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Outline

 Anatomy Subcortical Motor  Cerebellar cortex  Neuronal circuitry Systems:  Cerebellar connections  陽明大學醫學院 腦科所 Vestibulocerebellum  Spinocerebellum 陳昌明 副教授  Neocerebellum  Other cerebellar functions

Motor Loops Pyramidal Tract and Associated Circuits  Cortex ---> Subcortex ---> Cortex ---> Spinal cord upper motor neuron UMN  Cerebellum  coordination of movement Cerebellum BASAL  Basal Ganglia GANGLIA  pyramidal tract selection & initiation of voluntary movements ~ lower motor neuron UMN

Cerebellar functions Cerebellum: Anatomy

 The main functions:  Coordinating skilled voluntary movements by influencing muscle activity,  Controlling equilibrium and muscle tone through connections with the vestibular system and the spinal cord and its gamma motor neurons. 1. Found in the posterior Cranial fossa 2. Forms a roof over the 4th ventricle 3. Lies above and behind the medullar and pons

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Cerebellum: Anatomy Cerebellum: External features

 Folia & lobules  Longitudinal division  analogous to gyrus  Vermis, Paravermal  Vermis - along midline Region,  output ---> ventromedial  pathway Transverse division  Hemispheres  Anterior Lobe  Posterior Lobe  output ---> lateral pathway   Flocculonodular Lobe  fastigial, interposed, & dentate  Major output structures ~

Functional divisions of cerebellar cortex

Lobes Superior surface External Features

 Two deep fissures

 Primary fissure

 Posterosuperior fissure  Three lobs  絨球小結葉 and nodule

 Anterior lobe Corpus of cerebellar  Posterior lobe  Tonsil of cerebellum 小腦扁桃体  On inferior surface of hemispheral portion just nearby foramen magnum  IICP tonsilar herniation View from below

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Lobes & Lobules Subdivision of lobes

Subdivision of lobes Three peduncles

 Inferior 下小腦脚 － connect with medulla and with spinal cord, contain both afferent and efferent fibers  Middle cerebellar peduncle 中小腦脚－ connect with pons, contain afferent fibers  Superior cerebellar peduncle 上小腦脚－ connect with midbrain, contain mostly efferent fibers

Deep Cerebellar Nuclei Blood supply

Deep Cerebellar Nuclei: Dentate

Interposed Fastigial

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Internal structures Internal structures

Gray matter Cerebellar cortex  Cerebellar cortex  Cerebellar nuclei Emboliform nucleus  Dentate nucleus 齒狀核  Fastigial nucleus 頂核  中間核 Emboliform nucleus 栓狀核 medullary center Globose nucleus 球狀核 －medullary center 髓体

髓体 Medullary center Cerebellum: 3 layered cortex

 Molecular layer  parallel fibers • axons of granule cells • runs parallel to long axis of folium  of Purkinje cells  Purkinge cell layer  Large somas  Send axons to underlying white matter  perpendicular to main axis of folium ~

Cerebellum: 3 layered cortex  Granular layer  innermost layer  small, densely packed granule cells  > # neurons in ~

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Cerebellar Cortex Cerebellum: 3 layered cortex 3 layers, 2 kinds of input fibers, 5 types of neurons

Inputs Molecular • Climbing fibers •only from Inferior olive • Mossy fibers Purkinje Output • Purkinje neurons

Interneurons • Granule neurons Molecular Granule • Purkinje Stellate neurons Granular • Basket neurons • Golgi neurons Climbing fibers Mossy fibers

Inhibitory Intrinsic pathways & cells  The is found among the granule cells.  The stellate and basket cells live in the molecular layer.  The drops axon branches down into the layer where the branches wrap around the cell bodies like baskets.

Cerebellum: Internal configurations Cerebellum: Internal configurations

Cerebellar Cortex : I. Molecular Layer  Cerebellar Cortex : II. Purkinje Cell Layer  Purkinje Cell • Two types of interneurons  • Stellate Cell --- taurine (inhibitory) 15,000,000 in number afferent: parallel fiber  GABA (inhibitory)

efferent: Purkinje cell  • Afferent from: Basket Cell ---- GABA (inhibitory) parallel fiber afferent: parallel fiber efferent: Purkinje cell soma stellate cell • Two types of fibers basket cell • Parallel Fiber  Efferent to: deep cortical nuclei axon  Bergman’s glial cell • Purkinje Cell Dendrite

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Cerebellum: Internal configurations Cerebellum: Internal configurations

 Synaptic Glomerulus : Afferent  Cerebellar Cortex : III. Granular Layer terminals on granular layer  Granule Cell  Rosette  50,000,000,000 in number • Afferent fibers except inferior olivary  glutamic acid (excitatory) input  afferent: mossy fiber • 2/3 of medullary center

 efferent: Purkinje cell dendrite, basket cell,  Granule Cell Dendrite stellate cell, Golgi cell • main afferent input  Golgi Cell  Golgi Cell Axon  GABA (inhibitory) • synapse on granule cell dendrite  afferent: parallel fiber, mossy fiber rosette • GABA (inhibitory)  efferent: granule cell dendrite • Surrounded by

Mossy fibers Mossy fibers

 Originate in the pontine nuclei, the spinal  A mossy fiber has an axon cord, the brainstem reticular formation, terminal that ends in a large, and the vestibular nuclei bulbous swelling.   Enter the granule cell layer and Make excitatory projections onto the synapse on the dendrites of cerebellar nuclei and onto granule cells in granule cells the cerebellar cortex.  The granule cells reach out with little  Each mossy fiber innervates hundreds of "claws" to grasp the terminals.  granule cells The granule cells then send their axons up to the molecular layer, where they end in a T and run parallel to the surface, thus called parallel fibers.

The climbing fiber Role of climbing fibers

 Originate exclusively in the inferior  Intimate connections between the neurons olive and make excitatory projections of the and the onto the cerebellar nuclei and onto Purkinje cells.  the Purkinje cells. The inferior olivary may be an error detector  When a particular action goes off target, inferior  Each climbing fiber associates with olivary nucleus neurons are activated. only one Purkinje cell, and each  This results in powerful activation of the target climbing fiber only goes to one to Purkinje cells through the climbing fibers. three Purkinje cells.  Activation of Purkinje cells inhibits the deep cerebellar nucleus neurons, terminating the unwanted component of the action

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Cerebellum Classifications Connectivity of Cerebellar Cortex • Classification by Phylogenetic and Ontogenic Development Archicerebellum Paleocerebllum Neocerebellum

• Classification by Afferent Connection Vestibulocerebellum Spinocerebellum Pontocerebellum • Classification by Efferent Connection Vermis Paravermal Region Cerebellar Hemisphere

Developmental History of Cerebellum Three functional divisions  Vestibulocerebellum 前庭小腦

 Archicerebellum 原小腦

 Flocculonodular lobe Intermediate zone Vermis  Spinocerebellum Lateral zone 脊髓小腦

 Paleocerebellum 舊小腦

 Vermis and intermediate zone  Cerebrocerebellum 大腦小腦 Flocculonodular lobe  Neocerebellum 新小腦

 Lateral zone

Cerebellar divisions Vestibulocerebellum

Spinocerebellum: Vermis  Comprises the flocculonodular lobe and its Spinocerebellum Intermediate hem. (Vermis + Intermed. Hem) Cerebrocerebellum: connections with the vestibular nuclei. Control of limbs Lateral hem.  Phylogenetically the oldest of cerebellum. and trunk  Cerebrocerebellum Involved in vestibular reflexes (such as the (Lateral hemisphere) vestibuloocular reflex) and in postural Planning of movement+ Vermis maintenance. IVth vent Vestibulo-cerebellum Intermediate hem.  An important regulator of the vestibular (Floculo-nodular lobe) Lateral hem. Control of eye & system. head movements  Balance Damage to this region will result in vertigo and nystagmus NTA Fig. 13-1 Floculo-nodular lobe

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 Vestibulo- Responds to vestibular stimuli Vestibulocerebellum from internal ear (floculonodular lobe) cerebellum  assists in maintaining  Connections equilibrium by modification in  Afferents: input from ipsilateral vestibular nuclei muscle tone and primary vestibular nerve  postural muscles  Efferents: to bilat vestibular nucleus → □eye muscles (1) vestibulospinal tract → motor neurons of anterior □trapezius horn for reflexively control of equilibrium □sternomastoid (2) vestibulo-ocular tract → medial longitudinal → □erector spinae fasciculus CN nucleus 3, 4, 6 for EOM control. • Function: involved in eye movements and maintain  Main deciding factor: fastigial balance nucleus  Efferents: to reticular formation →  Which deep nucleus controls → equilibrium: fastigial nucles (1) Cerebello-reticular tract reticular nucleus in brain stem → reticulospinal tract → motor neurons of anterior horn for reflexively control of equilibrium

MiMain CConnections i of fh the Vestibulo-cerebellar connections Vestibulocerebellum

 The flocculonodular lobe Vestibular receives input from the Organ Floculonodular vestibular nerve & from Lobe Vermis the vestibular nuclei. VESTIBULAR NUCLEUS  Some of the Purkinje cells here may leave the vestibulospinal tract cerebellum to synapse in bilateral vestibular nuclei MLF FASTIGIAL NUCLEUS (the only exception to the rule of Purkinje projection to deep cerebellar nuclei) lower motor neuron ARCHICEREBELLUM LMN

Spinocerebellum (vemis and intermediate) Spinocerebellum

 The vermis & the intermediate zones of the cerebellar cortex, which connect to the fastigial & interposed nuclei, respectively.  Extensive input from the spinal cord.  Output projects to rubrospinal, vestibulospinal, and reticulospinal tracts  Integration of sensory input with motor commands to produce adaptive motor coordination, and for proper regulation of muscle tone and movement

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Several direct & indirect spinocerebellar pathways terminate in the spinocerebellum in a topographic Spinocerebellum manner in two somatotopic maps (one in the anterior lobe and one in the paramedian lobule).  Responds to  proprioception input from muscle spindle  touch/pressure input  Maintains posture of the body by  modifying muscle tone  regulate voluntary movements

Spinocerebellum : (Afferents) Posterior and ventral spinocerebellar tracts

Cuneocerebellar tract

End mainly in the anterior lobe, the paramedian lobule, • and the pyramis of Clark’s Nuc.: C8 to L2 the posterior lobe • M. afferent below L3: via Fasc. Gracilis to reach Clark’s Nuc. • The Lat cuneatus Nuc.: M afferent from upper body, via Fasc cuneatus • Ventral : double crossed

Spinocerebellum: The efferents Spinocerebellum: The efferents Medial & lateral systems • Vermis projects to the fastigial nucleus → vestibular nuclei and reticular formation → Interposed nuclei vestibulospinal tract and reticulospinal tract → motor neurons of anterior horn • Intermediate zone projects to the interposed Fastigial nuclei → Vestibulocerebellum via vestibular nuclei  Contralateral red nucleus → rubrospinal tract →motor neurons of anterior horn  Contralateral VL thalamus →cerebral cortex→ coticospinal tract→motor neurons of anterior horn  Control muscle tone & coordination of muscle movement on the same side of the body NTA Fig. 10-2

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Main Connections of the Cerebro-cerebellum (lateral zone) Paleocerebellum

 The largest functional RED NUCLEUS subdivision of the INTERPOSITUS NUCLEUS human cerebellum  Comprising the lateral hemispheres and the rubrospinal dentate nuclei. tract Inferior ANTERIOR  Extensive connections Olivry LOBE PARAVERMAL with the cerebral Nucleus ZONE cortex, via the pontine nuclei (afferents) and lower motor neuron PALEOCEREBELLUM the VL thalamus SPINAL CORD (efferents). spinocerebellar tract

Neo-cerebellum Cerebrocerebellum

 Input from the motor  Connection cortex, adjacent premotor & somatosensory cortices.  Afferents: receives input from the  Output back to the brain. cerebral cortex via a relay in pontine  Functions in a “feedback” nuclei manner with the cortical sensory-motor system  Efferents: projects to dentate nucleus  plan sequential voluntary → VL thalamus → primary motor body and limb movements → →  Planning these as much as a cortex corticospinal tract motor tenths of a second in neurons of anterior horn advance of the actual movements (mental rehearsal of complex motor actions)

Cerebrocerebellum Cerebrocerebellum

 Facilitates smooth coordinated voluntary  Involved in regulating the cerebral movements (planning & timing) cortical motor output.  Ensures that the force, direction & extent are  accurate The best-known effect of this is in  Role in motor learning (learn diff movements) procedural learning, such as riding a • Athletes, timing & amplitude of learned movements bike or learning to ski. are encoded here   Diverse cognitive functions Damage to the lateral hemispheres  Attention & Processing of language results in lack of coordination of limb  Smooth movements require perfect movement, with overshoot and synergism between agonist & antagonist undershoot (intention tremor). group of muscles

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Main Connections of the Cerebellar output from the 4 deep nuclei Neocerebellum

CEREBRAL THALAMUS DENTATE CORTEX NUCLEUS

pyramidal tract Pontine POSTERIOR LOBE Nucleus CEREBELLAR HEMISPHERE

lower motor neuron NEOCEREBELLUM LMN

Inferior cerebellar peduncle: Inferior cerebellar peduncle: destination of afferent fibers origin of afferent fibers

Inferior cerebellar peduncle: Middle cerebellar peduncle: Efferent fibers origin of afferent fibers

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Superior Cerebellar Peduncle: Superior cerebellar peduncle: Destinations of fibers origin of afferent fibers

Superior cerebellar peduncle: efferent fibers 2A

2B

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Cerebellar Motor Functions Ccerebellum in extra-pyramidal  Implemented via lateral and medial motor control pathways pathways, especially the  Vestibulospinal corticospinal tract   Incorporated into motor programs via Reticulospinal frontal motor areas (SMA, premotor  Rubrospinal cortex…)   Becomes part of motor strategy via Olivospinal prefrontal cortex  Role in extrapyramidal motor systems

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Olivo-cerebellar system Olivo-cerebellar system  The inferior olivary complex  Principal olive, medial and dorsal accessory olive, and medial lamina. 1.5 million cells  Send climbing fibers to all cerebellar cortex in a specific topographic manner caudal portion rostral portion Principal A Small area in the inferior olive is linked Inferior Olivary to a definite area of the cerebellar output medial and dorsal accessory olivary nucleus Nucleus

Dentato-rubro-olivary tract Reticular nuclei

 Lateral reticular nuclei (lateral to inferior olive)  Sent mossy fibers to bilateral cerebellum (ipsilateral dominant) via superior cerebellar peduncle.  Receive excitatory reciprocal input from the cerebellar nuclei

 The triangle is defined by dentate efferents ascending through the superior cerebellar Receive collaterals from propiospinal peduncle and crossing in the decussation of the brachium conjunctivum inferior to the red neurons nucleus, to finally reach the inferior olivary nucleus (ION) via the central tegmental tract (CTT). The triangle is completed by ION decussating efferents terminating on the original • Relay motor information to cerebellum dentate nucleus via the inferior cerebellar peduncle

Other functions of the Hypothalamo-Cerebellar & Cerebello-Hypothalamic Pathways Autonomic and endocrine homeostasis Cerebellum :  Cerebello-hypothalamic axons  Hypothalamo-Cerebellar axons  Arise from neurons of all four  Arise primarily from cells in the cerebellar nuclei, pass through the lateral, posterior, and dorsal superior cerebellar peduncle, cross hypothalamic areas; in its decussation, and enter the suprainammillary, hypothalamus. tuberomammillary, and lateral  Some axons recross the midline in mammillary nuclei; the dorsomedial caudal areas of the hypothalamus. and ventromedial nuclei; and the periventricular zone.  These fibers terminate primarily in lateral, posterior, and dorsal  Hypothalamo-cerebellar cortical hypothalamic areas and in the fibers may terminate in relation to dorsoinedial and paraventricular neurons in all layers of the nuclei cerebellar cortex.

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Limbic-Cerebellar & Cerebello-Limbic Coordinate eye movements & Pathways: speech  Cerebellum to hippocampus  Hippocampal-cerebellar  The & amygdala complex pathway  Arise from fastigial Nu  Bilaterally arranged  Receives visual input from the superior  Bilaterally arranged  End mostly in vermis colliculus and is involved in coordinating eye   Mono or polysynaptic Mediate excitation of the mesencephalic dopaminergic movements.  Paleocerebellar-limbic axons neurons   From anterior vermis & fastigial  Involved in non-motor function of Coordinates speech. nucleus cerebellum   Modulate hippocampal function Drunken speech derives from the effect of alcohol on  Cerebellar stimulation may stop the cerebellar vermis seizures associated with amygdala/hippocampal electric stimulation

Non-motor Function Cerebellar Syndromes Passive stimulation Discriminate roughness  Cerebellar motor syndrome  Lesion of motor cerebellum  Ataxia, dysmetria, dysarthria, oculomotor abnormalities  Cerebellar cognitive-affective syndrome  Lesion of cognitive & limbic cerebellum  Cognitive over- or under-shoot  Executive dysfunction,  Impaired visual spatial processing  linguistic deficits  Affective dysregulation . Attentional control, emotional control, autism spectrum, psychosis spectrum, social skill set

Manipulate only Manipulate + discriminate PNS Fig. 42-14

Cerebellar cognitive-affective syndrome Dysmetria of thought and emotion

Lesions of the posterior cortex and vermis Clinical cerebellar disorders & symptomatology

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Cerebellum: Damage Clinical cerebellar dysfunction

 Lesions ---> no paralysis  Ataxia: Incoordination of movement  loss of motor coordination  Decomposition of movement  Dysynergia  Dysmetria, past-pointing  no simultaneous movement of joints  Dysdiadocokinesia serial movement only  Rebound phenomenon of Holmes  Dysmetric movements  Gait ataxia, truncal ataxia,  to wrong coordinates titubation  Alcohol intoxiction  Intention tremor  depression of cerebellar circuits ~  Hypotonia, nystagmus

Clinical cerebellar syndromes Symptoms due to lesions of the cerebellar cortex  Archicerebellar Lesion:  imbalance, vertigo, dizziness, nystagmus  Paleocerebellar Lesion:  gait disturbance, ataxia  Neocerebellar Lesion:  hypotonia, ataxia, tremor

Cerebellar Ataxia

ab c Ataxic gait and position: Left cerebellar tumor

a. Sways to the right in standing position Thank you for

d b. Steady on the right leg your attention c. Unsteady on the left leg d. ataxic gait

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