the cerebellar nuclei during operations on the cerebellum.

The effects of the cerebellar syndrome appear on the same side of the lesion.

They include three main features; i.e. asthenia, atonia, ataxia (AAA).

1. ASTHENIA: Asthenia means lack of strength. The patient feels muscle

weakness cue to me difficulty in initiating and maintaining muscle contraction.

Asthenia appears because the function of the cerebellum in potentiating motor

signals is lost.

2. ATONIA (or hypotonia): Atonia means lack of muscle tone. This occurs due

to loss of the facilitatory effect of the dentate and interpositus nuclei. Atonia is

manifested by the flaccid feel of the muscles and pendular knee jerk.

3. ATAXIA: Ataxia means in coordination of voluntary movements. Cerebellar

ataxia is manifested by:

(a)

Dysmetria: It means inability to adjust a motor act for a certain distance. The

movement usually overshoots the target (past pointing or hypermetria), or

sometimes stops short of the target (hypometria). Dysmetria is caused by failure

of the timing and damping functions of the cerebellum

(b) Kinetic tremor (intention tremor): This is an oscillatory movement which

occurs on doing a voluntary movement. The tremor is absent during rest.

134

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).

(c) Adiadokokinesia: This means the inability to do rapid alternating

movements; e.g. pronation and. supination of the hand (fig. 12-4). This is due to

failure of the predictive and joining functions of the cerebellum.

Figure 1 2 -4 : Adiadokokinesia.

(d) Decomposition of movement: Movements which involve more than one

joint are broken up to their component simple movements.

(e) Dysarthria: this means difficulty in producing clear, normal speech. The lack

of predictive and joining functions leads to in coordination of the buccal, laryngeal and

135

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)

Figure 12 - 5: The arm flexion test

(g) Nystagmus: T h is is an oscillatory movement of the eye. Cerebellar

nystagmus appears on lateral gazing. It results from lesions in the

archicerebellum.

(h) Staggering gait: The patient walks on a wide base in a drunken, swaying or

zigzag manner and tends to fall on the diseased side. This is a manifestation of a

lesion in the archicerebellum.

136

PHYSIOLOGY

Dr. Basim Mohamad Alwan Lecture 13

REFLEXES

REFLEX ARC



It is the basic unit of the integrated neural activity.



It consists of sense organ, an afferent neuron, one or more synapses, and an

efferent neuron.



The simplest reflex arc is the one with a single synapse between the afferent

and the efferent neurons such as the "monosynaptic".



Those more than one interneuron are the "polysynaptic".



The number of the synapses in the arcs varying from 2 to many thousands.



Fig. 13-1 Spinal cord segment and vertebral canal

137

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.

138

Fig. 13-2 Spinal cord organization for sensory, motor and autonomic functions

139

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:

What is the length of the muscle?

II.

What is its tension?

III.

How rapidly is its length or tension changing?



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".

LENGTH-MONITORING SYSTEM AND THE STRETCH REFLEX



Absolute muscle length and changes in muscle length are monitored by

stretch receptors embedded within the muscle.



There are 2 kinds of stretch receptors:

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".

Intrafusal skeletal muscle fibers



They are small muscle fiber



The central region of which has either no or few actin and myosin filaments.

Therefore, this central portion does not contract when the ends do. Instead
they function as sensory receptors.



The end portions that do contract are excited by small gamma motor neurons.



They are of 2 types:

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

140

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:

The Primary Endings (Annulospiral) Fibers

They are large sensory fibers encircles the very center of the receptor area.

ii.

They are termination of type Ia afferent fibers.

iii.

They have 17 µm diameters.

iv.

They transmit signals to the spinal cord at a velocity of 70-120 m/second.

They discharge most rapidly while the muscle being stretched and less rapidly
during sustained stretch. Thus, respond to changes in length and change in
the rate of stretch.

The Secondary (Flowerspray) Fibers

They are the termination of usually one and some times two smaller type II
sensory nerve fibers.

ii.

Their diameter is 8 µm.

iii.

They innervate the receptor region on one side of the primary ending.

iv.

They discharge at increasing rate through out period when the muscle is
stretched.

They respond to change in the length alone.

Note: Both primary and secondary nerve endings are stimulated when the spindle is
stretched but the pattern of response is different.

Fig. 13-3 muscle spindle

141

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.

142

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).

Reciprocal Innervations: The activation of one muscle with simultaneous inhibition

of its antagonistic muscle.

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.

143

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



Therefore, feedback is necessary to inform the motor control systems of the

tension actually achieved.



Such feedback is provided by vision and by Golgi tendon organs which

monitors how much tension is being exerted by the contracting motor units.

Fig. (13-5) Golgi tendon organ

They are encapsulated sensory receptors through which a small bundle of
muscle tendon fibers pass.

ii.

They are located in the tendons near their junction with the muscle.

iii.

About 10-15 muscle fibers are usually connected in series with each Golgi
tendon organ.

iv.

Endings of the afferent nerve fibers are wrapped around collagen bundles
in the tendon.

When  he  attached  extrafusal  muscle  fibers  contract,  they  pull  on  the
tendon,  which  straightens  the  collagen  bundles  and  distorts  the  receptor
endings, and activating  them.

vi.

Thus,  the  Golgi  tendon  organs  discharge  in  response  to  the  tension
generated  by  the  contraction  and  initiates  action  potentials  that  are
transmitted  to the  CNS via large rapidly  conducting  type  IIb  nerve  fibers.

144

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.

Fig. 13-6 Withdrawal reflex

WITHDRAWAL REFLEX (fig.14-6)

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".

145

PHYSIOLOGY

Dr. Basim Mohamad Alwan Lecture 14

SPINAL CORD

Transection of Spinal Cord

(1) Hemi-section (Brown-Séquard Syndrome)



This occurs in only 1/2 of the spinal cord.



The following effects occur:

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.

146

Fig. 14-1 Brown sequard syndrom

(2) Complete Transverse Section

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:

(1) Arterial blood pressure falls to as low as 40 mmHg (blocking of the

sympathetic activity). This returns to normal within a few days.

147

(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.

Complication of Cord Transection

They develop negative nitrogen balance and catabolize large amounts of
body proteins.

II.

Decubitus ulcers due to compression of skin circulation by the body
weight.

III.

Hypercalcemia that lead to hypercalciuria and calcium stones.

IV.

The stones in combination with UB paralysis cause urine stasis which
predispose to urinary infection.

Death from septicemia and uremia.

Responses in Chronic Spinal Humans

In chronically quadriplegic humans, there is:

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:

 Major part of the body goes into strong flexor spasm

148

  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



Sectioning brainstem below the midlevel of mesencephalon (leaving both

pontine and medullary reticular system as well as vestibular system intact)
leads the animal to develop "decerebrate rigidity".



The rigidity occurs in antigravity muscles (the muscles of the neck, trunk and

extensors of the leg).

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.

Tonic labyrinthine Reflexes



The decerebrate animal stays in the position in which it put; no righting

responses are present, like:

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.

Tonic Neck Reflexes



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.

149

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.



These reflexes are initiated by stretch of proprioceptors in the upper part of

the neck and they can be sustained for long periods of time.

Upper and Lower Motor Neurons

(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:

a. Lesions in the extrapyramidal posture regulating pathway cause spastic

paralysis.

b. Lesions limited to the pyramidal tracts causes weakness (paresis rather than

paralysis) and the affected musculature is generally hypotonic.

c. Cerebellar lesions cause incoordination.

150

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.

Figure 15 - 1: The medial surface of the right hypothalamus

151

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.

The hypothalamus sends output fibers in three directions:

1. Upwards: To the thalamus and limbic system (the limbic lobe, the amygdala and

the hippocampus).

2. Downwards: To the reticular formation of the brainstem. Through the reticular

formation, the hypothalamus is connected to the vital centers in the brainstem and

spinal cord which control the autonomic functions.

3. To the posterior pituitary gland: through the hypothalamo hypophysial tract.

FUNCTIONS OF THE HYPOTHALAMUS

[I] AUTONOMIC FUNCTION

The lateral, dorsomedial; and posterior nuclei of the hypothalamus are considered as

a "Sympathetic center" which responds to emotions by generalized sympathetic

activation (the alarm response).

'The sympathetic center includes adrenaline and noradrenalin secretion centers

which selectively control the secretion of these catecholamine's from the adrenal

medulla in different conditions.

Stimulation of certain parts of the hypothalamus produces parasympathetic

153

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.

[II] ENDOCRINAL FUNCTION

The hypothalamus controls the secretion of hormones from the anterior and

posterior pituitary glands.

CONTROL OF SECRETION OF THE ANTERIOR PITUITARY GLAND

Some nuclei in the hypothalamus contain neurosecretory cells which produce

releasing or inhibiting hormones. These hormones stimulate or inhibit the release of

hormones from the anterior pituitary gland. The secretory hypothalamic cells are

grouped together in an area called "the hypophysiotropic area". This area includes

several nuclei; i.e. the paraventricular, the arcuate, and the ventromedial nuclei. The

axons of the neurosecretory hypophysiotropic cells terminate in the median

eminence, which is the basal part of the hypothalamus, just behind the optic chiasma.

The releasing and inhibiting hormones move inside the hypothalamic neurons by

axoplasmic flow to their terminals in the median eminence where they are released.

From the median eminence, they reach the anterior pituitary via the blood in the

hypothalamo-hypophysial portal circulation.

154

Table 15 -1: The hypothalamic releasing and inhibiting hormones.

Hypothalamic hormone

Main site of formation

The affected ant. Pit. hormone

l.TRH

(Thyrotropin-Releasing Hormone)

Paraventricular area

TSH (Thyrotropin, also called

Thyroid Stimulating

Hormone)

2.CRH

(Corticotropin-Releasing Hormone)

Paraventricular area

ACTH

(Adrenocorticotrophic Hormone)

3.GnRH

(Gonadotropin-Releasmg Hormone)

Arcuate nucleus

FSH and LH

Follicle-Stimulating Hormone

and Leutinizing Hormone (both are

called pituitary Gonadotropins)

4.PIHand PRH

(Prolactm-Inhibiting; Hormone and

Prolactin-Releasing Hormone)

Arcuate nucleus

Prolactin

5. GRH and GIH

Growth hormone-Releasing Hormone and

Growth hormone- Inhibiting Hormone.

Ventromedial

nucleus and nearby areas

Growth Hormone (also called

somatotropin or somatotrophic

hormone -STH)

CONTROL OF SECRETION OF THE POSTERIOR PITUITARY GLAND

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.

155

[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.

[IV] CONTROL OF FOOD INTAKE

The hypothalamus contains a food intake controlling system "hypothalamic

appestat" which controls the appetite for food. It consists of two centers; a

"feeding center" in the lateral hypothalamus which stimulates the appetite, and a

"satiety center" in the medial hypothalamus (ventromedial nucleus) which inhibits

the appetite. The satiety center acts by inhibiting the inherent tonic activity of the

feeding center. The damage of the satiety center leads to hyperphagia. The animal

eats large amount of any available edible food, thus leading to obesity

(hypothalamic obesity) (fig. 15-3). Damage of the feeding center leads to severe

anorexia which could be fatal

The hypothalamic appestat is adjusted to a "set point" to maintain a specific body

156

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).

[V] CONTROL OF WATER BALANCE

Thirst center is found in the lateral hypothalamus. It receives input signals from

different sources:

1. From osmoreceptors in the anterior hypothalamus.

2. From osmoreceptors in the liver.

3. From volume receptors in the right atrium and large veins.

157

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.

[VI] CONTROL OF SALT APPETITE

There is a "salt appetite center" in the anterior hypothalamus very close to the

osmoreceptors. Its cells are sensitive to changes in plasma osmolality, as well as the

level of sodium in the plasma (osmosodium receptors). They are stimulated by

hyponatremia, hypo tonicity or hypovolemia to increase the appetite for salt (craving

for salt).

[VII] CONTROL OF CYCLICAL PHENOMENA

Circadian rhythm occurs in more than 100 parameters of human organs and

functions. E.g. body temperature is lowest in the early morning and highest in the

evening, so is the heart rate. CRH, ACTH and cortisol secretions are highest at 8 AM

and lowest at midnight." Melatonin secretion from the pineal gland increases by

night and decreases in daylight. The menstrual cycle in adult females is an example

of a physiological monthly rhythrn.

The pacemakers of the circadian rhythm are found in two regions of the

hypothalamus.

158

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.

[VIII] ROLE IN LEARNING AND MEMORY

The hypothalamus contains a reward center in the lateral and ventromedial

nuclei. When stimulated, it gives a sense of reward; i.e. relaxation, pleasure and

satisfaction. There is a punishment center in the periventricular nuclei, when

stimulated it gives a sense of punishment; displeasure fear and terror. These centers

constitute important components of the reward and punishment systems which are

very important for emotions, motivation, memory and learning.

To keep any experience in the long term memory, it needs either of two

mechanisms; to stimulate the reward and punishment system or to be practiced

repeatedly. Otherwise, the experience is easily forgotten and will not add to the

memory stores of the individual.

The hypothalamus is also a relay station in the Papez circuit which is concerned with

short term memory

[IX] CONTROL OF MOTOR RESPONSES TO EMOTIONS

The motor responses to emotions are controlled by complex mechanisms that

involve the association areas of the cerebral cortex, the limbic system and the

hypothalamus. However, stimulation or damage of some hypothalamic areas

produces certain emotions with specific motor responses as follows:

159

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

160

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.

[X] SEXUAL BEHAVIOR

Libido and sexual activity is mainly under the control of the cerebral cortex and

limbic system which are sensitive to sex hormones. However, hypothalamus is

involved in the following way:

1. The hypophysiotropic area controls the release of the pituitary gonadotropins,

which in turn control the release of sex hormones from the gonads.

2. The anterior hypothalamus in the female contains estrogen sensitive neurons. When

stimulated, these neurons increase the sexual desire and initiate the heat of sexual

behavior. The female seeks out the male (the enticement reaction). Lesions in this area

abolish this behavior.

3. Stimulation of parts of the lateral hypothalamus produces sexual excitement and

penile erection in male monkeys.

[XI] RELATION TO SLEEP

Fibers of the ascending reticular activating system (ARAS) pass through the

hypothalamus in its way to the thalamus then to the cerebral cortex. ARAS fibers

which desynchronize the cerebral cortex and cause wakefulness pass through the

posterior hypothalamus. So, a lesion in the posterior hypothalamus produces sleep

due to damage of these desynchronizing fibers. An irritative lesion may stimulate

these fibers leading to insomnia

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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.

4. Sleep disturbances (insomnia or hypersomnia):

Destructive lesions in the dorsal hypothalamus produce narcolepsy; i.e. attacks of

strong, irresistible desire to sleep. Sleep lasts for short periods could be only few

minutes of which the patient wakes up fully recovered. Insomnia results from

irritative lesions in the dorsal hypothalamus.

162

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.

163

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.

Fig. 16-1 the reticular formation

(A) THE SENSORY PART

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.

FUNCTIONS OF THE RETICULAR FORMATION

1. Control of the level of consciousness via the ascending reticular

activating system.

2. Regulation of the stretch reflex and muscle tone via the

reticulospinal tracts

3.  Pain inhibition by the raphe Magnus nucleus.
4.  Control of sleep by 2 specific centers.
5.  Control  of  visceral  functions  (cardiac  activity)  by  controlling  the

spinal lateral horn cells.

ASCENDING RETICULAR ACTIVATING SYSTEM

(ARAS)

This is a multineuronal polysynaptic system of nerve fibers that originate at the
facilitatory  reticular  formation.  Its  fibers  extend  upwards,  then  some  project
directly  to  the  cerebral  cortex,  while  the  majority  relay  first  at  the  nonspecific
thalamic nuclei, from which other fibers arise and project diffusely to almost all
parts  of  the  cerebral  cortex,  the  latter  pathway  is  called  the  reticulo  thalamo
cortical pathway.

Functions of the ARAS

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

A. Factors that increase the ARAS activity

1. Sensory signals (especially pain).
2. Signals from the cerebral cortex (via the corticofugal fibers) which

increase alertness and decrease the desire to sleep ( during emotions and
voluntary movements)

3. Certain drugs called the analeptic drugs e.g. catecholamine’s,

amphetamine.

B. Factors that decrease the ARAS activity

1. Reduction of signals from either the sensory pathways or the cerebral

cortex

2.  Stimulation of the sleep centers.
3.  Extensive damage of the ARAS (e.g. by tumors’)
4.  General anesthetic drugs: these drugs lead to unconsciousness through

depressing the ARAS activity. They inhibit the synaptic transmission
between its neurons (by producing a state of hyper polarization in these
neurons.

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Physiology

Dr. Basim Mohamad Alwan Lecture 17

THE LIMB IC 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

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

CHARACTERISTIC FEATURES OF THE LIMBIC SYSTEM

• It contains a large number of excitatory neuronal circuits that act as reverberating

circuits.

• Impulses that excite the system produce a prolonged after discharge in the system

i.e. the response outlast the stimulus.

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• Its functions are closely associated with hypothalamic functions.

THE REWARD AND PUNISHMENT SYSTEMS

The limbic system contains reward and punishment systems. The reward system

consists of a major reward center in the lateral and ventromedial nuclei of the

hypothalamus, and less potent centers in the amygdala, the thalamus and the

tegmentum of the limbic midbrain area. Stimulation of the system gives a sense

of reward; i.e. relaxation, pleasure and satisfaction. The subject is motivated to

approach or repeat the rewarding experience (the approach reaction).

The punishment system consists of a major punishment center in the periventricular

nucleus of the hypothalamus which extends up to the thalamus and down to the

periaquiductal gray matter of the limbic midbrain area, and other less potent centers

in the amygdala and the hippocampus. Stimulation of the punishment system gives a

sense of punishment i.e. displeasure, fear, and terror. The subject is motivated to avert

the punishing experience (the aversion reaction).

Dopamine is the main chemical transmitter in the reward system. Cocaine produces a

sense of well-being and pleasure by increasing the release of dopamine from the

dopaminergic nerve endings in this system.

The reward and punishment systems are very important for motivation, emotions,

memory, and learning. Any experience that stimulates either of these systems can be

easily admitted into long-term memory. Without stimulating the reward or

punishment systems, the experience has to be rehearsed or practiced repeatedly before

it could be stored in the long-term memory.

FUNCTIONS OF THE LIMBIC SYSTEM

1. OLFACTION

Olfaction is the oldest function of the limbic system. The limbic system is

concerned with perception and discrimination of different odors. It stores olfactory

memories and controls the emotional responses to olfactory stimuli.

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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.

6. CONTROL OF FEEDING BEHAVIOR

The amygdaloid nucleus "sorts out" food into edible and inedible material on the basis

of past experience. Lesions in the amygdaloid nuclei lead to hyperphagia. However,

unlike animals with lesions in the hypothalamic satiety center, animals with

amygdaloid lesions try to eat any available object (omniphagia) before they discover

whether it is edible or not (oral exploration).

7. CONTROL OF SEXUAL BEHAVIOR
Sexual behavior in man is largely controlled by the orbitofrontal cortex. But the

instinctual desires and innate reactions that lead to mating and pregnancy are

functions of the limbic system and hypothalamus .

Lesions in the piriform cortex in the periamygdaloid area produce hypersexuality in

male animals. The sexual desire is intensified; the animals copulate with adult and

non-adult females of the same and of other species. They even mount male animals

and inanimate objects. The same lesions in female animals do not affect their

sexual behavior.

8. CONTROL OF MATERNAL BEHAVIOR

Nursing and care of young babies is an instinctual behavior in the female. The

instinctual maternal feelings and behavior are facilitated by the hormone prolactin.

They are markedly depressed by lesion in the cingulate and retrosplenial gyri.

9. CONTROL OF AUTONOMIC FUNCTIONS

Simulation of limbic structures produces autonomic effects; e.g. changes in heart

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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.

10. CONTROL OF RELEASE OF SOME HORMONES

Catecholamines and ACTH are released in response to stimulation different areas of

the limbic system. It is part of the response to emotions (the stress or alarm

response).

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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).

Figure 18 - 1: sleep cycle

WAKING / SLEEPING RHYTHM

Waking and sleeping periods follow each other in a circadian rhythm (i.e. 24 hr.

rhythm) which is synchronized with the daily light-dark cycle. This synchronization is

the function of the suprachiasmatic nucleus of the hypothalamus which receives

collateral from the visual pathway Physical and psychological factors affect the

onset and duration of sleep. E.g. cold and fear prevent the onset of sleep, whilst

fatigue and boredom facilitate its onset. In days preceding examinations, students

may use sleep as a legitimate escape way to avert studying.

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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.

1. THE METABOLIC THEORY

During wakefulness, brain cells produce a sleep-inducing factor (factor-S) which

accumulates in the CSF. When it reaches a certain level it induces NREM sleep.

This factor (a glucopeptide) was isolated from the CSF and urine of persons after

a period of sleep deprivation. When injected in humans of animals, factor-S

induces NREM sleep. A REM sleep factor also exists. Serotonin is considered as

a "sleep hormone" because it stimulates the production of these sleep-inducing

substances. A deep sleep-inducing peptide (DSIP) was isolated from the CSF and

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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

1. Incidence

Before REM sleep

After NREM sleep

2. Duration (per cycle)

Longer (80 rnin)

Shorter (20 min)

3, Depth of sleep

Variable

Very light

4. Threshold of
awakening stimulus

Variable

High

5. Rapid eye movement

Absent

Present

6. Dreams

Absent

Present

7. Muscle tone

Low

Very Low

8. Sleep talking & sleep
walking

May occur

Do not occur

9. Penile erection

Absent

Present

10. EEG

8- & δ-waves

β-waves

Nucleus ceruleus

11, Controlling center

Raphe nuclei

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.

2. THE PASSIVE THEORY (DEAFFERENTATION THEORY)

The ascending reticular activating system (ARAS) sends facilitatory signals to the

cerebral cortex to increase its excitability and maintain the wakeful, alert state.

According to the passive theory, sleep is induced when the facilitatory signals from

the ARAS to the cortex are withdrawn. This occurs when the activity of the

ARAS is depressed either by fatigue or by lack of sensory input signals or

corticofugal signals.

This theory explains how sleep is rapidly induced by physical and mental

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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.

3. THE ACTIVE THEORY (SLEEP CENTERS)

According to this theory there are specific centers which induce NREM sleep,

others which induce REM sleep. There is awaking/sleeping oscillator which

regulates the activity of these sleep centers.

Sleep is induced by induction of NREM sleep, REM sleep follows automatically.

(a) NREM SLEEP CENTER

The raphe magnus nuclei of the upper medulla and lower pons are considered as a

NREM sleeping center. Their stimulation induces NREM sleep. Their damage leads

to prolonged insomnia.

Inhibitory fibers from the raphe nuclei project to the ARAS and the cerebral

cortex. These fibers are serotonergic so drugs that block the synthesis of

serotonin, as chlorphenylalanin, produce prolonged insomnia. This insomnia can

be treated by 5-hydroxtrytophan. This is a precursor of serotonin, but unlike

serotonin, it can easily cross the blood-brain barrier.

(b) REM SLEEP CENTER

The nucleus ceruleus of the pons is considered as a REM sleep center. Its

stimulation converts NREM to REM sleep. It stimulates the cerebral cortex and

inhibits the raphe nuclei. The EEG shows the waking desynchronized β-rhythm

although the subject is asleep. It inhibits the facilitatory reticular formation

leading to marked decrease in the skeletal muscle tone. A lesion in the nucleus

ceruleus abolishes REM sleep, but NREM sleep can still occur.

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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.

PHYSIOLOGICAL CHANGES DURING SLEEP

NERVOUS SYSTEM

Voluntary activity and sensory perception are abolished. The brain is still

receptive and shows evoked potentials in response to sensory stimuli as clicking

sounds although these sounds may fail to arouse the sleeper. Protective spinal

withdrawal reflexes are depressed but can still be elicited. Sleeping synchronizes

various nervous centers together. This synchronization is disturbed during the

long periods of wakefulness which leads to increase in the rate of error in judgment

and behavior. The synchronization of nervous centers is the main function of

sleep; i.e. putting all the nervous centers back to the zero line.

CARDIOVASCULAR SYSTEM

There is slowing of the heart down to 60 beats/min and drop in the arterial blood

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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

PCO

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.

BED WETTING (Enuresis)

This is a, reflex micturition that occurs during sleep without any control from the

higher centers. It occurs during deep NREM sleep with no dreams.

Psychological factors may contribute to this condition.

NIGHT TERROR OF CHILDREN (Pavor nocturnus)

In this condition, the child sits up shortly after sleep onset, screaming and

appearing to stare at someone or something with wide open eyes. The face is pale

and covered with sweat, and breathing is difficult. After a short time, the child

wakes up, recognizing his surroundings and, if reassured, goes back to sleep. This

condition occurs during deep NREM sleep. The child usually cannot recall any

dreams.

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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.

186

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 10

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)

[I] SENSORY MEMORY (Immediate memory)

Any sensory signal is automatically stored in the sensory memory for few seconds.

This memory can accommodate 15-20 bits. Forgetting starts spontaneously

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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.

(

)

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.

[III] SECONDARY MEMORY

Secondary memory is made by formation of "memory engrams". A memory

engram is a long-lasting memory trace formed by structural changes in

presynaptic terminals. These changes inc lude:

(a) Increase in the total area of the specific release sites in the cell

membrane. Transmitter vesicles get attached to these sites before they rupture

and release their transmitter into the synaptic cleft. The increase in the release

sites increases the amount of transmitter released at the presynaptic terminal, thus

facilitating synaptic transmission.

(b) Increase in the number of transmitter vesicles in the presynaptic

terminal.

(c) Increase in the number of presynaptic terminals by formation of new

terminals.

The memory engrams remain for a long time, up to several years. Formation of

memory engrams requires protein synthesis. Antibiotics which inhibit protein

biosynthesis interfere with the formation of memory engrams. They prevent the

consolidation of memory but do not affect the primary memory.

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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

Table 19-1: Characteristics of different types of memory.

Sensory

Primary

Secondary

Tertiary

Capacity

Very small

Small

Very large

Duration

Few seconds

Minutes to hours

Hours to years

Permanent

Entry into storage Automatic during

perception

Verbalization

Practice or stim.

of reward or

punish, systems

Repeated practice

for long time

Speed of retrieval

Very rapid

Rapid

Slow

Very rapid

Type of stimulus

Sensory

Verbal

All forms

Forgetting

Spontan. fading &

extinction

New information

replaces the old

Pro.and retro.

active inhibition

No forgetting

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.

FACIAL RECOGNITION AREA

The impression effaces is stored in the "facial recognition area" in the

neocortex of the undersurface of the temporal and occipital lobes (fig. 19-2). In

right-handed persons and some of the left handed ones, the facial recognition area

is much better developed in the right (representational) hemisphere than in the left

(categorical) hemisphere.

Bilateral lesion in this area leads to "prosopagnosia" which is' inability to

recognize people by their faces. In this case, the patient can recognize persons by

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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.

NAMING OF OBJECTS AREA

This is the function of an area in the most lateral portion of both the anterior

occipital and posterior temporal lobes. In this area, the names of different objects

are stored. Like the facial recognition area, it is better developed on the right side

than in the left side. Damage of this area leads to inability to name objects,

although the patient is able to know what the object is, its value or its use. Only

the name is lost from memory.

This is probably the brain area which gave Adam

the advantage over angels. According to the holy Qur'an, after the creation of

Adam, angels failed to name objects when Allah asked them to do, Adam by

the command of Allah, preceded and told the names of objects.

Figure 19-2: basal view of the human facial recognition area.

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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.

3. PSYCHOGENIC OR HYSTERICAL AMNESIA

This is a rare condition characterized by sudden loss of memory for usually all

information in the secondary and tertiary memories. This usually follows a severe

psychological trauma or it may be an unconscious response to internal conflict or

an intolerable life situation. It is a purely functional disorder without any organic

disease. It can be differentiated from amnesia caused by damage or disease in

the brain tissue by three characteristics:

(I) All the personal data are forgotten, including the patient's own name.

(ii) The amnesia is not affected by key stimuli; seeing members of his

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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.

ALZHEIMER DISEASE AND SENILE DEMENTIA

Alzheimer disease is caused by degeneration of the cholinergic nerve fibers

which project from the nucleus basalis of Meynert to the neocortex, the

amygdala and the hippocampus. The disease is characterized by deterioration

of intellectual abilities as impairment of memory, lack of judgment and

inattentiveness. The disease may occur at any age. In old age, it is called senile

dementia. It is the commonest cause of dementia in old age (found in 10-15% of

the population above the age of 65). The anticholinesterase drug eserine

(physostigmine) produces some improvement but it does not stop the progress of

the disease.

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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.

LATERALIZATION OF THE SPEECH FUNCTION IN THE BRAIN

About 95% of the human populations are right handed. In those individuals, and

in some left-handed ones, the centers of speech are found in the left cerebral

hemisphere. The hand skills area is much better developed in the left hemisphere

as well.

It is because of this functional lateralization that the left hemisphere in those

individuals was called the "dominant" hemisphere. In the rest of the population,

the right hemisphere was the "dominant" one. However, the other hemisphere

cannot be called "nondominant" because it is more superior or "dominant" in

other functions as recognition of faces, stereognosis, recognition of musical

themes and spatial recognition of the body, That is why when speaking of

dominance it is better to talk about the "speech-dominant" or the "categorical"

hemisphere. The other hemisphere is better called the "nonspeech-dominant"

or the "representational" hemisphere.

* Categorical: Decisive; it takes important decisions and issues orders for actions

by the body.

* Representational: In which high sensory functions are represented, but with much

less role in making decisions or issuing of orders.

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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.

READING AND SPEECH

Written words are perceived by the primary visual area (area 17) in the occipital

lobe. The signals are then conveyed to the visual interpretative area (area 18 - 19)

which understands the meaning of words. The message is then fed to the angular

gyrus which correlates them with other related items stored in memory in the

process of thinking.

WERNICKE'S AREA (The language and speech center)

Wernicke's area is found in the posterior part of the superior temporal gyrus (fig.

20-1). It receives input signals from the angulr gyrus (general interpretative area -

area 39). It is the memory store tor language. It decides what words are suitable

and in what sequence to express a certain idea.

Wernicke's area is very well developed in the categorical but not in the

representational hemisphere. It is connected with Broca's area (word formation

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center) in the premotor cortex via the "arcuate fasciculus.

THE WORD-FORMATION CENTER (Broca's area, area 44)

This area is found in the premotor area. It stores the motor programs for

different words. It receives input signals from Wernicke's area through the

arcuate fasciculus. When it is activated it stimulates the motor cortex at a certain

pattern to produce words by coordinated contractions of the respiratory,

laryngeal, pharyngeal, lingual and labial muscles.

Figure 20-1: Wernicke's area, angular gyrus

the arcuate fasciculus, and

Broca's area.

THE WRITING CENTER (Earner's center)

This is part of the hand-skills area which stores the motor programs for writing of

words or drawing of figures by the muscles of the hand. It receives input signals

from Wernicke's area via the arcuate fasciculus.

THE MECHANISM OF SPEECH

Speech passes by four steps to occur :

1. Formation of thoughts and ideas that will be expressed in speech: This is

the function of the angular gyrus. The ideas are formed in response to signals

from the visual, auditory, and other sensory areas.

2. Choice of suitable sentences and phrases to express the ideas:

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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.

1. SENSORY (RECEPTIVE) 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.

2. MOTOR (EXPRESSIVE) APHASIA

Motor aphasia is found in two forms:

(a) Vocal aphasia: This is due to a lesion in Broca's area. The

atient is

perfectly capable of deciding what he wishes to say and is capable of

vocalization, but he simply cannot make his vocal system emit words, but only

noises (nonfluent aphasia).

(b) Writing aphasia (agraphia):

This is one to a lesion in Exner's center. The

patient knows what he wants to writs or draw and he is capable of moving the hand

voluntarily, but he cannot make his hands write words or draw graphs to express

his thoughts.''

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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