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PY10.1-20 | Central Nervous System Physiology — Part 2

Descending Motor Pathways — Pyramidal and Extrapyramidal Systems, UMN vs LMN (PY10.9, PY10.10)

The motor system is organised hierarchically: the cerebral cortex (highest level) plans and initiates voluntary movement; the basal ganglia and cerebellum modify and refine motor commands; the brainstem sets postural tone; and the spinal cord executes the final motor output through lower motor neurons.

Figure: Descending Motor Pathways — Pyramidal and Extrapyramidal Systems, UMN vs LMN (PY10.9, PY10.10)

The Pyramidal System (Corticospinal and Corticobulbar Tracts) is the pathway for voluntary, skilled, and discrete movements — particularly fine finger movements. The corticospinal tract originates primarily from the primary motor cortex (precentral gyrus, Brodmann area 4, about 30% of fibres), the premotor cortex (area 6, about 30%), and the somatosensory cortex (areas 3,1,2 — about 40%). The fibres descend through the corona radiata, converge in the posterior limb of the internal capsule (a critical bottleneck — a small stroke here causes devastating hemiplegia), descend through the crus cerebri (basis pedunculi) of the midbrain, the basis pontis, and form the pyramids of the medulla (hence "pyramidal tract").

At the junction of the medulla and spinal cord, approximately 85-90% of fibres cross (the pyramidal decussation or motor decussation) to form the lateral corticospinal tract, which descends in the lateral funiculus and controls limb muscles. The remaining 10-15% descend uncrossed as the anterior corticospinal tract in the anterior funiculus; these cross segmentally near their level of termination and control axial (trunk) muscles.

The lateral corticospinal tract terminates on motor neurons and interneurons in the ventral horn (Rexed laminae VII, VIII, IX). The final common pathway is the alpha motor neuron, whose axon exits through the ventral root to innervate skeletal muscle.

The corticobulbar tract follows a similar course but terminates on motor nuclei of cranial nerves (V, VII, IX, X, XI, XII) in the brainstem. Most cranial nerve nuclei receive bilateral corticobulbar input — except the lower face (CN VII) and the tongue (CN XII), which receive predominantly contralateral input. This is why a stroke causes contralateral lower face weakness (the upper face is spared because it gets bilateral input) but does not cause ptosis or loss of jaw movement.

The Extrapyramidal System is a clinical term for all descending motor pathways other than the pyramidal tract. The major extrapyramidal tracts are:

• Rubrospinal tract (from the red nucleus, crosses immediately, travels in the lateral funiculus alongside the corticospinal tract, facilitates flexor motor neurons — important in primates for gross limb movements).
• Reticulospinal tracts — pontine (medial) reticulospinal (facilitates extensors, increases muscle tone, anti-gravity) and medullary (lateral) reticulospinal (inhibits extensors, decreases muscle tone). These regulate postural tone.
• Vestibulospinal tract (from the lateral vestibular nucleus of Deiters, powerfully facilitates extensors — the basis of decerebrate rigidity).
• Tectospinal tract (from the superior colliculus, mediates reflex head turning toward visual or auditory stimuli).

UMN vs LMN Lesions — this distinction is the single most important concept in clinical neurology.

An upper motor neuron (UMN) lesion interrupts the descending pathway anywhere from the cortex to the level just above the anterior horn cell. Signs include: spastic paralysis (increased tone due to loss of inhibitory input from the cortex, leaving the reticulospinal and vestibulospinal tracts unopposed); hyperreflexia (exaggerated deep tendon reflexes because the reflex arc is intact but freed from cortical inhibition); positive Babinski sign (extensor plantar response — the great toe dorsiflexes and the other toes fan out, because the normal cortical suppression of this primitive reflex is lost); clonus (rhythmic, involuntary contractions when a muscle is stretched); no significant muscle atrophy (the muscle is still innervated); and no fasciculations.

A lower motor neuron (LMN) lesion damages the anterior horn cell or its axon. Signs include: flaccid paralysis (decreased or absent tone); areflexia or hyporeflexia (the reflex arc itself is broken); negative Babinski (flexor plantar response or no response); significant muscle atrophy (denervation atrophy, visible within weeks); and fasciculations (spontaneous twitching of motor units due to denervation hypersensitivity).

Spinal cord lesion syndromes (PY10.10):

Complete transection causes loss of ALL motor and sensory function below the level of the lesion. Initially, there is spinal shock — a period of flaccid paralysis, areflexia, and loss of autonomic function below the lesion lasting days to weeks. After spinal shock resolves, UMN signs emerge (spasticity, hyperreflexia, Babinski).

Figure: Spinal cord lesion syndromes (PY10.10):

Brown-Sequard syndrome (hemisection) produces the characteristic triad: ipsilateral UMN paralysis (corticospinal), ipsilateral loss of DCML (proprioception, vibration, fine touch), and contralateral loss of pain and temperature (spinothalamic) beginning 1-2 segments below the lesion.

Central cord syndrome (e.g., syringomyelia) damages the crossing fibres of the spinothalamic tract in the anterior white commissure. This causes bilateral loss of pain and temperature in a "cape-like" distribution (across the shoulders and upper limbs) while preserving fine touch and proprioception (DCML intact) and motor function initially.

Anterior cord syndrome (e.g., anterior spinal artery occlusion) damages everything except the dorsal columns. Result: bilateral motor paralysis and loss of pain/temperature, but preserved proprioception and vibration.

Posterior cord syndrome (rare) damages only the dorsal columns: loss of proprioception and vibration with preserved motor function and pain/temperature.

Cerebellum and Basal Ganglia — Motor Coordination and Movement Disorders (PY10.11, PY10.12, PY10.13)

The cerebellum and basal ganglia are the two great modulators of movement. Neither initiates voluntary movement — that is the cortex's job. Instead, they refine, coordinate, and smooth motor output. Their lesions produce characteristic and very different clinical pictures.

Figure: Cerebellum and Basal Ganglia — Motor Coordination and Movement Disorders (PY10.11, PY10.12, PY10.13)

Cerebellum (PY10.11)

The cerebellum ("little brain") contains more neurons than the rest of the brain combined, yet it constitutes only 10% of brain volume. It has three functional divisions, each with distinct connections and clinical significance:

Figure: Cerebellum (PY10.11)

Vestibulocerebellum (flocculonodular lobe) — receives input from the vestibular nuclei via the inferior cerebellar peduncle. It controls balance and eye movements. Lesion: truncal ataxia (the patient sways and falls when standing, cannot walk in a straight line) and nystagmus. This is the part damaged in medulloblastoma (a childhood posterior fossa tumour).

Spinocerebellum (vermis and paravermal zone) — receives proprioceptive input from the spinal cord (spinocerebellar tracts). The vermis controls axial muscles (trunk, proximal limbs); the paravermal zone controls distal limb muscles. It compares the intended movement (received from the cortex via the corticopontocerebellar pathway) with the actual movement (received from spinocerebellar tracts) and issues corrections in real time. Lesion of the vermis: truncal ataxia and gait abnormalities. Lesion of the paravermal zone: limb ataxia.

Cerebrocerebellum (lateral hemispheres) — the largest part in humans. Receives input from the cerebral cortex via the corticopontocerebellar pathway (cortex to pontine nuclei via the middle cerebellar peduncle to the contralateral cerebellar hemisphere). It is involved in planning of movement, motor learning, and timing. The output goes from the cerebellar deep nuclei (mainly the dentate nucleus) through the superior cerebellar peduncle, crosses in the midbrain, and reaches the VL nucleus of the thalamus, which projects back to the motor cortex. Lesion: intention tremor (tremor that worsens as the hand approaches the target, absent at rest — the opposite of Parkinson's tremor), dysmetria (overshooting or undershooting the target, tested by finger-nose test), dysdiadochokinesia (inability to perform rapid alternating movements), scanning (staccato) speech, and hypotonia.

Critical point: cerebellar lesions produce ipsilateral signs because the cerebellum connects with the ipsilateral side of the body. This is because the output pathway crosses twice (once from the cerebellum to the contralateral thalamus, and once from the cortex to the contralateral spinal cord via the pyramidal decussation) — two crossings = ipsilateral effect. The mnemonic: "the cerebellum is a double-crosser."

Basal Ganglia (PY10.12)

The basal ganglia are a group of subcortical nuclei: caudate nucleus, putamen (together called the striatum — the main input structure), globus pallidus (internal segment GPi and external segment GPe — GPi is the main output), subthalamic nucleus (STN), and substantia nigra (pars compacta SNc — dopaminergic, and pars reticulata SNr — output). The basal ganglia do not receive direct spinal input and do not project directly to spinal motor neurons. They form a loop: Cortex → Striatum → GPi/SNr → Thalamus (VA/VL) → Cortex.

Figure: Basal Ganglia (PY10.12)

Two parallel circuits regulate this loop:

Direct pathway (facilitates movement): Cortex excites the striatum (glutamate). Striatal neurons (GABAergic, containing D1 receptors) inhibit GPi. GPi normally inhibits the thalamus (GABAergic). So inhibiting the inhibitor = disinhibition of the thalamus = increased thalamic excitation of the motor cortex = facilitation of movement. Think of it as releasing the brakes.

Indirect pathway (inhibits movement): Cortex excites the striatum. Striatal neurons (GABAergic, containing D2 receptors) inhibit GPe. GPe normally inhibits STN. So inhibiting GPe = disinhibition of STN. STN excites GPi (glutamate). GPi inhibits the thalamus. Net result: increased inhibition of the thalamus = suppression of movement. Think of it as pressing the brakes.

Dopamine from the SNc modulates the balance: it excites D1 receptors (direct pathway — facilitating movement) and inhibits D2 receptors (indirect pathway — reducing the brake). Net effect of dopamine: facilitation of movement.

Parkinson's disease results from degeneration of dopaminergic neurons in the SNc. Loss of dopamine shifts the balance toward the indirect pathway. The cardinal features are the TRAP mnemonic: Tremor (resting, pill-rolling, 4-6 Hz — disappears during voluntary movement), Rigidity (lead-pipe, or cogwheel if combined with tremor), Akinesia/Bradykinesia (slowness of movement, masked face, micrographia, shuffling gait), and Postural instability (falls). Treatment: L-DOPA (dopamine precursor that crosses the blood-brain barrier, unlike dopamine itself), carbidopa (peripheral DOPA decarboxylase inhibitor that prevents peripheral conversion), dopamine agonists.

Huntington's disease results from degeneration of the striatal neurons (especially those projecting through the indirect pathway). Loss of the indirect pathway = loss of the brake = excessive movement. The hallmark is chorea (involuntary, irregular, flowing dance-like movements). It is autosomal dominant with CAG trinucleotide repeat expansion in the huntingtin gene. Psychiatric symptoms and dementia follow.

Hemiballismus results from a lesion (usually vascular) of the subthalamic nucleus. Loss of STN excitation of GPi = loss of thalamic inhibition = violent, flinging, involuntary movements of the contralateral limbs.

Maintenance of posture and tone (PY10.13): Posture is maintained by the interplay of the vestibulospinal tract (facilitates extensors), reticulospinal tracts (pontine facilitates extensors, medullary inhibits extensors), and the corticospinal tract (facilitates flexors). Decerebrate rigidity (extension of all four limbs) occurs when the brainstem is transected between the superior and inferior colliculi — the vestibulospinal and pontine reticulospinal tracts are intact (extensor facilitation) but the medullary reticulospinal and corticospinal tracts are cut (loss of extensor inhibition). Decorticate rigidity (flexion of upper limbs, extension of lower limbs) occurs with a lesion above the red nucleus — the rubrospinal tract (which facilitates flexors in the upper limb) is intact.

Thalamus — The Gateway to the Cortex (PY10.14)

The thalamus is the relay station for virtually all sensory, motor, and limbic information reaching the cerebral cortex. It is not a passive relay — it actively gates, filters, and modulates information based on the state of arousal and attention. It has been called the "gateway to consciousness" because no sensory information (except olfaction) reaches the cortex without passing through the thalamus.

Figure: Thalamus — The Gateway to the Cortex (PY10.14)

The thalamus is a paired, egg-shaped structure forming the lateral walls of the third ventricle. It contains approximately 50 nuclei, grouped into four major groups based on their position relative to the internal medullary lamina.

Specific relay nuclei have precise, point-to-point connections with defined cortical areas:

• Ventral posterolateral (VPL) nucleus — receives the medial lemniscus (DCML) and spinothalamic tract from the body. Projects to the primary somatosensory cortex (S1, areas 3,1,2). This is the relay for all body sensation.
• Ventral posteromedial (VPM) nucleus — receives the trigeminothalamic tract (sensation from the face, via the trigeminal nerve) and taste fibres. Projects to the face area of S1 and the gustatory cortex.
• Lateral geniculate nucleus (LGN) — receives the optic tract. Projects to the primary visual cortex (V1, area 17) via the optic radiation. This is the relay for vision.
• Medial geniculate nucleus (MGN) — receives the inferior colliculus (auditory pathway). Projects to the primary auditory cortex (areas 41, 42) in the superior temporal gyrus. This is the relay for hearing.
• Ventral lateral (VL) nucleus — receives output from the cerebellum (via the dentate nucleus and superior cerebellar peduncle) and the basal ganglia (GPi/SNr). Projects to the primary motor cortex and premotor cortex. This is the motor relay — it feeds the corrected motor plan back to the cortex.
• Ventral anterior (VA) nucleus — receives output primarily from the basal ganglia. Projects to the premotor and prefrontal cortex. Involved in planning of movement.
• Anterior nucleus — part of the Papez circuit (limbic system). Receives the mammillothalamic tract from the mammillary bodies of the hypothalamus. Projects to the cingulate gyrus. Involved in memory and emotion.
• Lateral dorsal (LD) and lateral posterior (LP) nuclei — association nuclei that connect with the parietal association cortex. Involved in spatial processing.

Non-specific nuclei have diffuse connections with wide areas of the cortex:

• Intralaminar nuclei (centromedian nucleus, parafascicular nucleus) — receive input from the reticular formation, spinothalamic tract, and basal ganglia. Project diffusely to the cortex and the striatum. They play a role in arousal, attention, and pain awareness. These are the nuclei targeted in deep brain stimulation for disorders of consciousness.
• Reticular nucleus — a thin shell of neurons surrounding the thalamus, forming a "gatekeeper" that does NOT project to the cortex. Instead, it sends inhibitory (GABAergic) projections back to the other thalamic nuclei. Cortical fibres passing through it excite reticular neurons, which then inhibit adjacent thalamic relay neurons — a feedback mechanism that sharpens thalamic output and is important in attention and sleep spindle generation.
• Midline nuclei — connect with the limbic system and are involved in memory and emotion.

The pulvinar is the largest thalamic nucleus in humans. It has reciprocal connections with the parietal, temporal, and occipital association cortices. It is involved in visual attention, language, and multimodal sensory integration.

Clinical correlates:

Thalamic syndrome (Dejerine-Roussy syndrome) results from a vascular lesion (usually a stroke in the thalamogeniculate artery, a branch of the posterior cerebral artery) affecting the VPL nucleus. Initially, there is contralateral loss of all sensation. As the lesion partially recovers, the patient develops excruciating, spontaneous, burning pain on the affected side — thalamic pain. This pain is poorly localised, emotionally distressing, and resistant to analgesics. It represents one of the most difficult pain syndromes in clinical medicine. The mechanism involves denervation hypersensitivity of thalamic neurons and loss of normal inhibitory gating.

Figure: Clinical correlates:

Thalamic lesions can also cause: contralateral hemianaesthesia (loss of all sensation), thalamic hand (abnormal posturing), and cognitive deficits if association nuclei are involved. Bilateral thalamic infarcts can cause coma because of the thalamus's role in maintaining cortical arousal.