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

The Cerebellum and Cognition: A The Cerebellum and Cognition: A 25-Year Check Up25-Year Check Up

Rich IvryCognition and Action LaboratoryUniversity of California, Berkeley

Where's the cerebellum?

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Where's the cerebellum?

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

“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)

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

Strick & Fiez, 2009 Krienen & Buckner, 2009

MC inject PFC inject

Lines of Evidence


PFC - Cerebellar loopsPolysynaptic mapping Human DTI

Pathology in psychiatric populations

Autism, ADHD, Schizophrenia, Fragile X, etc.

“Guilt by association”

Lines of Evidence


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?

Lines of Evidence



Petersen et al., 1988

Cerebellar activity when speaking.

Cerebellar activity when thinking.

Lines of Evidence



Hundreds of fMRI studies show cerebellar activation even Hundreds of fMRI studies show cerebellar activation even when movement is absent or is “equated” between when movement is absent or is “equated” between experimental and control conditions.experimental and control conditions.

Lines of Evidence



Neuropsychology: Behavior

Traditional assessment of ataxia:

Motor exam

New assessments:

Evaluate motor, cognitive, emotion

Lines of Evidence




Deficits on range of neuropsychological assessments.

Cerebellar cognitive affective syndromeSchmahmann (1991)

Lines of Evidence




Deficits on range of neuropsychological assessments.

Cerebellar cognitive affective syndromeSchmahmann (1991)

** Mixed bag of results.-- Many individuals and even group studies show no impairment.-- Bias to publish positive results.

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

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

1 Week 1-9 months later

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


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


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Executive Function

-- working memory (short term memory)

-- planning

-- multi-tasking

Functions associated with prefrontal cortex

Relating executive function to cerebellar degeneration?

Is the relationship

-- Indirect: correlated but not causal

-- Direct: correlated and causal

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.





b. Loss of cerebellar tissue disrupts activity in linked parts of cortex.





b. Loss of cerebellar tissue disrupts activity in frontal cortex.

c. Resource allocation.Everything is multi-tasking in ataxia!


2. Direct hypotheses:

Causal contribution of cerebellum to cognition



Causal contribution of cerebellum to cognition.

a. Thinking through internal movement.

** Give TEST **





Memory list:

2 - 6 - 8 - 5 - 4 - 7 - 1





Loss of coordinated "internal movement"(poor rehearsal)

People with ataxia are much more impaired on working memory tasks when rehearsal is emphasized.




b. Working memory for action.


WM in Perception WM in 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.


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.

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 **


Cerebellar contributions to cognition.




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)

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.

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.

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?

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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.

Memory

Long-term memory: stored knowledge

Working memory:

Maintenance of information that is important for current task.

e.g., making a 3-course dinnerremembering a phone number

Memory

Long-term memory: stored knowledge

Working memory:

Maintenance of information that is important for current task.

e.g., making a 3-course dinnerremembering a phone number

Individuals with ataxia have problems with working memory.

Get volunteer (who looks away from screen):


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


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

2. 3 6 2 9 5 4 9 1 (softly)


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)


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”)

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.



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.

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

Motoric regions, even if different


Three examples:

1. working memory

2. attention

Multi-tasking.

Rapidly changing focus of attention.


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.

Measuring Attention ShiftingMeasuring Attention Shifting

Press button for

Low Tones (Condition 1)


Press button for


Red Squares (Condition 2)


Press button for


Red Squares (Condition 2)

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

Problem is much more pronounced with divided attention.

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Focused Divided

Attention Condition

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Controls Ataxics

Modified Attention Shifting: Modified Attention Shifting: Reducing Motor RequirementsReducing Motor Requirements

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

50556065707580859095100

1-Response 2-Responses

Controls Ataxics

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

Making responses requires attention!

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1-Response 2-Responses

Controls Ataxics


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?

Sequence Learning

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

Sequence: Asterisks follow repeating pattern.

Random: Positions chosen at random.

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.

People with ataxia do not show learning on this task.

Ataxic

Non-ataxic


Ataxic

Non-ataxic

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


Ataxic

Non-ataxic

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

Related to working memory problems?

Simplify working memory demands:

Respond by directly pointing to location of the filled circle.

Simplify working memory demands:

Respond by directly pointing to location of the filled circle.

People with ataxia are slower.

But show excellent learning!

Two different questions:

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

Yes. Performance is below normal on wide range of 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.



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.

CognAc is always looking for new participants!

Email: [email protected]

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

Control participant

Person with ataxia

Control participant

Person with ataxia

Variable patterns of cerebellar degeneration.

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…



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?

Attention Demands: More Equal More

Response Demands: More More Less

Bischoff-Grethe et al., 2002

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

Documents

association slide

causal slide

berkeley slide

emotion slide

prefrontal cortex slide

structure neuroimaging

lines of evidence neuroanatomy

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