Subcortical Motor Systems: cerebellum

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Outline Subcortical Motor Systems: cerebellum 陽明大學醫學院腦科所陳昌明副教授 Anatomy Cerebellar cortex Neuronal circuitry Cerebellar connections

UMN pyramidal tract lower motor neuron UMN BASAL GANGLIA Motor Loops Cortex ---> Subcortex ---> Cortex ---> Spinal cord Cerebellum coordination of

movements by influencing muscle activity, Controlling equilibrium and muscle tone through connections with the vestibular system and the spinal cord

1 Outline Subcortical Motor Systems: cerebellum 陽明大學醫學院腦科所陳昌明副教授 Anatomy Cerebellar cortex Neuronal circuitry Cerebellar connections Vestibulocerebellum Spinocerebellum Neocerebellum Other cerebellar functions Cerebellum Pyramidal Tract and Associated Circuits upper motor neuron UMN pyramidal tract lower motor neuron UMN BASAL GANGLIA Motor Loops Cortex ---> Subcortex ---> Cortex ---> Spinal cord Cerebellum coordination of movement Basal Ganglia selection & initiation of voluntary movements ~ Cerebellar functions 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. Cerebellum: Anatomy 1. Found in the posterior Cranial fossa 2. Forms a roof over the 4 th ventricle 3. Lies above and behind the medullar and pons 1

Cerebellum: Anatomy Cerebellum: External features

midline output ---> ventromedial pathway

cerebellar nuclei fastigial, interposed, &

division Vermis, Paravermal Region, Cerebellar

Posterior Lobe Flocculonodular Lobe Functional

surface External Features Two deep fissures

lobs Flocculonodular lobe 絨球小結葉 flocculus and

cerebellar Tonsil of cerebellum 小腦扁桃体 On inferior

2 Cerebellum: Anatomy Cerebellum: External features Folia & lobules analogous to gyrus Vermis - along midline output ---> ventromedial pathway Hemispheres output ---> lateral pathway Deep cerebellar nuclei fastigial, interposed, & dentate Major output structures ~ Longitudinal division Vermis, Paravermal Region, Cerebellar Hemisphere Transverse division Anterior Lobe Posterior Lobe Flocculonodular Lobe Functional divisions of cerebellar cortex Lobes Superior surface External Features Two deep fissures Primary fissure Posterosuperior fissure Three lobs Flocculonodular lobe 絨球小結葉 flocculus and nodule Anterior lobe Posterior lobe Corpus of cerebellar Tonsil of cerebellum 小腦扁桃体 On inferior surface of hemispheral portion just nearby foramen magnum IICP tonsilar herniation View from below 2

3 Lobes & Lobules Subdivision of lobes Subdivision of lobes Three peduncles Inferior cerebellar peduncle 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 3

Internal structures Internal structures Gray matter

Fastigial nucleus 頂核 Interposed nucleus 中間核 Emboliform

髓体 Cerebellar cortex Dentate nucleus medullary center

Medullary center 髓体 Cerebellum: 3 layered cortex Molecular

long axis of folium dendrites of Purkinje cells Purkinge cell

perpendicular to main axis of folium ~ Cerebellum: 3 layered

4 Internal structures Internal structures Gray matter Cerebellar cortex Cerebellar nuclei Dentate nucleus 齒狀核 Fastigial nucleus 頂核 Interposed nucleus 中間核 Emboliform nucleus 栓狀核 Globose nucleus 球狀核 White matter-medullary center 髓体 Cerebellar cortex Dentate nucleus medullary center Fastigial nucleus Globose nucleus Emboliform nucleus Medullary center 髓体 Cerebellum: 3 layered cortex Molecular layer parallel fibers axons of granule cells runs parallel to long axis of folium dendrites 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 cerebral cortex ~ 4

Cerebellar Cortex 3 layers, 2 kinds of input fibers, 5 types of neurons Inputs Climbing fibers only from Inferior olive Mossy fibers Output Purkinje neurons Cerebellum: 3 layered cortex Molecular

fibers Mossy fibers Granule Intrinsic pathways & cells Mossy fiber inputs to the cerebellum convey the sensory information used to evaluate the overall sensory context of the movement The climbing

The basket cell drops axon branches down into the Purkinje cell layer where the branches wrap around the cell bodies like baskets. Cerebellum: Internal configurations Cerebellar Cortex : I.

5 Cerebellar Cortex 3 layers, 2 kinds of input fibers, 5 types of neurons Inputs Climbing fibers only from Inferior olive Mossy fibers Output Purkinje neurons Cerebellum: 3 layered cortex Molecular Purkinje Molecular Purkinje Granular Interneurons Granule neurons Stellate neurons Basket neurons Golgi neurons 10% of the brain s volume, & >50% of the total number of neurons in the brain Climbing fibers Mossy fibers Granule Intrinsic pathways & cells Mossy fiber 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 interneurons The Golgi cell is found among the granule cells. The stellate and basket cells live in the molecular layer. The basket cell drops axon branches down into the Purkinje cell layer where the branches wrap around the cell bodies like baskets. Cerebellum: Internal configurations Cerebellar Cortex : I. Molecular Layer Two types of interneurons Stellate Cell --- taurine (inhibitory) afferent: parallel fiber efferent: Purkinje cell dendrite Basket Cell ---- GABA (inhibitory) afferent: parallel fiber efferent: Purkinje cell soma Two types of fibers Parallel Fiber granule cell axon Purkinje Cell Dendrite 5

Cerebellum: Internal configurations Cerebellar Cortex : II.

Cerebellum: Internal configurations Cerebellar Cortex : III.

(inhibitory) afferent: parallel fiber, mossy fiber rosette efferent: granule cell dendrite Cerebellum: Internal configurations Synaptic Glomerulus : Afferent terminals on granular layer Mossy Fiber

Originate in the pontine nuclei, the spinal cord, the brainstem reticular formation, and the vestibular nuclei Make excitatory projections onto the cerebellar nuclei and onto granule cells in the

6 Cerebellum: Internal configurations Cerebellar Cortex : II. Purkinje Cell Layer Purkinje Cell 15,000,000 in number GABA (inhibitory) Afferent from: parallel fiber climbing fiber stellate cell basket cell Efferent to: deep cortical nuclei Bergman s glial cell Cerebellum: Internal configurations Cerebellar Cortex : III. Granular Layer Granule 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 Synaptic Glomerulus : Afferent terminals on granular layer Mossy Fiber Rosette Afferent fibers except inferior olivary input 2/3 of medullary center Granule Cell Dendrite main afferent input Golgi Cell Axon synapse on granule cell dendrite GABA (inhibitory) Mossy fibers Originate in the pontine nuclei, the spinal cord, the brainstem reticular formation, and the vestibular nuclei Make excitatory projections onto the cerebellar nuclei and onto granule cells in the cerebellar cortex. Each mossy fiber innervates hundreds of granule cells Surrounded by Astrocyte Foot Process Mossy fibers The climbing fiber A mossy fiber has an axon terminal that ends in a large, bulbous swelling. Enter the granule cell layer and synapse on the dendrites of granule cells 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. Originate exclusively in the inferior olive and make excitatory projections onto the cerebellar nuclei and onto the Purkinje cells. Each climbing fiber associates with only one Purkinje cell, and each climbing fiber only goes to one to three Purkinje cells. 6

Role of climbing fibers Intimate connections between the neurons of the inferior olivary nucleus and the Purkinje cells.

This results in powerful activation of the target Purkinje cells through the climbing fibers.

Classification by Phylogenetic and Ontogenic Development Archicerebellum Paleocerebllum Neocerebellum Developmental History of Cerebellum Classification by Afferent Connection

Archicerebellum 原小腦 Flocculonodular lobe Spinocerebellum 脊髓小腦 Paleocerebellum 舊小腦 Vermis and intermediate zone Cerebrocerebellum 大腦小腦 Neocerebellum 新小腦 Lateral zone Intermediate zone Vermis

7 Role of climbing fibers Intimate connections between the neurons of the inferior olivary nucleus 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 Connectivity of Cerebellar Cortex Cerebellum Classifications Classification by Phylogenetic and Ontogenic Development Archicerebellum Paleocerebllum Neocerebellum Developmental History of Cerebellum Classification by Afferent Connection Vestibulocerebellum Spinocerebellum Pontocerebellum Classification by Efferent Connection Vermis Paravermal Region Cerebellar Hemisphere Three functional divisions Vestibulocerebellum 前庭小腦 Archicerebellum 原小腦 Flocculonodular lobe Spinocerebellum 脊髓小腦 Paleocerebellum 舊小腦 Vermis and intermediate zone Cerebrocerebellum 大腦小腦 Neocerebellum 新小腦 Lateral zone Intermediate zone Vermis Flocculonodular lobe Lateral zone Cerebellar divisions Spinocerebellum (Vermis + Intermed. Hem) Control of limbs and trunk Cerebrocerebellum (Lateral hemisphere) Planning of movement+ Vestibulo-cerebellum (Floculo-nodular lobe) Control of eye & head movements Balance NTA Fig IVth vent Spinocerebellum: Vermis Intermediate hem. Cerebrocerebellum: Lateral hem. Vermis Intermediate hem. Lateral hem. Floculo-nodular lobe 7

Vestibulocerebellum Comprises the flocculonodular lobe and its connections with the vestibular nuclei. Phylogenetically the oldest of cerebellum.

Damage to this region will result in vertigo and nystagmus Vestibulocerebellum Responds to vestibular stimuli from internal ear assists in maintaining equilibrium by modification in muscle tone

8 Vestibulocerebellum Comprises the flocculonodular lobe and its connections with the vestibular nuclei. Phylogenetically the oldest of cerebellum. Involved in vestibular reflexes (such as the vestibuloocular reflex) and in postural maintenance. An important regulator of the vestibular system. Damage to this region will result in vertigo and nystagmus Vestibulocerebellum Responds to vestibular stimuli from internal ear assists in maintaining equilibrium by modification in muscle tone postural muscles eye muscles trapezius sternomastoid erector spinae Main deciding factor: fastigial nucleus Which deep nucleus controls equilibrium: fastigial nucles Connections Vestibulocerebellum (floculonodular lobe) Afferents: input from ipsilateral vestibular nuclei and primary vestibular nerve Efferents: to bilat vestibular nucleus (1) vestibulospinal tract motor neurons of anterior horn for reflexively control of equilibrium (2) vestibulo-ocular tract medial longitudinal fasciculus CN nucleus 3, 4, 6 for EOM control. Function: involved in eye movements and maintain balance Efferents: to reticular formation (1) Cerebello-reticular tract reticular nucleus in brain stem reticulospinal tract motor neurons of anterior horn for reflexively control of equilibrium Vestibulo-cerebellar connections The flocculonodular lobe receives input from the vestibular nerve & from the vestibular nuclei. Some of the Purkinje cells here may leave the cerebellum to synapse in bilateral vestibular nuclei (the only exception to the rule of Purkinje projection to deep cerebellar nuclei) Main Connections of the Vestibulocerebellum Spinocerebellum (vemis and intermediate) Vestibular Organ VESTIBULAR NUCLEUS Floculonodular Lobe Vermis vestibulospinal tract MLF FASTIGIAL NUCLEUS lower motor neuron LMN ARCHICEREBELLUM 8

Spinocerebellum The vermis & the intermediate zones of the cerebellar cortex, which connect to the fastigial & interposed nuclei, respectively. Extensive input from the spinal cord.

tone and movement Several direct & indirect spinocerebellar pathways terminate in the spinocerebellum in a topographic manner in two somatotopic maps (one in the anterior lobe and one in the

Spinocerebellum Responds to proprioception input from muscle spindle touch/pressure input Maintains posture of the body by modifying muscle tone regulate voluntary movements Spinocerebellum :

efferents Clark s Nuc.: C8 to L2 M. afferent below L3: via Fasc. Gracilis to reach Clark s Nuc. The Lat cuneatus Nuc.

9 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 Several direct & indirect spinocerebellar pathways terminate in the spinocerebellum in a topographic manner in two somatotopic maps (one in the anterior lobe and one in the paramedian lobule). Spinocerebellum 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 the posterior lobe Spinocerebellum: The efferents Clark s Nuc.: C8 to L2 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 spinocerebellar tract: double crossed 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 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 9

Spinocerebellum: The efferents Medial & lateral systems Main Connections of the Paleocerebellum Interposed nuclei RED NUCLEUS NUCLEUS INTERPOSITUS Fastigial Vestibulocerebellum via vestibular nuclei

10-2 lower motor neuron SPINAL CORD spinocerebellar tract PALEOCEREBELLUM Cerebro-cerebellum (lateral zone) The largest functional subdivision of the human cerebellum Comprising the lateral

Neo-cerebellum Input from the motor cortex, adjacent premotor & somatosensory cortices. Output back to the brain.

10 Spinocerebellum: The efferents Medial & lateral systems Main Connections of the Paleocerebellum Interposed nuclei RED NUCLEUS NUCLEUS INTERPOSITUS Fastigial Vestibulocerebellum via vestibular nuclei rubrospinal tract Inferior Olivry Nucleus ANTERIOR LOBE PARAVERMAL ZONE NTA Fig lower motor neuron SPINAL CORD spinocerebellar tract PALEOCEREBELLUM Cerebro-cerebellum (lateral zone) The largest functional subdivision of the human cerebellum Comprising the lateral hemispheres and the dentate nuclei. Extensive connections with the cerebral cortex, via the pontine nuclei (afferents) and the VL thalamus (efferents). Neo-cerebellum Input from the motor cortex, adjacent premotor & somatosensory cortices. Output back to the brain. Functions in a feedback manner with the cortical sensory-motor system plan sequential 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) Connection Cerebrocerebellum Afferents: receives input from the cerebral cortex via a relay in pontine nuclei Efferents: projects to dentate nucleus VL thalamus primary motor cortex corticospinal tract motor neurons of anterior horn 10

Cerebrocerebellum Facilitates smooth coordinated voluntary movements (planning & timing) Ensures that the force,

learned movements are encoded here Diverse cognitive functions Attention & Processing of language Smooth movements

Damage to the lateral hemispheres results in lack of coordination of limb movement, with overshoot and undershoot

11 Cerebrocerebellum Facilitates smooth coordinated voluntary movements (planning & timing) Ensures that the force, direction & extent are accurate Role in motor learning (learn diff movements) Athletes, timing & amplitude of learned movements are encoded here Diverse cognitive functions Attention & Processing of language Smooth movements require perfect synergism between agonist & antagonist group of muscles Cerebrocerebellum Involved in regulating the cerebral cortical motor output. The best-known effect of this is in procedural learning, such as riding a bike or learning to ski. Damage to the lateral hemispheres results in lack of coordination of limb movement, with overshoot and undershoot (intention tremor). Cerebellar output from the 4 deep nuclei Inferior cerebellar peduncle: destination of afferent fibers Inferior cerebellar peduncle: origin of afferent fibers Inferior cerebellar peduncle: Efferent fibers 11

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

Superior cerebellar peduncle: efferent fibers 2A 2B 3 1 Cerebellar Motor Functions

Incorporated into motor programs via frontal motor areas (SMA, premotor cortex )

12 Middle cerebellar peduncle: origin of afferent fibers Superior Cerebellar Peduncle: Destinations of fibers Superior cerebellar peduncle: origin of afferent fibers Superior cerebellar peduncle: efferent fibers 2A 2B 3 1 Cerebellar Motor Functions 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 prefrontal cortex Role in extrapyramidal motor systems 12

Ccerebellum in extra-pyramidal motor control pathways Vestibulospinal Reticulospinal Rubrospinal Olivospinal Olivo-cerebellar system The inferior olivary complex

5 million cells Send climbing fibers to all cerebellar cortex in a specific topographic manner A Small area in the inferior olive is linked to a definite area of the

nucleus Nucleus The triangle is defined by dentate efferents ascending through the superior cerebellar peduncle and crossing in the decussation of the brachium

The triangle is completed by ION decussating efferents terminating on the original dentate nucleus via the inferior cerebellar peduncle Reticular nuclei Lateral

13 Ccerebellum in extra-pyramidal motor control pathways Vestibulospinal Reticulospinal Rubrospinal Olivospinal 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 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 medial and dorsal accessory olivary nucleus Nucleus The triangle is defined by dentate efferents ascending through the superior cerebellar 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 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 Other functions of the Cerebellum 13

Hypothalamo-Cerebellar & Cerebello-Hypothalamic Pathways: Autonomic and endocrine homeostasis Cerebello-hypothalamic axons Arise from neurons of all four cerebellar nuclei, pass through the superior

These fibers terminate primarily in lateral, posterior, and dorsal hypothalamic areas and in the dorsoinedial and paraventricular nuclei Hypothalamo-Cerebellar axons Arise primarily from cells in the

Hypothalamo-cerebellar cortical fibers may terminate in relation to neurons in all layers of the cerebellar cortex.

14 Hypothalamo-Cerebellar & Cerebello-Hypothalamic Pathways: Autonomic and endocrine homeostasis Cerebello-hypothalamic axons Arise from neurons of all four cerebellar nuclei, pass through the superior cerebellar peduncle, cross in its decussation, and enter the hypothalamus. Some axons recross the midline in caudal areas of the hypothalamus. These fibers terminate primarily in lateral, posterior, and dorsal hypothalamic areas and in the dorsoinedial and paraventricular nuclei Hypothalamo-Cerebellar axons Arise primarily from cells in the lateral, posterior, and dorsal hypothalamic areas; suprainammillary, tuberomammillary, and lateral mammillary nuclei; the dorsomedial and ventromedial nuclei; and the periventricular zone. Hypothalamo-cerebellar cortical fibers may terminate in relation to neurons in all layers of the cerebellar cortex. Limbic-Cerebellar & Cerebello-Limbic Pathways: Cerebellum to hippocampus & amygdala complex Arise from fastigial Nu Bilaterally arranged Mono or polysynaptic Paleocerebellar-limbic axons From anterior vermis & fastigial nucleus Modulate hippocampal function Cerebellar stimulation may stop seizures associated with amygdala/hippocampal electric stimulation Hippocampal-cerebellar pathway Bilaterally arranged End mostly in vermis Mediate excitation of the mesencephalic dopaminergic neurons Involved in non-motor function of cerebellum Coordinate eye movements & speech The cerebellar vermis Receives visual input from the superior colliculus and is involved in coordinating eye movements. Coordinates speech. Drunken speech derives from the effect of alcohol on the cerebellar vermis Non-motor Function Passive stimulation Discriminate roughness Manipulate only PNS Fig Manipulate + discriminate Cerebellar Syndromes 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 Cerebellar cognitive-affective syndrome Dysmetria of thought and emotion Lesions of the posterior cortex and vermis 14

Cerebellum: Damage Clinical cerebellar disorders & symptomatology Lesions ---> no paralysis loss of motor coordination Dysynergia no simultaneous movement of joints serial movement only Dysmetric

past-pointing Dysdiadocokinesia Rebound phenomenon of Holmes Gait ataxia, truncal ataxia, titubation Intention tremor Hypotonia, nystagmus Clinical cerebellar syndromes Archicerebellar Lesion:

15 Cerebellum: Damage Clinical cerebellar disorders & symptomatology Lesions ---> no paralysis loss of motor coordination Dysynergia no simultaneous movement of joints serial movement only Dysmetric movements to wrong coordinates Alcohol intoxiction depression of cerebellar circuits ~ Clinical cerebellar dysfunction Ataxia: Incoordination of movement Decomposition of movement Dysmetria, past-pointing Dysdiadocokinesia Rebound phenomenon of Holmes Gait ataxia, truncal ataxia, titubation Intention tremor Hypotonia, nystagmus Clinical cerebellar syndromes Archicerebellar Lesion: imbalance, vertigo, dizziness, nystagmus Paleocerebellar Lesion: gait disturbance, ataxia Neocerebellar Lesion: hypotonia, ataxia, tremor Symptoms due to lesions of the cerebellar cortex Cerebellar Ataxia a b 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 15

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Located below tentorium cerebelli within posterior cranial fossa. Formed of 2 hemispheres connected by the vermis in midline.

The Cerebellum Cerebellum Located below tentorium cerebelli within posterior cranial fossa. Formed of 2 hemispheres connected by the vermis in midline. Gray matter is external. White matter is internal,