Motor & Integrative Neurophysiology PDF

MOTOR & INTEGRATIVE NEUROPHYSIOLOGY Spinal Reflexes BY GETAHUN C (MSC)  Spinal Cord Long, slender cylinder of nerve tissue that extends from the brain stem ~ 45 cm length in males & ~ 43 cm in females 2 cm in diameter Enclosed by the protective vertebral co...

MOTOR & INTEGRATIVE NEUROPHYSIOLOGY Spinal Reflexes BY GETAHUN C (MSC)  Spinal Cord Long, slender cylinder of nerve tissue that extends from the brain stem ~ 45 cm length in males & ~ 43 cm in females 2 cm in diameter Enclosed by the protective vertebral column covered by sheaths called meninges made up of 31 segments  Segments of spinal cord correspond to 31 pairs of spinal nerves in a symmetrical manner. Each spinal nerve is formed by an anterior (ventral) root and a posterior (dorsal) root. 9/14/2024 by GCD 2  Spinal Nerves 8 Cervical- sensory perception and motor function of the back of the head, neck, and arms 12 Thoracic- innervate the upper trunk 5 Lumbar 5 Sacral innervate the lower trunk, 1 Coccygeal back, and legs Function of spinal cord: Conducts nerve impulses to and from the brain Processes sensory input from the skin, joints, and muscles of the trunk and limbs and initiates reflex responses to this input 9/14/2024 by GCD 3  Internal Structure of Spinal Cord Neural substance of spinal cord is divided into inner gray matter and outer white matter 1. Gray matter is the collection of nerve cell bodies, dendrites and parts of axons. It is placed centrally in the form of wings of the butterfly and it resembles the letter ‘H’. It is the integrative area for the cord reflexes. Has three horns: ventral (anterior), dorsal (posterior) and lateral gray horn.  Cross-sectional view of the spinal cord 9/14/2024 by GCD 5  Gray matter cont’d Contains four types of neurons 1. Second-order sensory neurons cell bodies are found in the dorsal horn receive input from afferent neurons (first-order sensory neurons; their cell bodies are found in the dorsal root ganglia) through the dorsal root Function: transmit nerve impulses to higher levels in the CNS 2. Somatic motor neurons cell bodies are found in the ventral horn axons exit the spinal cord through the ventral root There are two types of motor neurons in the ventral horn Alpha motor neurons innervate skeletal muscle fibers to cause contraction. Gamma motor neurons innervate intrafusal fibers of the muscle spindle, which monitors muscle length Fig: Peripheral sensory fibers and anterior motor neurons innervating skeletal muscle 3. Visceral motor neurons cell bodies are found in the lateral horn axons form efferent nerve fibers of the ANS axons of these neurons exit the spinal cord by way of the ventral root 4. Interneurons Located in all areas of the spinal cord gray matter receive input from: higher levels of the CNS + sensory neurons entering the CNS through the spinal nerves about 30 times as numerous as the anterior motor neurons. small and highly excitable, often exhibiting spontaneous activity and capable of firing as rapidly as 1500 times per second. have many interconnections with one another and the motor neurons responsible for most of the integrative functions of the spinal cord 9/14/2024 by GCD 8  2. White matter Composed of myelinated axons of neurons Axons are grouped together to form tracts Ascending tracts - carry sensory information toward the brain Descending tracts-carry motor information away from the brain toward the motor neurons in the lateral or ventral horns of the spinal cord gray matter Both tracts cross from one side of the CNS to the other Cross over: in the medulla (most)  Reflex Any response that occurs automatically without conscious effort Are specific, predictable, and, furthermore, often purposeful Can be local axonic, enteric, hypothalamic, mesencephalic, medullary and spinal Simple, or basic, reflexes are preprogrammed (built-in), unlearned responses. Pulling the hand away from a burning hot object Acquired, or conditioned, reflexes are learned responses that require experience or training. Pianist striking a particular key on seeing a given note on the music staff 9/14/2024 by GCD 10  Properties of Reflex 4 properties: 1. Reflexes require stimulation: they are not spontaneous. 2. Reflexes are quick: involve few if any interneurons & minimum synaptic delay. 3. Reflexes are involuntary: they occur without intent or awareness, and are difficult to suppress. 4. Reflexes are stereotyped: they occur essentially the same way every time.  Reflex Arc Neural pathway involved in accomplishing reflex activity Includes five basic components: 1. Sensory receptor (e.g. Stretch receptor, pain receptor) 2. Afferent or first-order sensory neuron 3. Integrating center in the spinal cord (synapses) 4. Efferent or motor neuron 5. Effector tissue (skeletal muscle) 9/14/2024 by GCD 12  Monosynaptic reflex has a single synapse between afferent and efferent neurons. E.g. stretch reflex Polysynaptic reflex has two or more synapses between these neurons. E.g. withdrawal reflex 9/14/2024 by GCD 13  Muscle sensors Types of muscle sensors a. Muscle spindles (groups Ia and II afferents) are arranged in parallel with extrafusal fibers. They detect both static and dynamic changes in muscle length. b. Golgi tendon organs (group Ib afferents) are arranged in series with extrafusal muscle fibers. They detect muscle tension. c. Pacinian corpuscles (group II afferents) are distributed throughout muscle. They detect vibration. d. Free nerve endings (groups III and IV afferents) detect noxious stimuli.  Types of muscle fibers a. Extrafusal fibers make up the bulk of muscle. are innervated by α-motoneurons. provide the force for muscle contraction. b. Intrafusal fibers are smaller than extrafusal muscle fibers. are innervated by γ-motoneurons. are encapsulated in sheaths to form muscle spindles. run in parallel with extrafusal fibers, but not for the entire length of the muscle. are too small to generate significant force.  Muscle spindles are distributed throughout muscle & helps control basic muscle tone consist of small, encapsulated intrafusal fibers connected in parallel with large (force generating) extrafusal fibers. The finer the movement required, the greater the number of muscle spindles in a muscle. Types of intrafusal fibers in muscle spindles (1) Nuclear bag fibers detect the rate of change in muscle length (fast, dynamic changes). are innervated by group Ia afferents. have nuclei collected in a central “bag” region. (2) Nuclear chain fibers detect static changes in muscle length. are innervated by group II afferents. are more numerous than nuclear bag fibers. have nuclei arranged in rows.  Reflexes 1. Stretch (myotatic) reflex—knee jerk is monosynaptic. Muscle is stretched, and the stretching stimulates group Ia afferent fibers. Group Ia afferents synapse directly on α-motoneurons in the spinal cord. The pool of α-motoneurons that is activated innervates the homonymous muscle. Stimulation of α-motoneurons causes contraction in the muscle that was stretched. As the muscle contracts, it shortens, decreasing the stretch on the muscle spindle and returning it to its original length. At the same time, synergistic muscles are activated and antagonistic muscles are inhibited. Stretch reflex-Knee jerk Tapping on the patellar tendon causes the quadriceps to stretch. Stretch of the quadriceps stimulates group Ia afferent fibers, which activate α-motoneurons that make the quadriceps contract. Contraction of the quadriceps forces the lower leg to extend. 9/14/2024 by GCD 19  2. Golgi tendon reflex (inverse myotatic) is disynaptic, stimulated by high tension is the opposite, or inverse, of the stretch reflex Active muscle contraction stimulates the Golgi tendon organs and group Ib afferent fibers. The group Ib afferents stimulate inhibitory interneurons in the spinal cord. These interneurons inhibit `α-motoneurons and cause relaxation of the muscle that was originally contracted. At the same time, antagonistic muscles are excited. Protect tearing of muscles  3. Flexor Reflex Synonyms- withdrawal reflex, nociceptive reflex, pain reflex results in flexion on the ipsilateral side and extension on the contralateral side. Stimulus- noxious stimulus to an extremity Receptor- class II, III, OR IV afferents Number of synapse- multisynaptic Purpose- to remove affected part from danger On the ipsilateral side of the pain stimulus, flexors are stimulated (they contract) & extensors are inhibited (they relax), and the arm is jerked away from the stove. On the contralateral side, flexors are inhibited and extensors are stimulated (crossed extension reflex) to maintain balance.  4. Crossed extensor reflex Not a separate reflex, but is accessory to or part of the flexor reflex Stimulus, receptors, number of synapses are the same as flexor reflex not begin until 200 to 500 milliseconds after onset of the initial pain stimulus Purpose-contraction of extensor muscles of contralateral limb to support weight Afterdischarge – contraction outlasts stimulus (prolonged) Fig: Myogram of a crossed extensor reflex  The crossed extensor reflex coupled with the withdrawal reflex 9/14/2024 by GCD 23  Summary of major spinal reflexes 9/14/2024 By Yonas Teshome 24  5. Extensor thrust reflex Stimulus- pressure applied to the foot pads Receptors- tactile receptors and muscle spindles; group I, II, III, IV afferent fibers Number of synapses- multisynaptic Purpose- maintenance of posture  7. Scratch Reflex Stimulus – irritating stimulus on the skin of the dorsal or lateral surfaces of the thorax and neck Receptors- combination of tactile and pain receptors; group II, III,IV afferent fibers Number of synapses- multisynaptic Purpose- to remove source of irritant  Spinal organization of motor systems 1. Convergence occurs when a single α-motoneuron receives its input from many muscle spindle group Ia afferents in the homonymous muscle. produces spatial summation because although a single input would not bring the muscle to threshold, multiple inputs will. also can produce temporal summation when inputs arrive in rapid succession. 2. Divergence occurs when the muscle spindle group Ia afferent fibers project to all of the α-motoneurons that innervate the homonymous muscle. 3. Recurrent inhibition (Renshaw cells) Renshaw cells are inhibitory cells in the ventral horn of the spinal cord. They receive input from collateral axons of motoneurons and, when stimulated, negatively feed back (inhibit) on the motoneuron. Motor functions of cerebral cortex BY GETAHUN C (MSC) Cerebral hemispheres They are separate, but connected by nerve fibers: corpus callosum Have some degree of specialization  Left side: words and logic  Right side: art, music, intuition Crossover: right half connects to left side of body and vice versa 9/14/2024 by GCD 30  Histological organization of the cortex 6 layers (except: olfactory, cingulate and hippocampus, 3 layers). Layer I: Molecular layer/Plexiform layer Outer layer/horizontal running nerve cells. Layer II: External granular layer Granule cells Dendrites extend to layer I Axons extend to deeper cortical layers. (association projections). Layer III: External pyramidal layer Moderate-sized pyramidal cells Axons form commissural projections (via corpus callosum)  Cont’d Layer IV: Internal granular layer Small stellate cells Ascending input from thalamus. Layer V: Internal pyramidal layer Large pyramidal cells (Betz cells, motor cortex). Axons (subcortical + UMN). Layer VI: Multiform layer Pyramidal + fusiform cells. Axons project to thalamus.  Neuronal cell types Pyramidal neurons: layers III + V. Granular cells/stellate: layers II + IV. Layer I: Molecular layer/mainly neuronal processes. Layer VI: Multiform layer/output neurons of varying shapes and sizes. Pyramidal cells main output cells of the cortex. Granular neurons/stellate neurons o Shorter axons + smaller dendritic trees o Remain within the cortex. o Interneurons.  Motor functions of cerebral cortex Location  Located in precentral gyrus Areas of the motor cortex 1. primary motor area (M1) 2. premotor area (PMA) 3. supplemental motor area (SMA) 4. motor association area (MAA) 9/14/2024 by GCD 35 Primary motor area Occupies Brodmann areas A4 Body represented topographically, crossed and inverted Area of representation is proportional to the degree of fine movements in that part (motor homunculus) Contain two types of neurons Dynamic: discharges at high frequency for a short period Static: discharge at low frequency for a short time 9/14/2024 by GCD 36 Primary motor cortex Function of M1 area Voluntary movements involving conscious activities Initiation of fine discrete movements Facilitation of stretch reflex Note >= 50% control the muscles of the hands and the muscles of speech. Little cortex is devoted to motor pathways terminating in the trunk of the body or the lower extremities 9/14/2024 by GCD 37 Sensory and motor homunculus 9/14/2024 by GCD 38  Premotor area (Areas 6, 8, 44) Topographic representation of body as in M1 Mirror neurons are located in the premotor cortex and the inferior parietal cortex to transform sensory representations of acts that are heard or seen into motor representations of these acts. Specialized regions 1. Broca’s area (word formation= A44)- contain motor programs for verbalization 2. Eye field area (A8): direct eyes to a desired field 3. Head rotation area (A6)- direct head towards objects 4. Hand skill area (A6)- motor programs for skilled hand movements (Lesion result in motor apraxia)  Functions of the premotor area 1. Initiation of gross movements 2. Weak inhibition of stretch reflex 3. A center for head rotation 4. A center for voluntary eye movements – Voluntary fixation – Blinking movement 5. A center for skilled hand movements Damage produce motor apraxia 6. A center for verbalization Lesion cause vocal aphasia or nonfluent aphasia 7. Inhibition of the grasp reflex  Supplemental motor area Located in medial A6 It lies mainly in the longitudinal fissure but extends a few centimeters onto the superior frontal cortex Topographic representation of body is in inverted and horizontal manner Contractions elicited by stimulating this area are often bilateral rather than unilateral Involved in preparation for movements (readiness reaction). Programming, sequential motor actions Supplement the functions of the PMA in gross position of the body  Motor association area Located in the frontal lobe just anterior to premotor & the primary motor area Extensively interconnected with other brain structures Functions Setting goals and aims of movements and taking decision accordingly. The signals are sent to basal ganglia to convert the thought of motor movements into plans and programs of motor movement Elaboration of thought during deeper thinking for creativity and planning Organizes cognitions, emotions and behavior. 9/14/2024 by GCD 42  Function of Prefrontal cortex Directing and maintaining attention Morality Problem solving Adjusting behavior to social norm Planning Working memory Deliberate decisions  Functional regions of the cerebral cortex 9/14/2024 by GCD 44 9/14/2024 by GCD 45  Connections of the motor cerebral cortex Afferent connections 1. From cortical areas  From somatosensory, visual, auditory areas of the same side  From the corresponding opposite side 2. From the thalamus  Ventrobasal complex (somatic, visual, and auditory senses)  Intralaminar nuclei (increases excitability)  Ventral and medial nuclei ( cerebellum, basal ganglia) Efferent connections 1. Pyramidal tract fibers 2. Caudate and putamen circuit in basal ganglia 3. Red nucleus 4. Cerebellum as cerebro-ponto-cerebellar tracts 5. Lateral (surround) inhibition 9/14/2024 by GCD 46  The motor tracts 1. Pyramidal Tract Origin: a) Primary motor area (30%) b) Premotor and supplemental motor area (30%) c) Somatosensory area (40%) Pyramidal tract arises from lamina V of the cerebral cortex that contains the pyramidal cells. 9/14/2024 by GCD 47  Types of pyramidal tract a) Corticonuclear tract- From Area 8, terminate on motor nuclei in midbrain and pons (III,IV,VI) For voluntary conjugate movements of the eyes Facilitate stretch reflex of extraoccular muscles b) Corticobulbar tract- terminate on motor nuclei in pons and medulla (V, VII, IX, XI,XII). Voluntary movements of muscles in head area Facilitate stretch reflex c) Corticospinal tract – terminate on motor nuclei in spinal cord Lateral corticospinal tract (90%) Ventral corticospinal tract (8%) Uncrossed corticospinal tract (2%)  Properties of corticospinal tract Total fibers >= 1.0 x106/tract  Thick fiber (3%): Arise from Betz cells found only in the primary motor area.  Thin fiber (97%): Arise from small pyramidal cells found in different parts of the cortex Only one neuron is involved. Fibers occupy the pyramid of the medulla oblongata. 85-90% fibers descend crossing/ decussating to the other side. Cortical control is limited to M1 Its effects are facilitatory/ excitatory. Fibers descend corona radiata converge in anterior two-thirds of the posterior limb of the internal capsule cerebral peduncles basal pons brainstem medulla (pyramids). Corticospinal (pyramidal) tract Functions of corticospinal tract Influence LMNs in the anterior horn of the spinal cord or the motor nuclei of cranial nerves in the brainstem Control of movement. Provide gating for spinal reflexes. Responsible for descending influences on afferent (ascending sensory) systems. Trophic functions a. Lateral corticospinal tract o Descend in the posterolateral column of the spinal white matter o Terminate on the interneurons in the intermediate zone of gray matter, sensory relay neurons in the dorsal horn, anterior motor neurons o Crossed for the innervation of the limbs. o Function: Precise rapid, skilled voluntary movements. Control of movement of the entire limb. Gross and strength-related movements  Cont’d b. Anterior corticospinal tract o Descend directly in the ventral column of same side o cross over the segmental level at which they terminate o Bilateral for the innervation of the trunk. c. uncrossed corticospinal tract o Descend in a posterolateral column of the spinal white matter. o Terminate on the ventral horn cells of the same side. o Functions: Provide bilateral innervation of some muscles as the respiratory & abdominal muscles. Gross positioning movements controlled by the supplementary motor area. Help partial recovery of movements after injury of the crossed corticospinal tracts.  Voluntary movement requires coordinated activities of all motor systems that includes motor cortex, basal ganglia, thalamus, midbrain, cerebellum and spinal cord There are principal descending fibers and feedback connections 9/14/2024 by GCD 52 2. Extrapyramidal tracts Properties All fibers other than the pyramidal tract Arise from many subcortical structures including basal ganglia Controlled by cortical motor area (A4,6) via basal ganglia The fibers do not occupy the pyramid Few cross to the opposite side Formed of multiple neurons and synapse Cortical control is wide Useful during 1st year of life and during gross automatic mvnt 9/14/2024 by GCD 53 Fig: A schematic diagram of the extrapyramidal system Functions of the extrapyramidal tract Control muscle tone, posture, equilibrium for suitable background For gross coordinated movement or subconscious automatic associated movement Alternative route for voluntary activities Corticorubrospinal tract Exert strong inhibitory effect on lower motor neurons 9/14/2024 by GCD 55  2. Extrapyramidal tracts cont’d  Origins Red nucleus, Reticular formation of the brainstem, Tectum of midbrain ( + the inferior olive of the medulla) Vestibular nuclei  Types: Reticulospinal Rubrospinal Tectospinal Vestibulospinal tracts  Descending motor pathways  Originate in area 4 and area 6 and terminate in medial and lateral areas of the brain stem. 1. Medial pathways: Reticulospinal, Vestibulospinal & Tectospinal o Originates RF, VN & superior colliculus. o Descend in the ventral column & terminate in the ventromedial area of spinal gray matter. o Receives information from the cortex & other motor centers for the control of posture and locomotion. 2. Lateral pathway: Rubrospinal tract & corticospinal tract Originates in magnocellular portion of the red nucleus. Descends in contralateral dorsolateral column. It receives input from the cortex as well but is involved in the control of arm and hand movements. Terminates in dorsolateral area of spinal gray matter Spinal termination of descending fibers 9/14/2024 by GCD 58  Reticulospinal tract Origin: RF of the brainstem. Two descending extrapyramidal tracts:  Lateral reticulospinal tract/Medullary  Origin: inhibitory RF of the medulla  Most fibers descend ipsilaterally  Inhibits the -motor neurons inhibiting the stretch reflex and skeletal muscle tone. PRN receive strong  Inhibit the antigravity muscles excitatory signals from the  Ventral reticulospinal tract/Pontine vestibular nuclei and deep nuclei of the cerebellum  Origin: Facilitatory RF of the pons  All fibers descend ipsilaterally MRN receive strong input  Facilitates the -motor neurons collaterals from facilitating the stretch reflex and the corticospinal tract, skeletal muscle tone. rubrospinal tract, and other motor pathways  Excite the axial muscles of the body, which support the body against gravity  Rubrospinal tract Located in the midbrain. Origin - Red nucleus in the midbrain. Fibers decussate in the midbrain travel through the brainstem tegmentum descend on the contralateral side in the lateral column of the spinal cord LMN that innervate the flexors of upper limb (inhibiting the extensors).  Rubrospinal tract cont’d Receives projection fibers from: o Corticorubral tract from motor cortex. o Collateral from the corticospinal tract as it passes through the midbrain. o GP of the basal ganglia & cerebellum All these fibers synapse in the lower part of the red nucleus that contains giant pyramidal neurons similar to Betz cells. Functions of the red nucleus o Acts as an accessory pathway for the corticospinal tract. o Can initiate gross movements  Tectospinal tract Lateral tectospinal tract Origin: superior colliculus. Fibers travel bilaterally →brainstem and anterior white columns of the spinal cord → project to the cervical spinal cord → innervate motor neurons responsible for neck movements Responsible for orienting the head and neck during eye movements. Crosses to the opposite side and terminates in the cervical segments of the spinal cord. Concerned with directing the eye and turning the head towards a light source /visuospinal reflexes.  Ventral tectospinal tract Originates from the inferior colliculus. Crosses to the opposite side and terminates in the cervical segments of the spinal cord. Concerned with turning the head to direct the ears towards a sound source (audiospinal reflexes).  Medial vestibulospinal tract Origin: medial vestibular nucleus. Descends bilaterally brainstem anterior white columns of the spinal cord LMN of cervical + upper thoracic level. Influences motor neurons controlling the neck muscles and responsible for stabilizing the head as we move our bodies or as our head moves in space and plays a role in coordinating head movements with eye movements. Vestibular nuclei Facilitate stretch reflex + skeletal muscle transmit strong excitatory tone. signals to the antigravity muscles Mediate some postural reflexes. maintain equilibrium in response to signals from the vestibular apparatus.  Lateral vestibulospinal tract Origin- Lateral vestibular nucleus Descends ipsilaterally in the anteromedial area of brainstem uncrossed + travels in the anterior white column of the spinal cord to terminate on the - and -motor neurons. Terminate at all levels of the ipsilateral spinal cord to facilitate the activity of the extensor muscles + inhibit the activity of the flexor muscles. Input: inner ear.  Upper and Lower Motor Neurons To do a voluntary movement, signals start in the motor neurons of the cerebral cortex and reach the skeletal muscles through two orders of neurons: 1. Upper motor neurons (UMN): These are the neurons of the pyramidal and extrapyramidal tracts in the CNS. They extend from the cerebral cortex and the extrapyramidal nuclei down to the motor neuron pool of the brainstem and spinal cord. Neurons of the motor neuron pool themselves are not included in the upper motor neurons. 2. Lower motor neurons (LMN): These are the neurons of the motor neuron pool and their axons which form the motor nerves to the skeletal muscles.  Cerebrospinal fluid (CSF) Volume of Cerebral cavity = 1600-1700 ml Volume of CSF = 150 ml & remainder by the brain and cord CSF is found in Ventricle (cavity) of the brain Cisterns around the outside of the brain Subarachnoid space around brain and spinal cord Functions Cushing function Floating brain in cranial vault Medium of Exchange 9/14/2024 by GCD 67  Pathway of CSF CSF secreted in the lateral ventricles third ventricle aqueduct of Sylvius  fourth ventricle  two lateral foramina of Luschka and a midline foramen of Magendie,  cisterna magna  subarachnoid space  arachnoidal villi  venous 9/14/2024sinuses by GCD 68  Formation of CSF Rate of formation is 500 ml/day Source Mainly by choroid plexus in lateral ventricles Ependymal surfaces of all ventricles Arachnoid membranes Mechanism is by active pump of Na ion More amount of Cl- and less glucose move into CSF K+ and HCO3- move out (Low in CSF) 9/14/2024 by GCD 69 Perivascular spaces and CSF perivascular spaces Are specialized lymphatic system for the brain. Because no true lymphatics are present in brain tissue, excess protein in the brain tissue leaves the tissue flowing with fluid through the perivascular spaces into the subarachnoid spaces transport fluid, proteins and extraneous particulate matter out of the brain 9/14/2024 by GCD 70  Cerebrospinal Fluid Pressure Normal person lying in a horizontal position averages 130 mmH2O (10 mm Hg) may be as low as 65 mmH2O or as high as 195 mmH2O Hydrocephalus- means excess water in the cranial vault Divided into 1. Communicating  caused by blockage of fluid flow in the subarachnoid spaces around the basal regions of the brain or by blockage of the arachnoidal villi where the fluid is normally absorbed into the venous sinuses. 2. Noncommunicating  caused by a block in the aqueduct of Sylvius, resulting from atresia (closure) before birth in many babies or from blockage by a brain tumor at any age. 9/14/2024 by GCD 71  Anatomy of the blood–brain barrier (BBB) It is the barrier between cerebral capillary blood and the CSF. CSF fills the ventricles and the subarachnoid space. It consists of the endothelial cells of the cerebral capillaries and the choroid plexus epithelium. 9/14/2024 by GCD 72  Functions of the blood-brain barrier 1. It maintains a constant environment for neurons in the CNS and protects the brain from endogenous or exogenous toxins. 2. It prevents the escape of neurotransmitters from their functional sites in the CNS into the general circulation. 3. Drugs penetrate the BBB to varying degrees. For example, nonionized (lipid-soluble) drugs cross more readily than ionized (water-soluble) drugs. Inflammation, irradiation, and tumors may destroy the blood-brain barrier and permit entry into the brain of substances that are usually excluded (e.g., antibiotics, radiolabeled markers). 9/14/2024 by GCD 73  Basal Ganglia Are sub-cortical mass of gray matter found lateral to the thalamus. They include Three large nuclear masses Caudate (Paleostriatum) Corpus striatum Putamen (Neostriatum) Globus pallidus Lentiform nucleus Two functionally related nuclei Subthalamus- prevents unwanted movements Substantia nigra- coordination of muscle movements Divided into two subregions: a) pars compacta -involved in finer motor control b) pars reticulata - involved in rapid eye movement 74 Anatomy of Basal Ganglia 75  Connection of basal ganglia Afferent connection – mainly terminate in the caudate nucleus. Efferent connections – mainly originate from Globus pallidus. Connections of basal ganglia to 1. Cerebral cortex via Caudate and Putamen circuit 2. Brainstem via Extrapyramidal tracts 76 Circuits of the basal ganglia to the cerebrum Caudate circuit From motor association + premotor + sensory association area- to caudate nucleus- to globus pallidus- to VLNT- to motor association area 77 Putamen circuit Motor Association + Primary motor + Somatic association area - to Putamen - to Globus pallidus - to VLNT (Thalamus) - to Primary MA + Premotor Area -  Accessory circuit that involve subthalamus and substantia nigra. 78  Brainstem Connections of Basal ganglia From globus pallidus the extrapyramidal fibers arise as: 1. Reticular formation --- reticulospinal tract Enhance antigravity reflexes of the spinal cord 2. Red nucleus --- rubrospinal tract Control of muscle tone in flexor muscle 3. Vestibular nucleus --- vestibulospinal tract Keep the head balanced on the shoulder Guides head movement to keep the eyes stable 4. Inferior olive --- olivospinal tract Facilitate muscle tone 5. Tectum --- Tectospinal tract Receives input from retina, area 17, and proprioceptors. Constructs the image of visual scene Direct the head and eyes towards appropriate points in space Neurotransmitters of basal ganglia Substantia Cortex Cortex nigra Intarstriatal interneuron Glutamine Acetylcholine Dopamine Striatum Striatum Striatum 80  Striatum Subthalamus Subthalamus GABA Glycine Glycine Substantia Substantia nigra Pallidum nigra and Globus pallidus Fibers from the brainstem to the BG release NA, serotonin and enkephalin. Glutamate, acetylcholine and noradrenaline are excitatory transmitters to BG Dopamine, GABA, serotonin and enkephalin are inhibitory. 81  Functions of the basal ganglia A. Role in controlling muscle tone Caudate n. stimulates muscle tone through vestibular and inferior olive. Lentiform n. inhibits muscle tone through inhibition of M1 and stimulation of inhibitory reticular formation and red nucleus. B. Role in controlling voluntary movement Planning and programming of movements start in the BG. In collaboration with cerebral cortex, it produces a coordinated, organized purposeful movement. 82  Role of caudate circuit Convert motor thoughts and ideas into motor plan and motor action. It determines what pattern of movement will be used and In what sequence to achieve a complex goal e.g. when dressing, one puts on the shirt then the necktie before the jacket. Determines the time and scale movement. To what extent the movement will be fast For how long the movement will last Damage to caudate circuit. Disorganized motor activity; Wearing neck tie before a shirt Failure to scale a contra lateral side (when drawing) 83 Role of putamen circuit Storage of motor circuit of familiar actions: Signature, writing, lighting candle. Damage to this circuit Motor apraxia: Inability to carry out familial movements in the absence of motor paralysis. Two characteristic features of lesions of BG Involuntary movements during rest. Change in muscle tone 84 Cerebellum and Its Motor Functions BY GETAHUN C(MSC)  Cerebellum has long been called a silent area of the brain Second largest part of brain Part of the hindbrain and is attached to the dorsal surface of the upper region of the brainstem. It contains outer gray (extensively folded) and inner white matter Functional anatomy Vermis = midline structure. Two cerebellar hemispheres Flocculonodular lobe Three cerebellar peduncles superior cerebellar peduncle (SCP) connects cerebellum with midbrain middle peduncle (MCP) connects cerebellum with the pons inferior peduncle (ICP) connect cerebellum with the medulla. 9/14/2024 by GCD 86  Physiological divisions of the cerebellum Cerebellum consists of three functionally distinct parts Archicerebellum (vestibulocerebellum) is the oldest part of the cerebellum. consists of the flocculonodular lobe Connected to vestibular apparatus through vestibular nuclei. Maintenance of balance and equilibrium, and controls eye movements Paleocerebellum (spinocerebellum) Consists of vermis and paravermal areas Receives signals from propioceptors Control muscle tone and gross movements Neocerebellum (cerebrocerebellum) consists of lateral part of cerebellar hemisphere connected to cerebral cortex Plan, Sequence, and Time Complex Movements stores procedural memories  Layers of the cerebellar cortex Outer gray matter a. Granular layer: innermost layer. contains granule cells, Golgi type II cells, and glomeruli. In the glomeruli, axons of mossy fibers form synaptic connections on dendrites of granular and Golgi type II cells. b. Purkinje cell layer: middle layer. contains Purkinje cells. Output is always inhibitory c. Molecular layer: outermost layer. contains stellate and basket cells, dendrites of Purkinje and Golgi type II Deep white matter contains four nuclei cells, and parallel fibers (axons of granule Dentate nucleus- Cerebellar hemisphere cells). Nucleus interpositus (two)- Paravermal The parallel fibers synapse on dendrites Fastigeal nulcei - Vermis+Flocculonodular lobe of Purkinje cells, basket cells, stellate cells, and Golgi type II cells.  Afferent fibers to cerebellum 1. Climbing fibers Originate in inferior olive (medulla) terminate on deep nuclear cell layers and Purkinje cells. Signals in Climbing fibers produce initial excitatory output followed by prolonged inhibitory output. play a role in cerebellar motor learning. 9/14/2024 by GCD 89  Cont’d 2. Mossy fibers Originate in all areas of cerebral cortex include vestibulocerebellar, spinocerebellar, and pontocerebellar afferents. terminate on deep nuclear cells and Granular cells whose axon terminate finally on Purkinje cells. Synapses on Purkinje cells result in simple spikes. The axons of granule cells bifurcate and give rise to parallel cells. The parallel fibers excite multiple Purkinje cells as well as inhibitory interneurons (basket, stellate, Golgi type II). signals in Mossy fibers maintained facilitatory out put  Efferent from the cerebellum The efferent from the cerebellum is from the deep nuclear cells which receives continuous inhibitory input from the Purkinje and continuous excitatory input from the mossy and climbing fibers The net output from cerebellum at rest is continuous tonic facilitatory discharge.  Cerebellar connection 1. Afferent connections a. Olivocerebellar Servo-comparator feedback Climbing fibers here mostly carry skill info. b. Tectocerebellar visual and auditory impulse c. Corticopontocerebellar efferent copy d. Vestibulocerebellar posture and equilibrum. d. Reticulolcerebellar sensory information e. Dorsal spinocerebellar propioceptive signal f. Ventral spinocerebellar afferent copy of the motor order from motor cortex (bilateral) 9/14/2024 by GCD 93  Efferent from the cerebellum From vestibulocerebellum (archicerebellum) Fastigeal n.: Fastigiospinal tract– control posture From spinocerebellum (paleocerebellum) Fastigeal nuclei = Reticular formation – reticulospinal Muscle tones Vestibular nucleus - vestibulospinal Interpositus n.= Motor cortex via thalamus Coordinate & sequence motor activities, Control muscle tone Basal ganglia via thalamus Red nucleus - rubrospinal tract to control agonist & antagonist muscles From cerebrocerebellum Denatate n.: via thalamus end in sensorimotor cortex Form: cortico-ponto-cerebello-dento-thalamo-cortical circuit (Coordinate & sequence motor activities) 9/14/2024 by GCD 94 Efferent cerebellar connections 9/14/2024 by GCD 95  Output of the cerebellar cortex Purkinje cells are the only output of the cerebellar cortex. Output of the Purkinje cells is always inhibitory; the neurotransmitter is ɤ-aminobutyric acid (GABA). The output projects to deep cerebellar nuclei and to the vestibular nucleus. This inhibitory output modulates the output of the cerebellum and regulates rate, range, and direction of movement (synergy).  Functions of the cerebellum It is not an initiator of motion but acts as a monitor, great modulator and pre programmer 1. Control of posture and equilibrium plays a minor role in maintaining posture through a servocomparator function. signals from vestibular apparatus and propioceptives are compared to adjust muscle tone plays a major role in maintaining equilibrium during rapid motions and motions with rapidly changing direction through a predictive function. 2. Control of muscle tone Archicerebellum inhibits muscle tone Spino and cerebrocerebellum facilitates 9/14/2024 by GCD 97 3. Control of voluntary movement Monitoring motor plan: Efferent copy about motor intension and afferent copy about motor activity helps cerebellum to monitor any deviation from motor plan and program Timing of movements: determines the start and finish of any sequential movement Joining of movement. Rapid succession of sequential movement one after the other produce smooth joined complex movement 4. Predictive function: Knows rate and direction of any movement Thrust of goal keeper to catch a kicked ball Running towards a wall and stopping without hitting 9/14/2024 by GCD 98 5. Servocomparator (force regulator) Intension and performance comparison makes it able to adjust any deviation This function exist in inferior olive: but helpful only during learning a new skill 6. Damping of movement Means ending movement abruptly without oscillation The inhibitory signals in mossy fibers assist this Lack of this leads to intension or kinetic tremor 7. Modulation of the Initiation and termination of ballistic movement In ballistic movements (typing): the cerebellum potentiates the starting (mossy fiber +) and its abrupt stop via inhibitory signals. 9/14/2024 by GCD 99  Speech Information is transferred between the two hemispheres of the cerebral cortex through the corpus callosum. The left hemisphere is usually dominant with respect to speech and writing. Speech is the expression of ideas by spoken words. The right hemisphere is dominant for facial recognition, recognition of musical themes, and spatial recognition of body, understand complex pictures and three dimensions, but can not say any in words. The left hemisphere controls speech and right hemisphere comprehend language. 100  Hearing and speech The faculty of speech depends on ability to hear spoken words. Therefore, born deaf will be dump. Spoken word is perceived in area 41 (primary auditory area) and interpreted in area 42 (auditory interpretive area) in temporal cortex. The message of heard word is delivered to area 39 (general interpretive area) to connect the meaning to other items stored in memory for thinking process.  Reading and speech Written words are perceived by primary visual area (BA 17). The visual signals are interpreted in visual interpretive area (BA18-19) in occipital lobe. The meaning of the word is fed to the general interpretive area (BA 39) to connect with related stored item for thinking process. 102  Wernicke’s area Language and speech center It is a memory store for language. It decides what words are suitable and in what sequence to be used. It receives signal from angular gyrus (BA-39). It is connected to Broca’s area by arcuate fasciculus. 103  Word-formation center (broca's area, area 44) This area is found in the premotor area. Stores motor program for different words It receives input signals from Wernicke's area through the arcuate fasciculus. When activated it stimulate motor cortex at a certain pattern to produce words by contracting respiratory, laryngeal, pharyngeal, lingual muscles. 104 The writing center (exner's center)—BA6 This is part of the hand-skills area which stores the motor programs for writing of words or drawing of figures by the muscles of the hand. It receives input signals from Wernicke's area via the arcuate fasciculus. 105  Mechanism of speech Speech passes by four steps to occur : 1. Formation of thought and ideas that will be express in words (by angular gyrus). 2. Choice of suitable sentences and phrases to express the ideas (Wernicke's Area) 3. Word formation (Broca's area)- receive input signals from Wernicke's area through arcuate fasciculus and sends programmed impulses to the M1 4. Verbalization: It is the coordinated contraction of muscles of speech in a certain sequence to produce spoken words This is the function of the motor cortex, the motor nerves and the muscles of speech. Note: Wernicke's area feeds the signals to Exner's center to write the desired words. 106 Arcuate fasciculus 107 Speech disorders Global aphasia is caused by extensive lesions in the categorical hemisphere involving both frontal and temporal lobes. The aphasia is general; it involves the receptive and expressive functions. 108  Hypothalamus lies beneath the thalamus and above the pituitary gland Is a collection of specific nuclei and associated fibers It serves as an important link between the autonomic nervous system and the endocrine system It plays a vital role in maintenance of homeostasis in the body 9/14/2024 by GCD 109 9/14/2024 by GCD 110 Coronal view of the hypothalamus (mediolateral positions)  Functions of the Hypothalamus 1. Autonomic function Sympathetic center lateral, dorsomedial; and posterior nuclei of the hypothalamus “no parasympathetic center” 2. Thermoregulation preoptic area is concerned with regulation of body temperature "heat loss center" in the anterior hypothalamus contains thermosensitive cells responds mainly to any increase in core temperature "heat gain center" in the posterior hypothalamus contains "thermoresponsive" cells Responds mainly to cooling of the skin 9/14/2024 by GCD 112 Functions of the Hypothalamus cont’d 3. Control of food intake "feeding center" in the lateral hypothalamus "satiety center" in the medial hypothalamus (ventromedial nucleus) 4. Endocrinal function controls anterior pituitary hormone secretion (by ArN, VMN, PerVN, & medial preoptic nucleus) produces posterior pituitary hormones (by ParVN and SON) 5. Control of water balance Thirst center is located in the lateral hypothalamus. Control of renal excretion of water is vested mainly in the supraoptic nuclei. 6. Control of salt appetite in the anterior hypothalamus 9/14/2024 by GCD 113  Functions of the Hypothalamus cont’d 7. Control of cyclical phenomena participates in the sleep–wake cycle (by SCN) 8. Role in learning and memory A reward center in the lateral and ventromedial nuclei. Most potent punishment center in the periventricular nuclei Less potent punishment areas in the amygdala & hippocampus. 9. Control of motor responses to emotions fear center in the periventricular nuclei rage area in the lateral hypothalamus Placidity and Tameness area in the ventromedial nucleus 9/14/2024 by GCD 114 Functions of the Hypothalamus cont’d 10. Sexual behavior hypothalamus is involved in the following way: The hypophysiotropic area controls the release of the pituitary gonadotropins The anterior hypothalamus in the female contains estrogen sensitive neurons that increase the sexual desire and initiate the heat of sexual behavior Stimulation of parts of the lateral hypothalamus produces sexual excitement and penile erection in male monkeys. 9/14/2024 by GCD 115 Control centers of the hypothalamus (sagittal view). Components of limbic system (Broca’s Lobe) Limbic lobe Hippocampus project to hypothalamus by way of axons called fornix. Hypothalamic effect reach the cortex via a relay in the anterior thalamus. 117 Connection in the limbic system: Papez circuit 118 119 Connection in the limbic system Papez circuit 120 Cingulate cortex site where the “sensations” of emotions are perceived. Hippocampus important in the conversion of short- term memory to long-term memory and retrieval of memories. Amygdala involved in strong emotions, including fear and aggression, and linking emotions with memories. The main circuit of the limbic system. 121  Functions of the limbic system 1. Reward and punishment system: important for motivation, emotion, learning and memory Reward system: major reward center in the lateral and VMN of the hypothalamus less potent reward centers in the amygdala, thalamus & tegmentum Punishment system: major punishment center in the PerVN of hypothalamus - thalamus - periaquidactal gray area less potent punishment centers in the amygdala and the hippocampus. 122  Cont’d 2. Olfaction Limbic system is necessary for odor perception and discrimination. It stores olfactory memories and controls the emotional responses to olfactory stimuli. 3. Motivation: is the feeling, which activate a certain behavior to achieve a certain goal. 4. Emotion: are state of strong feeling associated with autonomic reflex, and endocrinal changes, and a strong affect. Nuclei in amygdala learn to respond to painful stimuli and produce fearful response. Destruction of the amygdala flatten emotions. Stimulation of the medial, forebrain bundle or the septal nuclei produces a sense of joy and happiness. 123 Neural circuit for learned fear 124  Cont’d 5. Control of feeding behavior Amygdaloid nucleus responsible for appetite 6. Control of sexual behavior Sexual behavior in man is largely controlled by orbifrontal cortex the instinctual desires and innate reactions that lead to mating and pregnancy are functions of the limbic system and hypothalamus. 125  Learning Learning is the ability of the brain to use previous experience to modify the inborn reactions or create new ones. The acquisition of new information or knowledge is learning. For the first 20 yrs of life we acquire & learn the skills we need to survive. 126  Types of Learning Two types a. Non associative learning in which the subjects learns to ignore or to respond to stimulus. It occurs through habituation and sensitization. b. Associative learning: the subject learns the correlation between one stimulus and the other. i. Classical conditioning are reflexes in which a nonspecific stimulus is made to produce the same response as the specific stimulus of a certain reflex. ii. Operant conditioning are 'reflexes in which the subject learns to take an action in response to a stimulus to get a reward or avert a punishment. 127  Memory System Memory is the ability of the brain to store information & retrieve it at a later time Information that flow into the brain are classified & important ones (