Motor Systems

  • Organization of Neural Structures Involved in the Control of Movement → Can be divided into four distinct subsystems, each of which makes a unique contribution to motor control

    • Spinal Cord + Brainstem

    • Upper motor neurons

    • Basal Ganglia

    • Cerebellum 

      • Basal Ganglia and Cerebellum have no direct access to local circuits or lower motor neurons, control is indirect; regulating upper motor neurons 

  • Motor Homunculus → Premotor Cortex + Primary Motor Cortex

  • Information Coding by Cortical Neurons 

    • Edward V. Evarts developed the technique to record the motor cortical neurons from awake monkeys performing motor tasks

    • Examined changes in the firing rate of motor cortex neurons as the monkey flexed its wrist under different load conditions 

    • Technique allowed a deeper understanding of how cortical motor areas contribute to specific motor behaviors 

  • Evarts Experiment (1966, 1968)

    • When no load was applied: the neuron fired before and during the flexion movement

    • When a load-opposing flexion was applied: The neuronal activity increased

    • When a load assisting flexion was applied: activity decreased 

    • In all conditions wrist displacement was the same, but neuronal activity changed as load changed 

    • Conclusion: the cells were muscle like; the force, not displacement of the wrist, correlates with neuron firing 

  • Georgopoulos Experiments (1982): How do M1 cells behave during reaching? 

    • A monkey was trained to move a joystick in the direction indicated by alight

    • The activity of a single neuron was recorded during arm movement in each of the eight direction 

    • Black lines indicate the discharge rates of individual primary motor cortex neurons

    • By combining the responses of all the neuron a population vector (red arrows) can be derived 

      • Population vector represents the movement direction encoded by the simultaneous activity of the the entire population of recorded neurons 

  • Neural Tuning in Motor Cortex Correlates to a LARGE number of movement parameters: force + movements

    • Force 

    • Movements in 2D

    • Movements in 3D 

  • Premotor Cortex

    • Lateral premotor area is concerned with movement selection 

    • Lesions impair the ability to perform visually cued conditional tasks, even though they can still respond to the visual stimulus can perform the same movement in a different setting

    • Patients with this damage have difficulty learning to select a particular movement in response to a visual clue, even though they understand the instruction and can perform the movements  

    • Individuals with lesions in the premotor cortex may also have difficulty performing movements in response to verbal commands 

  • Cerebellum 

    • Small brain

    • 10% of the weight, but 50% of the neurons in the entire brain

    • Highly regular structure – circuit modules for distinct function performed by distinct functions performed by connections to different parts of the motor system

    • Function: coordination, balance, motor learning

    • Damage: 

      • Dyssynergia (decomposition of synergistic multi-joint movement) 

      • Dysmetria (inaccuracy in range and direction of movement) 

      • Dysdiadochokinesia (irregular pattern of alternating movement) 

    • Vestibulocerebullum: Maintains equilibrium and stance

      • Input: from vestibular system, output to motoneurons of axial muscles

      • Function: Regulation of movements that maintain posture and equilibrium

      • Damage: loss of equilibrium, wide stance “drunken sailor’s gait” 

    • Spinocerebellum: Fine motor coordination (threading a needle) 

      • Input: from motor context and the spinal cord 

      • Function: compares motor command with movement feedback; sends correction to motor context

      • Damage: Decomposition of movement, inability to correct ongoing movement

        • Over or undershoot of target, timing deficit, slurred speech

    • Lateral Cerebellum: Motor learning, initiation of movement (cerebrocerebellum)

      • Input: From many areas in cerebral cortex 

      • Output: motor context

      • Function: Cognition and timing 

      • Damage: Loss of learned motor skills, delay in initiating movements

    • Basal Ganglia

      • Collection of subcortical nuclei consisting of: 

        • Caudate nucleus and putamen (receive input from cortex) 

        • Globus pallidus (internal/external, output to thalamus) 

        • Subthalamic Nucleus

        • Substantia Nigra 

      • Function: initiating and braking movements

      • Damage: Manifests as movement disorders 

  • Huntington Disease

    • Selective atrophy of the caudate and putamen 

      • Neurons that project to the external segment of the globus pallidus degenerate 

    • In the absence of their normal inhibition, the external globus pallidus becomes abnormally active; reduces the excitatory output of the subthalamic nucleus to the internal segment of the globus pallidus, and inhibitory outflow of the basal ganglia  is reduced 

    • Without the restraining influence of the basal ganglia, upper motor neurons can be activated by inappropriate signals, resulting in undesired ballistic and choreiform movements

    • Cause: An autosomal dominant disorder (IT15) on non-sex chromosome 4 causing an CAG triplet repeat

    • Size of caudate and putamen is dramatically reduced 

    • Symptoms: Chorea, abnormal involuntary writhing movements, behavioral or psychiatric disturbances, dementia, 15-20 years after onset

  • Parksinson’s Disease

    • The dopaminergic inputs provided by substantia nigra pars compacta are diminished 

    • More difficult to generate inhibition form the caudata/putamen, resulting in sustained or increased tonic inhibition from the internal segment of the globus pallidus to the thalamus 

    • Thalamic excitation of the motor cortex less likely 

    • A failure of the disinhibition; reduced movement amplitude, movements are difficult to initiate, and terminate 

    • Abnormal gene on chromosome 4 from either parent 

    • Progressive loss of dopaminergic neurons in substantia nigra pars compacta 

    • Symptoms: 

      • tremors at rest, slowness of movement, minimal facial expressions

      • Akinesia (loss or extreme difficulty voluntary initiating a movement) 

      • Walking, stooped posture

      • Paucity of movements

      • Dementia 

  • The Muscular Junction

    • 1. An AP in a motor neuron is propagated to the terminal 

    • 2. This local AP triggers the opening of voltage gated calcium channels and the subsequent entry of calcium ions into the terminal bouton 

    • 3. Calcium ions triggers release of acetylcholine by exocytosis from a potion of the vesicles

    • 4. Ach diffuses across the space separating the nerve and muscle cells and binds with receptor-channels specific for it on the motor end plate of the muscle cell membrane 

    • 5. This binding brings about the opening of these nonspecific cation channels, leading to a relatively large movement of Na+ into the muscle cell compared to a smaller movement of K+ outward

    • 6. The result is an end-plate potential. Local current flow occurs between the depolarized end plate and the adjacent membrane

    • 7. This local current flow opens voltage dNa+ channels in the adjacent membrane

    • 8. THe resultant Na+ entry reduces the potential to threshold, initiating an action potential, which is propagated throughout the muscle fiber

    • 9. ACh is subsequently destroyed by acetylcholinesterase, an enzyme located on the motor-end plate membrane, terminating the muscle cell’s response 

  • Motor Unit

    • A motor neuron and all muscle fibers it innervates

    • Each muscle fiber receives input from only one motor neuron, but each motor neuron can branch to contact several muscle fibers 

    • Motor unit size varies by function: 

      • Fine control (eye muscles): 1 motor neuron: 3-6 muscle fibers

      • Coarse control (calf muscle): 1 motor neuron: 2-3K muscle fibers

    • Motor neurons into motor pools

      • Each pool provides specific muscles these pools collect in bundles (motor nerves) and exit the spinal cord in the ventral horn/root

  • Size Principle: Motor Units are Recruited in a Fixed Order

    • Motor Neurons are recruited in rank order according to size

    • Smaller motor neurons are recruited before larger ones (at lower firing rates, the neurotransmitter is more effective on the smaller motor neuron

    • As the firing rate of the interneurons increases, the larger motor neurons are recruited 

  • The number of active motor units and their rate of firing both increase with voluntary force

    • As the amount of voluntary force increases, the number and the rate of active motor units increase

    • Lowest threshold motor units which generate the least amount of force are recruited first 

  • Corticospinal Tracts

    • Origin: primary motor cortex (30%), premotor (30%), somatosensory (30%) 

    • About 1 million fingers in humans

    • 90% of fibers cross at lower medulla 

      • Right motor cortical areas control left side of the body, specially the distal muscles

      • 10% do not cross

      • All are excitatory 

      • Small diameter, slow conducting fibers

    • Cortical neurons that project down the spinal cord often synapse at several levels, and in several motor neurons

    • Neurons that project to proximal diverge more broadly than those that project to distal muscles 

  • Motor Pools are organized within the spinal cord

    • Somatotopic organization of motor neuron pools in a cross section of the ventral horn at the cervical level of the spinal cord 

    • Medial-lateral topographical relationship: Motor neurons innervating axial (proximal) musculature are located medially, whereas those innervating the distal musculature are located more laterally 

  • Knee Jerk Reflex (Myostatic Reflex)

    • Monosynaptic component: From the spindle to the alpha motor neuron back to the muscle containing the spindle → excitatory loop

    • Disynaptic component: From the spindle to inhibitory interneurons, to the alpha motor neuron innervating the antagonistic muscle  

    • Due to the tap, sensory neuron is triggered to fire at a higher frequency, which triggers higher firing in the extensor neuron and interneuron 

      • Increase in firing in the interneuron causes a decrease in the firing of the flexor neuron 

    • Proper performance of knee jerk shows that sensory fibers, the input to motor neurons and muscles are all functioning normally 

    • One of the purposes of the reflex is to maintain upright posture in the face of permutations (ex: tripping)

  • The Myotatic/Stretch Reflex in Upper Limb

    • Stretching the muscle and spindle leads to an increase of activity in the afferents and the motor neurons that innervate the same muscle

    • Indirectly inhibit the motor neurons that innervate the antagonist muscle via interneuron 

    • Example of reciprocal innervation – results in rapid contact of the stretch muscle and simultaneous relaxation of the antagonist muscle 

    • The stretch operates as a negative feedback loop to regulate muscle length at a desired value → muscle tone

    • The appropriate muscle length is specified by the activity of descending upper motor neuron pathways that influence the lower motor neuron pool

    • Deviations from the desired length are sensed by the spindles that lead to changes in the activity of motor neurons 

  • The Flexion-crossed Extension Reflex

    • Mediates the removal of a limb or finger from a painful stimuli

    • Consists of: 

      • The withdrawal of the ipsilateral limb by activation of the ipsilateral flexors and reciprocal inhibition of the ipsilateral extension muscles

      • The opposite reaction in the contralateral limb; activation of the extension and reciprocal inhibition of the flexor muscles

      • Last part provides postural support during withdrawal of the affected limb