The Cerebellum and Cognition: A 25-Year Check Up

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

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

3. The Power of Advertising Where's the cerebellum? 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 brain in human brain MC inject PFC inject Krienen & Buckner, 2009 Strick & Fiez, 2009

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 Cerebellar activity when speaking. Cerebellar activity when thinking. Petersen et al., 1988

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. Performance Poor Normal 1 Week 1-9 months later

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

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

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. Poor Performance Good Half empty or half full? Implications of such rapid recovery?

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. Get volunteer (who looks away from screen): • 4 8 6 5 8 3 2 7 (immediate)

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

43. Get volunteer (who looks away from screen): • 4 8 6 5 8 3 2 7 (immediate) • 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): • 4 8 6 5 8 3 2 7 (immediate) • 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.