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General View of

 10 % total volume of the brain, but >50% of all its neurons The Cerebellum  Provided with extensive information (40 times more axons project into the cerebellum than exit from it)  Not necessary to basic elements of perception or movement. 陽明大學醫學院 腦科所  Damage to the cerebellum disrupts the spatial accuracy 陳昌明 副教授 and temporal coordination of movement. It impairs balance and reduces muscle tone and motor learning and certain cognitive functions.

Position

 Lies above and behind the medullar and pons and occupies posterior cranial fossa

Cerebellum

Cerebellum external configuration

• Located in posterior cranial fossa • Tentorium cerebelli (), 4th ventricle (brain stem) • Communicate with other structure via

•superior, middle, and inferior cerebellar

peduncle

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External features External features

Consists of two united in the Three peduncles midline by the vermis  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

Cerebellum Lobes Anterior lobe corpus of Primary fissure cerebellar  Longitudinal division Posterior lobe  Vermis, Paravermal Region, Cerebellar Hemisphere  Transverse division  Anterior Lobe Posterolateral fissure

 Posterior Lobe

 Flocculonodular Lobe

Lobes External features Superior surface  Two deep fissures  Primary fissure  Tonsil of cerebellum 小腦扁桃体 two elevated  Posterosuperior fissure masses on inferior  Three lobs surface of hemispheral  Flocculonodular lobe 絨球小結葉 portion just nearby and nodule foramen magnum  Anterior lobe Corpus of cerebellar  Posterior lobe

Tonsil

View from below

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External features Cerebellum & Brainstem, Inferior Surface, Anterior View

Internal structures Deep Nuclei

Gray matter

 Cerebellar cortex  Cerebellar nuclei

 Dentate 齒狀核 1. fastigial  頂核 nucleus  中間核 2. globose  Emboliform nucleus 栓狀核 nucleus  Globose nucleus球狀核 3. emboliform －medullary nucleus center 髓体 4.

Internal structures

Cerebellar cortex Fastigial nucleus

Globose nucleus

Dentate nucleus Emboliform nucleus

medullary center

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1. 2. 3. 4. 5. 6. 7. 8. parallel fiber 9. 10.

Neurons in the cerebellar cortex are organized Cerebellar Cortex into three layers Inputs Climbing fibers •from Inferior olive Mossy fibers Output Purkinje neurons

Interneurons Granule neurons Stellate neurons Basket neurons Molecular Golgi neurons Purkinje Granular

NTA Fig. 13-11

The Purkinje Cells Receive Excitatory Input From Two Geometrical Plan of Afferent Fiber Parallel and Systems and Are Climbing fibers Inhibited by Three Local

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Mossy and Climbing Fibers Encode Peripheral Climbing Fiber Activity Produces Long-Lasting and Descending Information Differently Effects on the Synaptic Efficacy of Parallel Fiber

Simple and complex spikes recorded intracellularly from Purkinje cells Complex spikes (right bracket) are evoked by climbing fiber synapses, while simple spikes (left bracket) are produced by mossy fiber input.

Cerebellum ：Internal Configurations

 Cerebellar Cortex Molecular Layer Stellate Cell --- taurine (inhibitory) afferent: parallel fiber efferent: Purkinje cell Basket Cell ---- GABA (inhibitory) afferent: parallel fiber efferent: Purkinje cell soma Parallel Fiber granule cell axon Purkinje Cell Dendrite

Mossy fibers

 A mossy fiber is an axon terminal that ends in a large, bulbous swelling.

 Enter the granule cell layer and synapse on the of granule cells (right)

 In fact the granule cells reach out with little "claws" to grasp the terminals.  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 parallel fibers synapse on the huge dendritic arrays of the Purkinje cells.

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Mossy fibers The climbing fiber

 Although each parallel fiber touches each  It goes straight to the Purkinje cell layer and Purkinje cell only once, the thousands of parallel snake up the Purkinje dendrites, like ivy climbing fibers working together can drive the Purkinje a trellis. cells to fire like mad.  Each climbing fiber associates with only one Purkinje cell, but when the climbing fiber fires, it provokes a large response in the Purkinje cell.

Cerebellar cortex Cerebellum: Internal Configurations interneurons  Cerebellar Cortex Purkinje Cell Layer  All are inhibitory interneurons.  Purkinje Cell

 The Golgi cell is found among the granule cells. -- 15,000,000 in number

 The stellate and basket cells live in the molecular layer. -- GABA (inhibitory)  The basket cell (right) drops axon branches down into afferent from: parallel fiber the Purkinje cell layer where the branches wrap around climbing fiber the cell bodies like baskets. stellate cell basket cell

efferent to: deep cortical nuclei  Bergman’s glial cell

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Cerebellum: Internal Configurations

 Cerebellar Cortex Granular Layer  Granular Cell -- 50,000,000,000 in number -- glutamic acid (excitatory) afferent: mossy fiber efferent: Purkinje cell dendrite basket cell, stellate cell Golgi cell  Golgi Cell -- GABA (inhibitory) afferent: parallel fiber, mossy fiber rosette efferent: granule cell dendrite

Cerebellum: Internal Configurations Neurons in the Cerebellar Cortex

 Synaptic Glomerulus  Afferent terminals on granular layer  Mossy Fiber Rosette -- afferent fibers except inferior olivary input -- 2/3 of medullary center  Granular Cell Dendrite A glomerulus is a -- main afferent input clear space where the bulbous terminal of a  Golgi Cell Axon mossy fiber makes -- synapse on granule cell dendrite synaptic contact with -- GABA (inhibitory) Golgi and granule cells. - Surrounded by Foot Process

Synaptic Glomerulus Cerebellum Classifications  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

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Archicerebellum (nodulus) Spinocerebellum

Archicerebellum (flocculus) Pontocerebellum Paleocerebellum

Neocerebellum Vestibulocerebellum

Cerebellum Connections Cerebellum Connections

 Afferent Connections (2):  Afferent Connections (1):  2. Middle Cerebellar Peduncle  1. Inferior Cerebellar Peduncle Pontocerebellar fiber  Restiform Body Corticopontocerebellar Fiber Posterior Reticulocerebellar Fiber  3. Superior Cerebellar Peduncle Cuneocerebellar Tract Anterior Spinocerebellar Tract Reticulocerebellar Tract Cerulocerebellar fiber  Juxtarestiform Body Raphecerebellar fiber Vestibulocerebellar Tract Rubrocerebellar fiber Primary Vestibular Fiber Hypothalamocerebellar fiber

Cerebellum Connections Three functional divisions

 Efferent Connections :  Vestibulocerebellum 1. Superior Cerebellar Peduncle 前庭小腦  Archicerebellum 原小腦

Cerebellothalamic fiber  Flocculonodular lobe

Intermediate zone

Vermis

- from 3 deep nuclei to VPLo, VLc, CL  Spinocerebellum Lateral zone

Cerebellorubral fiber 脊髓小腦

 Paleocerebellum 舊小腦 - from nucleus interpositus & dentate nucleus  Vermis and Ascending portion of uncinate fasciculus of Russell intermediate zone 2. Inferior Cerebellar Peduncle  Cerebrocerebellum 大腦小腦 Flocculonodular lobe Fastigiovestibular fiber  Neocerebellum 新小腦 Descending portion of uncinate fasciculus of Russell  Lateral zone

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Functional divisions of cerebellar cortex The Cerebellum Has Three Functionally Distinct Regions

The Three Functionally Distinct Regions Cerebellar divisions Have different inputs and outputs Spinocerebellum: Vermis Spinocerebellum Intermediate hem. (Vermis + Intermed. Hem) Cerebrocerebellum: Lateral hem. Control of limbs and trunk Cerebrocerebellum (Lateral hemisphere) Planning of movement+ Vermis IVth vent Vestibulo-cerebellum Intermediate hem. (Floculo-nodular lobe) Lateral hem. Control of eye & head movements Balance

NTA Fig. 13-1 Floculo-nodular lobe

Connections and function of cerebellum Vestibulo-cerebellum Vestibulocerebellum  Connections  Input:

 Afferents: receive input from vestibular nuclei and vestibular primary vestibular nuclei  Efferents: projects to the vestibular nucleus →  Output: (1) vestibulospinal tract → motor neurons of anterior horn vestibular for reflexively control of equilibrium nuclei (2) vestibulo-ocular tract → medial longitudinal fasciculus → CN nucleus 3, 4, 6 for EOM control.  Function: involved in eye movements and maintain balance

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Main Connections of the Vestibulocerebellum

Vestibular Organ Floculonodular Lobe BILATERAL VESTIBULAR NUCLEUS

Vestibulospinal Tract MLF FASTIGIAL NUCLEUS

Lower motor neuron ARCHICEREBELLUM LMN

Spinocerebellum (vermis & intermediate) Spinocerebellum

 Input: periphery and spinal cord  Output: cortex

Afferents: Spinocerebellar tracts The Ventral and dorsal spinocerebellar  End mainly in the anterior lobe, the paramedian lobule, and the pyramis of the posterior lobe tracts

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The efferents Connections and Function of Neo- cerebellum  Vermis projects to the fastigial nucleus → vestibular nuclei and reticular formation → vestibulospinal tract  Connection and reticulospinal tract → motor neurons of anterior  Afferents: receives input from the via horn a relay in pontine nuclei  Intermediate zone projects to the interposed nuclei  Efferents: projects to dentate nucleus →  Contralateral red nucleus → rubrospinal tract →crossed to contralateral VL thalamus → primary motor cortex motor neurons of anterior horn → corticospinal tract → crossed to motor neurons  Contralateral VL thalamus →cerebral cortex→ coticospinal of anterior horn tract→ crossed to motor neurons of anterior horn  Function: participates in planning movements  Function: play an important role in control of muscle tone and coordination of muscle movement on the same side of the body

Main Connections of the Neocerebellum Pyramidal Tract and Associated Circuits

upper motor neuron UMN

BASAL Cerebellum GANGLIA

pyramidal tract

lower motor neuron UMN

Cerebellum and Automatic Motor Control The cerebellum operates in 3's

Motor Cortex  There are 3 highways leading in and out of the CEREBELLUM cerebellum, there are 3 main inputs, and there are 3 Red Nucleus main outputs from 3 deep nuclei. They are:  The 3 highways are the peduncles, or "stalks".

Reticular Vestibular There are 3 pairs: the inferior, middle, and Formation Nucleus superior peduncles

Lower Motor Neuron (LMN) Proprioceptors

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The 3 inputs The 3 deep nuclei

 Mossy fibers from the spinocerebellar pathways  The fastigial, interposed, and dentate nuclei.  Climbing fibers from the inferior olive, and  The fastigial nucleus is primarily concerned with  Mossy fibers from the pons, which are carrying balance, and sends information mainly to vestibular information from cerebral cortex. and reticular nuclei.  These cortico-pontine fibers need to cross  The dentate and interposed nuclei are concerned  These fibers synapse in the pons, cross, and enter the more with voluntary movement, and send axons cerebellum as mossy fibers. mainly to thalamus and the red nucleus.

Olivo-cerebellar system Olivocerebellar Connections  Caudal portion of medial and dorsal accessory  The inferior olivary complex olivary nucleus  Principal olive, medial and dorsal accessory olive, and medial lamina.  vermis of cerebellar cortex (A and B)   1.5 million cells fastigial nucleus  Send climbing fibers to all cerebellar cortex in a specific  vestibular nucleus topographic manner  Rostral portion of medial and dorsal accessory  A Small area in the inferior olive is linked to a definite area of olivary nucleus the cerebellar output  paravermal region (C1, C2, C3)  nucleus interpositus  (3) Principal Inferior Olivary Nucleus  cerebellar hemisphere (D1, D2)  dentate nucleus

Olivo-cerebellar system The inferior olivary complex

 Receives projections from  The spinal cord  crossed ventral and dorsal spino-olivary tracts  The brainstem (esp. red nuclei)  Cerebellar nuclei  Interpositus & dentate nuclei exert an inhibitory effect  Pretectal nuclei  Relaying optokinetic information  Cerebrum Caudal portion Rostral portion Principal  Motor cortex (area 4), premotor cortex (area 6) medial and dorsal accessory olivary nucleus Inferior Olivary Nucleus  Visual and Vestibular areas  Zona incerta of the thalamus . Relay for the projections from the motor cortex, prefrontal, cingulate, parietal and temporal area

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Functional divisions of cerebellar cortex - Medial & lateral systems (Anterior and -> Deep nuclei Lateral corticospinal tracts) Spinocerebellum Interposed

Vermis nuclei Intermediate hemisphere Cerebrocerebellum Lateral hemisphere Fastigial

Vestibulocerebellum Inter Dentate posed via vestibular nuclei

Fastigial

Vestibulo- cerebellum

To frontal To To To motor areas lateral medial vestibular sysetms sysetms nuclei Motor Motor Eye mvt & Planning execution balance NTA Fig. 10-2 +++

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

 Receive collaterals from propiospinal neurons  Relay motor information to cerebellum

Organization of Motor Subsystems Spinocerebellum (vermis & intermediate)

 Provide the circuitry for coordinating mainly the movements of the distal portion of the limbs, esp the hands and fingers  Compared the “intentions” from the motor cortex and ted nucleus, with the “performance’ from the peripheral parts of the limbs  Send corrective output signals to the motor neurons in the spinal cord that control distal parts of the limb movements  Provide smooth, coordinate movements of the agonist and antagonist muscles of the distal limbs for the performance of acute purposeful patterned movements

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Neo-cerebellum (lateral zone) Other functions of the Cerebellum  Receives all its input from the motor cortex, adjacent premotor and somatic sensory cortices of  Motor learning/adaptation the brain. Transmits its output information back to  Non-motor functions: the brain.  Active tactile exploration  Functions in a “feedback” manner with all of the  Higher brain functions (cerebellar cortical sensory-motor system to plan sequential cognitive-affective syndrome) voluntary body and limb movements  Planning these as much as a tenths of a second in advance of the actual movements (mental rehearsal of complex motor actions)

Non-motor Function Motor Learning Passive stimulation Discriminate roughness

Before Before

Prisms Prisms

After After

PNS Fig. 42-15 Manipulate only Manipulate + discriminate PNS Fig. 42-14

Cerebellar Motor Functions Cerebellar Cognitive Affective Disorder  Implemented via lateral and medial pathways,  Lesions of the posterior cortex and vermis especially the corticospinal tract  Impairment of executive functions  Incorporated into motor programs via frontal  Planning, verbal fluency, abstract reasoning motor areas (SMA, premotor cortex…)  Difficulties with spatial cognition  Becomes part of motor strategy via prefrontal  Visuo-spatial organization, visual memory cortex  Personality changes  Blunting of affect, inappropriate behaviors  Language disorders

 Agrammatism

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Clinical cerebellar dysfunction Clinical cerebellar syndromes

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

Motor Skill Balance

Pablo Casals

a b c Posture Cerebellar Gait – Ataxia Ataxia Tremor Ataxic gait and position: d Left cerebellar tumor

a. Sways to the right in standing position b. Steady on the right leg c. Unsteady on the left leg d. ataxic gait

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Cerebellar Take home messages Medulloblastoma  Vestibulocerebellum (flocculonodular lobe)

Cerebellar tumors on vermis  Balance and body equilibrium - Truncal Ataxia  Spinocerebellum (vermis & intermediate) - Frequent Falling  Rectify voluntary movement The child in this picture:  Cerebrocerebellum (lateral zone) - would not try to stand unsupported  Plan voluntary movement - would not let go of the bed rail if she stood on the floor.

Take home messages: Cerebellar Conclusions  Cerebellar lesions produce Functions  Incoordination & errors not weakness

 Maintenance of Equilibrium  Lose ability to anticipate errors  Lose ability to correct  balance, posture, eye movement • Motor learning  Coordination of half-automatic movement of – Requires sensory awareness

walking and posture maintenance – Implemented via the descending cortical and brain stem pathways  posture, gait • Cognitive and emotional disturbances

 Adjustment of Muscle Tone – Anatomical connections to prefrontal and cingulate cortex (via thalamus)  Motor Leaning – Motor Skills  Cognitive Function • No single function – Clearly mostly motor; learning, optimizes – Functions may apply to cognitive and emotional behaviors

Thank you for your attention

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