INTRODUCTORY NEUROPHYSIOLOGY II

A.H. UMAR

DEPARTMENT OF HUMAN PHYSIOLOGY

FACULTY OF BASIC MEDICAL SCIENCES
AHMADU BELLO UNIVERSITY, ZARIA
THE MOTOR SYSTEM
 The motor system is the highly complex system that
controls body movement.
 It comprise all structures in the NS that support motor
functions
 Central structures involved in motor control include the
cerebral cortex, basal nucleus, brainstem, cerebellum,
spinal cord, pyramidal and extrapyramidal systems
 Motor neurons of these central structures are called
upper motor neurons (UMN)
 The motor system works closely with the muscular
system to produce movement
 Movement, whether voluntary or involuntary, is
produced by muscular contractions orchestrated by the
CNS.
Upper motor neurons (UMN)
 Both local circuit neurons and lower motor neurons receive input
from UMN.
 Most upper motor neurons synapse with local circuit neurons, which
in turn synapse with lower motor neurons. (A few upper motor
neurons synapse directly with lower motor neurons.)
 UMNs from the cerebral cortex, called cortico-spinal tracts or
pyramidal tracts, are essential for the execution of voluntary
movements of the body.
 Other UMNs originate in motor centres of the brain stem: the red
nucleus, the vestibular nucleus, the superior colliculus, and the
reticular formation. They form part of the extra-pyramidal tracts
 UMNs from the brain stem regulate muscle tone, control postural
muscles, and help maintain balance and orientation of the head and
body.
 Both the basal nuclei and cerebellum exert influence on upper motor
neurons.
Descending motor pathways
 The axons of UMN extend from the brain to LMN via two
types of somatic motor pathways—direct and indirect.

 Direct motor pathways provide input to lower motor

neurons via axons that extend directly from the cerebral
cortex (Pyramidal tract/pathway).
 Indirect motor pathways provide input to lower motor
neurons from motor centres in the basal nuclei,
cerebellum, and cerebral cortex (Extrapyramidal
tract/patway).

 Direct and indirect pathways both govern generation of

nerve impulses in the LMN
Direct motor pathways (Pyramidal tract)
 Nerve impulses for voluntary movements propagate
from the cerebral cortex to lower motor neurons via
the direct motor pathways/pyramidal pathways.

 Pyramidal cells are upper motor neurons with pyramid

shaped cell bodies located in the primary motor area
and the premotor area of the cerebral cortex (areas 4
and 6, respectively).

 The direct motor pathways consist of the corticospinal

tracts and the corticobulbar tracts
 Corticospinal tracts conduct impulses for the control of
muscles of the limbs and trunk.
 They are made of axons of UMN in the cerebral cortex
 After taking origin, they descend through the internal
capsule of the cerebrum and the cerebral peduncle of
the midbrain.
 In the medulla oblongata, the axon bundles form the
ventral bulges known as the pyramids.
 About 80% of the axons decussate (cross over) to the
contralateral (opposite) side in the medulla oblongata
and then descend into the lateral white fasciculus of the
spinal cord where they synapse with a local circuit
neuron or a lower motor neuron. These form the lateral
corticospinal tract
 It is responsible for precise, agile, and highly skilled
movements of the distal hands and feet.
 The 20% that remain on the ipsilateral (same) side
eventually decussate at the spinal cord levels where
they synapse with a local circuit neuron or lower motor
neuron. These forms the anterior corticospinal tract

 They control movements of the trunk and proximal parts

of the limbs.

 Thus, the right cerebral cortex controls most of the

muscles on the left side of the body, and the left
cerebral cortex controls most of the muscles on the right
side of the body.
 Corticobulbar tract conducts impulses for the control of
skeletal muscles in the head.

 Some of the axons of the corticobulbar tract decussate;

others do not.

 They terminate in the motor nuclei of cranial nerves in

the brain stem: the occulomotor (III), trochlear (IV),
trigeminal (V), abducens (VI), facial (VII),
glossopharyngeal (IX), vagus (X), accessory (XI), and
hypoglossal (XII).

 The lower motor neurons of the cranial nerves convey

impulses that control precise, voluntary movements of
the eyes, tongue, neck, mastication, facial expression,
speech, and swallowing.
Indirect motor pathways (Extrapyramidal tracts)
 The indirect motor pathways or extrapyramidal pathways include all
somatic motor tracts other than the corticospinal and corticobulbar
tracts.
 Their axons descend from various nuclei of the brain stem and
terminate on local circuit neurons or lower motor neurons.

 These tracts include

 Rubrospinal
 Tectospinal
 Vestibulospinal
 lateral reticulospinal
 medial reticulospinal

 They are responsible for the unconscious, reflexive or responsive

control of musculature, e.g. muscle tone, balance, posture and
locomotion.
Lower motor neurons (LMN)
 Signals that control movement converge on a group of
motor neurons called lower motor neurons (LMN) that
extend out of the brain stem and spinal cord to innervate
skeletal muscles in the body.
 The cell bodies of the lower neurons are located in the
ventral horn of the spinal cord gray matter and in the motor
nuclei of the cranial nerves in the brainstem
 From the brain stem, axons of LMNs extend through cranial
nerves to innervate skeletal muscles of the face and head.
 From the spinal cord, axons of LMNs extend through spinal
nerves to innervate skeletal muscles of the limbs and trunk.
 Only the LMN provide output from the CNS to skeletal
muscle fibres, thus, they are also called the final common
pathway.
The lower motor neurons are controlled:
 directly by local circuits within the spinal cord and
brainstem that coordinate individual muscle groups;
and
 indirectly by “upper” motor neurons in higher
centres that regulate those local circuits, thus
enabling and coordinating complex sequences of
movements.

The LMN (α and γ motor neurons) send axons

directly to skeletal muscles via the ventral roots and
spinal peripheral nerves, or via cranial nerves in the
case of the brainstem nuclei
 Contraction of skeletal muscles are controlled by
alpha motor neurons situated in ventral (anterior)
gray horn of spinal cord and nuclei of many of the
cranial nerves present in brainstem.
 Alpha motor neurons in the spinal cord, which
innervate the extrafusal fibres of skeletal muscles
are responsible for the contraction of muscles in
upper limbs, trunk and lower part of the body.
 The gamma motor neurons, which innervate the
intrafusal fibres of muscle, are responsible for the
maintenance of muscle tone.
 Comparison of UMN and LMN lesions

AHC = Anterior Horn cells

Motor homunculus
 The Motor Unit
 A motor unit consists of one alpha motor neuron and all the extrafusal
muscle fibres it innervates. The number of these muscle fibres can vary
from 1 or 2 to 1000.
 It is the smallest functional unit of the nervous system and it can be
regarded as the final output of motor commands.

 The term motor unit was coined by an English Neurophysiologist, Sir Charles
Scott Sherrington.

 Most extrafusal skeletal muscle fibres are innervated by a single α motor

neuron

 Since there are, by far, more muscle fibres than motor neurons, individual
motor axons branch within muscles to synapse on multiple extrafusal fibres.

 Because an action potential generated by a motor neuron typically brings to

contraction threshold all of the muscle fibres the neuron innervates, the
single α motor neuron and its associated muscle fibres constitute the
smallest unit of force that can be activated by the muscle. This is called the
Motor Unit
A motor unit
 Motor functions of cerebral cortex
 Cortical areas concerned with origin of motor
signals are the primary motor area, premotor area
and supplementary motor area in frontal lobe and
sensory area in the parietal lobe.
 Cortical areas send their output signals to spinal
cord via corticospinal tracts and to brainstem via
corticobulbar tracts.
 About 30% of the fibres forming corticospinal and
corticobulbar tracts take their origin from primary
and supplementary motor cortex, 30% from
premotor area and remaining 40% from parietal
lobe particularly from somatosensory area.
Some cortical areas for control of motor functions
 Role of the Brain Stem in control of Motor
function
 The brain stem contains motor and sensory nuclei that
perform motor and sensory functions for the face and head
regions
 The brain stem provides many special control functions, such
as:
 Control of respiration
 Control of the cardiovascular system
 Partial control of gastrointestinal function
 Control of many stereotyped movements of the body
 Control of equilibrium
 Control of eye movements
 The brain stem also serves as a way station for “command
signals” from higher neural centres.
 The Cerebellum
 The cerebellum is part of the
hind brain that lies between
brain stem and back of the
cerebrum

 It plays essential role in motor

output, posture, balance and
equilibrium

 The cerebellum is active in both

learning and performing rapid,
coordinated, highly skilled
movements such as hitting a
golf ball, playing tennis, riding a
bicycle, speaking, swimming,
running, typing, playing the
piano, talking.
 Anatomically, the cerebellum consists
of a narrow, worm-like central body
called vermis and two lateral lobes,
the right and left cerebellar
hemispheres
 It is divided into 3 lobes; anterior,
posterior and flocculonodular lobe
 The anterior and posterior lobes on
either side form two large
hemispheres (left and right)
separated by the vermis
 Three 3 pairs of peduncles connect
the cerebellum to the brain stem
 The superior peduncle to the
midbrain.
 The middle peduncle to the pons.
and
 The inferior peduncle to the
medulla oblongata
Parts of the vermis
 Physiologically, the cerebellum can
be subdivided into three main parts
based on differences
in their functions and sources of
input:
1) Cerebrocerebellum, the largest
subdivision in humans.
 It occupies most of the
lateral cerebellar
hemisphere and receives
input from many areas of
the cerebral cortex.
It includes lateral portions of lobulus
ansiformis and lobulus
paramedianus
 This region of the cerebellum
is especially well developed
in primates.
 The cerebrocerebellum is
concerned with the
regulation of highly skilled
movements, especially the
planning and execution of
complex spatial and temporal
sequences of movement
(including speech).

2) Vestibulocerebellum, the
phylogenetically oldest part of the
cerebellum.

 This portion comprises the

caudal lobes of the
cerebellum that includes:

 the flocculus; and

 the nodulus.
 As its name suggests, the
vestibulocerebellum receives
input from the vestibular nuclei
in the brainstem and is primarily
concerned with the regulation of
movements underlying posture
and equilibrium.

3) Spinocerebellum is the last of the

major subdivisions of the
cerebellum.

 The spinocerebellum occupies

the median and paramedian
zone of the cerebellar
hemispheres and is the only part
that receives input directly from
the spinal cord.
 The lateral part of the
spinocerebellum is primarily
concerned with movements of
distal muscles, such as the
relatively gross movements of
the limbs in walking.

 The central part, called the

vermis, is primarily concerned
with movements of proximal
muscles, and also regulates eye
movements in response to
vestibular inputs.
Connections between Cerebellum and other NS Regions

The connections between the cerebellum and other parts of the

nervous system occur via three large pathways called cerebellar
peduncles.

i) The superior cerebellar peduncle (or brachium conjunctivum)

is almost entirely an efferent pathway.
 The neurons that give rise to this pathway are in the deep
cerebellar nuclei, and their axons project to upper motor
neurons in the red nucleus, the deep layers of the superior
colliculus, and, after a relay in the dorsal thalamus, the primary
motor and premotor areas of the cortex.
ii) The middle cerebellar peduncle
(or brachium pontis) is an afferent
pathway to the cerebellum.

Most of the cell bodies that give

rise to this pathway are in the
base of the pons, where they form
the pontine nuclei.

The pontine nuclei receive input

from a wide variety of sources,
including almost all areas of the
cerebral cortex and the superior
colliculus.

The axons of the pontine nuclei,

called transverse pontine fibres,
cross the midline and enter the
cerebellum via the middle
cerebellar peduncle.
 The pontine nuclei receive
input from a wide variety of
sources, including almost all
areas of the cerebral cortex
and the superior colliculus.

The axons of the pontine

nuclei, called transverse
pontine fibres, cross the midline
and enter the cerebellum via the
middle cerebellar peduncle.

Each of the two middle

cerebellar peduncles contain
over 20 million axons, making
this one of the largest pathways
in the brain.
 Most of these pontine axons
relay information from the cortex
to the cerebellum.

iii) The inferior cerebellar

peduncle (or restiform body) is
the smallest but most complex
of the cerebellar
peduncles.

It contains multiple afferent

and efferent pathways:

 Efferent pathways in this

peduncle project to the
vestibular nuclei and the
reticular formation;
 the afferent pathways
include axons from the
vestibular nuclei, the spinal
cord, and several regions of
the brainstem tegmentum.
 Summary diagram of motor modulation by the
cerebrocerebellum
1. The central processing
component, the
cerebrocerebellar cortex,
receives massive input from
the cerebral cortex.

2. It then generates signals that

adjust the responses of upper
motor neurons to regulate the
course of a movement.

3. Note that modulatory inputs

also influence the processing
of information within the
cerebellar cortex.
Cerebellar cortex (grey matter)

 The cerebellum is made of an outer grey matter

(cerebellar cortex), made of neuronal cell bodies, and an
inner white matter made of neuronal processes.
 Four large cerebellar nuclei (Deep nuclei), are found in
the white matter. They include:
 dentate,
 fastigial,
 globosus and
 emboliform.

 The cerebellar cortex is made of three layers;

 Outer molecular (plexiforma) layer
 Purkinje cell layer
 Inner granular layer
 Molecular (plexiform) layer
 It is the outermost layer of the cerebellar cortex. It contains star shaped stellate
cells and basket cells. Axons of granule cells in granular layer ascend to the
molecular layer and form parallel fibres. It also contains terminal portions of
climbing fibres, and dendrites of purkinje cells and Golgi cells.

 Purkinje cell layer

 It is a thin intermediate layer between outer molecular layer and inner granular
layer. It is made of a single layer of flask-shaped purkinje cells. Dendrites of
purkinje cells ascend into the molecular layer and synapse with climbing fibres
or parallel fibres. Their axons descend into the white matter and terminate on
deep nuclei. Some of the axons pass out of the cerebellum and terminate in the
vestibular nuclei in pons and medulla. Impulses from cerebellar cortex are
transmitted to different parts of the CNS only through purkinje cells.

 Granular layer
 It is the innermost layer before the white matter, and is made of granule cells
and Golgi cells. Axons of granule cells ascend into the molecular layer and form
parallel fibres. Dendrites of granule cells and axons and dendrites of Golgi cells
synapse with Mossy fibres in the granular layer to form a large glomerulus.

 The cerebellar cortex receives afferent fibres through climbing fibres and
Mossy fibres.
 Climbing fibres
 They arise from inferior olivary nucleus in medulla, which
relay output signals from motor cortex, and from
proprioceptors in different parts of the body. After reaching
the cerebellum, the climbing fibres send collaterals to the
deep cerebellar nuclei, and then ascend to the molecular
layer to terminate on dendrites of purkinje cells.
 Mossy fibres
 They arise from motor cortex, pons, medulla and spinal cord.
After entering the cerebellum, they also send collaterals to
the deep nuclei and ascend to the granular layer, where they
divide into many terminals that end in a large granular
structure called glomerulus.

 NB. Stellate cells, basket cells, purkinje cells and Golgi

cells are GABAnergic inhibitory fibres, while climbing
fibres, Mossy fibres and granule cells are excitatory
White matter of cerebellum
 The white matter is made of neuronal processes. Deep
cerebellar nuclei (dentate, globosus, fastigial and
emboliform) are found in the white matter. The fibres are
classified into three groups;
 Projection fibres: they contain cerebellar afferent and
efferent fibres that connect the cerebellum with other parts
of the CNS. They are arranged in three bundles (cerebellar
peduncles) as follows:
 Superior cerebellar peduncle (brachium conjunctivum); contain
fibres that connect cerebellum to midbrain and fibres of
spinocerebellar tract.
 Middle cerebellar peduncle (brachium pontis); contain fibres that
connect the cerebellum with pons.
 Inferior cerebellar peduncle (restiform body); contain fibres that
connect the cerebellum to medulla and spinal cord.
 Association fibres: contain fibres that connect different parts
of the cerebellum within the same hemisphere.
 Commissural fibres: they connect areas of one cerebellar
hemisphere with the other.
Functions of cerebellum
 The cerebellum is concerned with
subconscious control of motor activities which
include:
 control of posture and equilibrium
 control of stretch reflex

 planning and timing of voluntary movement

 Monitoring intentions for movement.

 The cerebellum receives impulses from the motor
cortex and basal nuclei via the pontine nuclei in the
pons regarding what movements are planned
 Monitoring actual movement.
 The cerebellum receives input from proprioceptors in
joints and muscles that reveals what actually is
happening.
 These nerve impulses travel in the anterior and
posterior spinocerebellar tracts.
 Nerve impulses from the vestibular (equilibrium-
sensing) apparatus in the inner ear and from the eyes
also enter the cerebellum
 Comparing command signals with sensory
information.
 The cerebellum compares intentions for movement with
the actual movement performed.
 Sending out corrective feedback.
 Ifthere is a discrepancy between intended and
actual movement, the cerebellum sends feedback
to upper motor neurons.
 This information travels via the thalamus to UMNs
in the cerebral cortex but also goes directly to
UMNs in brain stem motor centres.
 As movements occur, the cerebellum continuously
provides error corrections to upper motor neurons,
which decreases errors and smoothes the motion.
Over longer periods it also contributes to the
learning of new motor skills.
Applied physiology (disorders of cerebellum)
 Lesions in the cerebellum may occur as a result of
tumor, injury, degenerative changes or thrombosis. It
leads to disturbances in movements, posture and
equilibrium. Symptoms in unilateral lesions appear on
the affected side because cerebellum controls the same
side (ipsilateral) of the body. Symptoms include;
 Atonia: loss of muscle tone. Partial loss of muscle tone
is hypotonia. It causes disturbances is postural reflexes
 Asthenia: muscle weakness
 Pendular knee jerk
 Staggering (drunken) gait
 Motor ataxia: incoordination of voluntary movements.
 Dysmetria: inability to control distance of motor act. It
either overshoots (hypermetria; past pointing) or
undershoots (hypometria)
 Kinetic/intention tremor: oscillatory motions when
performing a voluntary movement.
 Rebound phenomenon: overshooting of a limb when
resistance to its movement is removed.
 Adiadokokinesia/dysdiadokokinesia: inability to perform
opposite movements simultaneously at a rapid rate
 Dysarthria: difficulty in producing clear speech. The
speech become jumbled and scanning
 Nystagmus: to and fro movement of the eye ball on
fixing the eye at an object
 Basal Nuclei
 Deep within each cerebral hemisphere are three nuclei
(masses of gray matter) that are collectively termed the basal
nuclei (BN), which is part of the extra pyramidal system

 Like the cerebellum, the BN constitute accessory motor system

that functions usually not by itself but in close association with
the cerebral cortex and corticospinal motor control system.

 It receive most of their input signals from the cerebral cortex

itself and also return almost all their output signals back to the
cortex, forming the
cortico-basal-nuclei-cortical loop
 The BN are subcortical masses or gray matter made of
four group of nuclei
 The caudate nucleus.
 The lentiform (or lenticular) nucleus : This consists of 2 parts. i.e. outer
putamen and inner globus pallidus. Globus pallidus is divided into
interna (Gpi) and externa (Gpe)
 Subthalamic nucleus (in diencephalon)
 Substantia nigra (in midbrain): made of substantia nigra compacta and
subtantia nigra reticulata

 Caudate and putamen are collctively called the corpus

striatum.
 All motor and
sensory nerve
fibres connecting
the cerebral cortex
and spinal cord
pass through a
space that lies
between the
caudate nucleus
and the putamen.
This space is called
the internal
capsule of the
brain
The inputs from the cerebral cortex that reach the BN terminate
in the dendrites of the medium spiny neurons in the corpus
striatum.
 One of the principal roles of BN in motor control is to
function in association with the corticospinal system to
control complex patterns of motor activity, e.g. writing of
letters of the alphabet.
 When there is serious damage to the basal nuclei, the
cortical system of motor control can no longer provide
these patterns, thus, one’s writing becomes crude, as if
learning for the first time how to write.
 Other motor patterns that require the BN are cutting
paper with scissors, hammering nails, shooting a
basketball through a hoop, passing a football, throwing a
baseball, most aspects of vocalization, controlled
movements of the eyes, and virtually any other of our
skilled movements, most of them performed
subconsciously
Connections of BN
 The BN constitute a basic part of the
extrapyramidal system.
 Afferent (input) fibres are derived mainly from
the cerebral cortex to the corpus striatum.
 Efferent (output) fibres originate mainly from
globus pallidus.
 Their connections can generally be divided into
3 parts, vis cortical, interconnections and brain
stem connections
 Cortical connections of the BN
The Putamen circuit:
 Fibres from premotor,
supplementary motor and
somatosensory areas of the
cerebral cortex project to
the putamen
 From putamen to the
internal globus pallidus
(GPi).
 From the Gpi, fibres arise
and relay at the thalamic
ventrolateral nucleus (VLN),
 Fibres from VLN project to
the cortical motor areas,
specially the primary motor
area (area 4), and to
portions of the premotor
and supplementary cerebral
areas closely associated
with the primary motor
cortex.
Caudate circuit:
 Fibres project from
cortical motor and
sensory association
areas to the caudate
nucleus,

 From caudate nucleus to

Gpi

 From Gpi to VLN

 From VLN to prefrontal,

premotor, and
supplementary motor
areas of the cerebral
cortex
 The caudate nucleus
plays a major role in this
cognitive control of motor
activity
 Interconnections of the basal nuclei
 In addition to afferent and
efferent connections, different
components of corpus
striatum are interconnected by
intrinsic fibres.
 Putamen to globus pallidus
 Caudate nucleus to globus
pallidus
 Caudate nucleus to putamen.
 A negative feedback
interconnection between the
external globus pallidus (Gpe)
and the subthalamus.
 Dopaminergic nigro-striatal
connection.
 GABA-ergic striato-nigral &
striato-pallidal projections
 Different components of
corpus striatum in each side
are connected to those of the
opposite side by commissural
fibres.
 Brain stem connections of the BN

 Fibres from the globus pallidus project to

 Reticularformation

 Red nucleus
 Vestibular nucleus

 Inferior olivary nucleus.

 Signals from the BN are transmitted through

such connections to the spinal centres via the
extrapymmidal tracts
 Neurotransmitters in the BN
 Acetylcholine (mainly from intra-striatalneurons).
 Dopamine (from the nigro-striatal neurons).
 GABA (from the striato-nigra and striato-pallidal neurons
 Norepinephrine. serotonin and enkephalin (from the
neurons that project from various centres in the brain
stem
 Glutamate (from the cortico-striatal and subthalamic
neurons) .
 Acetylcholine, glutamate and norepinephrine: are
excitatory neurotransmitlers, while all the remaining are
inhibitory and the balance between inhibition and
excitation in the BN maintains normal motor function.
 Normally, the inhibitory effect predominates (which
decreases the excitatory discharge from the BN), and in
addition, discharge from BN to the thalamus is mainly
inhibitory via GABA-ergic neurons.

 These factors decrease the excitatory discharge from

the thalamus to the cortical motor areas.

 The predominance or inhibitory neurons in the BN

makes the circuits to act as negative feedback loops
that stabilise the motor control system, and prevent
excessive and undesirable movement
Functions of the Basal Nuclei
i. Act by modifying ongoing activity in motor pathways.

ii. Inhibit muscle tone (proper tone – balance the excitatory and
inhibitory inputs to motor neurons that innervate skeletal muscle).

iii. Select and maintain purposeful motor activity while

suppressing unwanted patterns of movement

iv. Monitor and coordinate slow and sustained contractions,

especially those related to posture and support.

v. Regulate attention and cognition

vi. Control timing and switching

vii. Motor planning and learning

Diseases of BN
Parkinsonism (paralysis agitans):
 Parkinson disease (PD) is a slowly progressive neuro-degenerative
disease associated with destruction of dopaminergic neurons.
 It is named after the discoverer James Parkinson.
 It results from widespread destruction of substantia nigra (pars
compacta) that sends dopamine-secreting neurons to the caudate
nucleus and putamen.
 The disease is characterized by
 Rigidity of much of the musculature of the body,
 Static/involuntary tremor of the involved areas even when the person is
resting at a fixed rate of 3 to 6 cycles per second. It disappears during sleep
 Akinesia: serious difficulty in initiating movement,
 Festinant gait. The patient walks quickly in short steps by bending forward.
 Dementia: In later stages, some patients develop dementia (loss of
memory)
 Bradyphrenia: slowing of thought processes
 Parkinsonism may be caused by cerebral arteriosclerosis,
injury to BN due to accident, longterm treatment with
antihypertensive drugs like reserpine (drug induced
parkinsonism).
 However, the causes of parkinsonism are largely unknown.

 Since the dopamine secreted in the caudate nucleus and

putamen is inhibitory, destruction of the dopaminergic
neurons in the substantia nigra of the parkinsonian patient
would allow the caudate nucleus and putamen to become
overly active and possibly cause continuous output of
excitatory signals to the corticospinal motor control system.

 These signals could overly excite many or all of the muscles

of the body, thus leading to rigidity.
Treatment of PD

 L-DOPA: because dopamine does not cross the BBB, a

dopamine precursor, levodopa (L-dopa) is used. L-dopa cross
the BBB and is converted to dopamine in the brain

 L-Deprenyl: L-deprenyl inhibits monoamine oxidase, which is

responsible for destruction of most of the dopamine after it
has been secreted. Therefore, any dopamine that is released
remains in the BN for a longer time.

 Subthalamic nucleus stimulation.

 Dopamine transplants.
Chorea
 Chorea means rapid jerky movements. It mostly
involves the limbs.
 It is due to lesion in caudate nucleus and putamen
 Chorea that occur at young age is called
Sydenham chorea

Athetosis
 Athetosis refers to slow rhythmic and twisting
snake-like movements.
 It is due to lesion in globus pallidus.
Huntington disease (HD)
 Huntington disease is an inherited progressive neural
disorder due to the degeneration of neurons secreting GABA
in corpus striatum and substantia nigra.

 It is characterized by chorea, hypotonia and dementia.

 It is otherwise called Huntington chorea, or hereditary
chorea.

 It is due to genetic defect in gene called huntington located on

chromosome 4
 Features of HD
 Heritability
 Age of onset is 30 – 50 years
 Behavioral/psychiatric disturbances
 Death within 15-20 years of onset
Hemiballismus
 Is characterized by violent involuntary abnormal movements on one
side of the body involving mostly the arm.
 While walking, the arm swings widely. These movements are called
the flinging movements.
 These movements are due to the release phenomenon because of
the absence of inhibitory influence on movements.
 Hemiballismus occurs due to degeneration of subthalamic nucleus of
Luys.
 Some of the symptoms include:
 Involuntary movements on one side of the body
 Involuntary muscle spasms on one side of the body
 Violent movements involving one side of the body
 Usually arms are more affected than the legs

Kernicterus
 Kernicterus is a form of brain damage in infants caused by severe
jaundice. basal nuclei are the mainly affected parts of brain.
HYPOTHALAMUS
 The hypothalamus is a part of the diencephalon located
below and anterior to the thalamus, and extends from optic
chiasma to mamillary body
 It is the main component and major output pathway of the
limbic system
 It contain the following groups of nuclei scattered in the wall
and floor of the third ventricle
 Anterior group (supraoptic, suprachiasmatic, preoptic and
paraventricular nuclei)
 Lateral group (mainly a large lateral nucleus)
 Medial group (dorsomedial and ventromedial nuclei as well as the
arcuate nucleus)
 Posterior group (posterior nucleus and the mamilllary bodies)
 Periventricular nuclei
 The hypothalamus send output signals three directions:
 backward and downward to the brain stem, mainly into the
reticular areas of the mesencephalon, pons, and medulla
and from these areas into the peripheral nerves of the
autonomic nervous system
 upward toward many higher areas of the diencephalon and
cerebrum, especially to the anterior thalamus and limbic
portions of the cerebral cortex
 into the hypothalamic infundibulum to control secretory
functions of pituitary glands.
 Thus, the hypothalamus, which represents less than 1
per cent of the brain mass, is one of the most important
of the control pathways of the limbic system.
 It controls most of the vegetative and endocrine
functions of the body as well as many aspects of
emotional behaviour
Nervous connections of the hypothalamus
 Afferent (input) fibres: The hypothalamus receives afferent fibres from
 Limbic cortex, hippocampus and amygdaloid nucleus
 Cerebral cortex
 Basal nuclei (globus pallidus)
 Thalamus
 Reticular formation (through which it receives collatcrals from the sensory tracts)
 Optic chiasma.

 Efferent (output) fibres: The hypothalamus send efferent fibres to

 Limbic system
 Midbrain (tegmentum)
 Thalamus
 Cerebral cortex
 Reticular formation (through which it controls centres in the brain stem and
spinal cord)
 Posterior pituitary gland
Functions of hypothalamus
 Control of autonomic functions: The anterior nuclei control
parasympathetic functions while the posterior and lateral nuclei
control sympathetic functions.
 Control of endocrine functions
 Regulation of body temperature: The hypothalamus contains
sensitive thermoreceptors as well as the thermoregulatory centre,
i.e. heat loss centre in the anterior nuclei and heat gain centre in the
posterior nuclei
 Control of water balance: This occurs by the hypothalamic
osmoreceptors which regulate water intake by affecting thirst centre
and Water loss by adjusting release of ADH from the posterior
pituitary gland
 Regulation of body temperature: Normal set point of body
temperature is 37°C. Hypothalamus regulate body temperature
through activities of heat loss centre in preoptic nucleus and heat
gain centre in posterior hypothalamic nucleus.
 Regulation of hunger and food intake: Food intake is regulated by
feeding centre and satiety centre.
 Control of circadian rhythms: This occurs by the suprachiasmatic
nuclei, which are the pacemakers for the circadian rhythms in the
body. They receive signals from the eyes (via the retino-hypothalamic
fibres)
 Regulation of sexual functions: The hypothalamus regulates release
of gonadotrophic hormones, which control spermatogenesis and
ovulation as well as the secretion or sex hormones from the gonads.
The anterior hypothalamic neurons are also excited by the circulating
estrogens and androgens, resulting in an increase in libido and
sexual ability.
 Regulation of sleep and wakefulness: Stimulation of mamillary body
causes wakefulness and its lesion leads to sleep
 Control of motivation: Hypothalamus has two centers for behaviorial
and emotional changes: Reward center and punishment center
Disorders of hypothalamus
 Endocrine disorders
 Diabetes insipidus due to ADH deficiency
 Hyperthermia or hypothermia.
 Sleep disturbances e.g. insomnia and narcolepsy
 Hyperphagia (overeating) or anorexia (loss of apetite).
 Autonomic disturbances e.g. spontaneous V.C. or V.D. or
sweating.
 Abnormal emotions (e.g. fear. rage or placidity).
 Sexual disturbances. Hypogonadism
 Dystrophia adiposogenitalis (Fröhlich Syndrome):
Obesity and sexual infantilism, associated with dwarfism
(if the condition occurs during growing period).
 Laurence-Moon-Biedl Syndrome: Disorder of hypothalamus
characterized by moon face, obesity, polydactylism (extra
digits), mental retardation and hypogenitalism.

 Narcolepsy: Abnormal sleep pattern. There is a sudden attack

of uncontrollable desire for sleep in the day time and the
person suddenly falls asleep. The duration of sleep is very
short, few seconds to 20 minutes. At night, sleep may be
normal but is often disturbed or there may be insomnia (loss of
sleep), and cataplexy (sudden uncontrolled outbursts of
emotion)
LIMBIC SYSTEM

 Limbic = Border
 The word “limbic” means “border.”
 Limbic was used to describe the border structures
around the basal regions of the cerebrum
 Limbic system has been expanded to mean the entire
neuronal circuitry that controls emotional behavior and
motivational drives

 Limbic system is a ring of structures in the inner border

of cerebrum and floor of diencephalon, encircling the
upper part of the brain stem and corpus callosum
 It is primarily related to emotion and is extensively
concerned with memory
Components of the limbic system
 Limbic lobe: a rim of cerebral cortex on the
medial surface of each hemisphere. It includes
the cingulate gyrus which lies above the corpus
callosum, and the parahippocampal gyrus in
the temporal lobe. The hippocampus is a
portion of the parahippocampal gyrus that
extends into the floor of the lateral ventricle.
 Dentate gyrus: lies between the hippocampus
and parahippocampal gyrus
 Amygdala: is composed of several groups of
neurons located close to the tail of the caudate
nucleus.
 Septal nuclei located within the septal area
formed by the regions under the corpus callosum
and the cerebral gyrus.
 Mammillary bodies of the hypothalamus
 Olfactory bulbs are flattened bodies of the
olfactory pathway that rest on the cribriform plate.
 The fornix: stria terminalis, stria medullaris, medial
forebrain bundle, and mammillo-thalamic tract
 Papez circuit
 Papez circuit is the interconnections
between various structures of limbic
system, which form a complex of
closed circuit.
 This circuit was described by an
American neuroanatomist, James
Wenceslas Papez.
 Hippocampus is connected to
mamillary bodies of hypothalamus
via fornix.
 Mamillary bodies are connected to
anterior thalamic nucleus via
mamillo-thalamic tract.
 Anterior thalamic nucleus projects
into cingulate gyrus through medial
thalamo-cortical fibers.
 Cingulate gyrus is in turn connected
to hippocampus
 Papez circuit plays a role in memory
encoding
 Functions of the limbic system
 Limbic system (emotional brain) plays a primary role in a range of
emotions, including pain, pleasure, docility, affection, and anger.
 It also is involved in olfaction (smell) and memory.
 Experimental stimulation of different areas of limbic system in
animals leads to reactions that indicate intense pain or extreme
pleasure.
 Stimulation of other limbic system areas in animals produces
tameness and signs of affection.
 Stimulation of a cat’s amygdala or certain nuclei of the hypothalamus
produces a behavioral pattern called rage—the cat extends its claws,
raises its tail, opens its eyes wide, hisses, and spits.
 By contrast, removal of the amygdala produces an animal that lacks
fear and aggression.
 Likewise, a person whose amygdala is damaged fails to recognize
fearful expressions in others or to express fear in situations where
this emotion would normally be appropriate, for example, while being
attacked by an animal
 Together with parts of the cerebrum, the limbic
system also functions in memory; damage to
the limbic system causes memory impairment.

 One portion of the limbic system, the

hippocampus, is seemingly unique among
structures of the central nervous system—it has
cells reported to be capable of mitosis. Thus,
the portion of the brain that is responsible for
some aspects of memory may develop new
neurons, even in the elderly???
Specific functions of the limbic system include:
 Olfactory sensation.
 Control of the feeding behaviour: This is one of the functions of the
amygdaloid nuclei. Its stimulation causes chewing and licking
movements while its damage causes severe hyperphagia (to food
and other objects).
 Control of autonomic functions: Many limbic structures control
autonomic effects (especially changes in the blood pressure and
respiration).
 Control of sexual behaviour: The behaviour that accompanies the
sexual act is regulated in the limbic system particularly the
amygdaloid nuclei. Bilateral damage of these nuclei in males leads to
abnormal sexual behaviour and hypersexuality.
 Memory and learning
 Regulation of food intake: Along with amygdaloid complex, the
feeding center and satiety center present in hypothalamus regulate
food intake
 Control of circadian rhythm: Hypothalamus is taking major role in the
circadian fluctuations of various physiological activities

 Control of emotions: Together with the hypothalamus, the limbic

system controls the emotional reactions. Stimulation of the
amygdaloid nuclei can produce fear or rage, while their damage
produces placidity & disappearance of the fear response.

 Control of motivation: Motivation is controlled by reward and

punishment systems. Reward system is located along the medial
forebrain bundle (especially the reward centre in the lateral and
ventromedial hypothalamic nuclei) while the punishment system
includes mainly a hypothalamic punishment centre in the
periventricular nucleus.
 The transmitter in the reward system is dopamine and the stimuli that
excite it produce a sense of pleasure and ecstasy (happiness) which
increases motivation and leads to repetition.
 On the other hand, stimuli that excite the punishment system produce a
sense of displeasure. fear or terror, which inhibits motvation and leads
to avoidance or these stimuli
THANK YOU