CNS 5 MG PDF

The Motor system  Voluntary movements are complex (different from reflexes & rhythmic movements)  Motor system generates & conveys accurately timed commands to many groups of muscles  Communicates our thoughts and abilities.  Extrapyramidal disorders are common in psychiatric patients. S...

The Motor system  Voluntary movements are complex (different from reflexes & rhythmic movements)  Motor system generates & conveys accurately timed commands to many groups of muscles  Communicates our thoughts and abilities.  Extrapyramidal disorders are common in psychiatric patients. Side effects of prescribed medications mimic extrapyramidal disorders  Components and organization (slide 4) 1) Arranged in a hierarchical & parallel manner ! (comprising a number of control systems each level receives information relevant for its function) 2) System constantly receives sensory information – Rich stimuli of environment, body position + extent of muscle contraction.  Motor system uses 2 control mechanisms: A) Negative feedback. Feedback signal subtracted from reference signal. The error of output of 5km/h controller is corrected appropriately. Ideal for movement of moderate rate B) Feed forward. Advance information 80km/h (memory!) provided so that output adjusted (ideal for rapid movement, a prerequisite?) Figure 2 Motor commands from the brain have been modified by a variety of excitatory and inhibitory control systems, including essential feedback from sensory afferent neurons, along with vision and balance cues (not shown). How does the system work?  Motivation for movement appears to be subcortical → limbic areas, hypothalamus & cerebellum (dentate nucleus) and areas of basal ganglia.  Role of cortex: 1) Motor program (sequence of intended movement) drawn up in premotor + supplementary motor areas and relayed to 1° motor cortex (slide 23) 2) Body represented somatotopically in this area so note the motor homunculus. (disproportionate representation) (slide 7)  “Plan” relayed via motor pathways (direct + indirect pathways), decussate before innervating muscles.  Cortex hence in “supreme” control !  All descending pathways have 2 neurons in series:  In upper motor neuron (UMN) (cell body in cortex) Lower motor neuron (LMN) has its cell body in anterior horn of spinal cord  Clinical significance! damage/lesion → ∆ symptoms:  UMN → ↑ spasticity, exaggerated reflexes, +ve Babinski sign (fanning + dorsiflexion of toes)  LMN → flaccid paralysis, loss of reflexes, muscle atrophy + fasciculation Axons from brain descend along two major pathways Lateral Pathways (Direct) Ventromedial Pathways (Brainstem/indirect)  There are two major subcortical areas that play a major role in ensuring purposeful movement is achieved: 1) Cerebellum 2) Basal ganglia  1) The Cerebellum  Located in the posterior cranial fossa. High surface area with large number of neurons. Distribution of white/grey mater.  Peduncles are conduction pathways  Mediolateral organization: (slide 11) 1) Midline – trunk muscles 2) Paravermal zone - proximal limbs 3) Lateral zone → digits  The 4 deep nuclei are dentate, globose, emboliform & fastigial (latter two = interpositus nucleus) largely responsible for output … …..  Vermal: Muscles of the trunk Paravermal: (intermediate hemisphere) Proximal limbs Lateral: Digits.. Organization of the cerebellum The five types of neurons arranged in three layers within the cerebellum viz molecular (ext), Purkinje & Granular (int) The 1° input to cerebellum: 1) Mossy fibres from ……. cortex + proprioceptors (direct) via pontine nucleus NB Weak excitatory input on Purkinje cells (PC) 2) Climbing fibres – + vestibular, proprioception + ocular …... (Brain stem + Thalamus)  NB nature of afferent information relayed to cerebellum, exciting data!  Output of the Purkinje cells (PC) to deep cerebellar nuclei (DCN) is inhibitory  Mossy + Climbing fibres also project to the DCN via collaterals – excitatory  Output of the DCN to brainstem + thalamus is always excitatory! i.e. primary activity is timing of excitatory output  Function  Ipsilateral control of activity  Coordination of complex muscle movement & its refinement. (Interpositus nucleus active after movement commences) Comparator?  Prevents rebound phenomenon  Concerned with learned adjustments of motor tasks (↑ activity of climbing fiber with new activity) due to synaptic plasticity.  Initiation of movement → dentate nucleus discharges prior to movement. Effects of a dysfunctional cerebellum  Lesions result in ataxic movement: Action tremor, abnormal path of movement, dysmetria (hypo or hypermetria),  In mild dysfunction, visual cues essential for smooth & purposeful movement.  Slurred speech & dysarthria.  Hypotonia  Posture – face turns contra- laterally & ipsilateral shoulder lowered.  Often affected by alcohol & thiamine deficiency 2) The Basal Ganglia  Comprises 5 prominent subcortical nuclei: Caudate nucleus, putamen, globus pallidus, subthalamic nucleus & substantia nigra  Extensive interconnection + links to motor areas of brain  Primary input from cerebral cortex, output via thalamus back to cortex (NB ∆ cerebellum!)  Output (GPi/SNr) tonic inhibition on thalamus Direct pathway: facilitates cortical output ie enhances motor activity (disinhibition) Indirect pathway: inhibits cortical output ie suppresses movement GP = Globus pallidus,external (e) & internal (i) segments STN = Subthalamic nucleus SN = Substantia nigra pars compacta (c) & reticulata(r) D1 & D2 = dopamine receptors Pedunculopontine nucleus * Caudate nucleus + putamen = striatum  Direct & Indirect pathways  The loop → cerebral cortex → basal ganglia, thalamus & back to cortex has two components, one direct (facilitating movements) and one indirect (inhibiting movements). Output via GPi & SNr is inhibitory to thalamus  The direct pathway – inherent /spontaneous activity of GPi is ↓ by striatal activity results in disinhibition! – thus facilitating movement  The indirect pathway includes 2 inhibitory synapses → stimulates inhibitory role GPi thus inhibiting movement  The SNc projection to the striatum is dopaminergic and acts on two receptors, influencing the direct (D1 receptor; excitatory.) & indirect (D2 receptor; inhibitory) pathways respectively  A fine control of movements is obtained by a precise balance of the direct and indirect pathways Function:  Neurons in BG discharge prior to & during movement! (initiate movement, switching from one to other)  Selects the appropriate pattern of movement to be used for a task (subconscious) –i.e. cognitive control (selection of motor pattern, inhibition of unwanted movement and facilitation of desired movement, stops movement)  Caudate nucleus projects to cortex (frontal) → lesions result in problems with task reversal + speech defects (no loss of cognitive ability)  Damage?  Motor dysfunction associated with lesions: 1) Hyperkinetic movement. eg chorea & ballism *Hungtington’s (hyperkinetic) 2) Hypokinetic movement. eg bradykinesia *Parkinson’s (hypokinetic)  Parkinson disease (PD) is a hypokinetic disease, reflected by a predominance of the indirect (inhibiting) pathway over the direct (facilitating) pathway, this corresponds to a poor gesture repertoire. In addition, muscle tone is high and there is tremor at rest  Huntington disease (chorea, ballism) is a hyperkinetic disease with a predominance of the direct pathway (loss of GABAergic neurons in striatum) over the indirect one, corresponding to an excess of uncontrolled movements  Therapy for PD → (L-dopa), topic lesions or chronic electrical stimulation to re-establish the balance between the direct and indirect pathways  Parkinson’s Disease  The substantia nigra (SN) of midbrain is located bilaterally.  Neurons in the SN inhibit the activity of basal nuclei by releasing dopamine. Damage to neurons Symptoms of Parkinson’s disease: of SN tremor, slow movement, inability to move, rigid gait, reduced facial expression ↓ in dopamine levels ↑ activity of basal Gradual increase in nuclei muscle tone (indirect pathway) Basal Ganglia Cerebellum SIMPLE FLEXION OF FINGER ACTIVATES M1 AND SS1 A COMPLEX MOVEMENT SEQUENCE ALSO ACTIVATES THE SUPPLEMENTARY MOTOR AREA THINKING ABOUT THE MOVEMENT SEQUENCE (WITHOUT MOVING) ACTIVATES THE SUPPLEMENTARY MOTOR AREA. Learning outcomes:  Highlight significant differences between reflex activity and voluntary movements  List the components of the motor system  Explain the differences between the two control systems used in the motor system  Define motor programs and explain how they eventually translate to movement.  Define and differentiate between the upper and lower motor neurons. The clinical significance of knowing this difference.  Explain the basic organization of the cerebellum and understand the sources of input (differences between information relayed by mossy and climbing fibers)  Explain the role of the cerebellum in voluntary movement  list the components of the basal ganglia and explain their cognitive role in movement.  Explain the basic difference the direct and indirect pathways, how movement is obtained by a fine balance between the activities of these two pathways  Define and explain the basic difference between Parkinson’s and Huntington’s diseases. Thank you ☺