Control of Complex Movements

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

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

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

Corticospinal tract

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

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

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)

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

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

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

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

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

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

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

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

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

Descending Pathways

Lateral corticospinal tract

Rubrospinal tract

Medial reticulospinal tractLateral reticulospinal tract

Anterior corticospinal tract

Tectospinal tract

Vestibulospinal tract

Lateral

Medial

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

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

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

Initiation of voluntary movement

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

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)

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

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)

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

Postural Reflexes

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

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

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

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

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

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

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

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

Semicircular Canals

• Thought to have a predictive function to prevent malequilibrium

• Anticipitory corrections

• works in close concert with cerebellum especially the flocculonodular lobe

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

Tilting room & chair

• One’s sense of upright is generally a combination of cues that include visual and vestibular information

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

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

Postural Adjustments• Functions

– support head & body against gravity– maintain center of the body’s 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

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)

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)

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

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

Basal Ganglia• Input nuclei

– Caudate – Putamen

• caudate + putamen = striatum

– Nucleus accumbens

• Output nuclei– Globus Pallidus-external segment– Subthalamic nucleus– Substantia nigra– Ventral tegmental area

Basal Ganglia

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

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

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

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 (Parkinson’s)

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

Cerebellum-”little brain”• By weight 10% of total brain

• Contains > 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

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

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

– 1:1 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

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

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

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

Clinical abnormalities-cerebellum

• Dysmetria

• Ataxia

• Past pointing

• Failure of Progression-Dysdiadochokinesia

• Dysarthria

• Intention tremor

• Nystagmus

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

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 tractspontocerebellar tracts– inferior- dorsal spinocerebellar tracts

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

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

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

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

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

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)

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

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

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

Horner’s 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

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

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

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

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

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

Enteric Nervous System• Myenteric Plexus (Auerbach’s)

– 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)

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

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

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

Neuropeptides (visceral afferent)– Angiotension II– Arginine-vasopressin– bombesin– calcitonin gene-related peptide– cholecystokinin– galamin– substance P– enkephalin– somatostatin– vasoactive intestinal peptide

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

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)

Effects of Stimulation• Eye:S dilates pupils

P- constricts pupil, contracts ciliary muscle & increases lens strength

• Glands:in general stimulated by P but S + will concentrate secretion by decreasing blood flow. Sweat glands are exclusively innervated by cholinergic S

• GI tract:S -, P + (mediated by enteric)• Heart: S +, P -• Bld vessels:S constriction, P largely absent

Effects of Stimulation

• Airway smooth muscle: S dilation P constriction

• Ducts: S dilation P constriction

• Immune System: S inhibits, P ??

Fate of released NT

• Acetylcholine (P) rapidly hydrolysed by aetylcholinesterase

• Norepinephrine– uptake by the nerve terminals– degraded by MAO, COMT– carried away by blood

Precursors for NT

• Tyrosine is the precursor for Dopamine, Norepinephrine & Epinephrine

• Choline is the precursor for Acetylcholine

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

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

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

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

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)

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

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

Important Central Autonomic Areas

• Nucleus tractus solitarius

• Parabrachial Nucleus

• Locus Coeruleus

• Amygdala

• Hypothalamus

• Circumventricular Organs – (no blood brain barrier-fenestrated capillaries)

• Cerebral Cortex

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.21;6, 281-289, Jun 2000)

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

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

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)

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

Segmental facilitation-end points

• Red reaction (SNS)

• Galvanic skin resistance (SNS)

• Sweat gland activity (SNS)

• EMG (skeletal muscle)

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

Segmental Facilitation

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

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.)

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