1. The Cerebellum and Cognition: A 25-Year Check Up Rich Ivry Cognition and Action Laboratory University of California, Berkeley

2. Where's the cerebellum? The Power of Advertising

3. Where's the cerebellum? The Power of Advertising Aha! 50% of all neurons (note grey matter!)

4. “Whereas the cerebellar connections to frontal motor areas enable the cerebellum to improve motor skills, cerebellar connections to association areas of the prefrontal cortex can enable the cerebellum to improve mental skills.” -- Leiner, Leiner, & Dow (Behav Neurosci, 1986)

5. Lines of Evidence Neuroanatomy: Structure Anatomical links between cerebellum and prefrontal cortex (PFC), not just motor cortex (MC). Polysynaptic mapping functional MRI (fMRI) of monkey brainin human brain Strick & Fiez, 2009 Krienen & Buckner, 2009 MC inject PFC inject

6. Lines of Evidence Neuroanatomy: Structure PFC - Cerebellar loops Polysynaptic mapping Human DTI Pathology in psychiatric populations Autism, ADHD, Schizophrenia, Fragile X, etc. “Guilt by association”

7. Lines of Evidence Neuroanatomy: Structure Neuroimaging: Physiology Methods developed around 1980 to observe function, not just structure. Functional Neuroimaging: fMRI Measure oxygen use by brain. What part of the brain is active when you think?

8. Lines of Evidence Neuroanatomy: Structure Neuroimaging: Physiology Petersen et al., 1988 Cerebellar activity when speaking. Cerebellar activity when thinking.

9. Lines of Evidence Neuroanatomy: Structure Neuroimaging: Physiology Hundreds of fMRI studies show cerebellar activation even when movement is absent or is “equated” between experimental and control conditions.

10. Lines of Evidence Neuroanatomy: Structure Neuroimaging: Physiology Neuropsychology: Behavior Traditional assessment of ataxia: Motor exam New assessments: Evaluate motor, cognitive, emotion

11. Lines of Evidence Neuroanatomy: Structure Neuroimaging: Physiology Neuropsychology: Behavior Deficits on range of neuropsychological assessments. Cerebellar cognitive affective syndrome Schmahmann (1991)

12. Lines of Evidence Neuroanatomy: Structure Neuroimaging: Physiology Neuropsychology: Behavior Deficits on range of neuropsychological assessments. Cerebellar cognitive affective syndrome Schmahmann (1991) ** Mixed bag of results. -- Many individuals and even group studies show no impairment. -- Bias to publish positive results.

13. Neuropsychological evaluation of people with acute ataxia one week after stroke. Performance Poor Normal

14. Change in performance at re-test after 1-9 months. 1 Week 1-9 months later Performance Poor Normal

15. Half empty or half full? Implications of such rapid recovery? 1 Week 1-9 months later Performance Poor Normal

16. Most common persistent cognitive problem is with "executive function". 1 Week 1-9 months later Performance Poor Normal

17. Executive Function -- working memory (short term memory) -- planning -- multi-tasking Functions associated with prefrontal cortex

18. Relating executive function to cerebellar degeneration? Is the relationship -- Indirect: correlated but not causal -- Direct: correlated and causal

19. 1. Indirect hypotheses a. Cortical atrophy seen in some patients. -- Multi-system atrophy -- SCA2 Lessons from autism: Cerebellar atrophy does not mean that cerebellar dysfunction causes autism. Relating executive function to cerebellar degeneration?

20. 1. Indirect hypotheses a. Cortical atrophy seen in some patients. -- Multi-system atrophy -- SCA2 b. Loss of cerebellar tissue disrupts activity in linked parts of cortex. Relating executive function to cerebellar degeneration?

21. 1. Indirect hypotheses a. Cortical atrophy seen in some patients. -- Multi-system atrophy -- SCA2 b. Loss of cerebellar tissue disrupts activity in frontal cortex. c. Resource allocation. Everything is multi-tasking in ataxia! Relating executive function to cerebellar degeneration?

22. 2. Direct hypotheses: Causal contribution of cerebellum to cognition Relating executive function to cerebellar degeneration?

23. 2. Direct hypotheses: Causal contribution of cerebellum to cognition. a. Thinking through internal movement. ** Give TEST ** Relating executive function to cerebellar degeneration?

24. 2. Direct hypotheses: Causal contribution of cerebellum to cognition. a. Thinking through internal movement. Memory list: 2 - 6 - 8 - 5 - 4 - 7 - 1 Relating executive function to cerebellar degeneration?

25. 2. Direct hypotheses: Causal contribution of cerebellum to cognition. a. Thinking through internal movement. Loss of coordinated "internal movement" (poor rehearsal) People with ataxia are much more impaired on working memory tasks when rehearsal is emphasized. Relating executive function to cerebellar degeneration?

26. 2. Direct hypotheses: a. Thinking through internal movement. b. Working memory for action. Relating executive function to cerebellar degeneration? WM in Perception WM in Action

27. 2. Direct hypotheses: a. Thinking through internal movement. b. Working memory for action. Planning requires retrieval of required actions. e.g., cooking dinner Without cerebellar signals about how to produce the action, the frontal lobes have difficulty keeping the goal in mind. Relating executive function to cerebellar degeneration?

28. Conclusions 1. Changes in cognition can accompany ataxia. Not true for all individuals. But, as a group, problems with executive function. 2. Unclear if changes are an indirect or direct consequence of cerebellar atrophy. ** Could be a combination of many factors. 3. Identifying factors is important for -- Understanding cerebellar function. -- Designing rehabilitation/training programs.

29. The Plug Cognition and Action lab at UC Berkeley is always looking for new participants! Just google “Rich Ivry” to find our webpage. Or stop by our table, just outside. ** Testing going on this weekend **

31. 2. Direct hypotheses: Cerebellar contributions to cognition. a. Thinking through internal movement. b. Working memory for action. Relating executive function to cerebellar degeneration?

32. Go on to develop dif WM ideas 1) Secondary to other system atrophy e.g., SCA2, MSA (cortical involvement 2) cerebellar related a) rehearsal: motor hypo But not sufficient b) response prep (WM for action)

34. Anatomy Traditional View: Cerebellum part of motor system. New evidence: Cerebellum has connections to parts of cerebral cortex that are not part of primary motor pathways.

35. Neurological Assessment of People with Ataxia Traditional tests: Focus on balance and coordination. Newer emphasis: Include assessments of non-motor function. Cerebellar cognitive affective syndrome (Schmahmann) Syndrome describing wide range of cognitive and emotional problems observed in some individuals with cerebellar degeneration or other types of cerebellar injury. Problems in memory, problem solving, expression of emotion. Highly variable from individual to individual.

36. Change in performance in stroke patients: Visit 1: First week after stroke. Visit 2: After 1-9 month recovery period. Half empty or half full? Implications of such rapid recovery? Poor Performance Good

37. Exploring the cause of cognitive problems in ataxia. Three examples: 1. memory 2. attention 3. skill learning People with ataxia have difficulty on such tasks. Does cerebellum play a role in these cognitive processes? Or are the these problems related to motor deficits.

38. Memory Long-term memory: stored knowledge Working memory: Maintenance of information that is important for current task. e.g., making a 3-course dinner remembering a phone number

39. Memory Long-term memory: stored knowledge Working memory: Maintenance of information that is important for current task. e.g., making a 3-course dinner remembering a phone number Individuals with ataxia have problems with working memory.

40. Get volunteer (who looks away from screen):

41. 1. 4 8 6 5 8 3 2 7(immediate)

42. Get volunteer (who looks away from screen): 1. 4 8 6 5 8 3 2 7(immediate) 2. 3 6 2 9 5 4 9 1 (softly)

43. Get volunteer (who looks away from screen): 1. 4 8 6 5 8 3 2 7(immediate) 2. 3 6 2 9 5 4 9 1 (softly) 3. 5 1 9 3 2 6 4 6 (10 sec delay)

44. Get volunteer (who looks away from screen): 1. 4 8 6 5 8 3 2 7(immediate) 2. 3 6 2 9 5 4 9 1 (softly) 3. 5 1 9 3 2 6 4 6 (10 sec delay) 2. 7 2 4 8 4 9 5 3 (while repeating “ACARM”)

45. Doing badly on working memory test doesn’t mean you have problem with working memory. “softly” example.

46. Doing badly on working memory test doesn’t mean you have problem with working memory. “softly” example. Working memory problem in ataxia is with rehearsal. When rehearsal is disrupted during memory testing, people with ataxia do as well as control participants.

47. Doing badly on working memory test doesn’t mean you have problem with working memory. “softly” example. Working memory problem in ataxia is with rehearsal. When rehearsal is disrupted during memory testing, people with ataxia do as well as control participants. Imagined or internal action using same parts of brain as real action. “Ataxic” inner speech.

48. Regions of the cerebellum that are active during word rehearsal task and finger tapping. Motoric regions, even if different

49. Exploring the cause of cognitive problems in ataxia. Three examples: 1. working memory 2. attention Multi-tasking. Rapidly changing focus of attention.

50. Exploring the cause of cognitive problems in ataxia. Three examples: 1. working memory 2. attention Multi-tasking. Rapidly changing focus of attention. Cognitive dysmetria hypothesis: Ataxia disrupts mental coordination, similar to how it disrupts motor coordination.

51. Measuring Attention Shifting Press button for Low Tones (Condition 1)

52. Measuring Attention Shifting Press button for Low Tones (Condition 1) Red Squares (Condition 2)

53. Measuring Attention Shifting Press button for Low Tones (Condition 1) Red Squares (Condition 2) Alternate responding to red squares and low tones. (Condition 3)

54. Problem is much more pronounced with divided attention.

55. Modified Attention Shifting: Reducing Motor Requirements

56. People with ataxia show large improvement when attention demands are held constant but motor requirements are reduced.

57. Making responses requires attention!

58. Exploring the cause of cognitive problems in ataxia. Three examples: 1. memory 2. attention 3. skill learning Problems in motor learning is classic symptom of ataxia. But is this true for all types of motor learning?

59. Sequence Learning Press key corresponding to position of asterisk. Repeat 60 times. Sequence: Asterisks follow repeating pattern. Random: Positions chosen at random.

60. Sequence Learning Press key corresponding to position of asterisk. Repeat 60 times. Sequence: Asterisks follow repeating pattern. Random: Positions chosen at random. Slower responses on Random block provides measure of learning.

61. People with ataxia do not show learning on this task. Ataxic Non-ataxic

62. People with ataxia do not show learning on this task. Ataxic Non-ataxic Puzzle since learning is one of pattern recognition (like Michael Jordan) more than finger coordination.

63. People with ataxia do not show learning on this task. Ataxic Non-ataxic Puzzle since learning is one of pattern recognition (like Michael Jordan) more than finger coordination. Related to working memory problems?

64. Simplify working memory demands: Respond by directly pointing to location of the filled circle.

65. Simplify working memory demands: Respond by directly pointing to location of the filled circle. People with ataxia are slower. But show excellent learning!

66. Two different questions: 1.Do people with ataxia have difficulty on non-motor tasks? Yes. Performance is below normal on wide range of tasks.

67. Two different questions: 1. Do people with ataxia have difficulty on non-motor tasks? 2.Are basic cognitive abilities compromised in individuals with ataxia? A skeptic’s response: Cognitive problems may be secondary to motor problems. Memory: Problems related to rehearsal, internal movement Attention and Skill Learning: Demands to attend to movements.

68. Two different questions: 1. Do people with ataxia have difficulty on non-motor tasks? 2.Are basic cognitive abilities compromised in individuals with ataxia? A skeptic’s response: Cognitive problems may be secondary to motor problems. Memory: Problems related to rehearsal, internal movement Attention and Skill Learning: Demands to attend to movements. **Understanding the underlying cause can be useful for developing strategies for rehabilitation.

69. CognAc is always looking for new participants! Email: ivry@berkeley.edu Or just google “Rich Ivry” and you will get to the lab.

71. Control participant Person with ataxia

72. Control participant Person with ataxia Variable patterns of cerebellar degeneration.

73. Why study cognition and action together? Traditional view: Divide brain by task domain: Cerebellum as part of “motor” system. Other areas involved in perception, memory, etc.

74. Why study cognition and action together? Traditional view: Divide brain by task domain: Cerebellum as part of “motor” system. Other areas involved in perception, memory, etc. Ataxia: Difficulty producing coordinated actions. Difficulty learning new motor skills. But also reports of cognitive problems with language, planning, emotion…

75. Why study cognition and action together? Traditional view: Divide brain by task domain: Cerebellum as part of “motor” system. Other areas involved in perception, memory, etc. Ataxia: Difficulty producing coordinated actions. Difficulty learning new motor skills. But also reports of cognitive problems with language, planning, emotion… Difficult to separate movement and cognition. What made Michael Jordan such a great basketball player?

76. Attention Demands:More Equal More Response Demands:More More Less Bischoff-Grethe et al., 2002