PhD MD MBBS Faculty of Medicine Al Maarefa Colleges of Science & Technology Faculty of Medicine Al Maarefa Colleges of Science & Technology Lecture – 8: Cerebellum Nervous System Physiology By Dr. SHAHAB SHAIKH PhD MD MBBS Faculty of Medicine Al Maarefa Colleges of Science & Technology Faculty of Medicine Al Maarefa Colleges of Science & Technology

LEARNING OBJECTIVES Know the Connections of Cerebellum Know the functions of different parts of cerebellum Role of cerebellum in control of movement 2

CEREBELLUM Cerebellum - Latin for "little brain" The cerebellum is highly folded and lies underneath the occipital lobes and is attached to the back portion of brain stem Neurons found in cerebellum are approximately four times more than that are present in the rest of brain 3 Cerebellum consists of a tightly folded layer of cortex, with white matter underneath and a fluid-filled ventricle at the base. There are four deep nuclei embedded in the white matter. The cerebellum does not initiate movement, but it contributes to coordination, precision, and accurate timing. Functional imaging studies have shown cerebellar activation in relation to language, attention, and other cognitive functions

1)Maintenance of balance 2)Enhancement of muscle tone 3)Coordination and planning of skilled voluntary muscle activity 4)Sequences the motor activities 5)Monitors and makes corrective adjustments in the activities initiated by other parts of the brain 6)Compares the actual motor movements with the intended movements and makes corrective changes. 7)The cerebellum does not initiate movement, but it contributes to coordination, precision, and accurate timing. 8)Functional imaging studies have shown cerebellar activation in relation to language, attention, and other cognitive functions. 9)Correlation studies have shown interactions between the cerebellum and non-motor areas of the cerebral cortex; and a variety of non-motor symptoms have been recognized in people with damage that appears to be confined to the cerebellum 10)functional MRI suggest that more than half of the cerebellar cortex is interconnected with association zones of the cerebral cortex. 4 CEREBELLAR FUNCTIONS

The cerebellum is located in the posterior cranial fossa posterior to the brain stem and anchored to it by three cerebellar peduncles. The cerebellum is divided into two hemispheres and having a narrow midline zone called the Vermis. The cerebellar cortex is made up of a very tightly folded layer of gray matter with a total surface area of about 500 square cm. Underneath the gray matter of the cortex lies white matter, made up of nerve fibers running to and from the cortex. Embedded within the white matter are four deep cerebellar nuclei, composed of gray matter. 5 CEREBELLAR ANATOMY

Based on the surface appearance, three lobes can be distinguished within the cerebellum: 1.The anterior lobe above the primary fissure 2.The posterior lobe Below the primary fissure 3.The flocculonodular lobe Below the posterior fissure. 6 CEREBELLAR ANATOMY

Functional Organization of the Cerebellum Functionally cerebellum can be divided into... The Floculonodular lobe – Vestibulocerebellum –participates mainly in balance and spatial orientation Intermediate zone - Spinocerebellum –Enhances muscle tone and coordinates skilled voluntary movements Lateral zone - Cerebrocerebellum –controls sequencing movements of the muscle. Important for timing and coordination of movement. –Plays role in planning and initiating voluntary activity –Stores procedural memories 7

Functional Organization of the Cerebellum 8

The Floculonodular lobe – Vestibulocerebellum: It is the oldest part in evolutionary terms Participates mainly in balance and spatial orientation; its primary connections are with the Vestibular Nuclei although it also receives visual and other sensory input. Damage to this region causes disturbances of balance and gait. 9

Functional Organization of the Cerebellum Intermediate zone - Spinocerebellum This sector of the cerebellum functions mainly to fine-tune body and limb movements. Enhances muscle tone and coordinates skilled voluntary movements It receives proprioceptive input from the dorsal columns of the spinal cord as well as from visual and auditory systems. It sends fibers to deep cerebellar nuclei that, in turn, project to both the cerebral cortex and the brain stem, thus providing modulation of descending motor systems 10

Functional Organization of the Cerebellum Cerebrocerebellum –Lateral regions of Cerebellar Cortex –Plays role in planning and initiating voluntary activity by providing input to cortical motor areas –Stores procedural memories 11

Functional and phylogenetic Role Phylogenetic denomination Anatomical parts Role Vestibulocerebellum (Archicerebellum) Flocculonodular lobe (+ adjacent vermis) Regulates balance and eye movements. Spinocerebellum (Paleocerebellum) Vermis and intermediate parts of the hemispheres ("paravermis") regulates body & limb movements. The spino cerebellum is able to elaborate proprioceptive input in order to anticipate the future position of a body part during the course of a movement. Cerebrocerebellum (Neocerebellum) Middle portion of the vermis & Lateral parts of the hemispheres involved in planning & initiation of movement.It has purely cognitive functions as well.

Neuronal Organization of the Cerebellar Cortex Cerebellar Cortex is organized in three layers – Molecular layer – Purkinje cell layer – Granular cell layer 13

Neuronal Organization of the Cerebellar Cortex Cerebellar Cortex is organized in three layers I.Granular layer –It is thick inner most layer and contains Granule cells, Golgi type II cells and other interneurons II.Purkinje cell layer –It is middle layer –Contains Purkinje cells –Output is always Inhibitory III.Molecular layer –It is outermost layer –Contains stellate and basket cells, dendrites of Purkinje and Golgi type II cells and parallel fibers (axons of granule cells) 14

Neuronal Organization of the Cerebellar Cortex Purkinje cell: Purkinje cells are among the most distinctive neurons in the brain The dendrites branch very profusely. The dendrites are covered with dendritic spines which receives synaptic input from a parallel fiber. 15 Their axons travel into the deep cerebellar nuclei. Purkinje cells use GABA as their neurotransmitter, and therefore exert inhibitory effects on their targets.

Neuronal Organization of the Cerebellar Cortex Granule cell: Granule cells are among the smallest neurons in the brain. They are the most numerous neurons in the brain; about 3/4 of the brain's neurons are cerebellar granule cells. A granule cell receives excitatory input from mossy fibers and inhibitory input from Golgi cells on its ‘Dendritic Claw’. The axons of granule cells rise vertically to the molecular layer, where they form parallel fibers, synapsing with Purkinje dendrites. The neurotransmitter is Glutamate and is excitatory. 16

Neuronal Organization of the Cerebellar Cortex Three types of axons play dominant roles: I.Mossy fibers –enter the cerebellum from outside II.Climbing fibers –enter the cerebellum from outside –project to Purkinje cells and also send collaterals directly to the deep nuclei III.Parallel fibers –are the axons of granule cells 17

Neuronal Organization of the Cerebellar Cortex Mossy fibers: –Originate from brain stem and spinal cord Includes Vestibulo- cerebellar, Spino- cerebellar and Ponto- cerebellar afferents. –Form excitatory synapses with the Granule cells and the cells of the deep cerebellar nuclei. 18

Neuronal Organization of the Cerebellar Cortex Climbing Fibers: –Originate from inferior olivary nucleus of contralateral side in the medulla. –Gives Collaterals to Deep Cerebellar Nuclei and make multiple synapses on Purkinje cells. –Each Purkinje cell receives input from exactly one climbing fiber; but this single fiber "climbs" the dendrites of the Purkinje cell, winding around them and making multiple synapses. –Play role in cerebellar motor learning. 19

20 Circuit of the Cerebellum

Thus in Summary …. Output of the Cerebellar cortex Purkinje cells are the only output of the cerebellar cortex which goes to Deep cerebellar Nuclei Output of the Purkinje cells is always inhibitory. the neurotransmitter is γ- aminobutyrie acid (GABA) Output of the cerebellum regulates rate, range and direction of movement. Input to the Cerebellar cortex From Mossy fibers originating from brain stem and spinal cord and From Climbing fibers originating from Inferior Olivary Nucleus in Medulla 21 Circuit of the Cerebellum

Deep nuclear cells receive excitatory and inhibitory inputs Excitatory afferent inputs from climbing fibers and mossy fibers Inhibitory from Purkinje cells 22 Circuit of the Cerebellum

Deep Cerebellar Nuclei These are clusters of gray matter lying within the white matter at the core of the cerebellum. These nuclei receive collateral projections from mossy fibers and climbing fibers as well as inhibitory input from the Purkinje cells of the cerebellar cortex. There are four nuclei … 1.Dentate: communicates exclusively with the lateral parts of the cerebellar cortex. 2.Globose: 3.Emboliform 4.Fastigial These nuclei are the sole sources of output from the cerebellum except for the Floculonodular lobe which does not project to the deep nuclei—its output goes to the vestibular nuclei instead. 23

Afferent Pathways to the Cerebellum from the periphery … Dorsal spinocerebellar tract transmits information mostly from muscles spindle but also from Golgi tendon organs, tactile, and joint receptors apprises the brain of the momentary status of muscle contraction, muscle tension and limb position and forces acting on the body surface Ventral spinocerebellar tract signals from anterior horn, and interneurons transmits information about which signals have arrived at the cord 24

Afferent Pathways to the Cerebellum from the Brain… Corticopontocerebellar tract Pathway from motor and premotor area, somatosensory cortex as well as some pontine nuclei which join this tract. Projects mostly to the lateral areas. These pathways transmit information about intended motion. Olivocerebellar tract, Vestibulocerebellar tract, and Reticulocerebellar tract These pathways transmit information about intended motion. 25

1.Fastigioreticular tract – equilibrium control 2.Cerebellothalamocortical tract – coordinates agonist and antagonist muscle contractions 26 Efferent Pathways to the Cerebellum

PeduncleDescription SUPERIOR The superior cerebellar peduncle is the major output pathway of the cerebellum. Most of the efferent fibers originate within the dentate nucleus which in turn project to various structures including the red nucleus, the ventral lat./ventral ant. nucleus of the thalamus, and the medulla. The dentato-rubro-thalamo-cortical & cerebello-thalamo-cortical pathways are two major pathways that pass through this peduncle and are important in motor planning. Some afferent fibers from the anterior spinocerebellar pass to the anterior cerebellar lobe via this peduncle. MIDDLE This is composed entirely of afferent fibers originating within the pontine nuclei as part of the massive cortico-ponto-cerebellar tract. These fibers descend from the sensory and motor areas of the cerebral neocortex and make the middle cerebellar peduncle the largest of the three cerebellar peduncles. INFERIOR Proprioceptive information from the body is carried to the cerebellum via the dorsal Spinocerebellar tract. This tract passes through the inferior cerebellar peduncle and synapses within the paleocerebellum. Vestibular information projects onto the archicerebellum. The climbing fibers of the inferior olive run through the inferior cerebellar peduncle. This peduncle also carries information from the Purkinje cells to the vestibular nuclei.Spinocerebellar tractclimbing fibersinferior olivePurkinje cellsvestibular nuclei

Tracts or fiber bundles Distribution Inferior cerebellar peduncle Afferent paths Olivocerebellar tract Lateral hemispheres and cerebellar nucleus Paraolivocerebellar tract Vermis, paravermis. and cerebellar nucleus Vestibulocerebellar tract Fastigial nucleus, flocculonodular lobe, and uvula Reticulocerebellar tract Spinal region of cerebellar vermis Posterior spinocerebellar tract Hind limb region of cerebellar cortex Trigeminocerebellar tract Dentate and emboliform nucleus Cuneocerebellar tract Forelimb and upper trunk region of cerebellar cortex Anterior exterior arcuate fibersFlocculus Arcuatocerebellar fibers (striae medullares) Flocculus Efferent paths Cerebellovestibular tractVestibular nucleus Cerebelloreticular tract Pontine and medullary reticular nucleus Cerebellar connections--

Middle cerebellar peduncle Afferent pathsPontocerebellar tract Neocerebellar cortex Superior cerebellar peduncle Afferent paths Anterior spinocerebellar tract Hind limb region of cerebellar cortex Tectocerebellar tract Intermediate vermis and lobulus simplex Trigeminocerebellar tract Efferent paths Dentatorubral fibersRed nucleus Dentatothalamic fibers Ventral intermediate (VI) and ventral anterior (VA) nucleus of thalamus Fastigioreticular fibers Reticular nucleus of midbrain, pons, and medulla oblongata Cont.

Clinical Signs In Cerebellar Disease 30 Drunken gait – wide based, unsteady gait Nystagmus – Rhythmic, oscillating eye movements Hypotonia - Reduced muscle tone but no paralysis Dysdiadokokinesia - Inability to perform rapid alternate movements smoothly Intention tremor – tremors on activity Dysmetria - patients overshoots intended target Dysarthria - Scanning, slurred speech

Clinical Signs 31 T – ANDDD T – Tremor (intention) A – Ataxia N – Nystagmus D – Dysarthria D – Dysdiadokokinesia D – Dysmetria

REMEMBER 32

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CEREBELLAR DISEASE NOTE Remember there is no resting tremor in cerebellar disease (Resting tremor is seen in Parkinson’s disease) Cerebellum and basal nuclei both monitor and adjust motor activity commanded from the motor cortex, but they do not directly influence the efferent motor neurons but work indirectly by modifying output of motor system in the brain 34

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References Human physiology by Lauralee Sherwood, 8 th edition Text Book Of Physiology by Guyton & Hall, 11 th edition

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