Motor Systems Neuroscience Lecture Notes PDF

09/02/2024 XY3291 Neuroscience Motor Systems Reflection Week Feb 2024 SGM104 Dr Harry Potter [email protected] 1 Part 1 Part 2 Part 3 Organisation Neural Basal...

09/02/2024 XY3291 Neuroscience Motor Systems Reflection Week Feb 2024 SGM104 Dr Harry Potter [email protected] 1 Part 1 Part 2 Part 3 Organisation Neural Basal of Motor Control of Ganglia Systems Motor Systems 2 1  09/02/2024 Part 1 Organisation of Motor Systems 3 01 Learning Outcomes Understand the major central and peripheral anatomical components of the motor system. Describe the anatomy of the spinal cord and associated outputs including dorsal horns, ventral horns, Rexed laminae, spinal interneurons and the motor unit. Describe the spinal neuronal circuitry involved in motor functions including reflexes. Explain the sensory input signals that are integrated to provide proprioceptive information, including the muscle spindle and Golgi tendon organ. 4 2  09/02/2024 02 Overview Motor system - Muscles and neurons that control muscles - Role: generation of coordinated movements - Parts of motor control (motor programs) 1. Spinal cord → control of coordinated muscle contraction 2. Brain → control of motor programs in spinal cord 5 03 Organisation of structures in motor systems 6 3  09/02/2024 04 Muscles (1) Smooth: digestive tract, arteries, related structures Striated: cardiac (heart) and skeletal (bulk of body muscle mass) 7 04 Muscles (2) Muscles pull, not push. - Flexion – decreases angle of bones that the muscle connects to. - Extension – increases angle of bones that the muscle connects to. 8 4  09/02/2024 04 Muscles (3) – distribution & innervation Axial muscles: trunk movement Proximal (girdle) muscles: shoulder, elbow, pelvis, knee movement Distal muscles: hands, feet, digits (fingers and toes) movement Innervation is coordinated through the spinal cord. - Sensory afferents via dorsal roots. - Motor efferents via ventral roots (“efferent externally”). 9 05 Tracts in the spinal cord (1) 10 5  09/02/2024 05 Tracts in the spinal cord (2) – grey matter Dorsal horn: - Somatic sensory - Visceral sensory Ventral horn: - Visceral motor - Somatic motor 11 05 Tracts in the spinal cord (3) – Rexed laminae Spinal cord is organised whereby information from different places feeds to a specific part of the grey matter. - Motor neurons controlling flexors lie dorsal to extensors. - Motor neurons controlling axial muscles lie medial to those controlling distal muscles. IX – innervating skeletal muscles 12 6  09/02/2024 06 Spinal cord distribution of motor neurons Axons of lower motor neurons bundle together to form ventral roots. Each ventral root joins a dorsal root to form a spinal nerve, exiting through notches between vertebrae. - 30 on each side in humans. - C1-8, T1-12, L1-5, S1-5. Innervation of muscles is not equal across these – nor are muscles across the body – so some roots appear ‘swollen’ to accommodate this. Also contain spinal interneurons which relay and modulate signals. 13 07 The motor unit (1) Lower motor neuron (alpha motor neurons) – cell body in the ventral horn of the spinal cord. Upper motor neurons – those that act upon lower motor neurons. - Descend from CNS down spinal cord and act upon lower (alpha) motor neurons. - Have their cell bodies within the cerebral cortex (e.g. corticospinal tract). - Also basal ganglia, cerebellum, other parts of brainstem and they go down. Why important? Upper motor neuron injury signs are different to lower motor neuron injury signs. 14 7  09/02/2024 07 The motor unit (2) Alpha motor neuron has cell body in ventral root of spinal cord. 1. Axon branches out and terminates on muscle fibres. 2. Releases acetylcholine onto muscle fibres. 3. Muscle fibres contract. The alpha motor neuron and the muscle fibres it innervates are the ‘motor unit’. - This is a single motor unit (see right). When a motor unit is active, that is the smallest amount of contraction you can have. 15 07 The motor unit (3) Motor units can vary in the number of muscle fibres: - Some motor units in extraocular muscles (need very delicate control) have less than 10 muscle fibres - Some larger extensor muscles have more than 1000 muscle fibres that they innervate. When an α neuron is severed, another α neuron will come across and reinnervate those muscle fibres. - Lose precise control but regain activity of muscle fibres. - Implications for rehabilitation? 16 8  09/02/2024 07 The motor unit (4) Contraction of one motor unit by a single action potential (AP) generates a twitch. To produce a smooth contraction, the motor unit must be activated by a train of APs at a frequency high enough to produce a smooth fused contraction. - This is known as a tetanus or tetanic contraction. - Tetanus is not a pathological condition – but how healthy muscles normally work. 17 07 The motor unit (5) We can increase/decrease the force by recruiting more of fewer motor units. Each will fire at its tetanus fusion frequency or not at all (‘all-or-nothing’). Contrasts to sensory fibres where frequency in a single nerve codes intensity of stimulation. - Motor unit: motor neuron and all the muscle fibres it innervates. - Motor neuron pool: all the alpha motor neurons that innervate a single muscle. 18 9  09/02/2024 08 Tetanus fusion frequency Varying firing rate of motor neurons. Recruiting additional synergistic motor units. 1 2 1. Single AP generates single twitch. 2. Series of APs separated long enough generates a series of separate twitches. 3. Shorted separation distance between APs (shorter ‘latency’) = partially fused twitch (still not smooth, almost tremor like – we 3 4 all have a physiological tremor, but slowing down of tremors slows down as part of normal ageing). 4. Fused twitches = tetanus (tetanus fusion frequency). 19 09 Excitation-contraction coupling (1) 1. Alpha motor neurons release ACh 2. ACh produces large EPSP in muscle fibre 3. EPSP evokes muscle action potential 4. Action potential triggers Ca2+ release 5. Fibre contracts 6. Ca2+ reuptake 7. Fibre relaxes 20 10  09/02/2024 09 Excitation-contraction coupling (2) Z lines: division of myofibril into segments by disks Sarcomere: two Z lines and myofibril Thin filaments: series of bristles anchored to Z lines Thick filaments: between and among thin filaments Sliding-filament model - Binding of Ca2+ to troponin causes myosin to bind to actin. - Myosin “heads” pivot, cause filaments to slide. - Repetition of process “walks” myosin heads along filament. 21 09 Excitation-contraction coupling (3) Sliding filament model of muscle contraction. 22 11  09/02/2024 09 Excitation-contraction coupling (4) Ca2+ binding to troponin allows myosin heads to bind to actin— myosin heads then pivot, causing filaments to slide. - Starving muscles of ATP prevents detachment of myosin heads. - Leaves myosin attachment sites on actin filaments exposed for binding - Forms permanent attachments between thick and thin filaments. - Leads to rigor mortis following death. 23 10 Inputs to alpha motor neurons Lower (alpha) motor neurons have three main types of synaptic input: 1. Descending tracts in the brain spinal cord from upper motor neurons. 2. Interneurons within spinal cord (cells with their processes inside CNS). 3. Local sensory nerve fibre input via reflexes (e.g. patella jerk reflex). 24 12  09/02/2024 11 The pyramidal system (corticospinal tract) Primary motor cortex has a specific pathway to cause voluntary movement – corticospinal tract: - Moves through brainstem at the front through specialised structures – pyramids. - This is therefore the pyramidal tract. 25 2 minute break 26 13  09/02/2024 12 What is a reflex? An involuntary motor action triggered by a sensory input. Classic examples are tendon jerk reflexes elicited by tapping the patella or Achilles tendon. - Myotactic reflexes. Information descending through e.g. corticospinal tract synapses in a region close to grey matter, which then activates interneurons within spinal cord. - These act upon lower motor neurons. - A few places at the top of the spinal cord where we have a direct connection (without interneurons). - Excitatory or inhibitory. - Therefore, we can modify the activity that goes through this route. - We can modify interneuron activity pharmacologically. 27 13 Rhythmic activity in spinal interneurons (1) 28 14  09/02/2024 13 Rhythmic activity in spinal interneurons (2) Possible circuit for rhythmically alternating activity: 29 14 Spinal interneurons Most input to alpha motor neurons mediated by spinal interneurons Polysynaptic - synaptic inputs to spinal interneurons: Primary sensory axons Descending axons from brain Collaterals of lower motor neuron axons Other interneurons Most of the input to the alpha motor neurons comes from interneurons of the spinal cord. 30 15  09/02/2024 15 Stretch reflexes Stretch reflex: muscle pulled → tendency to pull back. Feedback loop. Discharge rate of sensory axons: related to muscle length. Monosynaptic. Example: knee-jerk reflex. 31 16 Knee-jerk (patella) reflex (1) When you tap the patella tendon, there is a lengthening of the muscle spindle within the quadriceps. Muscle spindle is a muscle length detector. - Around its belly is a 1a afferent sensory neuron. - Conveys lengthening information through the spinal cord. Cell body in dorsal root ganglion. 32 16  09/02/2024 16 Knee-jerk (patella) reflex (2) Synapses at ventral root upon an alpha motor neuron. Contracts the same quadriceps muscle that is activated. - On the same side (homonymous). No interneurons within this circuit – monosynaptic (same as ankle, biceps, triceps, and supinator reflexes). Speed – fastest sensory neuron (1a afferent), fastest motor (α motor), one synapse. - Fast to maintain bipedal posture and balance. - We continually elicit spinal reflexes to adjust muscle tone. 33 16 Knee-jerk (patella) reflex (3) While one branch directly activates the α motor neuron, we also activate an interneuron (green). - An inhibitory interneuron. - Acts on a second set of α motor neurons which activate the antagonist flexor muscle (hamstring). - When the extensor contracts, the flexor relaxes. - Reciprocal inhibition. 34 17  09/02/2024 17 Reciprocal inhibition Reciprocal inhibition: contraction of one muscle set accompanied by relaxation of antagonist muscle - Example: stretch reflex. 35 18 Muscle spindle (1) Sensory feedback from muscle spindles—stretch receptor Muscle spindle is encapsulated by connective tissue. - Encapsulated receptor. - Smaller muscle fibres in the middle (intrafusal muscle fibres). - Normal skeletal muscle surrounds. Wrapped around each intrafusal fibre is a branch of the 1a afferent sensory fibre. - Around the belly of the muscle spindle (jelly-like, contains nuclei). When the intrafusal fibres are lengthened, a command goes up sensory nerve endings to the sensory nerve fibre. 36 18  09/02/2024 18 Muscle spindle (2) Muscle lengthened – message going down 1a afferent increases (increased frequency of APs). - Conveys proprioception – the position of our muscles (and therefore limbs). - Muscle spindle information goes to brain for conscious perception of limbs/body. Tapping patellar tendon induces a burst of APs in several muscle spindles: - Produces a volley (several) of APs acting on dendrites of motor neurons in the quads. - Both spatial and temporal summation on motor neurons. - Each motor neuron fires a single AP to produce a twitch. 37 18 Muscle spindle (3) – spatial summation One motor neuron dendrite may have 10s or 100s of synaptic contacts from muscle spindle 1a afferent nerve fibres. Activity at a single synapse will not activate a motor neuron. - Need at least 2 synapses active simultaneously to make a motor neuron fire. Spatial summation. 38 19  09/02/2024 18 Muscle spindle (4) – gamma motor neurons Muscle spindle contains modified skeletal muscle fibres within a fibrous capsule (intrafusal fibres). Extrafusal fibres form bulk of the muscle. - Only extrafusal fibres are innervated by alpha motor neurons. Gamma motor neurons: - Another type of lower motor neuron. - Provide motor innervation for intrafusal fibres. 39 18 Muscle spindle (5) Gamma motor neuron is the only known example of an efferent motor response on a sensory receptor. Causes contraction of the muscle spindle. When muscles stretch, the spindle lengthens, but there’s nothing stopping the spindle changing back to its normal shape. - Gamma motor neuron activity makes the spindle contract in line with the muscle activity. - Keeps muscle spindle sensitive, which causes reflex actions. - Overactivation of gamma motor neurons leads to hyperreflexia. 40 20  09/02/2024 18 Muscle spindle (6) – α/γ co-activation During voluntary movement of a muscle the brain (via the corticospinal tract) activates both α and γ motor neurons. Co-activation serves to keep the muscle spindle feedback at the right level during movement. When the muscle reaches the desired length, the γ motor neuron output adjusts to a level appropriate for this new length. 41 19 Stretch reflex circuitry (1) 42 21  09/02/2024 19 Stretch reflex circuitry (2) 43 20 Why do we have reflexes? Muscle spindles do not exist just to provide a muscle twitch during a tendon tap. Provide continuous feedback to motor neurons. Continually adjust motor neuron output during normal movement. Required because muscles fatigue. - Despite a ‘steady drive’ from the brain via descending motor pathways, the amount of contraction per muscle action potential decreases, the longer the muscle is contracting. - Without feedback from muscle spindles, if you tried to keep your arm or leg in a steady position, it would droop/collapse. Monosynaptic reflex is used by the brain as a form of negative feedback to maintain constant muscle length despite ongoing muscle fatigue. 44 22  09/02/2024 21 Golgi tendon organ (1) Tendons have meshwork of collagen. 1b sensory neuron goes into muscle tendons and has endings that wrap around collagen fibres. Golgi tendon organ (GTO) is a receptor acting as additional proprioceptive input—acts like strain gauge— monitors muscle tension. - Activated by muscle tension or the force of contraction (not length). - Located at the junction of the muscle and tendon. - Innervated by 1b sensory neurons (slightly smaller than 1a axons innervating muscle spindles. 45 21 Golgi tendon organ (2) When the GTO is lengthened, info goes into spinal cord which activates inhibitory interneurons in spinal cord. These acts upon alpha motor neuron of the same muscle group to suppress its activity. - Di-synaptic (interneuron) connection (glycinergic). - Reflexively relaxes muscle. If a muscle contracts so strongly that it increases tension in the tendon to a level where it might damage the muscle or joint tissue, the GTO ‘switches it off’ by powerful inhibitory action. - E.g. people with a stroke often have contracted limbs. 46 23  09/02/2024 21 Golgi tendon organ (3) Muscle spindles are in parallel with fibres. Golgi tendon organs in series with fibres. Determines type of information: 1a activity from spindle – muscle length. 1b from GTO – muscle tension. 47 21 Golgi tendon organ (4) Function: regulate muscle tension within optimal range. 48 24  09/02/2024 22 Proprioception from joints Along with muscle spindles and GTO, there are other proprioceptive (mechanosensitive) axons in joint tissues. Respond to changes in angle, direction, and velocity of movement in a joint Information from joint receptors, muscle spindles GTO, and skin receptors combine to estimate joint angle (and therefore position of limbs). Most receptors are rapidly adapting, bringing information about a moving joint – fewer neurons encode resting position. 49 Part 2 Neural Control of Motor Systems 50 25  09/02/2024 23 Learning Outcomes Describe the regions of the cortex involved in motor control. Describe the functional characteristics of the major motor tracts (pyramidal, reticulospinal, vestibulospinal) and their origins. Describe the pathophysiological mechanisms of spasticity, hyperreflexia, and decorticate and decerebrate postures. Describe the acute and chronic deficits arising from lesioning of individual motor tracts and the motor cortex. Compare lesions of the motor cortex with those of the lower motor neuron. 51 24 Which regions of the cortex are involved in motor control? (1) All of the frontal lobe, to a greater or lesser extent. Not just the primary motor cortex. In general, the more anatomically anterior the cortical region, the more complex or abstract its role in movement is. Damage is often a result of stroke affecting blood supply to the primary motor cortex (Brodmann’s area 4). - In front (anterior) of central sulcus. - Deficit equates to the amount of cortex that is damaged. - E.g. a small deficit that only affects one part of the motor homunculus. - E.g. down the side, involved with the facial region; at the top, the legs. - Damage to the more anterior portions gives more abstract deficits in movements. - Frontal parts are more well-developed (i.e. in humans), compared to the more primitive motor cortex. 52 26  09/02/2024 24 Which regions of the cortex are involved in motor control? (2) 53 25 Strokes Generally, the most common damage to the motor cortex is by a stroke. Strokes affect blood supply in some way. Our brains have 3 main cerebral arteries (anterior, middle, posterior). Strokes never just affect one anatomical area (e.g. the primary motor cortex), they always involve multiple cortical areas. - Anterior cerebral artery just feeds the leg area (an exception). Strokes involving occlusion of the MCA affect almost all of one side of the frontal lobe. - Produces severe motor disability in all parts of the contralateral body… - …except lower limb (anterior cerebral artery). 54 27  09/02/2024 26 Middle cerebral artery (MCA) Coronal slice shown with MCA location. - Goes between cerebellum and cerebrum. - Collateral offshoots (lenticulostriate arteries) feed basal ganglia. - Also feeds internal capsule (vital for movement, corticospinal tract fibres come down through this region) from primary motor cortex). - Stroke at blue circle blocks blood to basal ganglia, internal capsule, and primary motor cortex (except leg region). 55 27 Premotor cortex and supplementary motor cortex Anterior to primary motor cortex are premotor cortex (Brodmann's area 6) and supplementary motor cortex (Brodmann's area 8). - Very similar areas often grouped together. Motor association areas. Do not produce discreet movements. Involved in planning or conceiving complex movements. Damage to areas 6 and 8 leads to apraxia. - Normal reflexes, no muscle weakness, but have difficulty performing complex motor tasks. - Challenge in putting correct sequence of movements in the right order. - E.g. can’t play piano well (stiff, rigid). Lesions may also impair motor responses to visual and motor cues. Damage to one side (e.g. stroke) may only produce minimal symptoms as the contralateral area may compensate. 56 28  09/02/2024 28 Frontal eye fields and Broca’s area Two specialised cortical areas adjacent to the premotor areas. Dedicated to the motor control of two motor systems: - Broca’s area muscles regulating speech. Localised to left hemisphere (in most people, can develop in the right hemisphere following perinatal issues). - Frontal eye fields: extraocular eye fields. Broca’s area is in the left hemisphere in the posterior region of the frontal lobe. - Proximal to the face region of the motor homunculus. - Signals going between to allow us to articulate words. - Deficits to this region lead to expressive aphasia. Frontal eye fields (FEF) are for motion in the eyes, sending commands down to oculomotor nuclei. - Deficits lead to slow eye movements. - Inability to track a moving target. - Have to turn their heads to compensate. - Bilateral lesions of FEF leads to oculomotor apraxia (OMA). - E.g. deficits in fast eye movements (saccades), which can be assessed by asking a patient to track their finger. 57 29 Dorsolateral prefrontal cortex (DL-PFC) DL-PFC (Brodmann’s areas 9/10) has the most complex relationship with movement. Planning of movement – evaluation of possible future actions and decide which is best. Problem solving and judgement (executive function). Patients with DLPFC lesions tend to have: Apathy, personality changes, lack of ability to plan/sequence actions or tasks. Poor working memory for verbal information (left hemisphere lesions). Poor working memory for spatial information (right hemisphere lesions). MRI studies have shown that the frontal cortex may be easily damaged by impact with the frontal bone (e.g. in road traffic accidents) causing contusions (bruising). 58 29  09/02/2024 30 Orbitofrontal cortex Control (inhibition) of motor responses associated with the limbic system (‘emotions’). - Hunger, thirst, sexual drive. Disinhibition (e.g. after orbital damage) leads to ‘pseudopsychiatric’ behaviour. - Impulsiveness, puerility, a jocular attitude, sexual disinhibition, and a complete lack of concern for others. Phineas Gage (1823–1860) Railway worker who had a metal rod impale his frontal cortex, damaging the orbitofrontal cortex (and others). Survived. Behaviour changed – started to speak very crudely, angrily, affected decision making, would urinate in front of people. 59 31 Motor thalamus We need a set of instructions integrating multiple layers of information about our bodies. Sensory & association cortex – sensory receptors providing information about posture and sensory perception. Basal ganglia – speeding up and slowing down movements (impaired in PD). Cerebellum – coordination of movements. Ventro-lateral thalamic nuclei (motor thalamus) – important route for motor commands from the basal ganglia and cerebellum to feed into corticospinal tract. - Stroke damage to the motor thalamus causes severe paralysis. - Bidirectional communication with the primary motor cortex. - Feeds in sensory information, information about smoothness and timing of movement. 60 30  09/02/2024 32 Corticobulbar tract Runs from the cortex (‘cortico…’) through the internal capsule on its way to the brainstem (‘…bulbar). - Vulnerable to damage by stroke in this area. Terminates at nuclei of cranial nerves involved in facial actions. - Fibres cross to relevant nuclei on the other side to produce the wanted movements. - Motor actions to the eyes: CN-III (oculomotor); CN-IV (trochlear); CN- VI (abducens). - Movements of facial expression: CN-VII (facial); - Mastication: CN-V (trigeminal). Also terminates on other cells involved in movement (pontine nuclei, reticular formation, red nucleus). 61 33 Corticospinal tract (1) Innervates the rest of the body (neck, thorax, arms, pelvis, legs, feet). Through brainstem at the front (relevant for arteries feeding this region). Through front of medulla in regions which look like pyramids. - Pyramidal tract. Crossing fibres in motor decussation at C1-C5 (at top of medulla). - Vast majority cross earlier on in medulla (lateral corticospinal tract). - Except for a few which continue down and cross over later (anterior corticospinal tract). 62 31  09/02/2024 33 Corticospinal tract (2) Anterior corticospinal tract: - Stops at the neck. - Only innervates the neck (neck movements). Because of decussation: - If brain injury is above the spinal cord, the motor deficit is on the contralateral side. - If spinal cord is injured, the motor deficit is on the ipsilateral side. 63 33 Corticospinal tract (3) 64 32  09/02/2024 33 Corticospinal tract (4) Follows the spinal cord down and into Rexed laminae (ventral horn). - Alpha motor neurons have cell bodies in different regions. Those with cell bodies medially activate neck region (proximal to anterior corticospinal track). Lateral corticospinal tract is in the dorsal quadrant, near alpha motor neurons supplying distal muscles. - Spinal interneurons are involved in relaying signal. - The corticospinal tract therefore drives interneurons which modulate spatial reflexes. - E.g. inhibition of flexion (pain) reflexes. 65 2 minute break 66 33  09/02/2024 34 Extrapyramidal pathways (1) Damage to the corticospinal tract in the spinal cord causes loss of control of hands and fingers, but not normally loss of posture, locomotion, or gait. - Therefore, there must be other motor systems that mediate motor function of posture, locomotion, and gait. - Extrapyramidal fibres. - Originate from groups of cell bodies in the brainstem. Lateral vestibulospinal. - Maintenance of balance. Reticulospinal tracts. - Lateral (autonomic innervation e.g. heart rate). - Descent down spinal cord to maintain muscle tone. - Assist balancing during standing and moving. 67 34 Extrapyramidal pathways (2) – cerebellum Coordinates complex somatic motor patterns. Receives direct input from muscles and compares it with intended signal for movement from the motor cortex. Does not initiate movement. Helps motor cortex produce accurate and smooth movements by modulating and refining motor cortex commands. Uses feedback from proprioceptors and other sensory organs. Cerebellar lesions lead to e.g.: - Deficits in smooth eye movements (extraocular eye movements). - Clumsiness. - Abnormal fatigue. - Instability of movement and ataxia. 68 34  09/02/2024 34 Extrapyramidal pathways (3) – cerebellum 69 34 Extrapyramidal pathways (4) – cerebellum Proprioceptive (muscle spindle, GTO) information enters spinal cord and synapses with areas V/VI of the Rexed lamina. Pathway extends laterally to the dorsal spinocerebellar tract. - Ascends ipsilaterally to cerebellum. - Allows cerebellum to know the state of the muscles. - Processed unconsciously. 70 35  09/02/2024 34 Extrapyramidal pathways (5) Lateral vestibulospinal tract (2c) Origin: vestibular nuclei in upper medulla/lower pons. Nucleus projects ipsilaterally to antigravity muscles (e.g. jaw muscles). Tonically active during upright posture. Controls posture and balance. Maintains body when our head moves (e.g. spinning). Reticulospinal tract (2b) Rubrospinal tract (2a) Arises in reticular formation of pons and Origin: red nucleus (brainstem). medulla. Projects diffusely (bilaterally) down spinal Red nucleus receives main input from the cord. cerebellum. Autonomic control (drives sympathetic Carries cerebellar commands to spinal afferents e.g. bladder function), respiration cord. (phrenic nerve). General ‘arousal’ of spinal cord. Alters muscle velocity. 71 35 Decerebrate and decorticate postures Severely damaging the brain can lead to coma. Leads to spontaneous postures as a result of increased activity of the extrapyramidal network. Decorticate posture: - Severe damage to the corticospinal tract. - Arms are flexed (abnormal flexion) or bent inwards towards the centre of the body. Decerebrate posture: - Severe damage to the midbrain/pons. - Overactivation (increased tonic activity) of the vestibulospinal tract. - Vestibulospinal tract is normally under tonic inhibition by corticobulbospinal tract and red nucleus. For both, in general the patient will be either nonresponsive or responding to pain by posturing. 72 36  09/02/2024 36 Spinal injury 73 37 Upper vs lower motor neuron lesions (1) Hyperreflexia – without periodic stimulation of the Muscle weakness lower motor neurons, gamma motor drive increases Positive Babinski’s sign* – big toe dorsiflexion and the Atrophy of skeletal muscle other toes fan out (abduct) and dorsiflex Fasciculations – small localised involuntary muscle Clonus – rhythmic contraction of antagonist muscles contractions and relaxations under the skin Spasticity – increased muscle tone and exaggerated Hypertonia – loss of tone in resting position tendon reflexes Hypertonia – increased muscle tone in resting position. 74 37  09/02/2024 37 Upper vs lower motor neuron lesions (2) 75 38 Mirror neurons (1) A distinct class of neurons found in several areas: - Premotor cortex, the supplementary motor area, the primary somatosensory cortex, and the inferior parietal cortex. First identified in monkeys, then humans. Neurons that fire both when you execute a motor plan and observe someone else executing the same plan. 76 38  09/02/2024 38 Mirror neurons (2) Thought to develop in humans at 12 months. May help us understand other people's actions (‘intention understanding’). Thought to be impaired in many conditions including autism spectrum disorder. 77 Part 3 Basal Ganglia 78 39  09/02/2024 39 Learning Outcomes Understand the main functions of the basal ganglia. Describe the brain regions involved in basal ganglia circuitry. Explain the three main neuronal pathways involved in the coordination and execution of motor plans by the basal ganglia. Explain how dopamine and dopamine receptors modulate the basal ganglia circuitry. 79 40 Basal ganglia – summary video 80 40  09/02/2024 41 Motor functions (1) Cerebral cortex: - Organise & integrate motor & sensory signals. Basal ganglia: - Feedback mechanism for cerebral cortex. - Initiation & control of motor responses. - Output via thalamus. Thalamus: - ‘Dampens’ excitatory input to cerebral cortex. Figure from Essential Neuroscience, 2nd Ed. 81 41 Motor functions (2) Pathophysiology aids understanding of basal ganglia physiology: Cerebral cortex Excessive output Lesions: + + + from basal ganglia: - Reduced output. - Involuntary - Slowing of Basal - Thalamus movements ganglia movements (dyskinesia) 82 41  09/02/2024 42 Gross anatomy (1) Human* basal ganglia anatomy. Mouse basal ganglia anatomy. *Focus on human 83 42 Gross anatomy (2) Primary components & associated nuclei. - Functional relationships. Primary components Caudate putamen Globus pallidus - External (GPe) - Internal (GPi) + thalamus (specific nuclei) Associated nuclei Substantia nigra - Compacta (SNc) - Reticulata (SNr) Subthalamic nucleus (STN) 84 42  09/02/2024 42 Gross anatomy (3) – the striatum Terminology for the striatum is often confused. - Latin – ‘striped’ - Input to basal ganglia. Striatum Dorsal Ventral Lentiform nucleus Nucleus accumbens Caudate (reward, Globus addiction) Putamen pallidus Separated by internal capsule (white matter tract) 85 42 Gross anatomy (4) – the striatum 86 43  09/02/2024 43 Caudate nucleus C-shaped nucleus in dorsal striatum. Follows lateral ventricle for entire length. Head: - Largest part. - Rostral to thalamus. Body: - Caudal to head. Tail: - Narrowest part. - Follows ventricle and then rostral towards amygdala. 87 43 Putamen Large structure between globus pallidus and external capsule. Extends from level of head of caudate nucleus (anterior), to posterior 3rd of thalamus. Fused with caudate (no internal capsule at that level). 88 44  09/02/2024 44 Globus pallidus Immediately lateral to internal capsule; medial to putamen. - External (GPe). - Internal (GPi). Primary region for outflow of information from basal ganglia. Outputs arise from medial pallidal segment to thalamus. 89 45 Afferent sources Largest source – cerebral cortex. - Primary motor, secondary motor, primary somatosensory – directed to putamen. - Parietal association, frontal eye fields, limbic regions – directed to caudate. Putamen Caudate Motor functions. Varied and integrated cortical Somatotopically inputs. organised. Cognitive aspects of movement. 90 45  09/02/2024 46 Motor function Motor cortical regions project to upper motor neurons, synapsing with lower motor neurons. - Innervates skeletal muscles (voluntary movement). - Corticospinal tract. Cortical areas communicate motor plan with basal ganglia. - Signals are modified. - Sent back to cortical areas to: a) Initiate movement, b) stop movement, & c) modulate movement. 91 2 minute break 92 46  09/02/2024 47 Basal ganglia pathways Functions to a) initiate movement, b) stop movement, & c) modulate movement. Three pathways: a) Direct (initiation of movement). b) Indirect (inhibition of movement). c) Nigrostriatal (modulation of direct and indirect pathways). 93 48 Direct pathway Goal: initiate movement. Increased motor activity Nuclei: Ventral lateral (VL) Ventral anterior (VA) Disinhibition of thalamic nuclei Glutamate GABA 94 47  09/02/2024 49 Indirect pathway Goal: inhibit unwanted motor movement. Reduced activation of cortex Decreased motor activity Nuclei: Ventral lateral (VL) Ventral anterior (VA) Glutamate Disinhibition of GABA subthalamic nucleus 95 50 Direct vs indirect pathways 96 48  09/02/2024 51 Nigrostriatal pathway Goal: modulation of direct/indirect pathways. Dopaminergic neurons 97 52 Dopamine receptors Influx of + ions GPCR Increasing Dopamine D1R: intracellular voltage - Stimulatory. - Increases wanted motor activity. Raise resting membrane potential - Direct pathway. to threshold potential Dopamine D2R: Activation of - Inhibitory. voltage-gated ion channels - Increases unwanted motor activity. - Indirect pathway Initiation of action potential 98 49  09/02/2024 53 Clinical link? (1) Dopaminergic neurons 99 53 Clinical link? (2) 100 50