Neurophysiology

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, fluidfilled space called vesicles Prosencephalon
P. vesicles
Telencephalon Diencephalon
Mesencephalon
M. vesicle
Mesencephalon Mesencephalon Sylvian aquaeduct
Rhombencephalon
R. vesicle
Metenceph. Pons-Cereb. Myelenceph. MO-MS
Cerebral Cortex Diencephalon Lateral ventr. 3rd.ventricle
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 - Brodmanns 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 contralateral 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/ representing 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 F
2
3
P
2a
3a
2. Primary somatosensory area

4
1a
O1
3. Primari auditory area

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
3
2
the beginning of pyramidal tract 2. Broca area and Hand (Exner) areas 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 - visual - somatosensory : not deaf, but dont understand what is heard : not blind, but dont understand what is seen : not anesthesia, but dont 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 ;
- Brocas aphasia : comprehend spoken/ written language, but difficult with speech - Wernickes aphasia: poor speech comprehension, incorrect word to express thought, use words without precise meaning, or may substitute words
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S p i n a l
C o r d
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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 basis pontis pyramis diencephalic level pontine level medullary level cerebral peduncle - mesencephalic level
- end at the anterior horn of the spinal cords grey matter, sinaps with LMN / alpha motoneuron, whose axon or
efferen fibers end as motor end plate.
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Pyramidal / Corticospinal pathway
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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 corticospinal 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 :
*
Gamma motoneuron
Muscle spindle
Muscle fiber
Alpha motoneuron
- function as the power steering (providing the power needed) for purposeful 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 cords 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/extrafusal, 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 & increase 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)
Proprioceptive position sense
(dorsal/lemniscal)
Viscerosensory (GVA)
Interoceptive
Exteroceptive pain & thermal (anterolateral /spinothalamic)
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 receptors, 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.
2.
3.
4.
5.
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 s.c. hemisection (Brown-Sequard Syndrome): ipsilateral spastic paralysis, ipsilateral proprioception, and contralateral pain and temperature sensation 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) 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) 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
- caudate nuclei
(putamen &globus pallidus)
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 : motor cortex striatum motor cortex pontine globus pallidus thalamus (VL nuclei) cerebellum
diffuse BG excitation BIA excitation skeletal muscle tone down
thalamus (VA nuclei) BFA inhibition
BG destruction
inhibitory effect (-) 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.
3.
Hyperkinetic movement disorders: Ballismus, Chorea (Sydenhams chorea in rheumatic fever, Huntington disease in adult with dementia), & Athetosis
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. vituss 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 unilaterally, 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 Clarkes 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. 2. 3. 4. 5. Disorders of stance and gait; patients stands on a broad base, truncal ataxia, tandem walking impossible, without limb ataxia Titubation (rhytmic tremor of the body or head, several times per second) 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 Ocular motor disorders (most prominent is spontaneous nystagmus 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. 2. Decomposition of movement (motor act is jerky and irregular, not smooth) Gait disturbances accompanied by limb ataxia
3.
4. 5. 6. 7. 8.
Hypotonia (decrease in resistance to passive limb manipulation at joints)

Dysarthria (slow, slurred, and labored speech, but comprehension intact) Dysmetria (hypo or hypermetria, failure of placement of body part at motion) Dysdiadochokinesis and dysrhytmokinesis (decomposition of movements) Ataxia (veers from side to side, difficulty in walking in a staight line 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 homeostasis, 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.
2.
3.
Limbic structures in telencephalon (paralimbic cortex or mesocortex), consist of parahippocampal, cingulate, paraterminal gyri, and posterior orbitofrontal, insular, and temporal pole cortices The limbic cortex or allocortex, consist of hippocampal formation and primary olfactory cortex 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 homeostasis 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 Ammons horn, and Dentate gyrus) which are folded at the medial side of temporal lobe Important role in learning & memory, its integration with amygdala & other limbic areas builds cognitive maps (recognizing owns location in space & time and owns relation to external objects and events, past and present) Hippocampal sclerosis is the most common pathology found in Temporal Lobe Epilepsy (Psychomotor or Complex Partial Epilepsy), cured with Amygdalo-hippocampectomy
2.
3.
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Limbic System (4)

Amygdala
1. 2. Spherical mass of gray matter in the antero-superior of hippocampus, medially bulging into mesencephalic cistern as Uncus 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. 2. Functional imaging studies strongly support the importance of prefrontal cortex and its connections with amygdala for emotions and affective behaviors 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 facilitatory, 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 visceral & somatic sensation, reticular formation
SURVIVAL
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Regulatory mechanism of Hypothalamo-Pituitary axis
1. Direct mechanism :
(Neuroendocrine products directly secreted to systemic circulation)
supraoptic & paraventricular nuclei

hypothalamo-hypophyseal tract
oxytocin & vasopressin

(ADH) production
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

capillary of the pituitary portal system adenohypophyseal cells (subpopulation)
a variety of releasing hormone

secretion of trophic hormones (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 Galactorrhea
Acromegaly - Gigantism
Cushing Disease
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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
Coordination between hormonal secretion and behaviour by hypothalamus

- between sexual function /behaviour with neuroendocrine regulation of gonads & reproductive organs - between eating /dringking behaviour, feeling of hungry/ thirsty, with gastrointestinal & renal function - between body metabolism, vascular tone, sweating, and thermoregulatory behaviour - hypothalamus & limbic system influence many aspects of 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)
cortex
limbic system
hypothalamus
pituitary
target organ & its secretions
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Thermoregulatory mechanism
set point 37.6 C (if outside)
C up
Hipothalamic thermostat C
down
(-) (+)
symphatetic center
skin: vasodilatation muscle:shivering inhibited sweat gland: evaporation (heat loss , heatproduction ) skin: vasoconstriction, piloerection sweat gland: evaporation hypothalamus: - TRF (chemical thermogenesis) - shivering center facilitated (heat loss , heat production )
set point affected by: - peripheral temperature receptors heat : set point 0.1-0.3 0C cold : set point 0.1-1.0 0C - 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 doesnt 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. Norepinephrines 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 cholinergic neuron (preganglionic) - nicotinic : present in neuronal membrane of parasymphatetic post-ganglio nic nerve, and in skeletal muscle fibers (motor end-plate)
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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 brainstems 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).
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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
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Consciousness (3)
Nonspecific Thalamocortical Projection :
bilateral cortex
- RAS receives collateral signals from all sensory receptors passing through. - these signals go to nonspecific thalamic nuclei, then relayed diffusely to bilateral cerebral hemispheres to maintain hemispheric tone needed for conscious state (alpha or beta waves) - if RAS activity decreases to minimum cerebral cortex cant maintain its excitability (cortex becomes its own pacemaker, EEG : slow/delta waves).
thalamus
nonspecific nuclei specific nuclei
brainstem
Reticular formation
sensory organs
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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 extracellular electrical activity from about 1 million neurons closest to the electrode ).
- resting with closed eyes : there is synchronization of waves with frequency 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. 2. Routine examination in patients with epilepsy or sleep disturbances Recorded from scalp electrodes, 30 minute duration, interictally ( between epileptic/ seizure attack ) Long term monitoring (between 3-14 days), using video EEG sometimes needed to determine seizure foci, by observing several attacks (ictal EEG) Intracranial recording (subdural, and intracerebral) sometimes needed (electrodes inserted via craniotomy or stereotactic frame)
3.
4.
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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, vascular 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 semicircular 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 vestibular 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.
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Vestibular system
Vestibuloocular & Vestibulospinal Pathways
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Vestibuloocular pathway :
- Fiber projections from superior vestibular n. (uncrossed) & from other vestibular n. (crossed & uncrossed), via medial longitudinal fascicle, to reach cranial nerves III, IV, and VI. - important for regulating conjugate eye movement, in response to head position 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.
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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.
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Cerebral Blood Flow
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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

4th ventricle
3rd.ventricle
aquaeduct
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.
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Disturbances of CSF Dynamics
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Neurophysiology

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Neurophysiology

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Neurophysiology

Understanding how the nervous system works

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

Cerebral Cortex Diencephalon Lateral ventr. 3rd.ventricle

4th.ventricle - central canal

Department of Neurosurgery, Diponegoro University

CNS Imaging and Anatomy

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Primary, Secondary, and Tertiary cortical areas

Department of Neurosurgery, Diponegoro University

2. Primary somatosensory area

3. Primari auditory area

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

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

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Secondary/ association area ;

Tertiary/ interpretation area ;

Department of Neurosurgery, Diponegoro University

Cortical networks dysfunction :

Department of Neurosurgery, Diponegoro University

- efferen fibers descend through ventral part of the brain

efferen fibers end as motor end plate.

Department of Neurosurgery, Diponegoro University

Pyramidal / Corticospinal pathway

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Anterior horn of the spinal cord :

Department of Neurosurgery, Diponegoro University

Distinguishing UMN and LMN lesion :

Department of Neurosurgery, Diponegoro University

Exteroceptive pain & thermal (anterolateral /spinothalamic)

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

- peripheral pain transmission

- referred pain (fromviscera, felt in body surface, caused by synaptic sharing

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Differences between anterolateral and dorsal pathways

Department of Neurosurgery, Diponegoro University

Spinal Cord Lesions :

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

-c.o. : 1. Striatal body

(putamen &globus pallidus)

5. Dark nuclei (substansia nigra)

Department of Neurosurgery, Diponegoro University

diffuse BG excitation BIA excitation skeletal muscle tone down

thalamus (VA nuclei) BFA inhibition

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Basal Ganglia ( 3 cont.)

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Department of Neurosurgery, Diponegoro University

Cerebellar Dysfunction (1)