Ch 15-17: Cerebellum, Basal Ganglia, and Control of Movement- Week 6

Cerebellum (Ch 15)

  • Overview

    • Considered part of the motor system even though motor commands are not initiated in the cerebellum.
    • Why: cerebellar damage leads to impairments in motor control and posture; majority of cerebellum’s outputs go to parts of the motor system.
    • Function: not to initiate motor commands but to modify the motor commands of the descending pathways to make movements more adaptive and accurate.

  • Key inputs to the cerebellum

    • Cerebral cortex via pontine nuclei
    • Vestibular system
    • Spinal cord and proprioceptors
    • Midline connections and other sensory inputs (as depicted in the schematic, with cortex, pontine nuclei, vestibular system, spinal cord, proprioceptors)

  • Major cerebellar outputs

    • Project to motor systems primarily through the deep cerebellar nuclei to the motor thalamus and brainstem pathways, influencing downstream motor commands

  • Anatomy of the cerebellum

    • Lobes and lobular organization
    • Anterior lobe
    • Posterior lobe
    • Vermis and paravermis
    • Lateral hemisphere
    • Flocculonodular lobe (flocculus, nodulus)
    • Functional divisions
    • Vermis (midline), paravermis (intermediate), lateral hemisphere
    • Surface features and nuclei
    • Cerebellar tonsils
    • Fastigial nucleus
    • Interposed nuclei (emboliform and globose)
    • Dentate nucleus (not explicitly shown on all slides but typically included in discussions)
    • Cerebellar peduncles
    • Superior, middle, and inferior peduncles
    • Other terms encountered
    • Flocculus and nodulus as part of the flocculonodular lobe

  • High-fidelity pathways to the cerebellum

    • Posterior spinocerebellar pathway
    • Cuneocerebellar pathway
    • Internal (feedback) tracts:
    • Anterior spinocerebellar
    • Rostrospinocerebellar
    • Information carried: somatotopically organized, high-fidelity sensory information about limb movement and position

  • Functional roles of the cerebellum

    • Coordination of skeletal muscle contraction
    • Comparing actual motor output with intended movement and adjusting as needed
    • Involvement in learning timing and rhythm of movements, synchronization, and correction of motor errors
    • Cerebellum processes massive sensory information to refine movement
    • Clinical note: severe cerebellar damage does not abolish sensory perception or muscle strength; coordination and postural control are degraded

  • Decomposition of movement and motor errors (cerebellar dysfunction)

    • Movements are decomposed into components because of impaired coordination; e.g., finger-to-nose tasks break into shoulder, elbow, then wrist movements
    • Dysmetria: overshoot or undershoot when reaching a target
    • Intention tremor: tremor increases as one nears the target
    • Dysdiadochokinesia: difficulty performing rapidly alternating movements
    • Deficits in motor learning observed in cerebellar damage (humans and animals)

  • Cerebellar clinical disorders

    • Ataxia: a movement disorder common to cerebellar lesions; features include inaccurate, uncoordinated voluntary movements with normal muscle strength
    • Romberg test and related tests differentiate cerebellar vs somatosensory ataxia
    • Distinguishing cerebellar ataxia from somatosensory ataxia

  • Differentiating cerebellar from somatosensory ataxia (Romberg-related)

    • Romberg test measures reliance on proprioceptive information for standing balance
    • Procedure: stand with feet together first eyes open (30 s), then eyes closed (30 s)
    • Pass/fail criteria: arm movements to maintain balance, eyes opening during eyes-closed, starting to fall, or needing assistance
    • Cerebellar ataxia: unable to stand with feet together with or without vision; vibratory sense, proprioception, and ankle reflexes are normal
    • Sensory (somatosensory) ataxia: able to stand with eyes open but balance worsens with eyes closed, due to somatosensory input loss

  • Three related notes

    • Tandem Romberg and other clinical tests help differentiate etiologies (as mentioned in slides)

  • Summary connections to movement control

    • Cerebellum modulates timing, coordination, error correction, and motor learning to optimize movement execution

Basal Ganglia (Ch 16)

  • Core nuclei and location

    • Caudate (head, body, tail)
    • Putamen
    • Globus pallidus (external GPe and internal GPi)
    • Subthalamic nucleus
    • Substantia nigra (pars compacta, SNc)
    • Lentiform nucleus = globus pallidus + putamen
    • Striatum = caudate + putamen
    • Caudate tail located in the temporal lobe

  • Basal ganglia organization

    • Basal ganglia circuits are grouped by function and proximity;
    • Common composite names:
    • Lentiform nucleus = putamen + globus pallidus
    • Striatum = caudate + putamen

  • Basal ganglia circuits (loops)

    • Basal Ganglia Motor Circuit (major loop for movement)
    • Four additional basal ganglia–thalamic loops:
    • Oculomotor
    • Executive
    • Behavioral flexibility and control
    • Limbic

  • Basal ganglia motor circuit: role and characteristics

    • Regulates muscle contraction, muscle force, multi-joint movements, and the sequence of movements
    • Has a profound effect on movement but provides no direct output to lower motor neurons (LMNs)
    • Does not directly control LMNs; modulates the activity that ultimately influences LMN output

  • Disinhibition concept (Fig. 16.4)

    • Illustrates how inhibitory and excitatory interactions can release movement via disinhibition
    • Key idea: intermediate steps can inhibit or release downstream neurons depending on network state

  • Direct vs indirect pathways (functional overview)

    • 3-cortical-basal ganglia-thalamic motor circuit: Direct vs Indirect pathways
    • Direct pathway (GO/ facilitaion):
    • Pathway: Cortex → Striatum (caudate/putamen, D1 expressing MSNs) → GPi/SNr → Thalamus (VL/VA) → Cortex
    • Effect: increases motor activity
    • Schematic: "Direct path" strengthens thalamic drive to motor cortex
    • Indirect pathway (STOP/ suppression):
    • Pathway: Cortex → Striatum (D2 expressing MSNs) → GPe → Subthalamic nucleus → GPi/SNr → Thalamus → Cortex
    • Effect: decreases motor activity
    • The two pathways operate in opposition to shape motor output

  • Dopaminergic and cholinergic modulation in the basal ganglia

    • Dopamine from substantia nigra pars compacta (SNc) modulates the two pathways:
    • Dopamine excites the direct pathway (via D1 receptors)
    • Dopamine inhibits the indirect pathway (via D2 receptors)
    • Overall effect: increases motor activity
    • Expressed relations: extDASNc<br/>earrow<br/>ightarrowextDirectActivity<br/>earrow, extIndirectActivity</li></ul></li></ul><p>earrowextor</p><p>descend?ext{DA}_{SNc} <br /> earrow <br /> ightarrow ext{DirectActivity} <br /> earrow,\ ext{IndirectActivity} </li></ul></li> </ul> <p>earrow ext{ or } </p> <p>descend?
      - Note: in standard depictions, DA increases direct and decreases indirect activity, leading to a net increase in thalamic drive

      • Cholinergic interneurons in the striatum:

        • Acetylcholine inhibits the direct pathway and excites the indirect pathway
        • Overall effect: decreases motor activity
        • Expressed relation: extACh<br/>earrow<br/>ightarrowextDirectActivity</li></ul><p>→↓,</p><p>IndirectActivity↑ext{ACh} <br /> earrow <br /> ightarrow ext{DirectActivity} </li></ul> <p>\to \downarrow,</p> <p>\text{IndirectActivity} \uparrow

          • Neurotransmission basics in the basal ganglia

        • Cortical motor areas provide excitatory glutamatergic input to the striatum

        • Dopamine from SN to the striatum modulates the output nuclei (GPi/SNr)

        • Output nuclei (GPi/SNr) provide inhibitory signals to their target nuclei; this inhibition is relieved or reinforced to shape thalamic drive to cortex

          • Basal ganglia disorders (movement disorders spectrum)

        • Basal ganglia disorders range from hypokinetic to hyperkinetic movements; specific clinical signs depend on which part of the circuit is affected

          • Hypokinetic disorders

        • Excessive inhibition or too little movement

        • Parkinson’s disease (PD)

        • Parkinson-plus syndromes

        • Parkinsonism

          • Hypokinetic disorders in detail

        • Parkinson’s disease (PD): the most common basal ganglia motor disorder

        • Pathophysiology: death of dopamine-producing cells in the substantia nigra

        • Motor impact: interferes with voluntary and automatic movements

        • Classic motor features (TRIMM):

          • Bradykinesia / Akinesia

          • Freezing of gait

          • Postural control problems

          • Masked faces

          • Resting tremor

          • Rigidity

          • Parkinson’s disease treatments and management

        • Medication: Levodopa (a dopamine replacement)

        • Side effects: hallucinations, delusions, dyskinesia; disease progression with involvement of other cells and neurotransmitters; on-off fluctuations

        • Invasive procedures: Deep-brain stimulation, neuronal transplantation, ablative surgery

        • Rehabilitation: Physical therapy and occupational therapy to maintain mobility and functional status

          • Hypokinetic Parkinson-plus syndromes

        • Progressive supranuclear palsy (PSP): early gait instability with backward falls, axial rigidity, freezing of gait, depression/psychosis, supranuclear gaze palsy, dementia

        • Dementia with Lewy bodies: early cognitive decline, visual hallucinations, signs of akinetic/rigid PD

        • Multiple system atrophy: progressive degeneration affecting basal ganglia, cerebellar, autonomic systems; multiple systems involvement

          • Parkinsonism (vs PD)

        • Parkinsonism is a broader term for signs resembling PD but caused by toxins, infections, or trauma; drug-induced parkinsonism is a common pitfall in diagnosis

        • Characteristics: subacute bilateral onset with rapid progression, early postural tremor, and facial/mouth involuntary movements

          • Hyperkinetic disorders

        • Abnormal involuntary movements are characteristic of several conditions

        • Examples: Huntington’s disease, dystonia, Tourette’s disorder, some forms of cerebral palsy

          • Hyperkinetic: Huntington’s disease

        • Signs: chorea and dementia

        • Etiology: autosomal-dominant hereditary disorder

        • Pathology: degeneration in multiple brain areas, prominently the striatum and cerebral cortex

        • A video resource is referenced for a demonstration of symptoms

          • Hyperkinetic: Dystonia

        • Characterized by involuntary sustained muscle contractions causing abnormal postures, twisting, and repetitive movements

        • Often worsens with activity and emotional stress; may disappear during sleep

        • Can be focal or generalized

        • A video resource is referenced for demonstration

          • Basal Ganglia motor output (illustrative concept)

        • Internal globus pallidus (GPi) and downstream pathways influence motor thalamus and brainstem locomotor regions

        • Involvement of acetylcholine, GABA, glutamate, and dopamine in the modulation of movement

        • Motor cortex receives varying levels of thalamic drive depending on direct/indirect pathway activity

        • Effects on LMNs and movement patterns: bradykinesia, rigidity, gait abnormalities, and disturbances in movement sequencing

          • Treatments in summary

        • Medication: dopamine replacement with levodopa; adjuncts to manage side effects and long-term progression

        • Deep brain stimulation, neuronal transplantation, ablative surgeries

        • Rehabilitation: physical and occupational therapy

        Control of Movement (Ch 17)

        • Normal motor control: integrative framework

          • The peripheral region includes alpha motor neurons innervating skeletal muscle fibers and proprioceptive feedback from muscle spindles
          • The spinal region integrates information from other spinal segments, local circuits, and brain inputs
          • Descending tracts provide driving input from the brain (example: lateral corticospinal and reticulospinal tracts; reticulospinal projections are predominantly contralateral in the simplified depiction)
          • Control circuits (cerebellum and basal ganglia) modulate the level of activity in the descending tracts to shape movement

        • Three fundamental types of movement

          • Postural: controlled primarily by brainstem mechanisms
          • Ambulatory (gait): controlled by brainstem and spinal regions
          • Reaching/grasping: controlled primarily by the cerebral cortex
          • Note: all regions of the nervous system contribute to each movement type

        • Postural control

          • Provides orientation and balance
          • Orientation: adjustment of body and head to vertical alignment
          • Balance: maintaining the center of mass relative to the base of support
          • Achieved by central commands to LMNs, with sensory input adjusting the central output to environmental context
          • Inputs that aid postural control include vision, vestibular information, proprioception, and skin touch
          • Higher-level influences include volition and feed-forward control; integration with biomechanics and external constraints
          • The motor command is continuously refined to maintain appropriate posture in context

        • Visual, vestibular, and proprioceptive integration (illustrative)

          • Visual, vestibular, and proprioceptive inputs inform postural adjustments
          • Proprioceptive feedback from muscles and joints complements visual and vestibular cues
          • Proprioceptive and tactile inputs contribute to sensation for postural adjustments

        • Ambulation (gait and locomotion)

          • All regions of the nervous system contribute to normal ambulation
          • Cerebral cortex: goal orientation and control of ankle movements
          • Basal ganglia: govern generation of movement force
          • Cerebellum: contributes timing, coordination, and error correction
          • Sensory information supports adaptation of motor output to environmental constraints

        • Reaching and grasping

          • Requires vision and somatosensation
          • Visual information primarily provides feed-forward control; vision also guides corrections if the movement is inaccurate
          • Grasping is coordinated with the eyes, head, proximal upper limb, and trunk; postural preparation is integral
          • Grip force is adjusted quickly at contact, indicating feed-forward control
          • After grasp, somatosensory information corrects grip force errors

        • Practical implications for exams

          • Understanding how cerebellar timing and coordination contrast with basal ganglia-driven movement initiation and vigor
          • Distinguishing ataxia (cerebellar) from proprioceptive/somatosensory ataxia via Romberg and related tests
          • Recognizing how neurotransmitters (dopamine, acetylcholine) modulate motor circuits to influence movement quality
          • Differentiating direct and indirect basal ganglia pathways and how their balance shapes motor output