BASAL GANGLIA

1. BASAL GANGLIA Amirkabir University of Technology Supervisor:Dr Towhidkhah Designed by Yashar Sarbaz

2. Systems-Level Neural Modelling: What and Why? • We know a lot about the brain! • Need to integrate data: molecular/ cellular/ systems levels. • Complexity: Need to abstract away higher order principles • Models are tools to develop explicit theories, constrained by multiple levels (neural and behavioural). • Key: Models (should) make novel testable predictions on both neural & behavioural levels • Models are useful tools for guiding experiments

3. Movement Levels • Highest Level (Need & Plan): Limbic System Associative Cortex • Middle Level (Motor Program): Cerebellum Motor Cortex Basal Ganglia • Lowest Level (Movement): Spinal Cord Muscular-Skeletal System

4. Movement Block Diagram

5. Brain

6. Learning Strategies • Supervised Learning (Cerebellum) • Reinforcement Learning (Basal Ganglia) • Unsupervised Learning (Cerebral Cortex) • Symbolic Learning (Hippocampal System)

7. Learning Strategies

8. Cerebral Cortex：Unsupervised Learning output input Basal Ganglia: Reinforcement Learning reward output input Cerebellum: Supervised Learning target + error - output input Learning Strategies Cortex Basal thalamus Ganglia SN Cerebellum IO

9. Basal Ganglia • Collection of Subcortical Nuclui • We Know a little about BG • It has main role in movement • Many movement disorders related to this area • Involved in motor coordination, timing and control

10. Basal Ganglia • Directly Receive No Direct Sensory Inputs • Send Little Direct to Spinal Cord • Damage in BG has no loss of Specific Motor Function • Damage in BG Cause mainly Deficit in General Control and Initiation of Movement

11. Basal Ganglia • It is one of the Old Area of Brain • BG with Thalamus act like a Little Brain • It is Like Funnel

12. BG Functions • 1. Inhibition of muscle tone • 2. Coordination of slow, sustained movements • 3. Suppression of useless patterns of movements

13. Duty of the BG 1.Motor control 2.Reinforcement learning 3.Sensorymotor associative learning 4.Adaptive timing 5.Temporal order learning 6.Initiation of voluntary movement

14. BG is involved in a wide spectrum of functions ranging from simple sensory motor learning to planning, it does not tell to us how this might occur.

15. BG Blocks • Striatum: Putamen and Caudate • Globus Pallidus: External and Internal • Subthalamic Nucleus • Subtantia Nigra: Pars Compacta and Pars Reticulata

16. Basal Ganglia Anatomy

17. Basal Ganglia Anatomy

18. Basal Ganglia Anatomy

19. Basal Ganglia Anatomy

20. Blocks of BG

21. Converging Pathways • PF: Prefrontal • SMA: Supplementary Motor Area • M1: Primary Motor Cortex • PMv: Ventral pre-motor Area • C/P: Caudate Nucleus

22. Disorders of the BG • Hyperkinesia: an excess or spontaneous involuntary movements • Chorea abrupt movements of the limbs and facial muscles • Ballism violent, flailing movements • Athetosis slow writhing movements of the fingers and hands and sometimes toes • Hypokinesia: a lack of or resistance to voluntary movement • Akinesia lack of of slowness of spontaneous and associative movements • Rigidity increased tone on passive manipulation of joints • Irregularities: • Tremor rhythmic, involuntary, oscillatory movements around 4-6 Hz

23. BG Diseases • Parkinson: loss of Dopamine, with hypokinesia (akinesia & rigidity) and irregulaities • Huntington: death in striatum, with hyperkinesia (chorea, ballism, athrtosis) • Hemiballism: lesion in STN with ballism • Tardive Dyskinesia: Using Antipsychotic

24. BG Blocks in Diseases

25. BG and Action Selection BG selectively facilitates one command while suppressing others

26. Micro Circuitry of the BG • Striosomes: input from limbic system and output to dopaminergic neuron of SNc (reinforcement signal) • Matriosomes: Input from cortical (sensation and movement) and output to SNr and GP

27. Micro Circuitry of the BG

28. Conceptual Models • Such diversity of function embodied in such an intricately organized structure, has inspired numerous models of basal ganglia function ranging from sensory-motor associative to the formation of motor plans

29. Conceptual Models • BG as link between limbic system and motor output (eye movement)

30. Conceptual Models • BG and learning to cortex to select a sequence

31. Reinforcement Learning

32. Physiological Basis of Reinforcement Learning

33. Physiological Basis of Reinforcement Learning

34. Reinforcement Learning A general idea of “goodness” is used to adjust how the system learns Temporal Difference (TD) error:

35. reward r action a agent environment state s Reinforcement Learning • Framework for learning state-action mapping (policy) by exploration and reward feedback • Critic • reward prediction • Actor • action selection • Learning • external reward r • internal reward d: difference from prediction

36. Dopamine and Learning • There is significant evidence that dopamine acts as a reinforcement signal to neuron in striatum and training them to recognize patterns in their cerebral cortical input. • Dopamine modulates Go and No-Go reinforcement learning in the basal ganglia separately via D1 and D2 receptors

37. Reinforcement Learning and BG • Data from neuronal recording and lesion studies indicate that the basal ganglia are involved in learning and execution of goal-directed, sequential behaviour • Dopamine neuron activity encoding the reward prediction error

38. Reinforcement Learning and BG • It is suggested that the Striosome compartment works as the value prediction mechanism while the Matriosomes compartment works as the action selection mechanism

39. Reinforcement Learning and BG • Striatum • striosome & matrix • dopamine-dependent plasticity • Dopamine neurons • reward-predictive response • TD learning

40. Reinforcement Learning and BG

41. Striatum Learning Mechanism

42. Comparison of the Basal Ganglia and the Cerebellum • The basal ganglia receive input from the entire cortex, whereas the cerebellum is innervated only by parts of cortex directly related to sensorimotor function • Cerebellar output is directed back to the premotor and motor cortex, while the basal ganglia project to these as well as the prefrontal association cortex; • The cerebellum receives somatosensory information directly from the spinal cord and has major afferents and efferents with many brain stem nuclei which are directly connected with the spinal cord, while the basal ganglia have very few connections with the brainstem and no known direct connections with the spinal cord

43. One might also consider that the basal ganglia are the deep nuclei of the cortex, while the cerebellum itself consists of a cerebellar cortex and deep nuclei.

44. History of Parkinson’s disease • Ancient Indian Text: Kampavata • Galen 175 A.D.: Shaking Palsy • James Parkinson 1817: “An Essay on the Shaking Palsy” (6 patients) • Charcot 1860: Parkinson’s Disease • 1960: Role of Dopamine • 1981: Levo Dopa • 1990s: DBS Treatments

45. Parkinson’s Disease • An Ancient Progressive Disease • Second Wide-Spread Brain Disease (After Alzheimer) • Main Symptoms are Movement Disorders • Vast Range of Symptoms • Mean Age of onset is 60 • Degeneration of Basal Ganglia • Not Epidemic

46. Famous Parkinsonian People

47. Etiology • Not clear Exactly • Main Hypothesis: • Free Radicals: Antioxidant Molecules • Genetic Factors • Environmental Toxins: MPTP, Retenone, 6Hydroxy Dopamin • SNc Cells Age Faster than Normal

48. Symptoms of PD • Movement Symptoms • Cognition Symptoms

49. Cognition Symptoms • Dementia • Depression • Anxiety and Panic • Sleep Disorders • Cognitive impairment • Psychosis • Behavioural disturbances • Bradyphrenia: off Thinking

50. Cognition Symptoms • Different Movement and Cognition History • Lewy Body • Another Degeneration of Brain Area involve in Cognition (For Example in Dementia: Dorsal tier neuron and medial neuronal Groups) • Aging