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!)
“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
of monkey brain
MC inject
functional MRI (fMRI)
in human brain
PFC inject
Strick & Fiez, 2009
Krienen & Buckner, 2009
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”
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?
Lines of Evidence
Neuroanatomy: Structure
Neuroimaging: Physiology
Cerebellar activity
when speaking.
Cerebellar activity
when thinking.
Petersen et al., 1988
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.
Lines of Evidence
Neuroanatomy: Structure
Neuroimaging: Physiology
Neuropsychology: Behavior
Traditional assessment of ataxia:
Motor exam
New assessments:
Evaluate motor, cognitive, emotion
Lines of Evidence
Neuroanatomy: Structure
Neuroimaging: Physiology
Neuropsychology: Behavior
Deficits on range of neuropsychological assessments.
Cerebellar cognitive affective syndrome
Schmahmann (1991)
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.
Performance
Normal
Poor
Neuropsychological evaluation of people
with acute ataxia one week after stroke.
Performance
Normal
Poor
Change in performance at re-test after 1-9
months.
1 Week 1-9 months later
Performance
Normal
Poor
Half empty or half full?
Implications of such rapid recovery?
1 Week 1-9 months later
Performance
Normal
Poor
Most common persistent cognitive problem
is with "executive function".
1 Week 1-9 months later
Executive Function
-- working memory (short term memory)
-- planning
-- multi-tasking
Functions associated with
cortex
prefrontal
Relating executive function to cerebellar degeneration?
Is the relationship
-- Indirect: correlated but not causal
-- Direct:
correlated and causal
Relating executive function to cerebellar degeneration?
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?
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?
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?
2. Direct hypotheses:
Causal contribution of cerebellum to cognition
Relating executive function to cerebellar degeneration?
2. Direct hypotheses:
Causal contribution of cerebellum to cognition.
a. Thinking through internal movement.
** Give TEST **
Relating executive function to cerebellar degeneration?
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?
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?
2. Direct hypotheses:
a. Thinking through internal movement.
b. Working memory for action.
WM in Perception
WM in Action
Relating executive function to cerebellar degeneration?
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.
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 **
Relating executive function to cerebellar degeneration?
2. Direct hypotheses:
Cerebellar contributions to cognition.
a. Thinking through internal movement.
b. Working memory for action.
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.
Poor
Performance
Good
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?
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 dinner
remembering 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 dinner
remembering a phone number
Individuals with ataxia have problems with working
memory.
Get volunteer (who looks away from screen):
Get volunteer (who looks away from screen):
1. 4 8 6 5 8 3 2 7
(immediate)
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)
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)
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”)
Doing badly on working memory test doesn’t mean you
have problem with working memory.
“softly” example.
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.
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.
Regions of the cerebellum
that are active during word
rehearsal task and finger
tapping.
Motoric regions, even
if different
Exploring the cause of cognitive problems in ataxia.
Three examples:
1. working memory
2. attention
Multi-tasking.
Rapidly changing focus of attention.
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.
Measuring Attention Shifting
Press button for
Low Tones (Condition 1)
Measuring Attention Shifting
Press button for
Low Tones (Condition 1)
Red Squares (Condition 2)
Measuring Attention Shifting
Press button for
Low Tones (Condition 1)
Red Squares (Condition 2)
Alternate responding to red
squares and low tones.
(Condition 3)
Controls
Ataxics
% Correct Responses
100
90
80
70
60
50
Focused
Divided
Attention Condition
Problem is much more pronounced with divided attention.
Modified Attention Shifting:
Reducing Motor Requirements
Controls
Ataxics
100
95
90
85
80
75
70
65
60
55
50
1-Response
2-Responses
People with ataxia show large improvement when
attention demands are held constant but motor requirements
are reduced.
Controls
Ataxics
100
95
90
85
80
75
70
65
60
55
50
1-Response
2-Responses
People with ataxia show large improvement when
attention demands are held constant but motor requirements
are reduced.
Making responses requires attention!
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?
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
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.
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?
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.
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.
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.
CognAc is always looking for new participants!
Email: ivry@berkeley.edu
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.
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…
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?
Attention Demands:
More
Equal
More
Response Demands:
More
More
Less
Bischoff-Grethe et al., 2002