basal ganglia and its circuits connection.pptx

basal ganglia anatomy
connection
pathways
modulation
loops
defects
Parkinsonism
abnormal movement

1. Presented by Dr Shashank Agrawal Senior resident (DM neurology) Basal ganglia and its circuit

2. introduction Basal ganglia- basal nuclei Collection of mass of grey matter (subcortical nuclei) situated at the base of fore brain and top of midbrain within each cerebral hemisphere The basal ganglia are a key part of the network of brain cells and nerves that control your body’s voluntary movements. They can approve or reject movement signals that your brain sends, filtering out unnecessary or incorrect signals. This lets you control certain muscles without also using other muscles that are nearby

3. Embryology From the neural tube - 3 primary vesicle is formed with in 4th week Three primary brain vesicles: Forebrain (prosencephalon) Midbrain (mesencephalon) hindbrain(rhombencephalon)

4. Blood Supply Artery From Supply Lenticulostriate MCA Basal ganglia , internal capsule Anterior choroidal Internal carotid Globus pallidus, putamen, thalamus, posterior limb internal capsule Recurrent artery of heubner ACA Head of caudate, anterior putamen, globes pallidus, internal capsule Thalamoperforator PCA Thalamus , posterior limb of internal capsule

5. Neostraitum Caudate nucleus putamen Ventral straitum(nucleus accumbens) Paleostriatum Globus pallidus external segment (GPe) Globus pallidus internal segment (GPi) Substantia nigra Pars compacta(SNc) Par Reticulata(SNr) Sub thalamic nucleus(STN) Basal ganglia nuclei

6. Corpus Striatum . “ striatum ” - derived from the striated appearance produced by the stands of gray matter passing through the internal capsule and connecting the caudate nucleus to the putamen of the lentiform nucleus Situated lateral to the thalamus and is almost completely divided by a band of nerve fiber (internal capsule) into the caudate nucleus and lentiform nucleus.

7. Caudate Nucleus The caudate nucleus is a large C- shaped mass of gray matter that is closely related to the lateral ventricle and lies lateral to the thalamus The lateral surface of the nucleus is related to the internal capsule, which separates it from the lentiform nucleus. It can be divided into a head , body , and tail.

8. The head of the caudate nucleus is large and rounded and forms the lateral wall of the anterior horn of the lateral ventricle. The body of the caudate nucleus is long and narrow and is continuous with the head in the region of the interventricular foramen and from floor of lateral ventricle. The tail of the caudate nucleus is long and slender and is continuous with the body in region of the posterior end of the thalamus.

9. Role of caudate nuclei several types of dementia obsessive-compulsive disorder (OCD) attention deficit hyperactivity disorder (ADHD) bipolar disorder schizophrenia Huntington’s disease Parkinson’s disease autism Tourette syndrome planning movement learning memory reward motivation emotion romantic exchanges Dysfunction of caudate nuclei

10. Lenticular nucleus Biconvex lens Triangular in both coronal and horizontal section Medially to internal capsule Separate caudate to thalamus Divide by external lamina of white matter Putamen & Globus pallidus

11. Putamen Outer part of lenticular nucleus and it is Quadrangular in shape Its lies medial to the insula. Bounded laterally by external capsule Medially by globes pallidus The putamen is a common site for hypertensive bleed as well as infarction

12. Role of putamen nuclei Mixed motor and sensory Pure motor Pure sensory Ataxic hemiparesis Dysarthria with clumsy hands Hemiballism and hemichore Parkinson’s disease Learning Motor control Including speech articulation Language functions Reward Cognitive functioning Addiction Dysfunction of putamen nuclei

13. Globus Pallidus Lighter in colour due to highly concentric myelinated nerve fibre. lies beneath the insula The medial medullary lamina of the white matter divides the GP into globus pallidus internus (GPi) and globus pallidus externus (GPe)

14. Role of globes pallidus he primary function of the globus pallidus is to control conscious and proprioceptive movements. The GPe is the intrinsic nucleus, they act as a relay information whereas the GPi is the output nucleus, they primarily sends information to the thalamus dysfunction The dysfunction of the GP has been noted in (rare)ischemia, alcohol, and opiate abuse. This dysfunction gives rise to various cognitive and motor problems like ADHD, OCD, Tourette’s syndrome, acquired dystonia.

15. Substantia Nigra It is present in midbrain B/w the tegmentum & the basic peduncule Mesencephalic in origin Highest concentration of GABA in CNS Two component Pars compacta : dorsal cell- rich portion Pigmented (neuromelanin) neurons= contain dopamine Principal source of striata dopamine Par reticulate : ventral cell-sparse portion Inhibitory neurotransmitter GABA

16. Subthalmic Nuclei The neurone of the sub thalamic nuclie are glutaminergic and excitatory and have many connections to the globes pallidus and substantial nigra. It does not directly influence any muscles, but it does play a role in modulating movement with the other components of the basal ganglia. Damage to the subthalamic nucleus can result in a disorder of movement called hemiballismus . 

17. Function of basal ganglia Control of muscle tone Control of motor activity Regulation of voluntary movement Regulation of conscious movement Regulation of subconscious movement Control of reflex muscular activity control of automatic associated movements Role in arousal mechanism

18. Limbic loop Cingulate , temporal, orbitofrontal, hippocampus, amygdala are the main input The limbic loop is likely to be involved in giving motor expression to emotions, e.g. through smiling or gesturing, or adoption of aggressive or submissive posture. The loop is rich in dopaminergic nerve endings , and their decline may account for the mask like facies and absence of spontaneous gesturing characterstics of PD and later DEMENTIA

19. Cognitive loop(Prefrontal ) Head of caudate nucleus receives a large projection from the homolateral frontal cortex, parietal , temporal, occipital cortex and it participate in motor learning . The cortical connections of the caudate suggest that it participates in planning ahead , particularly with respect to complex motor intentions.

20. motor loop They seem to be involved in scaling the strength of muscle contraction and in organizing the requisite sequence of excitation of cell columns in the motor cortex. They come into action after the corticospinal tract has already been activated by ‘ premotor ‘ area including the cerebellum. It is believed that the putamen provides a reservoir of learned motor program which it is able to assemble in appropriate sequence for the movement , and transmit the code information to Sensory Motor Area.

21. Oculomotor loop While the eye fixated , SNpr is tonically active. Whenever a deliberate saccade is about to be made toward another object, the oculomotor loop is activated and the superior colliculus is disinhibited. In PD oculomotor hypokinesia is due to faulty disinhibition of the superior colliculus following associated neuronal degeneration within SNpr.

22. Basal ganglia circuit Two circuit important in regulation of movement Direct pathway Indirect pathway Hyper direct pathway Direct pathway decrease inhibition basal ganglia output Indirect pathway increase inhibitory basal ganglia output Balancing of these two circuit underlies regulation of movement Cortex P GPe GPi SN Pc SN Pr Thalamus STN C

23. Afferent fibre From cerebral cortex arising primarily from the pyramidal cells of the layer V, VI via corticostriate fibres. These are glutaminergic Sensorimotor cortex——-> putamen Association region———> Caudate nucleus Prefrontal regions ———-> head of caudate.N Thalamostriate fibres Intrealaminar nuclie of the thalamus —> caudate & putamen

24. Afferent fibers Nigrostriate fibers Substantia nigra ——> caudate & putamen Likely dopamine at their terminal, Inhibitory in function Brainstem striatal fibres Brainstem —-> caudate and putamen Serotonine at the terminals , inhibitory in function

25. Efferent fibres Striatopallidal fibers Caudate nucleus & putamen —-> globes pallidus (Gpe) and Gpi). GABA (inhibitory) neurotransmitter Striatonigral fibres Caudate nucleus & putamen —-> Substantia nigra . GABA inhibitory neurotransmitter

26. Connection to globes pallidus Afferent fibers - striatopallidial fibers. Efferent fibers- pallidofugal fibers. Types…… Ansa lenticularis —> thalamic nuclei Fascicles lenticularis —> sub-thalamus Pallidotegmental fibers —> caudal tegmentum of the midbrain Pallidosubthalamic fibers —> subthalamic nuclei

27. Direct pathway Direct pathway main function is to initiation and maintenance of movement Excitatory neuron from the cerebral cortex to putamen From putamen to GPi and SNr inhibitory projection From GPi /SNr to thalamus inhibitory flow Disinhibition of thalamus cause excitation of thalmocortical pathway and activate the motor cortex

28. Cortex P GPe GPi SN Pc SN Pr Thalamus STN C direct pathways

29. Indirect pathway Main function to play role in suppression of extraneous movement Excitatory neuron form cortex to putamen Inhibitory neuron from putamen it goes to GPe From GPe to substantial nigra inhibitory neutron SBn to GPi excitatory neuron GPi to thalmus inhibitory neuron

30. Cortex P GPe GPi SN Pc SN Pr Thalamus STN C Indirect pathways Cortex P GPe GPi SN Pc SN Pr Thalamus STN C direct pathways

31. Hyperdirect pathway substantia nigra receive strong excitatory signals from the cortex directly through STN and has a shorter conduction time compared to the direct and indirect pathways. cortex directly to the subthalamic nucleus (STN), skipping the striatum. Therefore, the glutamatergic excitatory neurons of the STN can then excite the GPi/SNr . thus suppressing thalamic activity on the cerebral cortex. Emergency brake

32. Cortex P GPe GPi SN Pc SN Pr Thalamus STN C Hyperdirect pathways

33. Modulation of the basal ganglia The neuronal circuits that modulate the function of the basal ganglia are: The Nigrostriatal Pathway The Cholinergic Pathway

34. Substantia nigra effect on direct pathway Substantia nigra release dopamine on Both pathway. Receptor on direct pathway is D1 , which is excitatory. So combine effect of glutamic and dopaminergic is always excitatory. Effect of dopamine is to initiate the movement and tuning of the movement

35. Without dopamine effect on indirect pathway

36. Dopamine effect on indirect pathway

37. Cortex P GPe GPi SN Pc SN Pr Thalamus STN C direct pathways Cortex P GPe GPi SN Pc SN Pr Thalamus STN C Indirect pathways D1 D2

38. Dopaminergic and cholinergic modulation of direct and indirect pathways Dopamine produce y substantia nigra par compacta Dopamine has an excitatory effect upon Direct Pathway via D1 receptor Dopamine has an inhibitory effect on indirect pathway via D2 receptors Both of these lead to increase motor activity

39. Continue… Cholinergic (Ach) interneurons synapse on the GABAergic striatal neurons that project ti GPi and GPe . The cholinergic action s INHIBIT striatal cells of the Direct Pathway and EXCITE striatal cell of the Indirect Pathway Thus effect of ACH are opposite of Dopamine on direct and indirect pathway and decrease the motor activity

40. Dopamine Acetylecholine Substantia nigra and cholinergic cause tuning of the movement by controlling the indirect pathway GABA neuron fibers

41. Two type of disorder Hypertonic- hypo kinetic Hypotonic - hyperkinetic Hypertonicity is an abnormal increase of the muscle tone in response to passive stretch. when the indirect pathway of the basal ganglia is stimulated, it sends signals to the motor cortex and brainstem, which ultimately inhibit muscle tone. when a lesion of the basal ganglia occur, this inhibitory influence is lost and hypertonicity is manifested contralateral to the side of the lesion Dyskinesia is a presence of the unintentional purposeless movements. Dyskinesias are classified further as: Hypokinesia Hyperkinesia Disorder of basal ganglia

42. Hypertonic-hypokinetic disorders These disorders result from the degeneration of the neurons that form the direct pathway . Since this is the pathway that serves for the planning of the movement , the problems that patients will have been presented in two forms: Bradykinesia represents a generalized slowness of movement and is the most common hypokinesia. Akinesia is presented with the inability to move at all because the individual is unable to plan or to direct a movement toward a desired position or target.

43. Parkinson’s disease Parkinson’s disease (PD) is a chronic progressive nurodegenrative disorder characterised by slowness in the initiation and execution movement ( bradykinesia), increase muscle tone ( rigidity), tremor at rest, and gait changes. Lack of dopaminergic response Defect in Substantia Nigra

44. Parkinson disease Hypokinesia- bradykinesia/akinesia It is the result of the degeneration of the dopaminergic neurons of the pars compacta of the substantia nigra. direct pathway less excited Indirect pathway less inhibited which lead to lost of the excitation of the supplementary motor area which cause loss pf planning and execution of movement . Cortex P GPe GPi SN Pc SN Pr Thalamus STN C Indirect pathways

45. Rigidity Rigidity means stiff or inflexible muscles. It can stop your muscles from stretching and relaxing, which can lead to pain and muscle cramps and problems with balance. Due to less excitation of the cortex , which cause less stimulation of cortical reticular fibre which lead to over excitation of or reticulating system and cause in increase of tone Tone of both flexor and extensor increase together and cause rigidity

46. Rigidity swinging your arms because your muscles are too tight and stiff. turning around, getting out of chairs, and turning over in bed. doing everyday tasks, such as writing or doing up buttons. chewing and swallowing. Stiff face muscles can make it harder to chew and swallow. breathing and speaking clearly. Rigidity can also affect chest muscles and make them weaker. This can lead to problems with breathing and issues like chest infections. Breathing difficulties can also affect the tone and loudness of your voice, and make pronounciation hard. Action affected

47. Tremors Involuntary rhythmic oscillatory movements of distal parts of limb and head Resting tremors Absent at sleep and increase by stress and excitement 4-6 times/sec Fill rolling movement

48. Management of Parkinsonism Medical Surgical Deep brain stimulation

49. Surgical management Ablative Thalamotomy Pallidotomy Subthalamotomy Deep brain stimulation VIM thalamus (VIM) Globus pallidus internus(GPi) Subthalamic nucleus(STN) Transplant Human fetal , xenotransplant, genetically engineered transplants

50. Deep brain stimulation Inroduced in the 1990s By Benavides ET AL neurosurgical procedure involve ng the implantation of a medical device called a neurDstimulator sends electrical impulses, through implanted electrodes, to specific targets in the brain (brain nuclei) for the treatment of movement and neuropsychiatric disorders

51. Indication of DBS Patients with uncontrollable tremor for whom medications have not been effective. Patients with symptoms that respond well to medications but who, when the drugs wear off, experience severe motor fluctuations and dyskinesias, despite medication adjustments. Patients whose movement symptoms might respond to higher or more frequent medication doses, but who are limited to do so because of side effects. Essential tremor , dystonia Psychiatric illness- OCD , Tourette disorder

52. Mechanism and target of DBS Mechanism of action Inhibit of target Activation of target Combined effect Disruption of pathological oscillation to restore rhythmic activity and synchronisation Target site for stimulation Subthalmic nucleus Globus pallidus interna Thalamus

53. Component of DBS The LEAD or electrode : a thin, insulated wire—is inserted through a small opening in the skull and implanted in the brain. The tip of the electrode is positioned within the targeted brain area The EXTENSION Is an insulated wire that is passed under the skin of the head, neck, and shoulder, connecting the lead to the neuro stimulator The NEUROSTIMULATOR : is the third component and is usually implanted under the skin near the collarbone.

54. Technique of DBS Targeted area Is located by ct or mri imaging Quadripolar leads are connected to stimulator and to battery Once electrodes are implanted it is attached top wires that run inside body from head down to collar bone where battery operated stimulator are implanted From stimulator electrical impulses are continuously delivered over wire to electrode in brain Reprogramming can be done with 3,4 months

55. Side effects of DBS Confusion Numbness and weakness of body Difficulty in speech Mood changes Bleeding in brain Movement disorder Seizures Lead - migration, fracture, erosion, malfunction

56. Hypotonic-hyperkinetic disorders Disturbance of the indirect loop that causes a loss of the inhibition of the thalamic neurons , which ultimately results in excess cortical activity and movement. They are presented as: Tremor, that is a rhythmic, low amplitude movement that may be manifested as the nodding of the head, or in the hands and feet. Dystonia is characterized by involuntary, sustained muscle contraction that leads to abnormal postures of the neck, toes, hands, or other parts of the body.

57. Chorea Chorea is a sequence of rapid involuntary movements involving mostly the hands and feet, the tongue, and facial muscles. In this many motor program are abnormally release. Hunginton chorea Sydenhams chorea Chorea gravidum Wilsons disease ( hepatic lenticular) Michael Jackson dance

58. Huntington’s disease A rare inherited condition. Defect manifesting as a CAG repeat on chromosome 4p on the HTT. Which leads to neuronal death in the caudate and the putamen. The indirect pathway is interrupted and leads to a hyperkinetic. Symptoms include involuntary movements such as chorea, cognitive degeneration, and psychiatric dysfunction. Tetrabenazine and reserpine are palliative medicines that decrease the disease symptoms.  Tetrabenazine which is a vesicular monoamine transporter inhibitor. It inhibits monoamine (serotonin, dopamine, norepinephrine) uptake into synaptic vesicles. This reduces the intense stimulation of the striatum from the nigrostriatal pathway. Cortex P GPe GPi SN Pc SN Pr Thalamus STN C Indirect pathways

59. Athetosis Athetosis is a movement dysfunction. It’s characterized by involuntary writhing movements. These movements may be continuous, slow, and rolling.. With athetosis, the same regions of the body are repeatedly affected. These typically include the hands, arms, and feet. The neck, face, tongue, and trunk can be involved, too. Mostly distal part involve.

60. Hemiballismus A condition where the patient exhibits involuntary ballistic (violent striking) movements on only one side of the body, that affect only the proximal muscles of a limb. Lesion in the contralateral subthalamic nuclei. Given that the subthalamus is part of the indirect pathway this lesion reduces or eliminates indirect pathway signaling Leading to a relative overabundance of activity in the direct pathway.  Cortex P GPe GPi SN Pc SN Pr Thalamus STN C Indirect pathways

61. Ballismus is the equivalent to the hemiballismus, with the difference that it affects the entire body. It is the most extreme type of dyskinesia. Tics are brief, stereotyped semi-voluntary movements, which means that unlike other movement disorders, they are partially suppressible. Tics can be either motor (motor tics) or sounds (vocal tics).These tics have been associated with dysfunction of the GABAergic projections from the striatum,  Myoclonus i s a jerky, involuntary, and usually arrhythmic movement. Continue.. Tourette syndrome

62. Now use your limbic system to smile and get arouse from the boring topic And clap your hand by using motor pathway Relax your ocolomotor loop as the seminar the end.

63. Zona increta and pedunculopontine nucleus pal a important role in locomotion , muscle tone and akinesia Gullian mollarate triangle- red nucleus, dentate nucleus, inferior Oliver nucleus is involve and cause palatal myoclonus and myothermia