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The Cerebellum and Cognition: A 25-Year Check Up. Rich Ivry Cognition and Action Laboratory University of California, Berkeley. The Power of Advertising. Where's the cerebellum?. The Power of Advertising. Where's the cerebellum?. Aha! 50% of all neurons (note grey matter!).

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the cerebellum and cognition a 25 year check up

The Cerebellum and Cognition: A 25-Year Check Up

Rich Ivry

Cognition and Action Laboratory

University of California, Berkeley

slide2

The Power of Advertising

Where's the cerebellum?

slide3

The Power of Advertising

Where's the cerebellum?

Aha! 50% of all neurons (note grey matter!)

slide4

“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)

slide5

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

slide6

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”

slide7

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?

slide8

Lines of Evidence

Neuroanatomy: Structure

Neuroimaging: Physiology

Cerebellar activity when speaking.

Cerebellar activity when thinking.

Petersen et al., 1988

slide9

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.

slide10

Lines of Evidence

Neuroanatomy: Structure

Neuroimaging: Physiology

Neuropsychology: Behavior

Traditional assessment of ataxia:

Motor exam

New assessments:

Evaluate motor, cognitive, emotion

slide11

Lines of Evidence

Neuroanatomy: Structure

Neuroimaging: Physiology

Neuropsychology: Behavior

Deficits on range of neuropsychological assessments.

Cerebellar cognitive affective syndrome Schmahmann (1991)

slide12

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.

slide13

Neuropsychological evaluation of people with acute ataxia one week after stroke.

Performance Poor Normal

slide14

Change in performance at re-test after 1-9 months.

Performance Poor Normal

1 Week 1-9 months later

slide15

Half empty or half full? Implications of such rapid recovery?

Performance Poor Normal

1 Week 1-9 months later

slide16

Most common persistent cognitive problem is with "executive function".

Performance Poor Normal

1 Week 1-9 months later

slide17

Executive Function

-- working memory (short term memory)

-- planning

-- multi-tasking

Functions associated with prefrontal cortex

slide18

Relating executive function to cerebellar degeneration?

Is the relationship

-- Indirect: correlated but not causal

-- Direct: correlated and causal

slide19

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?

slide20

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?

slide21

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?

slide22

2. Direct hypotheses:

Causal contribution of cerebellum to cognition

Relating executive function to cerebellar degeneration?

slide23

2. Direct hypotheses:

Causal contribution of cerebellum to cognition.

a. Thinking through internal movement.

** Give TEST **

Relating executive function to cerebellar degeneration?

slide24

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?

slide25

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?

slide26

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

slide27

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?

slide28

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.

slide29

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 **

slide31

2. Direct hypotheses:

Cerebellar contributions to cognition.

a. Thinking through internal movement.

b. Working memory for action.

Relating executive function to cerebellar degeneration?

slide32
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)

slide34

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.

slide35

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.

slide36

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?

slide37

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.

slide38

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

slide39

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.

slide42

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)
slide43

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)
slide44

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”)
slide45

Doing badly on working memory test doesn’t mean you have problem with working memory.

“softly” example.

slide46

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.

slide47

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.

slide48

Regions of the cerebellum that are active during word rehearsal task and finger tapping.

Motoric regions, even if different

slide49

Exploring the cause of cognitive problems in ataxia.

Three examples:

1. working memory

2. attention

Multi-tasking.

Rapidly changing focus of attention.

slide50

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.

slide51

Measuring Attention Shifting

Press button for

Low Tones (Condition 1)

slide52

Measuring Attention Shifting

Press button for

Low Tones (Condition 1)

Red Squares (Condition 2)

slide53

Measuring Attention Shifting

Press button for

Low Tones (Condition 1)

Red Squares (Condition 2)

Alternate responding to red squares and low tones. (Condition 3)

slide55

Modified Attention Shifting:

Reducing Motor Requirements

slide56

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

slide57

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

Making responses requires attention!

slide58

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?

slide59

Sequence Learning

Press key corresponding to position of asterisk. Repeat 60 times.

Sequence: Asterisks follow repeating pattern.

Random: Positions chosen at random.

slide60

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.

slide61

Ataxic

Non-ataxic

People with ataxia do not show learning on this task.

slide62

Ataxic

Non-ataxic

People with ataxia do not show learning on this task.

Puzzle since learning is one of pattern recognition (like Michael Jordan) more than finger coordination.

slide63

Ataxic

Non-ataxic

People with ataxia do not show learning on this task.

Puzzle since learning is one of pattern recognition (like Michael Jordan) more than finger coordination.

Related to working memory problems?

slide64

Simplify working memory demands:

Respond by directly pointing to location of the filled circle.

slide65

Simplify working memory demands:

Respond by directly pointing to location of the filled circle.

People with ataxia are slower.

But show excellent learning!

slide66

Two different questions:

  • Do people with ataxia have difficulty on non-motor tasks?
  • Yes. Performance is below normal on wide range of tasks.
slide67

Two different questions:

  • 1. Do people with ataxia have difficulty on non-motor tasks?
  • 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.
slide68

Two different questions:

  • 1. Do people with ataxia have difficulty on non-motor tasks?
  • 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.

slide69

CognAc is always looking for new participants!

Email: ivry@berkeley.edu

Or just google “Rich Ivry” and you will get to the lab.

slide71

Control participant

Person with ataxia

slide72

Control participant

Person with ataxia

Variable patterns of cerebellar degeneration.

slide73

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.

slide74

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…

slide75

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?

slide76

Attention Demands: More Equal More

Response Demands: More More Less

Bischoff-Grethe et al., 2002