Control of Complex Movements

1
Control of Complex Movements

• Involve
• Cerebral Cortex
• Basal Ganglia
• Cerebellum
• Thalamus
• Brain Stem
• Spinal Cord

2
Motor Cortex

• Primary motor cortex
• somatotopic arrangement
• greater than 1/2 controls hands speech
• of neuron stimulate movements instead of
  contracting a single muscle
• Premotor area
• anterior to lateral portions of primary motor
  cortex below supplemental area
• projects to 10 motor cortex and basal ganglia

3
Motor Cortex (cont.)

• Supplemental motor area
• superior to premotor area lying mainly in the
  longitudnal fissure
• functions in concert with premotor area to
  provide
• attitudinal movements
• fixation movements
• positional movements of head eyes
• background for finer motor control of arms/hands

4
Corticospinal tract

• Originates
• Primary Motor Cortex- 30
• Premotor and Supplemental Areas- 30
• somatic sensory areas- 40

5
Corticospinal tract (cont.)

• Descends via the posterior limb of the internal
  capsul- (lies between caudate putamen)
• forms the pyramids of medulla
• most fibers cross midline form lateral
  corticospinal tract
• some fibers stay ipsilateral form ventral
  corticospinal tract

6
Effect of Transection

• Spinal preparation
• All tracts cut, cord completely isolated from
  brain
• Flaccidity (flaccid or floppy paralysis)
• Decerebrate preparation
• Transection at mid collicular level
• Extensors are tonically hyperactive, decerebrate
  rigidity
• Decorticate preparation
• Destruction of the cerebral cortex
• Creates a different type of rigidity, clinically
  known as decorticate spasticity due to tonic
  excitation from upper areas of the reticular
  formation no longer under inhibitory cortical
  influence (release phenomenon)

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Decorticate Spasticity

• Removal or lesion of cerebral cortex
• loss of cortical inhibition of gamma efferent
  discharge mediated by the medullary reticular
  formation
• seen in humans on the hemiplegic side after
  stroke
• small arteries in internal capsul prone to
  rupture or thrombosis
• 60 of intracerebral hemorrhages

9
Decerebration

• Experimental procedure useful for study of
  reflexes
• transection of midbrain often at intercollicular
  level
• loss of sensation
• motor control is profoundly altered
• cortical descending pathways are interrupted
• brain stem control remains intact

10
Decerebration (cont)

• Activity in some descending pathways becomes
  hyperactive
• flexion reflexes suppressed
• stretch reflexes are exaggerated
• selective excitation of gamma motor neurons
• leads to decerebrate rigidity
• Humans with brainstem damage signs of
  decerebration can appear w/ poor prognosis

11
Spinal Cord Transection

• Spinal shock
• initially all cord functions including spinal
  reflexes are depressed
• lack of tonic excitation from higher centers
• spinal cord neurons gradually regains
  excitability (days to weeks)
• some spinal cord reflexes become hyperactive
• Mass reflex
• spinal cord becoming excessively active
• flexor spasm evacuation of bladder colon

12
Spinal Shock

• Arterial blood pressure falls dramatically
• All skeletal muscle reflexes integrated in cord
  are blocked
• Sacral reflexes for control of bladder and colon
  evacuation are suppressed

13
The reticular nuclei

• Pontine reticular nuclei
• transmit excitatory signals via the pontine
  (medial) reticulospinal tract
• stimulate the axial trunk extensor muscles that
  support the body against gravity
• receive stimulation from vestibular nuclei deep
  nuclei of the cerebellum
• high degree of natural excitability

14
The Reticular Nuclei (cont.)

• Medullary reticular nuclei
• transmit inhibitory signals to the same
  antigravity muscles via the medullary (lateral)
  reticulospinal tract
• receive strong input from the cortex, red
  nucleus, and other motor pathways
• counterbalance excitatory signals from the
  pontine reticular nuclei
• allows tone to be increased or decreased
  depending on function needing to be performed

15
Role of brain stem in controlling motor function

• Control of respiration
• Control of cardiovascular system
• Control of GI function
• Control of many stereotyped movements
• Control of equilibrium
• Control of eye movement

16
Descending Pathways

• 5 important tracts that descend from brain to SC
• Ipsilateral
• Ventral corticospinal tract (1)
• Reticulospinal tracts (2)
• Pontine (medial) reticular formation
• Medullary (lateral) reticular formation
• Vestibulospinal tracts (3)
• Origin from the lateral vestibular nucleus to
  mainly extensors
• Contralateral
• Lateral corticospinal tract (1)
• Rubrospinal-innervate mainly flexors (4)
• Tectospinal-innervate cervical musculature only
  (5)
• Superior colliculus-orienting reactions

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Descending Pathways
Lateral corticospinal tract
Lateral
Rubrospinal tract
Medial reticulospinal tract Lateral
reticulospinal tract
Vestibulospinal tract
Tectospinal tract
Medial
Anterior corticospinal tract
18
Motor Control

• Lateral motor system of the cord
• Lateral corticospinal tracts
• rubrospinal tracts
• controls more distal muscles of limbs
• Medial motor system of the cord
• Reticulospinal, vestibulospinal, tectospinal
  anterior corticospinal tracts
• controls mainly the axial girdle muscles
• terms lateral medial refer to where these
  tracts lie in the spinal cord

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Primary Motor Cortex

• Vertical Columnar Arrangement
• functions as an integrative processing system
• 50-100 pyramidal cells to achieve muscle
  contraction
• Pyramidal cells (two types of output signals)
• dynamic signal
• excessively excited at the onset of contraction
  to initiate muscle contraction
• static signal
• fire at slower rate to maintain contraction

20
Voluntary movement

• Planning Program phase (occurs first)
• Signals for movement originate in the sensory
  association cortex output to premotor cortex
  directly indirectly via
• Basal ganglia
• Cerebrocerebellum
• Execution phase
• Signals from the premotor cortex ? primary motor
  cortex (PMC)?spinal cord (corticospinal
  projections)
• Signals from the PMC also ? spinocerebellum
• Feedback from periphery ? spinocerebellum ? PMC

21
Initiation of voluntary movement
22
Electromyography

• The electrical activity within an accessible
  muscle can be recorded via insertion of a needle
  electrode into it.
• Patterns of activity at rest and during
  contraction have been characterized under normal
  and abnormal conditions

23
Electromyography (EMG)

• Activity at rest
• Normal
• no spontaneous electrical activity except at the
  end-plate region (neuromuscular junctions)
• Abnormal
• fibrillation potentials positive sharp waves
  are associated with muscle fiber irritability
  are typically found in denervated muscle or
  sometimes in myopathies (especially in
  inflammation)
• fasciculation potentials - spntaneous activation
  of individual motor units (occasionally in normal
  muscle), characteristic of neuropathic disorders
  with primary involvement of anterior horn cells
  (e.g. ALS)

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EMG

• Activity during voluntary muscle contraction
• Normal
• a slight voluntary contraction of a muscle
  activates a small number of motor units
• normal motor unit potentials have limits of
  duration, amplitude, configuration, firing
  rates characteristic for muscle tested of
  motor units activated
• Abnormal
• in many myopathies- ? incidence small short
  duration polyphasic motor units increased
  number of motor units activated for a given
  degree of voluntary activity
• in neuropathies- loss of motor units ? of units
  activated

25
Postural Reflexes

• Impossible to separate postural adjustments from
  voluntary movement
• maintain body in up-right balanced position
• provide constant adjustments necessary to
  maintain stable postural background for voluntary
  movement
• adjustments include static reflexes (sustained
  contraction) dynamic short term phasic reflexes
  (transient movements)

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Postural Control (cont)

• A major factor is variation of in threshold of
  spinal stretch reflexes
• caused by changes in excitability of motor
  neurons changes in rate of discharge in the
  gamma efferent neurons to muscle spindles

27
Postural Reflexes

• Three types of postural reflexes
• vestibular reflexes
• tonic neck reflexes
• righting reflexes

28
Vestibular function

• Vestibular apparatus-organ that detects
  sensations of equilibrium
• Consists of semicircular canals utricle
  saccule
• embedded in the petrous portion of temporal bone
• provides information about position and movement
  of head in space
• helps maintain body balance and helps coordinate
  movements

29
Vestibular apparatus

• Utricle and Saccule
• Macula is the sensory area
• covered with a gelatinous layer in which many
  small calcium carbonate crystals are imbedded
• hair cells in macula project cilia into
  gelatinous layer
• directional sensitivity of hair cells to cause
  depolarization or hyperpolarization
• detect orientation of head w/ respect to gravity
• detect linear acceleration

30
Utricle vs. Saccule

• Macula of utricle lies mainly in horozontal plane
• Plays important role in determining orientation
  of the head when person is upright
• Macula of saccule lies mainly in verticle plane
• Plays important role in determining orientation
  of the head when person is lying down

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Vestibular apparatus (cont)

• Semicircular canals
• Crista ampularis in swelling (ampulla)
• Cupula
• loose gelatinous tissue mass on top of crista
• stimulated as head begins to rotate
• 3 pairs of canals bilaterally at 90o to one
  another. (anterior, horizontal, posterior)
• Each set lie in the same plane
• right anterior - left posterior
• right and left horizontal
• left anterior - right posterior

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Semicircular Canals

• Filled with endolymph
• As head begins to rotate, fluid lags behind and
  bend cupula
• generates a receptor potential which alters the
  firing rate in VIII CN which projects to the
  vestibular nuclei
• detects rotational acceleration deceleration

33
Semicircular Canals

• Stimulation of semicircular canals on side
  rotation is into. (e.g. Right or clockwise
  rotation will stimulate right canal)
• Stimulation of semicircular canals is associated
  with increased extensor tone
• Stimulation of semicircular canals is associated
  with nystagmus

34
Semicircular Canals

• Connections with vestibular nucleus via CN VIII
• Vestibular nuclei makes connections with CN
  associated with occular movements (III,IV, VI)
  and cerebellum
• Can stimulate nystagmus
• slow component-(tracking)can be initiated by
  semicircular canals
• fast component- (jump ahead to new focal spot)
  initiated by brain stem nuclei

35
Semicircular Canals

• Thought to have a predictive function to prevent
  malequilibrium
• Anticipitory corrections
• works in close concert with cerebellum especially
  the flocculonodular lobe

36
Other Factors - Equilibrium

• Neck proprioceptors-provides information about
  the orientation of the head with the rest of the
  body
• projects to vestibular nucleus cerebellum
• cervical joints proprioceptors can override
  signals from the vestibular apparatus prevent a
  feeling of malequilibrium
• Proprioceptive and Exteroceptive information from
  other parts of the body
• Visual signals

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Tilting room chair

• Ones sense of upright is generally a combination
  of cues that include visual and vestibular
  information

38
Posture

• Represents overall position of the body limbs
  relative to one another their orientation in
  space
• Postural adjustments are necessary for all motor
  tasks need to be integrated with voluntary
  movement

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Vestibular Neck Reflexes

• Have opposing actions on limb muscles
• Most pronounced when the spinal circuits are
  released from cortical inhibition
• Vestibular reflexes evoked by changes in position
  of the head
• Neck reflexes are triggered by tilting or turning
  the neck

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Postural Adjustments

• Functions
• support head body against gravity
• maintain center of the bodys mass aligned
  balanced over base of support on the ground
• stabilize supporting parts of the body while
  others are being moved
• Major mechanisms
• anticipatory (feed forward)-predict disturbances
• modified by experience improves with practice
• compensatory (feedback)
• evoked by sensory events following loss of balance

41
Postural adjustments

• Induced by body sway
• Extremely rapid (like simple stretch reflex)
• Relatively stereotyped spatiotemporal
  organization (like ssr)
• appropriately scaled to achieve goal of stable
  posture (unlike ssr)
• refined continuously by practice (like skilled
  voluntary movements)

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Postural mechanisms

• Sensory input from
• cutaneous receptors from the skin (esp feet)
• proprioceptors from joints muscles
• short latency (70-100 ms)
• vestibular signals (head motion)
• longer latency (2x proprioceptor latency)
• visual signals
• longer latency (2x proprioceptor latency)

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Postural Mechanisms (cont)

• In sway, contraction of muscles to maintain
  balance occur in distal to proximal sequence
• forward sway
• gastro-ham-para
• backward sway
• tib-quad-abd
• Pattern of contraction elicited by a stimulus
  depends on prior experience expectation
• responses that stabilize posture are facilitated
• responses that destabilize posture adapts

44
Effect of tonic neck reflexes on limb muscles

• Extension of neck extensors of arms/legs
• Flexion of neck flexors of arms/legs
• Rotation or lateral bending
• extensors ipsilateral
• flexors contralateral

45
Basal Ganglia

• Input nuclei
• Caudate
• Putamen
• caudate putamen striatum
• Nucleus accumbens
• Output nuclei
• Globus Pallidus-external segment
• Subthalamic nucleus
• Substantia nigra
• Ventral tegmental area

46
Basal Ganglia

• Consist of 4 principal nuclei
• the striatum (caudate putamen)
• the globus pallidus (internal external)
• the substantia nigra
• subthalamic nucleus

47
Basal Ganglia

• Do not have direct input or output connections
  with the spinal cord
• Motor functions of the basal ganglia are mediated
  by the motor areas of the cortex
• Disorders have three characteristic types of
  motor disturbances
• tremor other involuntary movements
• changes in posture muscle tone
• poverty slowness of movement

48
Two major circuits of BG

• Caudate circuit
• large input into caudate from the association
  areas of the brain
• caudate nucleus plays a major role in cognitive
  control of motor activity
• cognitive control of motor activity
• Putamen circuit
• subconcious execution of learned patterns of
  movement

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Abnormalities of BG

• Athetosis
• lesion in globus pallidus
• spontaneous continous writhing movements
• Hemiballismus
• lesion in subthalamus
• sudden violent flailing movements of a limb
• Chorea
• muliple small lesions in putamen
• flicking movements in hands, face, etc
• Rigidity, akinesia, resting tremors
• substantia nigra (Parkinsons)

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Basal Ganglia

• Four re-entrance loops
• neocortex to basal ganglia to thalamus to frontal
  cortex
• external globus pallidus (GP) to subthalamic N.
  to both internal external GP
• striatum (GABA) to substantia nigra (dopamine) to
  striatum
• striatum caudate putamen
• striatum to GP to centromedial N of thalamus to
  striatum

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Cerebellum-little brain

• By weight 10 of total brain
• Contains gt 1/2 of all neurons in brain
• Highly regular structure-almost crystalline
• Sensory motor systems are mapped here
• Complete destruction produces no sensory
  impairment no loss in muscle strength
• Plays a crucial indirect role in movement
  posture by adjusting the output of the major
  descending motor systems

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Functional Divisions-cerebellum

• Vestibulocerebellum (floculonodular lobe)
• input-vestibular nuclei output-vestibular nuclei
• governs eye movement body equilibrium
• Spinocerebellum (vermis intermediate)
• input-periphery spinal cord output-cortex
• major role in movement, influencing descending
  motor systems
• Cerebrocerebellum (lateral zone)
• input-pontine N. output-pre motor cortex
• planning initiation of movement extramotor
  prediction
• mental rehersal of complex motor actions
• conscious assessment of movement errors

53
Major efferent cell in cerebellar cortex

• Purkinje cells
• major inhibitory cell in cerebellar cortex
• axons project to and inhibit the deep cerebellar
  nuclei
• generates two types of output signals
• complex AP from climbing fiber input from
  inferior olivary nucleus
• 11 ratio of climbing fibers to purkinje cells
• simple AP from mossy fiber input via granule cell
  
• 1 mossy fiber excites hundreds-thousands of
  purkinje cells
• Mossy fiber input is from everywhere else except
  inferior olivary nucleus

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Cerebellar Hemispheric Circuitry

• Impulses from the motor cortex ? Pontine N
• Pontine N ? Purkinje cells (cerebellar cortex)
• Purkinje cells ? Dentate N
• Dentate N ? Red N of midbrain (N Rubor)
• Red N ? Thalamus
• Thalamus ? motor cortex (closing the loop)
• Corticopontocerebellorubrothalamocorticospinal
  pathway

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Role of inferior olivary nucleus

• Acts as a comparator
• comparing intention with performance
• effects the cerebellum via climbing fiber input
• if intention matches performance no change in
  climbing fiber activity
• if intention differs from performance change in
  climbing fiber activity to alter cerebellum
  activity which in turn will alter descending
  corticospinal traffic

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Lesions in Cerebellum

• Disrupt coordination of limb eye movements
• Impair balance
• Decreased muscle tone
• Removal of cerebellum
• does not alter sensory thresholds
• no change in strength of muscle contraction
• Lesions in cerebellum create ipsilateral findings
  in body due to pathway crossing twice. (double
  cross) eg. rebound

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Clinical abnormalities-cerebellum

• Dysmetria
• Ataxia
• Past pointing
• Failure of Progression-Dysdiadochokinesia
• Dysarthria
• Intention tremor
• Nystagmus

58
Cerebellar functions

• The cerebellum participates in motor learning
• The cerebellum may have a role in cognitive
  processing and emotion
• The cerebellum is loaded by the integrity of
  joint mechanoreceptors
• Anatomical studies also reveal direct and
  reciprocal connections between the cerebellum and
  the hypothalamus

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Cerebellum

• Cerebellar cortex
• three pairs of deep nuclei
• most of output originates from
• Fastigial
• Interposed (globose emboliform)
• Dentate
• connected to brain stem by 3 sets of peduncles
• superior - contains most efferent projections
  ventral spinocerebellar tracts
• middle- 1o pontocerebellar tracts
• inferior- dorsal spinocerebellar tracts

60
Major features of cerebellum fxn

• receives info about plans for movement from brain
  structures concerned with programming execution
  of movement
• corollary discharge/internal feedback
• cerebellum receives information about motor
  performance from peripheral feedback during
  course of movement
• reafference/external feedback
• compares central info w/ actual motor response
• projects to descending motor systems via cortex

61
Homeostasis

• Concept whereby body states are regulated toward
  a steady state
• Proposed by Walter Cannon in 1932
• At the same time Cannon introduced negative
  feedback regulation
• an important part of this feedback regulation is
  mediated by the ANS through the hypothalamus

62
Autonomic Nervous System

• Controls visceral functions
• functions to maintain a dynamic internal
  environment, necessary for proper function of
  cells, tissues, organs, under a wide variety of
  conditions demands

63
Autonomic Nervous System

• Visceral largely involuntary motor system
• Three major divisions
• Sympathetic
• Fight flight fright
• emergency situations where there is a sudden ? in
  internal or external environment
• Parasympathetic
• Rest and Digest
• Enteric
• neuronal network in the walls of GI tract

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ANS

• Primarily an effector system
• Controls
• smooth muscle
• heart muscle
• exocrine glands
• Two neuron system
• Preganglionic fiber
• cell body in CNS
• Postganglionic fiber
• cell body outside CNS

65
Sympathetic Nervous System

• Pre-ganglionic cells
• intermediolateral horn cells
• C8 to L2 or L3
• release primarily acetylcholine
• also releases some neuropeptides (eg. LHRH)
• Post-ganglionic cells
• Paravertebral or Prevertebral ganglia
• most fibers release norepinephrine
• also can release neuropeptides (eg. NPY)

66
Norepinephrine release

• Release of norepinephrine from post ganglionic
  SNS terminals can regulate its own release
  (negative feedback)
• This is due to the presence of alpha2
  adrenoceptors in SNS terminals
• Norepinephrine binding to these receptors
  inhibits norepinephrine release
• Yohimbine (Alpha2 blocker) increases
  norepinephrine release

67
Mass SNS discharge

• Increase in arterial pressure
• decreased blood flow to inactive organs/tissues
• increase rate of cellular metabolism
• increased blood glucose metabolism
• increased glycolysis in liver muscle
• increased muscle strength
• increased mental activity
• increased rate of blood coagulation

68
Normal Sympathetic Tone

• 1/2 to 2 Impulses/Sec
• Creates enough constriction in blood vessels to
  limit flow
• Sympathocotonia- increased sympathetic activity
  (Hyperactivity)
• Most SNS terminals release norepinephrine
• release of norepinephrine depends on functional
  terminals which depend on nerve growth factor

69
Horners Syndrome

• Interruption of SNS supply to the head
• (Can also be descending pathways from
  hypothalamus that control SNS activity)
• Partial ptosis
• Drooping of eyelid (paralysis of superior tarsal
  muscle of eyelid
• Pupillary constriction
• Anhydosis (inability to sweat)
• Lack of sweat gland innervation by cholinergic
  sympathetics
• Enophthamos
• Retraction of the globe due to lack of
  innervation of smooth ms.
• Image

70
Parasympathetic Nervous System

• Preganglionic neurons
• located in several cranial nerve nuclei in
  brainstem
• Edinger-Westphal nucleus (III)
• superior salivatory nucleus (VII)
• inferior salivatory nucleus (IX)
• dorsal motor (X) (secretomotor)
• nucleus ambiguus (X) (visceromotor)
• Mediates reflex bradycardia
• intermediolateral regions of S2,3,4
• release acetylcholine

71
Parasympathetic Nervous System

• Postganglionic cells
• cranial ganglia
• ciliary ganglion
• pterygopalatine
• submandibular ganglia
• otic ganglia
• other ganglia located near or in the walls of
  visceral organs in thoracic, abdominal, pelvic
  cavities
• release acetylcholine

72
Parasympathetic nervous system

• The vagus nerves innervate the heart, lungs,
  bronchi, liver, pancreas, all the GI tract from
  the esophagus to the splenic flexure of the colon
• The remainder of the colon rectum, urinary
  bladder, reproductive organs are innervated by
  sacral preganglionic nerves via pelvic nerves to
  postganglionic neurons in pelvic ganglia

73
Enteric Nervous System

• Located in wall of GI tract (100 million neurons)
• Activity modulated by ANS
• Post ganglionic SNS 1O from prevertebral gang. to
  plexuses in stomach, SI colon
• NE - intestinal motility contracts sphincters
• NE NPY regulates blood flow
• NE Somatostatin inhibit intestinal secretion

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Enteric Nervous system

• Preganglionic Parasympathetic project to enteric
  ganglia of stomach, colon, rectum via vagus
  pelvic splanchnic nerves
• increase motility and tone
• relax sphincters
• stimulate secretion

75
Enteric Nervous System

• Myenteric Plexus (Auerbachs)
• between longitudenal circular muscle layer
• controls gut motility
• can coordinate peristalsis in intestinal tract
  that has been removed from the body
• excitatory motor neurons release
• Ach sub P
• inhibitory motor neurons release
• Dynorphin vasoactive intestinal peptide (VIP)

76
Enteric Nervous System

• Submucosal Plexus
• Regulates
• ion water transport across the intestinal
  epithelium
• glandular secretion
• communicates with myenteric plexus
• releases neuropeptides
• well organized neural networks

77
Visceral afferent fibers

• Accompany visceral motor fibers in autonomic
  nerves
• supply information that originates in sensory
  receptors in viscera
• never reach level of consciousness
• responsible for afferent limb of viscerovisceral
  and viscerosomatic reflexes
• important for homeostatic control and adjustment
  to external stimuli

78
Visceral afferents

• Many of these neurons may release an excitatory
  neurotransmitter such as glutamate
• Contain many neuropeptides
• can include nociceptors visceral pain
• distension of hollow viscus

79
Neuropeptides (visceral afferent)

• Angiotension II
• Arginine-vasopressin
• bombesin
• calcitonin gene-related peptide
• cholecystokinin
• galamin
• substance P
• enkephalin
• somatostatin
• vasoactive intestinal peptide

80
Autonomic Reflexes

• Cardiovascular
• baroreceptor
• Bainbridge reflex
• GI autonomic reflexes
• smell of food elicits parasympathetic release of
  digestive juices from secretory cells of GI tract
• fecal matter in rectum elicits strong peristaltic
  contractions to empty the bowel

81
Intracellular Effects

• SNS-postganglionic fibers
• Norepinephrine binds to an alpha or beta receptor
  which effects a G protein
• Gs proteins adenyl cyclase which raises cAMP
  which in turn protein kinase activity which
  increases membrane permeability to Na Ca
• Parasympathetic-postganglionic fibers
• Acetylcholine binds to a muscarinic receptor
  which also effects a G protein
• Gi proteins - adenyl cyclase has opposite
  effect of Gs
• G proteins (G proteins)

82
Effects of Stimulation

• EyeS dilates pupils P- constricts
  pupil, contracts ciliary
  muscle increases lens strength
• Glandsin general stimulated by P but S will
  concentrate secretion by decreasing blood flow.
  Sweat glands are exclusively innervated by
  cholinergic S
• GI tractS -, P (mediated by enteric)
• Heart S , P -
• Bld vesselsS constriction, P largely absent

83
Effects of Stimulation

• Airway smooth muscle S dilation P constriction
• Ducts S dilation P constriction
• Immune System S inhibits, P ??

84
Fate of released NT

• Acetylcholine (P) rapidly hydrolysed by
  aetylcholinesterase
• Norepinephrine
• uptake by the nerve terminals
• degraded by MAO, COMT
• carried away by blood

85
Precursors for NT

• Tyrosine is the precursor for Dopamine,
  Norepinephrine Epinephrine
• Choline is the precursor for Acetylcholine

86
Receptors

• Adrenergic-bind epinephrine norepinephrine
• Alpha (alpha 1, alpha 2)
• Beta (beta 1, beta 2)
• Acetylcholine receptors
• Nicotinic
• found at synapses between pre post ganglionic
  fibers (both S P)
• Muscarinic
• found at effector organs

87
Affinity for receptors

• Norepinephrine has equal affinity for both alpha
  and beta
• Epinephrine has a greater affinity for beta
  compared to alpha. illustration
• For example in small quantities, epinephrine may
  unmask a beta effect in vascular smooth muscle
  causing vasodilatation, whereas larger quantities
  will cause vasoconstriction due to alpha
  receptors outnumbering beta receptors.
• Norepinephrine and Epinephrine are equally potent
  at both alpha1 alpha2

88
Receptors

• Receptors are proteins in the cell membrane
• Receptor populations are dynamic
• Up-regulate
• increased of receptors
• Increased sensitivity to neurotransmitter
• Down-regulate
• decreased of receptors
• Decreased sensitivity to neurotransmitter
• Denervation supersensitivity

89
Modulation

• In primary cultures of postganglionic SNS neurons
• Facilitate release of norepinephrine
• ACH, epinephrine, Ang II, corticotropin, PACAP,
• Inhibit release of norepinephrine
• GABA, adenosine, NPY, somatostatin, opiods, PGE,
  NO, dopamine
• Whether this extends in vivo is unknown,
  especially in humans

90
Higher control of ANS

• Many neuronal areas in the brain stem reticular
  substance and along the course of the tractus
  solitarius of the medulla, pons, mesencephalon
  as well as in many special nuclei (hypothalamus)
  control different autonomic functions.
• ANS activated, regulated by centers in
• spinal cord, brain stem, hypothalamus, higher
  centers (e.g. limbic system cerebral cortex)

91
Central Autonomic Regulation

• Major relay cell groups in brain regulate
  afferent and efferent information
• Convergence of autonomic information onto
  discrete nuclei
• Autonomic function is modulated by ?s in
  preganglionic SNS or Para tone and/or ?s in
  neuroendocrine (NE) effectors

92
Central Autonomic Regulation

• Different components of central autonomic
  regulation are reciprocally innervated
• Parallel pathways carry autonomic information to
  other structures
• Mutiple chemical substances mediate transduction
  of neuronal information

93
Important Central Autonomic Areas

• Nucleus tractus solitarius
• Parabrachial Nucleus
• Locus Coeruleus
• Amygdala
• Hypothalamus
• Circumventricular Organs
• (no blood brain barrier-fenestrated capillaries)
• Cerebral Cortex

94
Neural immunoregulation

• Nerve fibers project into every organ
• involved in monitoring both internal external
  environment
• controls output of endocrine exocrine glands
• essential components of homeostatic mechanisms to
  maintain viability of organism
• local monitoring modulation of host defense
  CNS coordinates host defense activity
• (Immunology today V.216, 281-289, Jun 2000)

95
Segmental Facilitation

• The concept of segmental facilitation was
  formulated and researched originally by Denslow
  Korr at the osteopathic college in Kirksville MO.
• Original observation was based on palpatory data
• these dysfunctional (lesioned) segments were
  palpable

96
Segmental Facilitation

• Normal vertebrae
• When pressure was applied to the spinous
  processes, up to 7 Kg of pressure would elicit a
  minimal response in the adjacent paraspinal
  muscles
• Abnormal vertebrae
• Much lower pressure (1-3 Kg) would elicit an
  exaggerated response in the adjacent paraspinal
  muscles

97
Segmental facilitation

• In addition exaggerated responses in the adjacent
  paraspinal muscles to the lesioned segment could
  be observed when decreased pressure was applied
  to normal spinous processes at levels above or
  below the lesioned segment without that level
  responding. (key finding)

98
Segmental facilitation

• Lesioned segments shows both exaggerated ventral
  horn activity, but also intermediolateral horn
  activity, which is the site of preganglionic SNS
  neurons. (C8-L3)
• Additional studies confirmed the presence of
  sympathicotonia (hyperactivity of the SNS) at the
  level of the segmental facilitation
• decreases galvanic skin resistance associated
  with increased sweat gland activity

99
Segmental facilitation-end points

• Red reaction (SNS)
• Galvanic skin resistance (SNS)
• Sweat gland activity (SNS)
• EMG (skeletal muscle)

100
Segmental facilitation

• Clinical significance
• The facilitated segment acts as a focusing lens
  and bombards its targets with an exaggerated
  neural traffic.
• This increased neural segment outflow can result
  from any increased cord traffic either afferent
  or efferent
• results in increased local muscle spasm and
  hyperactive SNS activity
• Long term effects may result in premature
  dysfunction of tissues or organs as the tissue
  tries to override the effects of increased SNS
  activity

101
Segmental Facilitation
102
Neurophysiological effects of spinal manipulation
(SM)

• Introduction
• Biomechanical considerations of SM
• Neurophysiological and biomechanical mechanisms
  underlying the effects of SM
• The effects of SM
• on sensory receptors in paraspinal tissues
• on neural tissue in the IVF
• on central facilitation
• on somatosomatic (muscle) reflexes
• on somatovisceral reflexes

103
Evidence as of 2002 on effects of SM

• In favor
• Alters Group Ia and II mechanoreceptor discharge
• Influences sensory processing in the spinal cord
• central facilitation
• Affects neuroendocrine system
• Impacts control of skeletal muscle reflexes
• somatosomatic reflexes
• Negative
• Affects neuroendocrine system
• (Pickar. The Spine Journal 2 (2002) 357-371.)

104
Evidence as of 2002 on effects of SM

• Unknown
• Alters group III and IV mechanoreceptor or
  chemoreceptor discharge
• Alters mechanical environment of the IVF
• Alters chemical environment of the IVF
• Impacts control of autonomic reflexes
• Somatovisceral reflexes