Neurophysiology: Understanding How The Nervous System Works

Neurophysiology
Understanding
how the nervous system works
Zainal Muttaqin, M.D., Ph.D.
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Department of Neurosurgery, Diponegoro University
Embryology :
Neuroectodermal origin,
forming the neural tube,
consist of the walls and
their respective, fluid-
filled space called vesicles
Prosencephalon Mesencephalon Rhombencephalon
P. vesicles M. vesicle R. vesicle
Telencephalon Diencephalon Mesencephalon Metenceph. Myelenceph.
Cerebral Cortex Diencephalon Mesencephalon Pons-Cereb. MO-MS

Lateral ventr. 3rd.ventricle Sylvian aquaeduct 4th.ventricle - central canal
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CNS Imaging
and
Anatomy
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Cortical Divisions
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Cerebral Cortex
- total area about 0.25m2, consist of about 10 billion neurons
- cell variation : granular , agranular, fusiform, pyramidal, etc.
- cell layers, motor cortex c.o. 6 layers; I-IV sensory function,
and pyramidal neurons in layer V and VI
- Brodmann‘s numbering, according to histological studies ;
area 4 : primary motor cortex; 1,2,3 : primary sensory cortex
- presence of afferen and efferen pathways between thalamus
and cortex, cortex is an outgrowth of thalamus
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Cerebral Cortex
Somatotopic Arrangement :
- receptor for each sensory modality represented separately by

different neurons in the somatosensory area of the cortex.
- somatotopically arranged as each hemisphere controls contra-
lateral side of the body; the lower part of the body controlled
by neurons located in the upper part of the respective cortex.
- number of neurons (so as its cortical area) controlling/ repre-
senting a certain body part is proportional to function of the
respective body part, not anatomical size of the body part (s).
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Somatotopic Arrangement
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Primary, Secondary, and Tertiary cortical areas
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Sensory Functions
I. 1. Primary visual area
P
F 2 2. Primary somatosensory area
2a
4 3. Primari auditory area
3a O1
1a
3
T just for simple analysis, such as localization
II. Secondary area : association area, for more difficult analysis

located just outside or surrounding the specific primary areas : 1a, 2a, 3a.
III. Tertiary area : for complex analysis, center of interpretation

located between main association areas, only in the dominant hemisphere/cortex : 4
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Motor Functions
1. Primary motor cortex
2 1 the beginning of pyramidal tract
3
2. Broca area and Hand (Exner) areas
2
coordinating activity of all muscles
related to speech & hand movements
(located at pre-motor cortex)
3. Prefrontal cortex : additional area for cerebration or thinking

- planning the future, planning sequence of movements
- postponing planned works related to incoming new information
- solving difficult problems, mathematic, datas - diagnosis, etc.
- correlating behavior with values, polite or unpolite, good or bad
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Sensory Perception :
Primary area ;
- auditory : not deaf, but don･t understand what is heard
- visual : not blind, but don･t understand what is seen
- somatosensory : not anesthesia, but don･t understand what is felt
Secondary/ association area ;

- understood what is heard / seen, but not in a coherent manner; such
as reading without understanding the meaning of sentences
Tertiary/ interpretation area ;

- a higher brain function / cerebration, mainly developed in the left /
dominant side; from birth to 6 year-old right and left side still same
- the word “dominant” is for intellectual /verbal /language function
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Cortical networks dysfunction :
Agnosia ;
- auditory agnosia : not deaf but fails to recognize specific sounds/ speech/ music
- visual agnosia : not blind, but fails to recognize object visually, prosopagnosia
means failure to recognize familiar faces
- tactile agnosia : inability to recognize objects by touch
Apraxia ;
- ideomotor apraxia: inability to perform complex acts on command, but the same
acts can be performed automatically
- ideational apraxia: failure to perform sequences of acts, but not individual act
- kinetic/ motor apraxia/ gait apraxia: paient has his feet ‘glued to the floor’
Aphasia ;
- Broca’s aphasia : comprehend spoken/ written language, but difficult with speech
- Wernicke’s aphasia: poor speech comprehension, incorrect word to express thought,
use words without precise meaning, or may substitute words
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Motor System
Pyramidal / Corticospinal pathway (1 ) :
- starts from the pre-central gyrus or motor cortex or
Brodmann area 4 or Upper Motor Neuron
- efferen fibers descend through ventral part of the brain
internal capsule - diencephalic level
cerebral peduncle - mesencephalic level
basis pontis - pontine level
pyramis - medullary level
- end at the anterior horn of the spinal cord‘s grey matter,
sinaps with LMN / alpha motoneuron, whose axon or
efferen fibers end as motor end plate.
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Pyramidal / Corticospinal pathway dnS

Motor system
Pyramidal pathway ( 2 ) :
- most fibers decussate to the contralateral side at lower medulla, and descend as
lateral corticospinal tract ; some fibers descend ipsilaterally as ventral cortico-
spinal tract and cross midline at the level of their sinaps with respective LMN .
- those fibers that go to the nuclei of the cranial motor nerve ( nn. 3, 4, 6, 7, 12 ),
decussate at the level of the respective nuclei in the brainstem/
- some fiber from the motor cortex ends in the brainstem (cortico bulbar tract )
- direct all conscious / purposeful movement of the body (as the driver of a car)
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Motor System
Extrapyramidal Pathway :
Muscle spindle
Muscle fiber
* Gamma motoneuron
*
* Alpha motoneuron
*
- function as the power steering (providing the power needed) for purpose-
ful motion of the muscles (performed by the pyramidal system)
- coordinated by many nuclei in the basal ganglia and cerebellum, via the
reticular formation of the brainstem, brought to the gamma motoneuron
at the anterior horn of the spinal cord･s grey matter.
- efferen fibers of the gamma motoneuron activates muscle spindle, which
in turns activates alpha motoneuron. Activation of alphamotoneuron will
then facilitate muscle contraction (increase of muscle tone)
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Motor system
Anterior horn of the spinal cord :

- alpha motoneuron; larger cells, innervate true muscle fibers/ex-
trafusal, secondary neuron (LMN) of the corticospinal pathway,
with afferen fiber of muscle spindle form stretch reflex circuitry
- gamma motoneuron; smaller cells, innervate intrafusal fibers or
muscle spindle, which in turns activate alpha motoneuron & in-
crease muscle tone, strong effect from extrapyramidal centers
(basal ganglia,cerebellum, and reticular formation of brainstem)
- motor unit: c.o.a number of muscle fibers innervated by 1 alpha
motoneuron ( large: >100 fibers; small: <10 fibers per neuron )
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Motor system
Distinguishing UMN and LMN lesion :

LMN (starting from anterior horn to the motor end plate)
- Destroys the stretch reflex circuitry, there is no muscle tone
- Called flaccide paralysis, no physiological reflexes/ areflexia
- Quick atrophy of the involved muscles
UMN (from the motor cortex until just before anterior horn)
- Stretch reflex circuitry intact & uncontrolled by consciousness
(pyramidal pathway) so that muscle tone increases (spastic),
- Causing hyperreflexia & the appearance of pathological reflexes
- Called spastic paralysis, atrophy occurs only after a long time
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Sensory System
Sensory receptors :
Somatosensory (GSA) Viscerosensory (GVA)
Proprioceptive Exteroceptive Interoceptive

position sense pain & thermal (anterolateral /spinothalamic)
(dorsal/lemniscal) touch & pressure - tactile discrimination (dorsal/lemniscal)
- simple touch (anterolateral /spinothalamic)
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Sensory System
Pain ( 1 )
- protect body from noxious stimuli (stimuli that may cause tissue destruction )
- receptors found in skin, periosteum, duramater, arterial wall, and joint surface.
- receptors consist of mechanosensitive, thermosensitive, and chemosensitive.
- different form of pain: sharp pain, burning pain, and dull pain (bad localization)
- pathophysiology of pain sensation;
tissue destruction (secretion of bradykinine, prostaglandine, histamine,
serotonin)
ischemia (decrease of blood flow will result in lactic acidosis)
muscle spasm (overcontraction of muscle may cause ischemia)
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Sensory system
Pain ( 2 )
- pain transmission in the CNS
1. Spinothalamic/ anterolateral (good localization, consciously perceived)
2. Diffuse spino-reticulo-thalamic system
( via reticular formation, then intralaminar & reticular nuclei of thalamus, to
bilateral cerebral hemisphere; badly localized, related to mood of suffering)
- peripheral pain transmission
1. A delta fiber ( 3 - 20 U, myelinated, for sharp pain)
2. C fiber ( 0.5 - 2 U, unmyelinated, for burning pain & dull pain)
- referred pain (fromviscera, felt in body surface, caused by synaptic sharing
in the spinal cord between visceral and external/ surface fibers, in gastritis etc.)
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Sensory System
Temperature Sense
- Cold receptor ( active at 10-40 0C, max. at 25 0C, < 10 0C activates pain recept.)
-Heat receptor ( active at 30-50 0C, max. at 45 0C, warm if cold & heat together )
Position Sense
- static sensation (awareness of position/orientation of body parts, Ruffini receptor
at joint capsules & ligament, activated during motion, long lasting signal)
- kinesthetic sensation (awareness of speed of motion, Golgi tendon &Pacini recep-
tors, quick adaptation of signal )
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Sensory System
Anatomy of Transmission (1)
Pain & Temperature
1. sinaps at dorsal horn, cross midline,

ascend as lateral spinothalamic tract
to thalamic nuclei.
2. area innervated by Vth.nerve, fibers

cross the midline at medulla, & then
ascend to thalamus as trigemino-tha
lamic tract.
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Sensory System
Anatomy of Transmission ( 2 )
Proprioceptive & Tactile discrimination
1. Enters CNS as dorsal root, ascend at
the same side as dorsal funniculi (Goll
& Burdach or Gracilis & Cuneatus) to
dorsal medulla (change neuron/ sinaps)
2. New fiber (from Goll & Burdach) then
crosses midline and ascend to thalamus
as lemniscal fibers.
3. Some fiber sinaps at dorsal horn, cross
midline, ascend as ventral spinocerebel
lar tract (contralaterally,subconscious)
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Sensory System
Anatomy of Transmission ( 3 )
Proprioceptive & Tactile discrimination
1. Enters CNS as dorsal root, ascend at
the same side as dorsal funniculi (Goll
& Burdach or Gracilis & Cuneatus) to
dorsal medulla (change neuron/ sinaps)
2. New fiber (from Goll & Burdach) then
crosses midline and ascend to thalamus
as lemniscal fibers.
3. Some fiber sinaps at dorsal horn, cross
midline, ascend as ventral spinocerebel
lar tract (contralaterally,subconscious)
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Sensory System
Differences between
anterolateral and dorsal pathways
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Sensory System
Spinal Cord Lesions :

1. s.c. transection: spinal shock (flaccid paralysis) occurs in acute stage, sign of
UMN lesion can be detected after several weeks with spasticity and Babinsky
(extensor plantar reflex), lesions at C1-C3 disturb respiration
2. s.c. hemisection (Brown-Sequard Syndrome): ipsilateral spastic paralysis,
ipsilateral proprioception, and contralateral pain and temperature sensation
3. central gray matter lesion: occurs in Syringomyelia (cavitation around central
canal), interupt the crossing spinothalamic fibers affecting pain and temperature
sensation of the bilateral upper extremities, with intact proprioception (sensory
dissociation)
4. Amyotrophic Lateral Sclerosis (ALS): Progressive and fatal degeneration of LMN,
corticobulbar and corticospinal tract bilaterally (weakness and atrophy in some
muscles and spasticity and hyperreflexia in other muscles, followed by difficulty in
speaking and swallowing)
5. Poliomyelitis: a viral infection, usually in children, affecting LMN of the anterior
horn, result in flaccid paralysis of the involved limb, fatal if involves the brainstem
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Sensory System
Spesific Thalamocortical Projections :
- medial geniculate body - auditory area 41, 42
- lateral geniculate body - visual area 17
- VPM nuclei - sensory area I
(1, 2, 3 face )
- VPL nuclei - sensory area II,I
(1, 2, 3 body)
- VL nuclei - motor area (4, 6)
- VA nuclei - motor area (6, 8) & orbitofrontal c.
- anterior nuclei - limbic cortex
- lateral n. & pulvinar - parietal association & occipitotemp.c
- dorsomedial nuclei - prefrontal cortex
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Motor System
Basal Ganglia ( 1 )
-a group of subcortical nuclei, in the depth of the cerebral hemisphere
-functionally act as one unit, part of the extrapyramidal system, indirectly
influence LMN via modulation of cerebral cortex and brainstem
-c.o. : 1. Striatal body - lenticular nuclei
(putamen &globus pallidus)
- caudate nuclei
2. Amygdaloid body
3. Claustrum
4. Subthalamic nuclei
5. Dark nuclei (substansia nigra)
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Motor System
Basal Ganglia ( 2 )
Several basal ganglia circuitry : diffuse BG excitation

motor cortex thalamus (VA nuclei) BFA inhibition BIA excitation
striatum globus pallidus skeletal muscle tone down
BG destruction
motor cortex thalamus (VL nuclei) inhibitory effect (-)
pontine cerebellum decerebrate rigidity
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Motor System
Basal Ganglia ( 3 )
BG dysfunction in human causes difficulty in initiating movement,
disturbances in continuing or stopping ongoing movements,
abnormalities of muscle tone (rigidity), and development of
involuntary movement (tremor or chorea)
These manifestations can be divided into 3 functional categories :
1. Parkinsonism or Paralysis agitants: bradykinesia (slowness of movement),
rigidity, gait instability, and tremor. Masked face, no automatic arm swing
2. Hyperkinetic movement disorders: Ballismus, Chorea (Sydenham’s chorea in
rheumatic fever, Huntington disease in adult with dementia), & Athetosis
3. Dystonia: common in children with cerebral palsy, frequent focal form in
adult is spasmodic torticollis or wryneck
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Motor System
Basal Ganglia ( 3 cont.)

1. Chorea : continuous uncontrolled contraction of many muscles, named as ‘st.
vitus･s dance’,and ‘ piano-playing’,related to wide destruction of striatal body
causing disinhibition of thalamocortical neurons. If one side only: hemichorea
2. Athetose : fine & slow motion of distal muscles, mainly superior extremities,
usually rythmic, ‘worm like’ and aggravated by emotion, destruction of globus
pallidus (& striatum), related to feed back deficit from BG to thalamus & cortex
3. Hemiballismus : severe uncontrolled contraction of proximal muscles unilate-
rally, person my be ‘thrown’. Lost of subthalamic nuclei excitation on the internal
globus pallidus resulted in disinhibition of thalamocortical neurons.
4. Parkinson disease (paralysis agitans) : degeneration in substansia nigra and
locus ceruleus (and lewy bodies in the remaining neurons),lead to depletion of
dopamine in the striatum, causing enhanced pallidothalamic & nigrothalamic
inhibition of thalamocortical neurons.
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Cerebellum (1)
Means : ‘little cerebrum’
Volume : 10% of the brain
Neurons : 50% of the brain
Maintains fine control and coordination of both simple & complex movements:
• Coordinating posture and balance in walking and running
• Executing sequential movements in eating, dressing, and writing
• Producing rapidly alternating repetitive movements & smooth-pursuit movements
• Controlling certain properties of movements, including trajectory, velocity, and
acceleration
Voluntary movements can proceed without cerebellum, but such movements will be
lack of precision and appear clumsy and disorganized. Functional division of
cerebellum consist of Vermal region with fastigial nuclei, Paravermal region or the
intermediate zone, and the Lateral Hemisphere region with dentate nuclei
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Cerebellum (2)
Cerebellar inputs :
• Sensory information about muscle length, tension, limb position, brought by
posterior root, synapse at Clarke’s nuclear column (for lower limbs) and lateral
cuneate nucleus (for upper limbs and head), project to ipsilateral cerebellar nuclei.
Other fibers synaps at posterior horn & double cross to reach ipsilateral cerebellum.
These peripheral information enter cerebellum via inferior cerebellar peduncle
• Feedback information from cerebral cortex, projected to ipsilateral neuron at basis
of the pons, then cross the midline to reach contralateral cerebellum. These higher
cortical information enters via middle cerebellar peduncle
Cerebellar outputs :
• Outputs from cerebellum originates from its deep nuclei (Fastigial, Globose,
Emboliform, & Dentatus or Fat Girls Eat Donut). These neurons receive excitatory
signals from various cerebellar inputs, & inhibitory signal from Purkinye neurons
(output of cerebellar cortex is only inhibitory from GABAergic Purkinye neurons)
• These outputs project mainly top the contralateral Red nucleus & Thalamus. From
here, the signals transmitted to both cerebral cortex and to the lower brainstem and
spinal cord
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Cerebellum (3)
Cerebellar Functional Divisions
Vestibulo Cerebellum : oldest and most primitive,
main component is flocculus and nodulus (the
lowest folia of vermis). Essential for the control
of balance (vestibulospinal tracts) and eye
movements (inputs into eye muscle nuclei)
Spino Cerebellum : main component is most of vermis
& intermediate lobe. Essential for axial stability
(gait), tracking movement (finger to nose testing),
and control of fine movements. Vermis control the
body, while paravermal region (intermediate
hemispheres) control the limbs.
Cerebro Cerebellum : most developed in human species, the lateral hemispheres,

receives input from the cerebral cortex via relay neurons at basis pontis, and output fron
dentate nucleus to both red nucleus and thalamus. Its function is the least understood,
might has role in cognition and personality
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Motor System
Cerebellar Dysfunction (1)

Midline Zone dysfunction
1. Disorders of stance and gait; patients stands on a broad base, truncal ataxia,
tandem walking impossible, without limb ataxia
2. Titubation (rhytmic tremor of the body or head, several times per second)
3. Rotated or tilted postures of the head (the head may be maintained rotated or
tilted to left or right). The side does not indicate the site of the disease
4. Ocular motor disorders (most prominent is spontaneous nystagmus
5. Affective disturbances (flattening or blunting of emotional expression, and
disinhibited or inappropriate behavior)
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Motor System

Lateral (Hemispheric) Zone dysfunction (1)
1. Decomposition of movement (motor act is jerky and irregular, not smooth)
2. Gait disturbances accompanied by limb ataxia
3. Hypotonia (decrease in resistance to passive limb manipulation at joints)
4. Dysarthria (slow, slurred, and labored speech, but comprehension intact)
5. Dysmetria (hypo or hypermetria, failure of placement of body part at motion)
6. Dysdiadochokinesis and dysrhytmokinesis (decomposition of movements)
7. Ataxia (veers from side to side, difficulty in walking in a staight line
8. Tremor (intentional tremor, nose-finger test, there is static& kinetic tremors)
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Motor System

Lateral (Hemispheric) Zone dysfunction (2)
9. Impaired check and rebound (extended arm is easily displaced & overshoot
inreturning to original position
10. Ocular motor disorder: most common is nystagmus
11. Disturbance of executive functioning: consist of deficient shifting, abstract
reasoning, working memory, and decreased verbal memory
12. Impaired spatial recognition (disorganized & impaired visuospatial memory)
13. Personality change: flattening or blunting of affect, and disinhibited or
inappropriate behavior
14. Linguistic difficulties: abnormalities in rhythm and intonation of speech and
language (dysprosody), and naming disorder (anomia)
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Limbic System (1)
Limbic system integrates our experience of external world with the
fundamental physiologic processes (endocrine system, autonomic
nervous system, and behavior) to maintain our internal environment
‘within normal limit’, a process called ‘homeostasis’
Behavior serves as the primary
mechanism to achieve homeo-
stasis, such as in regulation of
water balance & thermoregulation
by eating food, drinking fluids,
seeking a more comfortable
environment. Social behavior
(reproduction, parenting behavior,
territorial aggression) is controlled
directly by limbic telencephalon
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Limbic System (2)
Anatomy of the limbic structures (extend from cortex to brainstem)
1. Limbic structures in telencephalon (paralimbic cortex or mesocortex), consist of
parahippocampal, cingulate, paraterminal gyri, and posterior orbitofrontal, insular,
and temporal pole cortices
2. The limbic cortex or allocortex, consist of hippocampal formation and primary
olfactory cortex
3. The corticoid areas, consist of amygdala, septal area, and substantia innominata
There are 2 fundamental connection for limbic functions:

1. Intracortical networks (particularly with association cortices) for cognitive
function (emotion, comportment, attention, and memory)
2. Subcortical pathways through hypothalamus and brainstem that regulate homeo-
stasis and social behaviors. LS is the only major route connecting hypothalamus to
the neocortex (and therefore external environment)
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MRI
Limbic System (3)

Hippocampal Formation
1. Includes three parallel zones (Subiculum,
Hippocampus or Ammon’s horn, and
Dentate gyrus) which are folded at the
medial side of temporal lobe
2. Important role in learning & memory, its
integration with amygdala & other limbic
areas builds cognitive maps (recognizing
own’s location in space & time and own’s
relation to external objects and events, past
and present)
3. Hippocampal sclerosis is the most common
pathology found in Temporal Lobe Epilepsy
(Psychomotor or Complex Partial Epilepsy),
cured with Amygdalo-hippocampectomy
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Limbic System (4)
Amygdala
1. Spherical mass of gray matter in the antero-superior of hippocampus, medially
bulging into mesencephalic cistern as Uncus
2. Important in linking emotion, motivation & autonomic responses to external
stimuli, regulates fear & stress, modulates & integrates pituitary function &
social behaviors (via its connections with hypothalamus)
Role of Prefrontal Cortex

1. Functional imaging studies strongly support the importance of prefrontal cortex and
its connections with amygdala for emotions and affective behaviors
2. Working hypothesis: activity in the dorsolateral prefrontal cortex of the left
hemisphere generates a state of happyness or positive affect, and activation of the
right prefrontal cortex, especially in the ventromedial orbital area, leads to sadness
or disgust ( so that these functions are lateralized within the brain )
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Memory
Types & their physiological mechanisms :
1. sensory memory (<1 sec.), present while the event occurs.
2. short term/primary memory (<1 min.), the event just occurred;
theories : reverberatory circuitry, post-tetany/ electrotonic potential; cellular
membrane is more sensitive for a very short time.
3. long term memory, long after the event had finished ;
secondary: until years, difficult to recall & tertiary: last for life, easy to recall.
synaptic change theory (permanent/semipermanent, increase of neuronal faci-
litatory, more often being recalled deepen the memory); RNA function theory
(analogy); extraneuronal theory (changes of glial cells / mocopolysaccharides
surrounding neuronal synaps).
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Neuroendocrine physiology
Hypothalamus & Limbic system
- maintain homeostasis of the “internal
environment” by hormon secretions,
autonomic nervous system, emotion
and motivation.
cerebral cortex
amygdala & hippocampus
coordination of visceral
hypothalamus function and behaviour SURVIVAL
visceral & somatic sensation, reticular formation
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Regulatory mechanism of Hypothalamo-Pituitary axis
1. Direct mechanism :
(Neuroendocrine products directly secreted to systemic circulation)
supraoptic & paraventricular nuclei oxytocin & vasopressin

(ADH) production
hypothalamo-hypophyseal tract
Posterior pituitary/ neurohypophysis ADH & oxytocin secretion
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Regulatory mechanism of Hypothalamo-Pituitary axis
2. Indirect mechanism :
(secretion of releasing hormones/factors that affect adeno hypophysis, except
for prolactin/ inhibiting factor)
arcuate & ventromedial nuclei a variety of releasing hormone
capillary of the
pituitary portal system secretion of trophic hormones
adenohypophyseal cells (subpopulation) (TSH, FSH, LH, GH, ACTH, PRL)
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Endocrine disturbance from pituitary disease

Acromegaly - Gigantism
GH producing pituitary adenoma, gigantism in children and acromegaly in adult,
produces diabetes mellitus and cardiovascular diseases
Cushing Disease
ACTH producing pituitary adenoma, causing secondary adrenal hyperplasia
leading to hypertension, hyperglycemia,central obesity (buffaloo hump), hirsutism/
hypertrichosis, amenorrhea and impotence, osteoporosis, linea atrophica/ striae
Amenorrhea - Galactorrhea
Prolactin producing pituitary adenoma (30-40% of all adenoma), causing infertility
TSH producing adenoma, LH & FSH producing adenoma
Very rare
Vasopressin (ADH)
Diabetes Insipidus in deficiency, and Syndrome of Inappropriate secretion of ADH
(SIADH) in excess
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Endocrine disturbance from pituitary disease
Amenorrhea - Acromegaly - Gigantism Cushing Disease

Galactorrhea
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Hypothalamic Nuclear groups & their functions

Preoptic Area
Sexual & parental behavior, thermoregulation, sleep-waking cycles
Anterior Hypothalamic Area
- Suprachiasmatic : primary circadian clock for sleep, locomotion, hormones
- Supraoptic & Paraventricular : secrete oxytocin and vasopressin ( axons
terminate in posterior pituitary), regulate water balance
Tuberal Area
- Ventromedial nucleus & Arcuate nucleus:
regulating anterior pituitary, control sexual behavior and food intake
- Dorsomedial nucleus and Lateral tuberal nucleus
Histaminergic neurons, with preoptic area integrates sleep-waking cycles
Mamillary Area
Cholinergic projections to isocortex, & noncholinergic projections to allocortex
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Neuroendocrine Physiology cortex
Coordination between hormonal secre-
tion and behaviour by hypothalamus
limbic system
- between sexual function /behaviour with neuroendocrine
regulation of gonads & reproductive organs
- between eating /dringking behaviour, feeling of hungry/ hypothalamus
thirsty, with gastrointestinal & renal function
- between body metabolism, vascular tone, sweating, and
thermoregulatory behaviour
- hypothalamus & limbic system influence many aspects of pituitary
emotional expression (acceleration of heart rate, elevation
of blood pressure, flushing or pallor of the skin, sweating,
dryness of the mouth, disturbances of gastrointestinal tract) target organ &
its secretions
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Thermoregulatory mechanism
(if outside) skin: vasodilatation
set point 37.6 C C up (-) muscle:shivering inhibited
Hipothalamic thermostat C down (+) sweat gland: evaporation
symphatetic center (heat loss , heatproduction )
skin: vasoconstriction, piloerection

sweat gland: evaporation
set point affected by: hypothalamus:
- peripheral temperature receptors - TRF (chemical thermogenesis)
heat : set point 0.1-0.3 0C - shivering center facilitated
cold : set point 0.1-1.0 0C (heat loss , heat production )
- fever producing agent/pyrogen
set point
- dehydration, set point up
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Thermoregulatory mechanism
Important notes :
1. - shivering increases heat production (5 times) better compared to muscle

contraction only (1.5 times).
- chemical thermogenesis ( increase of epinephrine/norepinephrine ), will
increase cellular metabolism 10% per 1 degree Celcius.
- brown fat plays important role in animal & infant.
2. Pyrogen increases the set point, and antipyretics will bring it down.
3. Most important factor in thermoregulation : human behavioral control.
4. During extreme body temperatures ( > 42 0C , < 34 0C ) thermostat doesn‘t
work, creating a vicious cycle (positive feed-back) in temp. regulation.
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Autonomic Nervous System
Symphatetic nerve
1. Composed by 2 neurons, pre and post ganglionic;
- pre-ganglionic neurons located at the spinal cord, it is cholinergic
- post-ganglionic neurons form the symphatetic trunc, most is adrenergic, and
secretes norepinephrin (short pre-ganglionic fiber, long post-ganglionic fiber)
2. Adrenal medulla is analog to post-ganglionic neuron, secretes
epinephrine (80%) and norepinephrine (20%).
3. Norepinephrine’s neutralization:
reuptake/active transport/ 50-80%, diffusion to surrounding fluid, by MAO & COMT
4. Adrenergic receptors (in organ may have excitatory or inhibitory effect)
alpha: strongly affected by both norepinephrin and epinephrine
beta: strong effect of epinephrine, but weak effect of norepinephrine
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Autonomic Nervous System
Parasymphatetic nerve
1. Composed by 2 neurons, pre and post ganglionic;
- pre-ganglionic neurons located at brainstem & sacral cord ; post-ganglionic
neurons located close to the target organ (long pre-ganglionic fiber, & short
post-ganglionic fiber).
- both are cholinergic, secretes acetylcholine (neutralized by cholinesterase)
2. Distributed to cranial nerves III, VII, IX, and mainly X (75%), and
2nd. and 3rd. sacral nerve (nervi erigentes).
3. Cholinergic receptors (may have excitatory or inhibitory effect in organ)
- muscarinic : present in all parasympathetic effector & symphatetic choliner-
gic neuron (preganglionic)
- nicotinic : present in neuronal membrane of parasymphatetic post-ganglio
nic nerve, and in skeletal muscle fibers (motor end-plate)
dnS
Consciousness (1)
1. Defined as awareness of self and environment ;
- content of consciousness (function of cerebral hemisphere)
- level of consciousness (function of ARAS, mainly brainstem structures)
2. ARAS (Ascending Reticular Activating System)
a function of brainstem’s reticular formation, diffusely & polysynaptically
integrates signals from all sensory organs, via thalamic non-specific nuclei,
toward neurons of the cerebral cortex bilaterally.
3. Activity of ARAS (may be monitored by electroencephalogram/EEG)
maintains sleep-awake cycle & level of consciousness ( a certain level of
‘hemispheric tone’ is needed to keep the ‘conscious’ or ‘awake’ state).
dnS
Consciousness (2)
Cerebral hemispheres : Content of Consciousness
ARAS (including bilateral hemispheres) : Level of Consciousness (L o C)
Content of consciousness could only be evaluated if the level of consciousness is good or
there is enough ‘hemispheric tone’ to process and respond to all incoming stimuli
properly. Decrease of L o C will disturb this process and stronger stimuli will be needed
dnS
Consciousness (3) bilateral cortex
Nonspecific Thalamocortical Projection :

- RAS receives collateral signals from
all sensory receptors passing through.
- these signals go to nonspecific thala-
thalamus
mic nuclei, then relayed diffusely to nonspecific specific
bilateral cerebral hemispheres to ma- nuclei nuclei
intain hemispheric tone needed for

conscious state (alpha or beta waves)
brainstem
- if RAS activity decreases to minimum Reticular
cerebral cortex can’t maintain its ex- formation
citability (cortex becomes its own pa-

sensory
cemaker, EEG : slow/delta waves). organs
dnS
Consciousness
Electroencephalogram :
- spontaneous rythmic/ fluctuating potential recorded from cortex

- an amplification of synchronized activation of cortical neurons
below the electrode ( at scalp recording, an electrode recieves extracellu-
lar electrical activity from about 1 million neurons closest to the electrode ).
- resting with closed eyes : there is synchronization of waves with fre-
quency of 8-14 cycle/second, or ALPHA wave. Opening eyes causes desyn-
chronization and creates BETA wave ( 15- 30 cycle/second).
- deep sleep causes strong synchronization, creates DELTA wave (4 / second).
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Consciousness
Electroencephalogram :
1. Routine examination in patients with
epilepsy or sleep disturbances
2. Recorded from scalp electrodes, 30
minute duration, interictally ( between
epileptic/ seizure attack )
3. Long term monitoring (between 3-14
days), using video EEG sometimes
needed to determine seizure foci, by
observing several attacks (ictal EEG)
4. Intracranial recording (subdural, and
intracerebral) sometimes needed
(electrodes inserted via craniotomy or
stereotactic frame)
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Consciousness
Sleep
1. Deep slow wave sleep
- RAS activity decreases to minimum, and cannot maintain the cortical exci-
tability. EEG shows high voltage delta wave, cortically indigenous wave.
- most of the night sleep, starts after 30-60 minutes, restfull &dreamless, vas-
cular tone decreases, so as blood pressure, respiration, and basal metabolism.
2. Rapid Eye Movement (REM) or Paradoxical sleep

- last for 5-20 minutes every 90 minutes interval, last shorter in tired state.
- EEG shows desynchronization, low voltage beta wave, like awake state.
- irregular muscle contraction, eye shows REM, difficult to be awakened.
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Vestibular system ( 1 )
Function ;
- maintaining stability of the body
- coordinating movement of eyes, head, and body, to enable eye
fixation while the head is moving.
- dynamic portion (semicircular canals);
detect head movement in space.
- static portion (utricle);detect position of the head & the body in
space, to enable postural positioning of the body.
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Anatomy ;
c.o. membranous & bony labirynth, with perilymph in between and endolymph
inside. In the membranous labirynth, there are utricle, saccule, & 3 semicircu-
lar canals (anterior, lateral/horisontal, and posterior). In the base of the utricle
(within the macule) hair cells’ receptors were covered by gelatinous materials
filled with CaCO3 crystals or otocony.
Physiological principles ;
In neutral/horisontal position, otocony is just above the hair cells. During head
movement, otocony compresses hair cells, inducing action potential transmitted
to the peripheral branches of vestibular ganglion.
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Tests of vestibular function :
1. Nystagmus ; repeated pendular movement of the eye ball
- continuous excitation to the ampula of semicircular canal causes the eye to
move slowly to one side, then quickly to the other side.
- direction of nystagmus is named according to fast component
(opposite direction of movement caused by semicircular canal stimulation)
2. Vertigo ;
feeling like moving around, or rotated; related to stimulation of the vestibu-
lar apparatus ; occurred during motion sickness, or sea sickness
3. Rotation test ( Barany chair );
‘after nystagmus’ or nystagmus ‘post-rotatory’, for about 30 seconds.
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Vestibulospinal pathways :
1. Lateral vestibulospinal tract
from lat. vestibular n., uncrossed; descend ipsilaterally cervical to lumbosacral.
2. Medial vestibulospinal tract
from medial vestibular n., crossed & uncrossed, descend bilaterally to cervical r.
Function :
1. Highly facilitatory to motoneurons of postural muscles & extensors (antigravity)
2. Support the myotatic reflex.
Decerebrate rigidity :
Loss of cerebral function, strong facilitation of brainstem activity affecting gamma
motoneuron (via vestibulospinal & reticulospinal tract), all extremities extended.
dnS
Vestibular system
Vestibuloocular &
Vestibulospinal Pathways
dnS
Vestibuloocular pathway :
- Fiber projections from superior vestibular n. (uncrossed) & from other vesti-
bular n. (crossed & uncrossed), via medial longitudinal fascicle, to reach cra-
nial nerves III, IV, and VI.
- important for regulating conjugate eye movement, in response to head positi-
on and head movement in space. Vestibular and ocular reflexes will keep eye
fixed in a stationary object, while the head/ body is moving in space.
- head move to right, endolymph move to left (horisontal canal), creates action
potential from ampular receptors to vestibular n., then to MLF ( activation of
lt. VI n. & rt. III n., inhibition of lt. III n. & rt. VI n. so eye moves to the left.
dnS
Cerebral Blood Flow
1. Supplied by bilateral carotid arteries anteriorly (80%) and bilate-

ral vertebral arteries posteriorly (20%), to form the Willis circle.
2. Regional CBF 50-80 cc/100g/minute. Brain weight is 1500g, each
minute about 1 litre of blood is pumped in (20% of cardiac output).
3. This amount of blood is provided by cerebral perfusion pressure
(CPP=MAP- ICP), about 95-100 mmHg. Decrease in CPP is compen-
sated by vasodilation, this mechanism is maximum at CPP> 55 -
60 mmHg. Below this level, ischemia ensues.
4. Brain metabolism uses only glucose provided by the blood flow.
dnS
Cerebral Blood Flow
dnS
Cerebrospinal Fluid
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Cerebrospinal Fluid
- ultrafiltrat of the serum, almost 100% water, fills the ventricles,
cerebral & spinal subarachnoid spaces, its volume is 90-150cc.
- produced 70% by ventricular choroid plexus, the other results
from constant motion of interstitial fluid toward ventricles.
- direction of flow: lateral ventricle 3rd.ventricle aquaeduct
4th ventricle subarachnoid spaces absorption at SSS.
- about 20ml/hour or 500 ml/day is produced or absorbed, absorption
is passive process, caused by pressure gradient across arachnoid
granulations, & depends on permeability state of the membrane.
dnS
Disturbances of CSF Dynamics
dnS

Neurophysiology: Understanding How The Nervous System Works

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Neurophysiology: Understanding How The Nervous System Works

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Neurophysiology

Zainal Muttaqin, M.D., Ph.D.

Cerebral Cortex Diencephalon Mesencephalon Pons-Cereb. MO-MS

- receptor for each sensory modality represented separately by

T just for simple analysis, such as localization

II. Secondary area : association area, for more difficult analysis

III. Tertiary area : for complex analysis, center of interpretation

3. Prefrontal cortex : additional area for cerebration or thinking

Secondary/ association area ;

Tertiary/ interpretation area ;

Department of Neurosurgery, Diponegoro University

Anterior horn of the spinal cord :

Distinguishing UMN and LMN lesion :

Proprioceptive Exteroceptive Interoceptive

Pain & Temperature

1. sinaps at dorsal horn, cross midline,

2. area innervated by Vth.nerve, fibers

Spinal Cord Lesions :

Several basal ganglia circuitry : diffuse BG excitation

Basal Ganglia ( 3 cont.)

Cerebro Cerebellum : most developed in human species, the lateral hemispheres,

Cerebellar Dysfunction (1)

Cerebellar Dysfunction (2)

Cerebellar Dysfunction (2)

There are 2 fundamental connection for limbic functions:

Limbic System (3)

Role of Prefrontal Cortex

supraoptic & paraventricular nuclei oxytocin & vasopressin

Posterior pituitary/ neurohypophysis ADH & oxytocin secretion

arcuate & ventromedial nuclei a variety of releasing hormone

Endocrine disturbance from pituitary disease

Endocrine disturbance from pituitary disease

Amenorrhea - Acromegaly - Gigantism Cushing Disease

Hypothalamic Nuclear groups & their functions

skin: vasoconstriction, piloerection

1. - shivering increases heat production (5 times) better compared to muscle

Nonspecific Thalamocortical Projection :

intain hemispheric tone needed for

citability (cortex becomes its own pa-

- spontaneous rythmic/ fluctuating potential recorded from cortex

2. Rapid Eye Movement (REM) or Paradoxical sleep

1. Supplied by bilateral carotid arteries anteriorly (80%) and bilate-

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