Gals 132 Cerebellum eG NINCRO StS ve List the afferent inputs to cerebellum. LUst and describe the functions of cerebellum. st the features of cerebellar disorder. LUst the cerebellar function tests. 9. Describe the connections and functions of cerebellum. ‘The student MAY also be able to 1. Describe the detalls of connections and functions of cerebellum, 2. Explain the physiological basis of dysfunctions. 23. Describe cerebellar function tests. Cerebellum literally means the ‘little brain’. Cerebellum is situated posterior to the brainstem. Cerebellum is vital for regulation of posture and movement. 1. Itreceives inputs of almost all sensory modalities. 2. From spinal cord, it receives proprioceptive inputs. It receives special sensory inputs from visual, auditory and vestibular structures. 3. Itprojects to almost all areas of brain that are involved in control of motor activities. 4, Thus, cerebellum plays.a critical role in motor control by integrating sensory and motor information in the brain. 5. Therefore, cerebellum strongly influences all aspects of movement, starting from the rate, range, force, and direction to the termination of movement. 6. Hence, damage to cerebellum results in severe incoor- dination of movement. 7. Cerebellum directly projects to the brainstem nuclei that give rise to major descending pathways. 8. Therefore, damage to cerebellum results in severe postural abnormalities. 9. Cerebellum also regulates vestibulo-occular reflex and motor learning. ‘On completion of study of ths chapter, the student MUST be able to: 1. Drawa schematic diagram to depict divisions and functions of cerebellum. Remember the arrangement and functions of cells in different layers of cerebellum, ‘Appreciate the internal neuronal arrangements and their functions within the cerebellum. Understand the influence of deep cerebellar nuclei with descending pathways Johan Evangelista Purkinje (1787-1869), a Czech Physiologist, created the words frst Department ‘of Physiology atthe University of Bresau in Prussia (Poland) in 1839 and the worlds first official Physiology laboratory in 1842. He is best known for his 1837 discovery of Purkinje calls large neurons with many branching dendites found in 7 2 cerebellum Purkinje aso pioneered in subjective EPurkinje ‘sual phenomena. He described germinalvesidein (1787-1865) ‘embryo and dassfied fingerprints He described Gilary epithelial motion land its function. He studied the structure of cerebellum. He f ako popular for describing the Purkinje fibers inthe ventricle of heart and Purkinje images inthe eyes. (essa kel Cerebellum is located in the posterior cranial fossa, behind the brainstem. 1. It is connected to midbrain through superior cere- bellar peduncle, to pons through middle cerebellar peduncle and to the medulla through inferior cerebe- Nar peduncle (Fig. 132.1).Chapter 132:Cerebellu ‘Tracts in corebellar peduncle (CP) ‘Superior CP (brachium conjunctivum): Midale CP (Brachium pontis): = Pontocerebalar Inferior CP (Restiform body): = Cerebelloreticular = Vesbbulocorebeliar = Ovocerebellar = Arcuocerebeliar = Trigeminocerebellar = Cerebelospinal = Spinocerebeliar Fig. 132.1: Location of cerebellum and connection of cerebellum ‘with brainstem via cerebellar peduncles. 2. The surface area of cerebellum is about 75% of the cerebral cortex, but in weight it is only 10% of the cortex. Thus, cerebellar cortical tissue is much folded. 3. There are two main fissures in the cerebellum that divide it into two major parts: the posterolateral fis- sure that separates flocculonodular lobe from rest of the cerebellum and the primary fissure that separates the anterior lobe from the posterior lobe. Functional ns and Functions of Cerebellum Functionally, cerebellum is divided into three major sul visions: vestibulocerebellum, spinocerebellum and cere- brocerebellum (Fig.132.2). Vestibulocerebellum This is also called archicerebellum, as phylogenetically it is the oldest part. 1. It consists of flocculonodular lobe. 2. This part of cerebellum is called vestibulocerebellum for its extensive and reciprocal connection with the vestibular nuclei 3. Itis concerned with equilibrium and learning induced changes in vestibulo-ocular reflex. Spinocerebellum ‘This is also called paleocerebellum, as it is intermediate in development. 1. It consists of the vermis and the paravermal regions of cerebellum 2. It is called spinocerebellum, as it receives proprio- ceptive and other sensory inputs from all the body parts through the spinal cord. 3. It also receives inputs from the motor cortex, where motor planning is carried out. By comparing plan with performance, it smoothes and coordinates move- ment, 4, The vermal portion of spinocerebellum projects to the brainstem areas that control axial and proximal limb muscles. Therefore, vermal spinacerebellum controls posture, 5. The paravermal region of spinocerebellum projects to the brainstem nuclei that influence distal limb mus- les. Therefore, paravermal spinocerebellum controls skilled voluntary movements.1090 Section 11:Neurophysiology i ; 5 i i ‘Climbing fier Mossy ber i ras a ‘Axons of Purkinje cells ed Efferents Fig. 132.3: Layers of cerebellar cortex. Note the outer molecular layer, middle Purkinje cell (P) layer and inner granular layer. Cerebrocerebellum This is also called neocerebellum, as it is newest phyloge- netically. 1. It consists of the two main cerebellar hemispheres. 2. This is called cerebrocerebellum for its connections with the cortex 3. Cortex projects to neocerebellum via the pontine nuclei; hence, this is also called corticopontocere- bellum. 4. Asit interacts with the cortex, itis involved in planning, and programming of the movements. Functional Cerebellum is divides part containing deep cerebellar nuclei. Cerebellar Cortex ‘The cerebellar cortex has three layers: outer molecular layer, middle Purkinje cell ayer, and inner granular layer (Fig. 132.3) Molecular Layer This layer contains interneurons that are basket cells and stellate cells. Purkinje Cell Layer This layer contains Purkinje cell. 1. Purkinje cells are the largest neurons with extensive dendritic branches. 2. Dendrites of Purkinje cells enter into the molecular layer. The axons of the interneurons of the molecular layer project to the dendrites of the Purkinje cell. 3. Purkinje cells also receive inputs directly from the climbing fibers. 4. Purkinje cells are the only cells that project form the cortex of cerebellum to the deep cerebellar nuclei. ‘Thus, Purkinje cells are connecting links between cere- bellar cortex and deep cerebellar nuclei. Granular Cell Layer ‘This ayer contains granule cells and Golgi cell (interneurons). 1. The Golgi cells project to the granule cells and modify granular cell output. 2. The granule cells receive inputs from the mossy fibers and project to the Purkinje cells, basket cells, stellate cells and Golgi cells via parallel fibers Deep Cerebellar Nuclei ‘There are four deep cerebellar nuclei (Fig. 132.4). ius is present in the deep vermal por- tion of the cerebellum. The vermal cortical portion of spi- nocerebellum projects to the fastigial nucleus. Nucleus Globosus and Nucleus Emboliformis ‘The globos and emboliform nuclei are combinely known as nucleus interpositus. The paravermal portion of spino- cerebellum projects to nucleus interpositus.Chapter 132: Cerebellum Nucleus Dentatus This Is present in the hemispheric portion of the cere- bellum. It receives inputs from neocerebellum. The name of the nucleus is ‘dentate’ for its appearance, which has teeth-like serrated morphology. The deep cerebellar nuclei project to the different parts of the brainstem and thalamus (discussed in Cere- bellar Outputs). Cerebellar Connections Cerebellar Inputs Cerebellum receives somatosensory inputs from almost all parts of the body and inputs of all sensory modalities including special sensory inputs. The cerebellar afferents are: 1. Vestibulocerebellar tract: Through this tract, cere- bellum receives impulses directly from the vestibular apparatus and also from the vestibular nuclei. Nucleus interpositus Globose rucieus Embokform nucleus Hemispheric Paravermal Dentate ‘zone zone nucleus cation of deep cerebellar nuclei Fig. 132. 2. Dorsal spinocerebellar tract: This tract conveys pro- prioceptive and exteroceptive impulses from different parts of the body to cerebellum 3. Ventral spinocerebellar tract: This pathway also con- veys proprioceptive and exteroceptive impulses from different parts of the body. 4. Cuneocerebellar tract: This tract originates from lat- eral cuneate nucleus in the caudal medulla and con- veys proprioceptive inputs from head and neck. 5. Tectocerebellar tract: This tract conveys visual infor- mation from superior colliculus and auditory infor- mation from inferior colliculus to the cerebellum. 6. Pontocerebellar tract: Impulses from motor cortex reach cerebellum via pontine nuclei 7. Olivocerebellar tract: Proprioceptive inputs from the whole body reaches cerebellum via inferior olive. Infe- rior olivary nucleus is located in the rostral medulla that receives input from the vestibular system, spinal cord and cerebral cortex. It projects to cerebellum via climbing fibers. Mode of Inputs Inputs to cerebellum reach via three routes: mossy fibers, climbing fibers and other inputs (Table 132.1). Mossy Fiber Inputs: Mossy fibers are major source of inputs to cerebellum. These fibers carry direct proprio- ceptive inputs from all parts of the body and also convey input from cerebral cortex. Mossy fibers project mainly to the granule cells, Climbing Fiber Inputs: Climbing fibers convey inputs from inferior olivary nucleus to cerebellum. Inferior olive receives proprioceptive input from all parts of the body. Climbing fibers project to Purkinje cells of cerebellum. Other Inputs: Cerebellum receives monoaminergic inputs, and inputs from thalamus and other parts of the brain. These fibers project to the deep cerebellar nuclei. Tracts Nature of input Through climbing fibers Olivocerebellartract Proprioceptive inputs from whole body via relay in inferior olivary nucleus ILThrough mossy fibers 1. Dorsal spinocerebellar tract Proprioceptive and exteroceptive inputs 2.Ventral spinocerebellar tract Proprioceptive and exteroceptive inputs 3.Vestibulocerebellartract_ Inputs from vestibular nuclei 4.Tectocerebellar tract sua formate fom superior olla and sudan Inputs fom ror ol 5.Cuneocerebellar tract Proprioceptive inputs from head and neck 6.Corticopontocerebellar tract _ Inputs from cortex via pontine nuclei LOther fiber systems 1. Monoaminergic inputs a. Serotonergic inputs From nucleus raphe magnus b.Noradrenergic inputs __-Fromnucleus locus ceruleus 2.Thalamicand other inputs From thalamus and other brain areas 10911092 Section 11: Neurophysiology Cerebellar Outputs Different parts of cerebellum project to various descen- ding pathways via deep cerebellar nuclei (Fig. 132.5). Deep cerebellar nuclei are the output pathway of cerebel- lum. Output from Vestibulocerebellum Vestibulocerebellum directly projects to the vestibular nuclei without any relay in the deep cerebellar nuclei. Thus, vestibulocerebellum directly controls vestibulo- spinal tract activity ‘Output from Spinocerebellum 1. The vermal portion of the spinocerebellum projects to fastigial nucleus, which, in turn, projects to pontine reticular formation and vestibular nuclei in the brain- stem. Thus, vermal part of spinocerebellum controls the activity of pontine reticulospinal tract and vestib- uulospinal tract. 2. The paravermal portion of the spinocerebellum projects to the nucleus interpositus, which, in turn, projects to the red nucleus. Thus, paravermal part of the spinocerebellum controls the activity of rubrospi- nal tract. Output from Cerebrocerebellum The cerebellar hemisphere projects to the dentate nucleus, which, in turn, project to the motor cortex via thalamus. Thus, cerebrocerebellum controls the activity of the certi- cospinal tract. ‘As different parts of the cerebellum project to all the motor nuclei in the brainstem and to the motor coriex, cerebellum controls activities of all the descending path- ways (corticospinal and extrapyramidal systems). There- fore, diseases of the cerebellum affect both regulation of posture and skilled voluntary movements. Internal Connections of Cerebellum Cerebellum receives inputs from two sources: the climb- ing fibers (from olivary nucleus), and the mossy fibers. 1. Purkinje cells are stimulated directly by climbing fiber input, whereas mossy fibers stimulate Purkinje cells indi- rectly via granule cell-parallel fiber pathways (Fig. 132.6). 2. Mossy fibers project to granule cell. Granule cells via its parallel fibers provide excitatory input to the basket and stellate cells, and Purkinje cell 3. Basket and stellate cells that are activated by mossy fiber-parallel fiber pathway finally inhibit Purkinje cell. This is an example of feed-forward inhibition.Chapter 132: Cerebelur 4, Granule cell also stimulates the Golgi cells (the interneu- rons in granular cel layer), which, in tur, inhibit the a vity of granule cells. This is an example of local feedback inhibition and is meant to regulate the granule cell output. Excitatory Output from Cerebellum The Purkinje cell output to the deep cerebellar nuclei is, inhibitory because the neurotransmitter secreted by Pur- kinje cells is GABA. Paral! fiber (Other inputs Fig. 132.6: Inputs and intemal connections of cerebellum. Note, inspite of inhibitory inputs from Purkinje cells the output of deep cerebellar ‘nudelis always excitatory. 8: Basket cet SC:Stelate cell GC: Golgi cell However, deep cerebellar nuclei receive excitato inputs from mossy fibers and climbing fibers, and from other sources. 2. Therefore, inspite of inhibition by the Purkinje cells, the output of deep cerebellar nuclei to the brainstem is always excitatory. The internal circuitry of cerebellar neurons is designed mainly to modulate the excitatory output of the deep cerebellar nuclei 4. Therefore, lesion of the cerebellum in human beings results in hypotonia. Purkinje Cell Activity Purkinje cells exhibit two types of action potentials: the simple spikes, and the complex spikes (Figs. 132.7A and B). ‘Simple Spikes: Simple spike action potential is gen- erated in response to stimulation of mossy fiber-parallel fiber input. ‘Complex Spikes: Complex (multi-peaked) spike action potential is generated in response to stimulation of climb- ing fiber input that comes from olivary nucleus. These com- plex spike action potentials are involved in motor learring as climbing fiber activity is observed to be increased when a new motor task is learned. They also produce long-term adjustment in motor responses. Functions of Cerebellum 1. Control of postural balance and equilibrium: This is the function of vestibulocerebellum, which has extensive and reciprocal connection with the vestibular nuclei Afferents from vestibular apparatus in the inner ear project to vestibulocerebellum via vestibular nuclei 2. Vestibulo-ocular reflex: Vestibulocerebellum is con- cerned with learning induced changes in vestibulo- ocular reflex. 3. Smoothening and coordination of movement: This is the function of spinocerebellum that receives proprioceptive and other sensory inputs from all the Figs. 132.78 anc Purkinje cell responses. (A) Simple spike; (8) Complex spike1094 Section 11:Neurophysiology Corticospinal ——| Anterior hom call Fig. 132.8: The cerebellar connection to explain its comparator of a servo mechanism. body parts through the spinal cord. It also receives inputs from the motor cortex, where motor planning is carried out. By comparing plan with performance, it ‘smoothens and coordinates movement. |. Control of posture: The vermal portion of spinocere- bellum projects to the brainstem areas that control axial and proximal limb muscles. Therefore, ver- mal spinocerebellum has profound influence on posture. Control of skilled voluntary movements: The para- vvermal region of spinocerebellum projects to the brain- stem nuclei that influence distal limb muscles. Therefore, paravermal spinocerebellum controls skilled voluntary movements. =. Cerebellum controlsall aspects of movement starting, from rate, range, force, and direction to termination of movement. Although functionally cerebellum has three lobes (vestibulo-, spino- and neocerebellum), they work in a coordinated manner, that means it acts as “comparator of a servo mechanism’. = Cerebellum receives information from cortico- spinal output transmitted to the muscles, receives proprioceptive inputs from muscles (via spinocere- bellar tracts) that informs about ongoing movements, and position of the limbs, and also receives all spe- cial sensory inputs (visual, auditory and vestibular inputs). = Cerebellum projects to cortex via red nucleus and pontine nuclei (Fig. 132.8). Cerebellum coordinates all the cortical and spinal information and appro- priately modifies the ongoing movements via its influence on all descending pathways. — It sends error signal to the cortex for alteration in programming of the movement for any desirable change in motor outputs to be achieved. 6. Planning and programming of the movements: This is the function of neocerebellum that interacts with the cortex. Hence, neocerebellum controls planning and programming of the movements. Control of muscle tone and stretch reflexes: Cere- bellum influences the activity of the major descencing medial system pathways through its output from fest geal nucleus, especially the vestibulospinal and ret cu- lospinal tracts = As vestibulospinal tract mainly controls a. neuron activity and reticulospinal tract controls y neuron activity in the spinal cord, cerebellum is one of the major sites of c.~y co-linkage. — In human beings, the output of deep cerebellar nuclei to the to the brainstem motor nuclei is exci tatory that facilitates muscle tone. Therefore, cere- bellar disorder produces hypotonia. — Though cerebellum has profound influence on all descending brainstem pathways, its influence on stretch reflexes is minimal, except in some patients itis pendular in whom knee jerk is observed (pen- dular knee jerk). Therefore, stretch reflexes remain usually normal in cerebellar disorder.Chapter 132: Cerebellum — However, in animals, the connection of cerebellum with brainstem nuclei is complex, which inhibits the output of inhibitory reticular area. Therefore, cerebellectomy in decerebrate animals increases spasticity of extensor group of muscles (facilitates decerebrate rigidity). 8. Control of movements of one side of the body: Motor cortex of one side is connected to the cerebellar hemi sphere of opposite side through a closed feedback cir- cuit, known as cerebral-cerebellar-cerebral circuit via cortico-ponto-dentato-thalamo-cortical connections. — Thus, each cerebellar hemisphere influences the output of opposite cerebral cortex. - However, cerebral cortex via corticospinal tract that decussates to opposite site just after passing through pyramid controls the motor functions of contralateral half of the body. = Therefore, due to double decussation, each cere- bellar hemisphere controls movements of its own side of the body. 9. Learning and improvement of motor skill: Cere- bellum plays a critical role of comparing information of the ongoing movements and the changes required to improve performance. — Hence, for every activity, cerebellum improves the learning and performance. ~ Cerebellum also controls long-term adjustment of motor skills. ~ Especially, climbing fiber inputs that produce com- plex spikes in Purkinje cells (Figs. 132.7A and B) is involved in motor learning. — Climbing fiber activity is increased every time a new activity is learned, Eyeball movement: The paraflocculus and pyramis of cerebellum are concerned with movement of eye ball especially in upward direction. Stimulation of these parts of cerebellum causes upward eye movement of the ipsilateral side. Especially, visual judgment of distance is the function of cerebellum, which is more developed in monkeys. Vestibular functions: For its dense and reciprocal connection with vestibular refiex, vestibulocerebellum is involved in control of all vestibular functions, such as balance during movement, execution of vestibule- ocular reflex, vestibular postural reflexes, and change in body posture and movement in response to head movement and acceleration. (asia ena eis Diseases affecting flocculonodular lobe result in abnor- malities in maintaining equilibrium. For example, stimu- lation of vestibulocerebellum or vestibular nuclei leads to the motion sickness. intractable motion sickness, in fact, is cured by selective removal of flocculonodular lobe. 10. 11 Features of cerebellar disorder depend on the part of cerebellum affected and whether the cortex or the deep cerebellar nuclei are involved in the disease process. Effects of lesion of one side cerebellar hemisphere mani- {fest on the ipsilateral side of the body. In general, cerebellar disorders have the following features: 1._ No paralysis (voluntary movements are intact, though defective) 2. Usually, reflexes are normal, except that sometimes, pendular knee jerk is elicited. 3. No sensory deficit. 4. Hypotonia is a usual feature. 5. Ataxia: Motor deficit in cerebellar disorder manifests mainly in the form of ataxia, which is defined as a defect in coordination due to errors in the rate, range, force, and direction of movement. If only cerebel- lar cortex is involved in the disease process, ataxia is temporary. But, if the lesion involves deep cerebellar nuclei, the ataxia almost becomes permanent. Ataxia manifests in the following forms: i, Drunken gait: Unsteady and wide-base gait. i. Scanning speech: Ataxia involving muscles of speech manifests in the form of scanning speech. Patient scans the syllables while speaking. ili, Dysmetria: When patient attempts to touch an ‘object, usually the hand overshoots instead of reaching the target. This is called dysmetria (inal lity to measure the length or distance). This is also called past pointing. iv, Intention tremor: Due to dysmetria, the correc- tive measures are immediately initiated, but tl time hand overshoots in the opposite direction Repeated overshoot and recorrection results in intention tremor (hand oscillating back and forth). Tremors not seen at rest. v. Rebound phenomenon: This results due to inabi- ity to put on brake (suddenly stop) of the ongoing movement. For example, if the patient is asked to flex his limb against resistance and then asked to stop immediately by withdrawing the resistance, he cannot stop, rather his arm moves with a wide arc. This is called rebound phenomenon. vi, Adiadochokinesia: Inability to perform alternate ‘movements rapidly is called adiadochokinesia For ‘example, patient cannot perform supination and pronation rapidly. Decomposition of movement: Inability to perform movement that involves more than one joint simul- taneously. Therefore, cerebellar patient dissects such complex movement and performs movement at each joint slowly and separately. 6. Inability to carry out long-term adjustment in motor response. 7. Defect in vestibulo-occular reflex leads to pathological nystagmus. vii, 1095