1. Cerebellum Dr Taha Sadig Ahmed, MBBS, PhD ( England ). Consultant, Clinical Neurophysiology. Associate Professor, Physiology Department, College of Medicine 18 November 201518 November 201518 November 20151

2. 2 The cerebellum is located at the bottom of the brain, in the posterior cranial fossa, over the occipital bone. It is separated from the overlying cerebrum by a layer of leathery dura mater called Tentorium Cerebelli Anterior to it is Pons and 4 th ventricle 4 th Ventricle

3. 18 November 201518 November 201518 November 2015 3 Flocculonodular Lobe Posterolateral Fissure  It consists of  (1) two Cerebellar Hemispheres, connected by (2) a middle part called Vermis, and a (3) a posterior Flocculonodular Lobe.

4. 18 November 201518 November 201518 November 2015 4 Flocculonodular Lobe (1)Neocerebellum ( Cerebrocerebellum ) (2)Spinocerebellum ( Paleocerebellum), & (3)Vestibulocerebellum ( Floculonodular Lobe, Archicerebellum ) Neocerebellum (Lateral parts of hemispheres ) Spinocerebellum ( Vermis + medial parts of hemispheres ) Hemisphere Posterolateral Fissure Functionally, the Cerebellum is divided into 3 parts :

5. 18 November 201518 November 201518 November 2015 5 Inputs to the cerebellum from the Cerebrum Inputs to the Cerebellum from from the Pons Inputs to the Cerebellum from the Medulla Oblongata It is connected to the brainstem on each side by 3 peduncles : Superior, Middle & Inferior Superior Cerebellar Peduncle Middle Cerebellar Peduncle Inferior Cerebellar Peduncle

6. 18 November 201518 November 201518 November 20156 Although it weighs only 10 % as much as the cerebral cortex, its surface area is about 75 % of that of the cerebral cortex. Cerebellar motor pathways are uncrossed, so that injuries on one side will result in symptoms & signs on the same side of the body.

7. 18 November 201518 November 201518 November 2015 Neocerebellum ( (Cerebrocerebellum ) Comprises the lateral parts of cerebellar hemispheres. in planning/ execution It closely cooperates with the cerebrum ( including motor cortex ) cerebral cortex in planning/ programming + execution of voluntary movements. It is involved in motor learning of voluntary, skilful movements. It coordinates activity of muscles involved in execution It coordinates activity of muscles involved in execution of skilled movements. These skilled movements are mainly performed by distal limb muscles ( namely hand muscles ). These skilled movements are mainly performed by distal limb muscles ( namely hand muscles ). Thus the Neocerebellum helps us to monitor,coordinate, and execute fine, skilled movement ( which is primarily voluntarily initiated by the motor cortex ). And makes us able to perform complex skilful movements such as writing, drawing, playing musical instruments, singing etc

8. 18 November 201518 November 201518 November 2015 8 Spinocerebellum ( Paleocerebellum) Consist of Vermis & Medial Parts of the Cerebellar Hemispheres. areas concerned with control of axial and proximal limb muscles (which are concerned with gross postural adjustments ). The vemis projects to the brainstem areas concerned with control of axial and proximal limb muscles (which are concerned with gross postural adjustments ). The Spinocerebellum receives  (1) Proprioceptive inputs afferents from all parts of the body + (2) a copy of the “ Motor Plan ”from the motor cortex It functions to  (1) Regulates & maintains muscle tone (2) Acts as a comparator

9. 18 November 201518 November 201518 November 2015 9 Vestibulocerebellum ( Floculonodular Lobe) It has connections to the vestibular nuclei, consequently, it is concerned with maintenance of body balance & equilibrium It also controls the Vestibulocular Reflex ( VOR)

10. Efferents from Cerebellar Cortex 18 November 201518 November 201518 November 201510

11. Neocerebellar Cortical Efferents Neocerebellar cortex projects to to the Dentate Nucleus  Neocerebellar cortex projects to to the Dentate Nucleus  & from there to the Thalamus ( its Ventrolateral Nucleus ), & from there to the Thalamus ( its Ventrolateral Nucleus ), which, in turn, will project to the  Motor & Premotor Areas of the Cerebral Cortex. which, in turn, will project to the  Motor & Premotor Areas of the Cerebral Cortex.  in order to  (1) aid in motor planning  (2) coordinate activity of different muscle groups during execution of voluntary, skilled movement

12. Spinocerebellar Cortical Efferents : The projects to the Fastigial Nucleus  & from there to  Brainstem Nuclei The Vermis projects to the Fastigial Nucleus  & from there to  Brainstem Nuclei The Hemispheric Portions of the Spinocerebellum Nucleus Interpositus ( i.e., The Hemispheric Portions of the Spinocerebellum project to  Nucleus Interpositus ( i.e., Emboliform and Globose nuclei ) & from there to  Brainstem Nuclei & from there to  Brainstem Nuclei These Brainstem Nuclei receiving inputs from the spinocerebellum are concerned with control of axial and proximal limb muscles ( in order to adjust muscle tone & body posture ). These Brainstem Nuclei receiving inputs from the spinocerebellum are concerned with control of axial and proximal limb muscles ( in order to adjust muscle tone & body posture ).

13. 18 November 201518 November 201518 November 2015 13 Vestibulocerebellar Cortical Efferents : Efferents from the Vestibulocerebellum pass directly to Brainstem Nuclei ( & not through the DCN) These vestibulocerebellar efferents function to regulate of body balance & equilibrium + the VOR ).  Hence, it should be remembered that, though the DCN provide the only outlet for the Neocerebellum and Spinocerebellum, they are not the outlet/gateway for Vestibulocerebellum

14. 18 November 201518 November 201518 November 2015 14 Functions of Cellular Elements of Cerebellar Cortex

15. 18 November 201518 November 201518 November 2015 15 Cerebellar Cellular Organization The cerebellum comprises The cerebellum comprises Cortex and Deep Cerebellar Nuclei (DCN) The DCN are 4 in number, & The DCN are 4 in number, & are named : (1) Dentate, (2) Fastigial. (3) Globose, (4) Emboliform, NB : Globosus & Emboliform are collectively called Interpositus Nucleus. Cerebellar Afferents : These are Mossy Fibers & Climbing Fibers. These are Mossy Fibers & Climbing Fibers.  Climbing Fibers come from the Inferior Olivary Nucleues, & they provide indirect proprioceptive inputs to the cerebellar cortex  Mossy Fibers, come from (1) all parts of the body, + (2) cerebral cortex. As they ascend, they send collaterals to the DCN, and thereafter proceed ( pass on ) to synapse on cerebellar cortical cells.

16. 18 November 201518 November 201518 November 2015 16 Layers of the Cerebellar Cortex The cerebellar cortex is made of layers  (1) External Molecular layer, ( 2) Middle Purkinje Cell layer that is only one cell thick, (3) Internal Granular layer

17. 18 November 201518 November 201518 November 201517 The cerebellar cortex contains mainly 5 types of neurons : Purkinje, Granule, Basket, Stellate & Golgi cells. (1) Purkinje Cells : Are amongst the biggest neurons in the body. Have very extensive dendritic arbors that extend throughout the Molecular Layer. Their axons, which are the only output from the cerebellar cortex, pass to the deep nuclei. Cells of the Cerebellar Cortex

18. 18 November 201518 November 201518 November 201518 (2) Granule Cells (2) Granule Cells Their cell-bodies are situated in the Granular layer. They receive inputs from the Mossy fibers and they innervate the Purkinje cells. Each sends an axon to the Molecular layer, where the axon bifurcates to form a T. Because the branches of this “ T ” are straight and run for long distances, they are called Parallel Fibers.

19. 18 November 201518 November 201518 November 201519 The other 3 types of neurons in the cerebellar cortex are inhibitory neurons : (3) Basket cells : (3) Basket cells : Are located in the Molecular layer They receive inputs from Parallel fibers, and each projects to many Purkinje cells. Their axons form a basket around the cell-body and axon hillock of each Purkinje cell they innervate. They are excited by Parallel fibers of Granule cells, & their output inhibits Purkinje cell discharge by a process of Feed-Forward Inhibition. (4) Stellate cells Similar to Basket cells, these cells are excited by Parallel fibers of Granule cells, & their output inhibits Purkinje cell discharge by a process of Feed-Forward Inhibition. They differ from Basket cells only in being more superficially located in the cortex than Basket cells.

20. 18 November 201518 November 201518 November 201520 Golgi cells are located in the Granular layer. Their dendrites, which project into the Molecular layer, receive inputs from the Parallel fibers. Their cell bodies receive input via collateralsfrom the incoming Mossy fibers and the Purkinje cells Their axons project to the dendrites of the Granule cells. They are excited by (1) Mossy fibers (2) Purkinje cells, & (3) Parallel fibers. They inhibit the action of Mossy fibers on Granule cells.

21. 18 November 201518 November 201518 November 201521 The Main Inputs (Afferents ) to the Cerebellar Cortex (1) There are 2 main inputs to the cerebellar cortex : the Climbing Fibers and Mossy Fibers, both of which are excitatory. Climbing Fibers : The climbing fibers come solely from the Inferior Olivary Nucleues They provide an indirect proprioceptive input to the cerebellar cortex  bringing to it proprioceptive information from all parts of the body via relays in the Inferior Olive (which receives proprioceptive inputs from all over the body parts ) Each climbing fiber projects to the dendrites of Purkinje cells, around which it entwines like a climbing plant.

22. 18 November 201518 November 201518 November 201522 The Main Inputs (Afferents ) to the Cerebellar Cortex (2) Mossy Fibers : (1) These, unlike Climbing Fibers ( which provide an indirect proprioceptive input ) do provide a direct proprioceptive pathway ( input ) to the cerebellar cortex, from all parts of the body, and, in addition ( which provide an indirect proprioceptive input ) do provide a direct proprioceptive pathway ( input ) to the cerebellar cortex, from all parts of the body, and, in addition (2) Provide inputs from the Motor Area ( M1) & related areas of the Cerebral Cortex ( indirectly, via relays in the pontine nuclei ). They end on the dendrites of Granule cells in complex synaptic groupings called Glomeruli. The Glomeruli also contain the inhibitory endings of the Golgi cells. Climbing FibersMossy Fibers

23. 18 November 201518 November 201518 November 201523 Corollary ( summary ) of effects of different cells & afferents on Purkinje cells (A) Excitatory The fundamental circuits of cerebellar cortex are thus relatively simple : (1) climbing fiber inputs exert a strong excitatory effect on single Purkinje cells, whereas (1) climbing fiber inputs exert a strong excitatory effect on single Purkinje cells, whereas (2) Mossy fiber inputs exert a weak excitatory effect on many Purkinje cells via the Granule cells. (2) Mossy fiber inputs exert a weak excitatory effect on many Purkinje cells via the Granule cells. (B) Inhibitory (1) Basket cells (1) Basket cells (2) Stellate cells (2) Stellate cells (3) Golgi cells  (3) Golgi cells  Golgi cells are excited by Golgi cells are excited by (1) Mossy fibers (2) Purkinje cells, & (3) Parallel fibers. They inhibit the action of Mossy fibers on Granule cells Both are excited by Parallel fibers of Granule cells, & their output inhibits Purkinje cells ( Feed-Forward Inhibition ).

24. 18 November 201518 November 201518 November 201524 Q : What are the Neurotransmitters Secreted by in the Cerebellar Cortex Neurons ? Purkinje cells Basket cells Stellate cells Golgi cells Granule cells  Glutamate Secrete GABA

25. 18 November 201518 November 201518 November 201525 Summary of Connections & Functions FunctionOutputsInputsCortexDeepNuclei In cooperation with cerebral cortex  Planning, orogramming and execution of voluntary & skilled movements SCP to VA/VL Corticopontine/pontocerebellar Lateral portions of Cerebellar Hemisphere DentateNeo-cerebellum (1) Muscle tone (2) Postural adjustmen& (3) Coordination of different of different muscle groups muscle groups activity for activity for smooth smooth performance of performance of movement movement SCP to Red Nucleus; Fastigial to RF Spinal and brainstem paths Vermis & Medial portions of Cerebellar hemispheres Interposed ; Fastigial Spino-cerebellum Balance, equilibrium & VOR Vestibular nuclei; RF Vestibular nuclei Flocculo Nodular Lobe FastigialVestibulo-cerebellum

26. 18 November 201518 November 201518 November 201526 Summary of Cerebellar Cortex Efferenrts Projections of Neocerebellar Cortex : The Neocerebellar Cortex projects ( sends its efferents ) to the Dentate Nucleus  & from there to the Ventrolateral Nucleus of the Thalamus. Projections of Spinocerebellar Cortex : The medial part of the Spinocerebellum ( Vermis ) projects to the Fastigial Nuclei  & from there to the brainstem. The hemispheric portions of the Spinocerebellum ( i.e.,  & from there to the brainstem nuclei. The hemispheric portions of the Spinocerebellum ( i.e., medial parts of the cerebellar hemispheres ) project to the Emboliform and Globose nuclei  & from there to the brainstem nuclei. Projections of the Vestibulocerebellar Cortex : Most of the Vestibulocerebellum cortex outputs ( efferents ) pass directly to the brainstem ( to regulate balance, equilibrium & the VOR ). However, unlike it, the rest of the cerebellar cortex ( i.e., that of the Neocerebellum and Spinocerebellum ) sends fibers first to the deep cerebellar nuclei, and then, these in turn will project ( send their efferents ) to the brainstem. Consequently, the Deep Cerebellar Nuclei provide the only output of the Neocerebellum and Spinocerebellum.

27. 18 November 201518 November 201518 November 201527Summary The cerebellum influences movement on the ipsilateral side of the body. Neocerebellum is involved, in conjunction & close cooperation with the cerebral cortex, in programming, planning & execution of voluntary movement ; especially skilled movements ( which is mostly performed by the distal limb muscles ( e.g., hand ) Spinocerebellum is primarily involved with (1) regulation & Spinocerebellum is primarily involved with (1) regulation & maintenance of muscle tone, (2) gross postural adjustments, & (3) coordination between different muscle groups for smoothening of movement ( it acts as a comparator ) (The vermis helps coordinate movements of the. (The vermis helps coordinate movements of the axial and proximal limb muscles ). Floculonodular lobe is mainly concerned with balance equilibrium as well as VOR.

28. 18 November 201518 November 201518 November 201528 Contd Summary …….. Climbing fibers originate in the inferior olivary nuclei and synapse directly onto Purkinje cells. All other sources of input to the cerebellum enter as mossy fibers. Purkinje cells are the main output neurons of the cerebellar cortex & project to the deep nuclei of the cerebellum. They are inhibitory to the DCN. The deep cerebellar nuclei ( DCN ) project out to brainstem and thalamic targets via the superior cerebellar peduncles. They are excitatory, but in turn, are themselves inhibited ( switched off ) by Purkinje cells.

29. 18 November 201518 November 201518 November 201529 Cerebellar Syndromes

30. Signs of Cerebellar Disorders DeficitManifestation AtaxiaReeling, wide-based gait Decomposition of movement Inability to correctly sequence fine, coordinated acts DysarthriaInability to articulate words correctly, with slurring and inappropriate phrasing DysdiadochokinesiaInability to perform rapid alternating movements DysmetriaInability to control range of movement HypotoniaDecreased muscle tone NystagmusInvoluntary, rapid oscillation of the eyeballs in a horizontal, vertical, or rotary direction, with the fast component maximal toward the side of the cerebellar lesion Scanning speechSlow enunciation with a tendency to hesitate at the beginning of a word or syllable TremorRhythmic, alternating, oscillatory movement of a limb as it approaches a target (intention tremor) or of proximal musculature when fixed posture or weight bearing is attempted (postural tremor)

31. 18 November 201518 November 201518 November 201531 The Difference Between Lesions of the Cerebellar Cortex & Lesions of DCN If only the cortex of the cerebellum is involved, the movement abnormalities gradually disappear as “ compensation ” occurs. However, lesions of the DCN produce more generalized defects, and abnormalities are permanent. For this reason, care should be taken to avoid damaging the DCN when surgery is undertaken to remove a tumor involving part of the cerebellar cortex.

32. 18 November 201518 November 201518 November 201532 Cerebellar Hemispheric Lesions Cerebellar lesions cause no paralysis or sensory deficit. When not moving, there are no externally obvious signs. However, upon physical examination, signs such as hypotonia and pendular reflexes can be elicited. Once the patients attempts movement, ataxia appears. What is ataxia ? Ataxia is incoordination of due to errors in the rate, range, force and direction of movement. Wth circumscribed lesions, the ataxia may be confined/localized to only one part of the body.

33. 18 November 201518 November 201518 November 201533 I/Ataxia (lack of coordination of muscle movement ), which is manifested by  (1) Wide-based, unsteady “ drunken, or staggering “ gait. (2) Scanning speech (3) Dysmetria ( also called Past-Pointing ) : attempting to touch an object with a finger results in overstretching to one side or the other  this promptly initiates a gross correction action ( corrective action ), but the correction overshoots to the other side  Consequently, the finger oscillates back and forth. This oscillation is the (4) “ Intention Tremor ”, which is characteristic of cerebellar disease. This cerebellar tremor, unlike that of Parkinson’s disease, is absent at rest. A/ Hemispheric Lesions

34. 18 November 201518 November 201518 November 201534 II/ Inability to “ put on the brakes ”  i.e., inability to stop movement promptly. Normally, for example, flexion of the forearm against resistance is quickly checked when the resistance force is suddenly broken off. The patient with cerebellar disease can not break the movement of the limb, and the forearm flies back in a wide arc. This abnormal response is known as the “ Rebound Phenomenon ”. III/ Adiadochkinesia ( Dysdiadochkinesia ) : Inability to perform rapidly alternating opposite movements such as repeated pronation and supination of the hands. IV/ Difficulty in performing actions that involve simultaneous motions at more than one joint. The patient dissects such movements and carries them out one joint at a time, a phenomenon known as “ Decomposition of Movement ”. Hemispheric Lesions ( Contd )

35. 18 November 201518 November 201518 November 201535 B/ Flocculonodular Lobe Lesions Midline cerebellar tumors in children, arising from the “ Nodule ”, early in their course (& before affecting the rest of the cerebellum), damage first the Flocculonodular lobe. (& before affecting the rest of the cerebellum), damage first the Flocculonodular lobe. Such a child is afraid ( & reluctant ) to stand erect and move without support. This is because if he tries to walk, he does so in a staggering fashion on a broad base, & tends to fall. Moreover, selective Flocculonodular lobe lesions may cause vertigo

36. 18 November 201518 November 201518 November 201536 Role of the Cerebellum in Learning (1) The cerebellum is concerned with learned adjustments that make coordination easier when a given task is performed over & over As a motor task is learned, activity in the brain shifts from the Prefrontal ( cerebral ) Cortex to the (1) Parietal Cortex, (2) M1, & (3) Cerebellum. The basis of learning in the cerebellum is the input via the Olivary Nucleus. It is worth noting, in this regard, that each Purkinje cell receives inputs from 250,000 to 1,000,000 Mossy fibers. By contrast, each Purkinje cell receives only a single ( only one ) Climbing fiber from the inferior olive, and this fiber makes 200-3000 synapses on the Purkinje cell. Climbing fiber activation produces a large complex spike in the Purkinje cell This spike produces lomg-term modification of the pattern of Mossy fiber input to that particular Purkinje cell. Climbing fiber activity is increased when a new movement is being learned, and lesions of the Olivary Nucleus abolish the ability to produce long-term adjustments in motor responses..

37. 18 November 201518 November 201518 November 201537 Finished