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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 ---> upper motor UMN  Cerebellum  coordination of movement Cerebellum BASAL  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 and the spinal cord and its gamma motor . 1. Found in the posterior Cranial fossa 2. Forms a roof over the 4th ventricle 3. Lies above and behind the medullar and

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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 , 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 Fastigial  Cerebellar cortex  Cerebellar nuclei Emboliform nucleus  Dentate nucleus 齒狀核  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 • 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 10% of the ’s volume, & >50% of the total number of neurons in the brain

Intrinsic pathways & cells inputs to the cerebellum convey the sensory information used to evaluate the overall sensory context of the movement

The climbing fibers may convey information about movement errors

Inhibitory Cerebellum: Internal configurations Cerebellar Cortex : I. Molecular Layer  The is found among the granule cells. • Two types of interneurons •  --- taurine (inhibitory) The stellate and basket cells live in afferent: parallel fiber the molecular layer. efferent: • ---- GABA (inhibitory)  The basket cell drops afferent: parallel fiber branches down into the Purkinje efferent: Purkinje cell cell layer where the branches wrap • Two types of fibers around the cell bodies like baskets. • Parallel Fiber axon • Purkinje Cell Dendrite

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Cerebellum: Internal configurations Cerebellum: Internal configurations

 Cerebellar Cortex : II. Purkinje Cell Layer  Cerebellar Cortex : III. Granular Layer  Purkinje Cell  Granule Cell  15,000,000 in number  50,000,000,000 in number  GABA (inhibitory)  glutamic acid (excitatory)  Afferent from:  afferent: mossy fiber parallel fiber  efferent: Purkinje cell dendrite, basket cell, stellate cell stellate cell, Golgi cell basket cell  Golgi Cell  Efferent to: deep cortical nuclei  GABA (inhibitory)  Bergman’s glial cell  afferent: parallel fiber, mossy fiber rosette  efferent: granule cell dendrite

Cerebellum: Internal configurations Mossy fibers

 Synaptic Glomerulus : Afferent  Originate in the , the spinal terminals on granular layer cord, the ,  Mossy Fiber Rosette and the • Afferent fibers except inferior olivary  input Make excitatory projections onto the • 2/3 of medullary center cerebellar nuclei and onto granule cells in the cerebellar cortex.  Granule Cell Dendrite  • main afferent input Each mossy fiber innervates hundreds of granule cells  Golgi Cell Axon • synapse on granule cell dendrite • GABA (inhibitory) • Surrounded by Foot Process

Mossy fibers The climbing fiber

 A mossy fiber has an axon  Originate exclusively in the inferior terminal that ends in a large, bulbous swelling. olive and make excitatory projections  Enter the granule cell layer and onto the cerebellar nuclei and onto synapse on the dendrites of the Purkinje cells. granule cells  Each climbing fiber associates with  The granule cells reach out with little "claws" to grasp the terminals. only one Purkinje cell, and each  The granule cells then send their climbing fiber only goes to one to axons up to the molecular layer, where they end in a T and run three Purkinje cells. parallel to the surface, thus called parallel fibers.

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Role of climbing fibers Connectivity of Cerebellar

 Intimate connections between the neurons Cortex of the and the Purkinje cells.  The inferior olivary may be an error detector  When a particular action goes off target, inferior olivary nucleus neurons are activated.  This results in powerful activation of the target Purkinje cells through the climbing fibers.  Activation of Purkinje cells inhibits the deep cerebellar nucleus neurons, terminating the unwanted component of the action

Cerebellum Classifications Developmental History of Cerebellum • 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

Three functional divisions Cerebellar divisions  Vestibulocerebellum Spinocerebellum: 前庭小腦 Vermis Spinocerebellum Intermediate hem.  Archicerebellum 原小腦 (Vermis + Intermed. Hem) Cerebrocerebellum:  Flocculonodular lobe Lateral hem. Intermediate zone

Vermis Control of limbs  Spinocerebellum Lateral zone and trunk 脊髓小腦 Cerebrocerebellum  Paleocerebellum 舊小腦 (Lateral hemisphere) Planning of movement+  Vermis and Vermis intermediate zone IVth vent Vestibulo-cerebellum Intermediate hem.  Cerebrocerebellum (Floculo-nodular lobe) Lateral hem. 大腦小腦 Flocculonodular lobe Control of eye &  Neocerebellum 新小腦 head movements Balance  Lateral zone

NTA Fig. 13-1 Floculo-nodular lobe

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 Responds to vestibular stimuli Vestibulocerebellum Vestibulo- from internal ear cerebellum  assists in maintaining  Comprises the flocculonodular lobe and its equilibrium by modification in connections with the vestibular nuclei. muscle tone  postural muscles  Phylogenetically the oldest of cerebellum. □eye muscles  Involved in vestibular reflexes (such as the □trapezius vestibuloocular reflex) and in postural □sternomastoid maintenance. □erector spinae  An important regulator of the vestibular  Main deciding factor: fastigial system. nucleus  Damage to this region will result in  Which deep nucleus controls and nystagmus equilibrium: fastigial nucles

Vestibulocerebellum (floculonodular lobe) Vestibulo-cerebellar connections  Connections   Afferents: input from ipsilateral vestibular nuclei The flocculonodular lobe and primary receives input from the vestibular nerve & from  Efferents: to bilat vestibular nucleus → the vestibular nuclei. (1) → motor neurons of anterior horn for reflexively control of equilibrium  Some of the Purkinje cells (2) vestibulo-ocular tract → medial longitudinal here may leave the fasciculus → CN nucleus 3, 4, 6 for EOM control. cerebellum to synapse in • Function: involved in eye movements and maintain bilateral vestibular nuclei balance (the only exception to the  Efferents: to reticular formation → rule of Purkinje projection (1) Cerebello-reticular tract → reticular nucleus in to deep cerebellar nuclei) brain stem → reticulospinal tract → motor neurons of anterior horn for reflexively control of equilibrium

MiMain CConnections i of fh the Spinocerebellum Vestibulocerebellum (vemis and intermediate)

Vestibular Organ Floculonodular Lobe Vermis VESTIBULAR NUCLEUS

vestibulospinal tract

MLF FASTIGIAL NUCLEUS

lower motor neuron ARCHICEREBELLUM LMN

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Several direct & indirect spinocerebellar pathways Spinocerebellum terminate in the spinocerebellum in a topographic manner in two somatotopic maps (one in the anterior lobe and one in the paramedian lobule).  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

Spinocerebellum Spinocerebellum : (Afferents) Posterior and  Responds to ventral  proprioception spinocerebellar input from muscle tracts spindle Cuneocerebellar  touch/pressure tract input  Maintains posture End mainly in the of the body by anterior lobe, the  modifying muscle paramedian lobule, tone and the pyramis of the posterior lobe  regulate voluntary movements

Spinocerebellum: The efferents

• Vermis projects to the fastigial nucleus → vestibular nuclei and reticular formation → vestibulospinal tract and reticulospinal tract → motor neurons of anterior horn • Intermediate zone projects to the interposed nuclei →  Contralateral → →motor neurons of anterior horn  Contralateral VL →cerebral cortex→ coticospinal tract→motor neurons of anterior • Clark’s Nuc.: C8 to L2 horn • M. afferent below L3: via Fasc. Gracilis to reach Clark’s Nuc.  Control muscle tone & coordination of muscle • The Lat cuneatus Nuc.: M afferent from upper body, via Fasc cuneatus movement on the same side of the body • Ventral : double crossed

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Spinocerebellum: The efferents Main Connections of the Medial & lateral systems Paleocerebellum

Interposed nuclei RED NUCLEUS INTERPOSITUS NUCLEUS Fastigial

Vestibulocerebellum via vestibular nuclei rubrospinal tract Inferior ANTERIOR Olivry LOBE PARAVERMAL Nucleus ZONE

lower motor neuron PALEOCEREBELLUM SPINAL CORD spinocerebellar NTA Fig. 10-2 tract

Cerebro-cerebellum (lateral zone) Neo-cerebellum

 Input from the motor  The largest functional cortex, adjacent premotor subdivision of the & somatosensory cortices. human cerebellum  Output back to the brain.  Comprising the lateral  hemispheres and the Functions in a “feedback” dentate nuclei. manner with the cortical sensory-motor system  Extensive connections  plan sequential voluntary with the cerebral body and limb movements cortex, via the pontine  Planning these as much as a nuclei (afferents) and tenths of a second in the VL thalamus advance of the actual (efferents). movements (mental rehearsal of complex motor actions)

Cerebrocerebellum

 Connection  Afferents: receives input from the cerebral cortex via a relay in pontine nuclei  Efferents: projects to dentate nucleus → VL thalamus → primary → corticospinal tract → motor neurons of anterior horn

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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 ). group of muscles

Cerebellar output from the 4 deep nuclei Inferior cerebellar peduncle: destination of afferent fibers

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

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

Superior cerebellar peduncle: Superior cerebellar peduncle: origin of afferent fibers efferent fibers

Cerebellar Motor Functions 2A

 2B Implemented via lateral and medial pathways, especially the corticospinal tract  Incorporated into motor programs via frontal motor areas (SMA, premotor cortex…)  Becomes part of motor strategy via 3 prefrontal cortex 1  Role in extrapyramidal motor systems

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Olivo-cerebellar system Ccerebellum in extra-pyramidal motor control pathways  The inferior olivary complex  Principal olive, medial and dorsal  Vestibulospinal accessory olive, and medial lamina.  Reticulospinal 1.5 million cells  Rubrospinal  Send climbing fibers to all cerebellar  Olivospinal cortex in a specific topographic manner A Small area in the inferior olive is linked to a definite area of the cerebellar output

Olivo-cerebellar system Dentato-rubro-olivary tract

caudal portion rostral portion Principal Inferior Olivary The triangle is defined by dentate efferents ascending through the superior cerebellar medial and dorsal accessory olivary nucleus Nucleus peduncle and crossing in the decussation of the brachium conjunctivum inferior to the red 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 dentate nucleus via the inferior cerebellar peduncle

Reticular nuclei Other functions of the Cerebellum  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  Receive collaterals from propiospinal neurons • Relay motor information to cerebellum

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Hypothalamo-Cerebellar & Cerebello-Hypothalamic Limbic-Cerebellar & Cerebello-Limbic Pathways: Autonomic and endocrine homeostasis Pathways:  Cerebello-hypothalamic axons  Hypothalamo-Cerebellar axons  Cerebellum to  Hippocampal-cerebellar  Arise from neurons of all four  Arise primarily from cells in the & amygdala complex pathway cerebellar nuclei, pass through the lateral, posterior, and dorsal  Arise from fastigial Nu  Bilaterally arranged superior cerebellar peduncle, cross hypothalamic areas;   End mostly in vermis in its decussation, and enter the suprainammillary, Bilaterally arranged  hypothalamus. tuberomammillary, and lateral  Mono or polysynaptic Mediate excitation of the mesencephalic dopaminergic  Some axons recross the midline in mammillary nuclei; the dorsomedial  Paleocerebellar-limbic axons and ventromedial nuclei; and the neurons caudal areas of the hypothalamus.  From anterior vermis & fastigial periventricular zone.  Involved in non-motor function of  These fibers terminate primarily in nucleus  cerebellum lateral, posterior, and dorsal Hypothalamo-cerebellar cortical  Modulate hippocampal function hypothalamic areas and in the fibers may terminate in relation to  Cerebellar stimulation may stop dorsoinedial and paraventricular neurons in all layers of the seizures associated with nuclei cerebellar cortex. amygdala/hippocampal electric stimulation

Coordinate eye movements & Non-motor Function speech Passive stimulation Discriminate roughness  The  Receives visual input from the and is involved in coordinating eye movements.  Coordinates speech.  Drunken speech derives from the effect of alcohol on the cerebellar vermis

Manipulate only Manipulate + discriminate PNS Fig. 42-14

Cerebellar Syndromes Cerebellar cognitive-affective syndrome Dysmetria of thought and emotion  Cerebellar motor syndrome  Lesion of motor cerebellum Lesions of the posterior cortex and vermis  , 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

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Cerebellum: Damage

 Lesions ---> no paralysis Clinical cerebellar disorders  loss of motor coordination  Dysynergia & symptomatology  no simultaneous movement of joints serial movement only  Dysmetric movements  to wrong coordinates  Alcohol intoxiction  depression of cerebellar circuits ~

Clinical cerebellar dysfunction Clinical cerebellar syndromes

 Ataxia: Incoordination of movement  Archicerebellar Lesion:  Decomposition of movement  imbalance, vertigo, dizziness,  Dysmetria, past-pointing nystagmus   Dysdiadocokinesia Paleocerebellar Lesion:  Rebound phenomenon of Holmes  gait disturbance, ataxia   Gait ataxia, truncal ataxia, Neocerebellar Lesion: titubation  hypotonia, ataxia, tremor  Intention tremor  Hypotonia, nystagmus

Symptoms due to lesions of the Cerebellar Ataxia cerebellar cortex ab c Ataxic gait and position: Left cerebellar tumor

a. Sways to the right in standing position

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

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Thank you for your attention

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