Cerebellum, and Basal Ganglia by Dr. Rabia Inam Gandapore.pptx

Neuro-Anatomy

1. Cerebellum & Basal Ganglia Dr. Rabia Inam Gandapore Assistant Professor Head of Department Anatomy (Dentistry-BKCD) B.D.S (SBDC), M.Phil. Anatomy (KMU), Dip. Implant (Sharjah, Bangkok, ACHERS) , CHPE (KMU),CHR (KMU), Dip. Arts (Florence, Italy )

2. Teaching Methodology LGF (Long Group Format) SGF (Short Group Format) LGD (Long Group Discussion, Interactive discussion with the use of models or diagrams) SGD (Short Group) SDL (Self-Directed Learning) DSL (Directed-Self Learning) PBL (Problem- Based Learning) Online Teaching Method Role Play Demonstrations Laboratory Museum Library (Computed Assisted Learning or E-Learning) Assignments Video tutorial method

3. Goal/Aim (main objective) To help/facilitate/augment the students about the : Describe the gross anatomy & blood supply of the cerebellum. Discuss the connections and functions of cerebellum . Enumerate the basal nuclei and its most important structures. Recall important functions of basal nuclei along with their clinical correlations

4. Specific Learning Objectives (cognitive) At the end of the lecture the student will able to: Describe the gross anatomy & blood supply of the cerebellum. Discuss the connections and functions of cerebellum. Enumerate the basal nuclei and its most important structures. Recall important functions of basal nuclei along with their clinical correlations

5. Psychomotor Objective: (Guided response) A student to draw labelled diagram of cerebellum & connections of Basal Nuclei with their clinical correlations

6. Affective domain To be able to display a good code of conduct and moral values in the class. To cooperate with the teacher and in groups with the colleagues. To demonstrate a responsible behavior in the class and be punctual, regular, attentive and on time in the class. To be able to perform well in the class under the guidance and supervision of the teacher. Study the topic before entering the class. Discuss among colleagues the topic under discussion in SGDs. Participate in group activities and museum classes and follow the rules. Volunteer to participate in psychomotor activities. Listen to the teacher's instructions carefully and follow the guidelines. Ask questions in the class by raising hand and avoid creating a disturbance. To be able to submit all assignments on time and get your sketch logbooks checked.

7. Lesson contents Clinical chair side question: Students will be asked if they know what is the function of Outline : Activity 1 The facilitator will explain the student's about: Gross anatomy & blood supply of the cerebellum. Discuss the connections and functions of cerebellum. Enumerate the basal nuclei and its most important structures . Activity 2 The facilitator will ask the students to make a labeled diagram cerebellum & connections of Basal Nuclei with their clinical correlations Activity 3 The facilitator will ask the students a few Multiple Choice Questions related to it with flashcards.

8. Recommendations Students assessment: MCQs, Flashcards, Diagrams labeling. Learning resources: Langman’s T.W. Sadler, Laiq Hussain Siddiqui, Snell Clinical Anatomy , Netter’s Atlas , BD Chaurasia’s Human anatomy, Internet sources links.

9. C erebellum (little brain) Lies in Posterior Cranial Fossa of skull Separated from cerebrum by tentorium cerebelli ( i nvagination of meningeal layer of   dura mater) Folia (Folds in cortex-gray matter/ unmyelinated dendrites, cell body) Increase surface area of cerebellum. 3 layers 1. Molecular layer (External layer) 2. Purkinje cell layer (Middle layer) 3. Granular layer (Internal layer) Arbor Vitae = white matter/ myelinated axons-pathways, deep intracerebellar nuclei

10. Arbor vitae Folia

11. Functions Responsible for coordinating muscle activity Sequences the motor activities Monitors and makes corrective adjustments in the activities initiated by other parts of the brain Compares the actual motor movements with the intended movements and makes corrective changes

12. Gross Appearance 2 cerebellar Hemisphere (Left & Right ) Joined by vermis 3 peduncles (Superior, Middle, Inferior) connects cerebellum posteriorly 3 Lobes Anterior lobe- Superior surface Middle lobe (Posterior lobe) Flocculonodular lobe ( Archies ) Separated by Primary Fissure Horizontal Fissure= Separates superior & inferior surface Between Primary & Uvulonodular Fissure Posterior to Uvulonodular Fissure

13. Functional Organization of the Cerebellum Balance & Equilibrium , Muscle tone , Coordination of movements , Motor learning . Functionally arranged along the longitudinal axis : Anterior Lobe ( Spinocerebellum Zone ): Proprioceptive pathway-Sensory 1. Vermis : located at center , controls axial movements of neck, head, shoulders, and hips 2. Para Vermis ( Intermediate zone ) controls motion of distal portions of upper & lower limbs especially hands & feet Middle Lobe (Posterior- Neocerebellum Zone ): Cerebrum- Motor-plan -Cerebellum 1. Lateral zone controls sequencing movements of muscle . Important for timing & coordination of movement Flocculonodular lobe ( Vestibulocerebellum ) : Inner Ear Information from vestibular system

14. Anterior Lobe Middle (Posterior) Lobe Flocculonodular lobe Intermediate Zone Cerebrocerebellum (Lateral Zone /Hemisphere

15. Intracerebellar Connections & Nuclei Superior Cerebellar peduncle – Midbrain Middle Cerebellar peduncle – Pons Inferior Cerebellar peduncle – Medulla

16. Deep ( Intracerebellar ) Nuclei Fastigial Nucleus ( center vermis , connected with flocculonodular lobe) I nterposed Nucleus (Anterior Lobe- vermis,Paravermis ) Globose Emboliform Dentate Nucleus ( Lateral Hemisphere ) D ON’T E AT G REASY F OOD

17. Cerebellar Cortex Gray Matter (cell body, dendrites)

18. Neuronal Organization of the Cerebellar Cortex Organized in 3 layers 1. M olecular cell layer (Stellate cell, basket cell, parallel fibers of granular cell ) 2. Purkinje cell layer ( Purkinji neurons/cell-Golgi type 1) 3. G ranular cell layer O utput from the cerebellum comes from a 4.deep nuclear cell layer (Dentate, Emboliform , Globose , Fustigial ) located below these layers of cortex This makes internal circuiting crucial for neural sharpening - Perfect planning for movement coordination

19. Golgi Cells Golgi Cells & Granular cells called Glomeruli Stellate Cells Basket Cells

20. Neuronal Circuit

21. 1. Climbing Fibers Inferior Olives = Spino-olivary tract: Proprioceptive information enters spinal cord and cross over enter the inferior olives , crosses over to enter the contralateral cerebellum. Enter the inferior cerebellar peduncles to enter the cerebellum and synapses with the deep nuclei (neurotransmitter: aspartate-stimulatory) in the cerebellum to cause action potential downward ( Descending pathway- brainstem ). CLIMBING FIBERS It also can also ascend up and crosses the granular layer, then enter purkinji layer superiorly and give axons to release the neurotransmitter called aspartate-stimulatory to act on the purkinji fibers. The action potential flows down purkinji fibers to release the neurotransmitter called GABA-inhibitory on the deep cerebellar nuclie

22. Climbing fibers send branches to deep nuclear cells before they make connections with dendrites of Purkinje cell. Causes complex spike output from Purkinje cell

23. Deep nuclear cells receive excitatory and inhibitory inputs

24. 2. Mossy Fibers Mossy fibers relay all other afferent input (Sensory pathways) into cerebellum , also send branches to deep nuclear cell Fibers come & stimulate deep nuclei by releasing Glutamate-Excitatory (Maintain posture, balance, movement & equilibrium, muscle tone & motor learning) It also ascends up into granular layer to give multiple axons & connect with granular cells (Glomeruli) & golgi cells- Release neurotransmitter Glutamate-Stimulator G ranular cell fibers ascends to pass purkinji layer & enter molecular layer to spread like parallel fibers and release stimulatory neurotransmitters to act on stellate cells & basket cells. Granular cell fibers also give off direct branches to purkinji fibers & stimulates it. Which can decends down to release inhibitory GABA on to the deep cerebellar nuclei causes them to fire S tellate & basket cells releases inhibitory neurotransmitters to inhibit the purkinji cell/fibers. G olgi cells also release inhibitory neurotransmitters onto the granular cells

25. Afferent Pathways

26. Predictive and Timing Function of the Cerebellum Motion is a series of discrete sequential movement T he planning and timing of sequential movements is the function of the lateral cerebellar hemisphere T his area communicates with premotor and sensory cortex and corresponding area of the basal ganglia where the plan originates T he lateral hemisphere receives the plan and times the sequential events to carry out the planned movement

27. Afferent Pathways to the Cerebellum Superior Cerebellar Peduncles : Dentate, emboliform & globose nuclei Mossy or Climbing Fibers-Afferent Dorsal spinocerebellar tract: ( above L2-T1 ) transmits information mostly from muscles spindle but also from Golgi tendon organs, tactile, and joint receptors. A pprises the brain of the momentary status of muscle contraction, muscle tension and limb position and forces acting on the body surface V entral S pinocerebellar tract: ( below L2/L3 ) sensory signals from anterior horn, and interneurons, transmits information on which signals have arrived at the cord Rostral cerebellar tract: Cervical region of spinal cord Tecto -cerebellar tract: (superior colliculus / Visual /Lateral-geniculate body & IC- MG

28. Middle Cerebellar Peduncles : – Corticopontocerebellar pathway: Fibers from motor and premotor area, somatosensory cortex as well as some ipsilateral pontine nuclei goes to contralateral cerebellum which join this tract. Projects mostly to the lateral areas. (It can then process the information and send via dentorubro or dentothalamic pathway back in the cortex)

29. Inferior Cerebellar Peduncles : – Dorsalspinocerebellar tract: ipsilateral cerebellum C8-L2/L3 ( clarks nucleus ) – Cuneocellebellar tract: Above C8 ipsilateral cerebellum via accessory cuneate nucleus –external arcuate fibers – Vestibulocerebellar tract: inner ear , ipsilateral cerebellum – Olivocerebellar tract: Originates from inferior olive Inferior olive receives input from motor cortex, basal ganglia, reticular formation & spinal cord, Properioceptive /Contralateral olive but ipsilateral cerebellum- CLIMBING FIBERS- purkinji – Reticulocerebellar tract : All sensory information These pathways transmit information about intended motion.

30. Efferent Pathways

31. Efferent Pathways from the Cerebellum Superior Cerebellar peduncles 1. Dentate Nucleus- cerebrocerebellum /Lateral hemispheres 2 Pathways: Send fibers from cerebellum to contralateral Red Nucleus (mid brain) Thalamus (cerebrum)- Dentothalamic pathway Interconnecting fibers between red nucleus & thalamus- Dentorubrothalamic pathway & Dento-Rubrospinal pathway (Red nucleus, decussates to spinal cord- flexor muscle limbs) 2. Interpose nucleus: Globose & Emboliform nucleus Cerebellovestibular pathway- Purkinji fibers ( Donot go to the deep nuclei) directly go via SCP & stimulate the Vestibular complex in the medulla- activates the vestibilospinal tract (activates extensor muscles, ascends to activate connects CN3,4,6 responsible for extra ocular muscles) medial longitudinal faciculus -

32. Inferior Cerebellar Peduncles : Cerebello / Fastigioreticular tract: equilibrium control , fastigial nucleus connects with the reticular formation and go back to the subcortical tracts(Medullary-flexion & pontine-extention tracts) Cerebellothalamocortical tract (Vestibular): Purkinji fibers go to vestibular nuclie complex –ascend via medial longitudinal fasiculus controls the extra ocular eye movements or coordinates agonist and antagonist extensor muscle contractions-antigravity

33. Blood Supply The cerebellum receives its blood supply from three pairs of arteries: Superior cerebellar arteries A nterior inferior cerebellar arteries P osterior inferior cerebellar arteries . These arteries arise from the vertebral arteries and the basilar artery , providing oxygenated blood to different regions of the cerebellum.

34. Clinical Abnormalities

35. Clinical Abnormalities of the Cerebellum Ataxia and intention tremor – failure to predict motor movement, patients will overshoot intended target D ysdiadochokinesia – failure of orderly progression of movement D ysarthria – failure of orderly progression in vocalization C erebellar nystagmus – intention tremor of the eyes

36. Basal Ganglia

37. Basal Ganglia Consist of Four Nuclei 1. NeoStriatum Caudate nucleus Putamen 2. Globus pallidus Globus pallidus internus Globus pallidus externus 3. Amygdaloid nucleus - Thalamus Ventral Anterior Nucleus Ventral Lateral Nucleus - Sub-thalamic nuclei (glutamate-excitatory) - Substansia nigra ( zona compacta contain dopamine) Lentiform Nucleus Corpus Striatum

38. Basal Nuclei Control Posture & voluntary movements-motor (no direct input &output with spinal cord-sensory) Paired masses of gray matter within the cerebral hemispheres. These nuclei lie within each hemisphere inferior to the floor of the lateral ventricle. They are embedded within the central white matter T he radiating projection and commissural fibers travel around or between these nuclei. Consists of – Caudate nucleus (input) – Lentiform • Putamen (input) • Globus pallidus (output)

39. 1. Caudate Nucleus C audate nucleus has a massive head and a slender, curving tail that follows the curve of the lateral ventricle & a body At the tip of the tail is a separate nucleus, the amygdaloid body Three masses of gray matter lie between the bulging surface of the insula and the lateral wall of the diencephalon i.e. C laustrum P utamen G lobus pallidus Several additional terms are used to designate specific anatomical or functional subdivisions of the basal nuclei.

40. 2. Lentiform Nucleus Gray matter deep in white matter. Dark- Putamen and lighter- globus palidus are often considered subdivisions of a larger lentiform (lens-shaped) nucleus, for when exposed on gross dissection, they form a rather compact, rounded mass.

41. 3. Amygdaloid Nucleus Suitated in temporal lobe Part of limbic system Change heart rate, blood pressure, skin color, rate of respiration-Body response to environmental changes .

42. Motor Function of the Basal Ganglia C ontrol of complex patterns of motor activity – writing /Drawing – using scissors – throwing balls – shoveling dirt – some aspects of vocalization , eye muscle looking at object Not much is known about the specific functions of each of these structures Thought to function in timing and scaling of motion and in the initiation of motion Most information comes from the result of damage to these structures and the resulting clinical abnormality

43. Caudate Circuit Caudate extends into all lobes of the cortex and receives a large input from association areas of the cortex Mostly projects to globus pallidus , no fibers to subthalamus or substantia nigra Most motor actions occur as a result of a sequence of thoughts. Caudate circuit may play a role in the cognitive control of motor functions

44. Putamen Circuit Mostly from premotor and supplemental motor cortex to putamen then back to motor cortex .

45. Basal Ganglia 3 pathways: Direct pathway (initiate wanted movement) Indirect pathway (stop unwanted movement) Nigra striatal pathway (Modulate movement )

46. 1. Direct Pathway (Initiate Movement) Information from cortex striatum (caudate nucleus + putamen) globus pallidus internus thalamus 2 nuclei (ventral anterior + ventral lateral nuclei information taken to cerebral cortex as modified stimulus to initiate movement (motor activity of muscle) Corticostriate fibers Thalamostriate fibers Striatopallidal fibers Pallidofugal ansa lenticularis fibers

47. Neurotransmitters : Glutamate (stimulating neurotransmitter) Cortex to the striatum via glutaminergic fibers release glutamate GABA : From the striatum to globus pallidus internus via GABA (gamma amino butyric acid) is inhibiting neurotransmitter increased release of GABA inhibits globus pallidus internus decrease action potential of neurons GABA : from globus pallidus to thalamus 2 nuclei (VAN, VLN) Motor cortex to initiate motor activity of muscle .

48. Cortex Caudate Nucleus Putamen Externus Internus Globus pallidus Thalamus Striatum Glutamate (Stimulate) GABA (Inhibitor) GABA (Inhibitor) Ventral Anterior Nucleus Ventral Lateral Nucleus Direct Pathway (Initiate Movement) Corticostriate fibers Striatopallidal fibers Pallidofugal ansa lenticularis fibers Thalamostriate fibers

49. 2. Indirect Pathway Cortex striatum globus pallidus externus sub thalamic nucleus globus pallidus internus sub thalamic 2 nuclei (VAN, VLN) cortex movement stops. Neurotransmitter: Glutamate (EPSP): cortex to striatum GABA (IPSP): striatum to globus pallidus externus GABA (IPSP): globus pallidus externus to sub-thalamic nuclei Glutamate (EPSP): sub thalamic nuclei to globus pallidus internus GABA (IPSP): globus pallidus internus to thalamus 2 nuclei (VAN, VLN) Then goes to cortex to decrease motor activity (unwanted movement) Striatopallidal fibers

50. Cortex Caudate Nucleus Putamen Externus Internus Globus pallidus Thalamus Striatum Glutamate (Stimulate) GABA (Inhibitor) GABA (Inhibitor) Ventral Anterior Nucleus Ventral Lateral Nucleus Indirect Pathway (Inhibit Movement) Corticostriate fibers Striatopallidal fibers Pallidofugal ansa lenticularis fibers Thalamostriate fibers Subthalamic Nucleus GABA (Inhibitor) Glutamate (Stimulate) Pallidofugal Fasciculus Lenticularis fibers Pallidofugal Pallido-subthalamic fibers

51. 3. Modulate Activity Of Both Direct & indirect Pathway( Nigro -striatal Pathway) Modulation of both: Direct Pathway I ndirect Pathway Amplify activity – motor movement

52. Influence on Direct Pathway Stimulus from cortex striatum (caudate nucleus + putamen) globus pallidus internus thalamic nuclei (VAN, VLN) cortex . D ifference here is the neurons from substantia nigra particularly from zona compacta ascend to striatum & release dopamine on neuron of striatum (caudate nucleus + putamen). The type of dopamine receptors here is actually D1 . it is a stimulating receptor so now on striatum we have two neurotransmitters which are glutamate and dopamine giving extra stimulus from cortex + substantia nigra and go to globus pallidus internus and send a lot of action protentional to the globus pallidus internus which will release now GABA (inhibitory stimulus) & lots of inhibition. The nucleus will be super inhibited & decrease action potential to thalamic nucleus and causes increase action potential to cerebral cortex and increased motor movement of muscles( wanted movement ). Importance: d amage to pathway particularly substantia nigra causes Parkinsons ’ disease(decrease motor activity , difficulty to initiate and maintain movement. D1 Zona Compacta Substantia Nigra Nigrostriate fibers Striatopallidal fibers

53. Cortex Caudate Nucleus Putamen Externus Internus Globus pallidus Thalamus Striatum Glutamate (Stimulate) GABA (Inhibitor) GABA (Inhibitor) Ventral Anterior Nucleus Ventral Lateral Nucleus D irect Pathway (Modulation) Corticostriate fibers Striatopallidal fibers Pallidofugal ansa lenticularis fibers Thalamostriate fibers Zona Compacta Dopamine ( D1 ) (stimulator) Substantia Nigra Nigrostriate fibers

54. Influence On Indirect Pathways Cortex striatum(caudate nucleus + putamen) globus pallidus externus subthalamic nuclei globus pallidus internus thalamic nuclei (VAN, VLN) Cortex . Now extra is substantia nigra here so from substantia nigra zona compacta the stimulus ascends to striatum (caudate nucleus + putamen )& neurotransmitter releases is D 2 (dopamine 2 receptors-inhibitory) So now 2 neurotransmitter i.e. glutamate (stimulator) & dopamine 2 (D2) inhibitory. Decrease action potential to globus pallidus externus i.e GABA ( inhibitory) S timulate and increase action potential to subthalamic nucleus (GABA inhibitory) which increase inhibition & decrease action potential to globus pallidus internus ( Glutamate-Stimulator-) decrease action potential to thalamus (GABA inhibition) increase action potential stimulation of cortex motor activity increased(unwanted motor movements) D2 Zona Compacta Substantia Nigra Nigrostriate fibers Striatopallidal fibers

55. Cortex Caudate Nucleus Putamen Externus Internus Globus pallidus Thalamus Striatum Glutamate (Stimulate) GABA (Inhibitor) GABA (Inhibitor) Ventral Anterior Nucleus Ventral Lateral Nucleus Indirect Pathway (Modulation) Corticostriate fibers Striatopallidal fibers Pallidofugal ansa lenticularis fibers Thalamostriate fibers Subthalamic Nucleus GABA (Inhibitor) Glutamate (Stimulate) Zona Compacta Substantia Nigra Dopamine ( D2) (Inhibitor) Nigrostriate fibers Pallidofugal Fasciculus Lenticularis fibers Pallidofugal Pallido-subthalamic fibers

56. Dopamine (neurotransmitter) Steps D1 Receptor D2 Receptors 1 Binds to G-protein coupled receptor called G- stimulator receptor Binds to G- inhibitory protein 2 Increases cyclic AMP Decrease cyclic AMP 3 Activate protein kinase Decrease protein kinase 4 Phosphorylate particular channels Decrease phosphorylate channels 5 Allows positive ions to move into cells Decreases positive ions 6 Stimulation of increased voltage into the cell Decrease voltage 7 Normal RMP goes into threshold potential RMP cannot go to the threshold potential 8 Activates voltage-gated channels = Action Potential Decrease action potential moves down the neurons

57. Functions Of Basal Ganglia Involved in motor movements coordinated by the cerebral cortex. Central sulcus in the cerebral cortex (middle). Posterior is post-central gyrus ( primary somatosensory cortex ). Anterior is pre-central gyrus ( primary motor cortex ), Next to it is pre-motor cortex . These three make the voluntary motor movement= called motor cortex They send the information to the muscle via the upper motor neuron to the lower motor neuron to the skeletal muscles to contract called cortico spinal tract and communicate the motor plan back to the basal ganglia in cerebral cortex area. It will take the motor plan and modify it and send it back to the cerebral cortex area to modulate, initiate or regress movements

58. Functions B asal nuclei are involved with: S ubconscious control & integration of skeletal muscle tone Coordination of learned movement patterns P rocessing , integration & relay of information from cerebral cortex to thalamus Under normal conditions, these nuclei do not initiate particular movements But once a movement is under way, the basal nuclei provide the general pattern and rhythm, especially for movements of the trunk and proximal limb muscles

59. When a person is walking, the caudate nucleus and putamen control the cycles of arm and leg movements that occur between the time the decision is made to “start walking” and the time the “stop” order is given C laustrum appears to be involved in the processing of visual information at the subconscious level A mygdaloid body is an important component of the limbic system G lobus pallidus controls and adjusts muscle tone , particularly in the appendicular muscles, to set body position in preparation for a voluntary movement

60. Neurotransmitters in the Basal Ganglia

61. Clinical Relevance

62. Basal Ganglia Damage Clinical damage to D irect pathway : Parkinson's disease = substantia nigra damage. Causes: Decrease movement of limbs (motor activity) Clinical damage to Indirect pathway : Decrease motor activity causes: Huntington’s disease Wilson’s disease: copper buildup in the liver (damage to CNS) Rheumatic fever causes Sydenham’s chorea . A ntibodies can attack the basal ganglia Drugs: extrapyramidal syndrome = Patients who take first generation anti-psychotic alters the pathway, particularly D2 receptors which lead to problem like Tardive dyskinesia that leads to acathy i.e. restless movement & leads to dystoric reactions

63. Lesions of Basal Ganglia G lobus pallidus – athetosis : spontaneous writing movements of the hand, arm, neck, and face P utamen – chorea: flicking movements of the hands, face, and shoulders S ubstantia nigra – Parkinson's disease: rigidity , tremor and akinesia – loss of dopaminergic input from substantia nigra to the caudate and putamen subthalamus – hemiballismus : sudden flailing movements of the entire limb caudate nucleus and putamen – huntington’s chorea : loss of GABA containing neurons to globus pallidus and substantia nigra

64. Integration of Motor Control

65. Integration of Motor Control S pinal cord level – preprogramming of patterns of movement of all muscles (i.e., withdrawal reflex, walking movements, etc.). B rainstem level – maintains equilibrium by adjusting axial tone C ortical level – issues commands to set into motion the patterns available in the spinal cord – controls the intensity and modifies the timing

66. Cerebellum – function with all levels of control to adjust cord motor activity, equilibrium , and planning of motor activity B asal ganglia – functions to assist cortex in executing subconscious but learned patterns of movement , and to plan sequential patterns to accomplish a purposeful task

67. Overall Scheme For Integration Of Motor Function

68. Thank You