FMRI studies of the human basal ganglia learning system

Carol A. SegerCognitive and Behavioral Neuroscience programs

Department of Psychology

Colorado State University

W. W. Norton

Memory and Habit

Habit: Slowly acquired associations between stimuli and responses/outcomes.

Memory: Memory for particular episodes

Baited arm

Place learning: always go to the east arm (memory)

Response learning: always turn right (habit)

Training trials: Rat starts at S armProbe trials: Rat starts at N arm

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Packard & McGaugh, 1996

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Caudate Hippocampal

Did injections of lidocaine to temporarily deactivate area.

Caudate Nucleus / Basal Ganglia

Basal ganglia: Caudate Putamen Globus Pallidus

Caudate and Putamen together are known as the striatum

SMA/PMCSSC

Motor

GP / SN

thalamus

DLPFCParietal

Spatial or Cognitive

GP / SN

thalamus

Visual

GP / SN

thalamus

Affective

GP / SN

thalamus

Putamen Head of caudate

Tail ofcaudate

VentralStriatum /NA

VLPFCInf tempSup temp

OFC, cinghipp, amg

Cortico-striatal processing loops

Striatal learning in humans

Problem: Humans use the medial temporal lobe memory system for tasks that other animals learn using the striatal system.

Probabilistic Classification

Task View set of cards Decide if the cards indicate “rain” or “shine”

Category Structure Cues P(pattern) P(rain)0 0 0 0 ---- ----0 0 0 1 0.140 0.150 0 1 0 0.084 0.380 0 1 1 0.087 0.100 1 0 0 0.084 0.620 1 0 1 0.064 0.180 1 1 0 0.047 0.500 1 1 1 0.041 0.211 0 0 0 0.140 0.851 0 0 1 0.058 0.501 0 1 0 0.064 0.821 0 1 1 0.032 0.431 1 0 0 0.087 0.901 1 0 1 0.032 0.571 1 1 0 0.041 0.791 1 1 1 ---- ----

76% 56% 43% 24%Cue Strength

Amnesia

Amnesics are not impaired for 1st 50 trials.

Knowlton, Gluck & Squire, 1994Knowlton, Gluck & Squire, 1994

Huntington’s disease

Damage to the striatum

Impaired on probabilistic classification

A possible human correlate of habit learning.

Knowlton et al. 1996Knowlton et al. 1996

Methods

BaselinePredict Predict Baseline

Alternated blocks of prediction and baseline trials.4 scans total24 prediction trials per scanParticipants:8 right-handed, fluent English speakers

Predict • • •

Poldrack, R. A., Prabhakaran, V., Seger, C. A., & Gabrieli, J. D. E. (1999). Striatal activation during cognitive skill learning. Neuropsychology, 13, 564-574.

Weather Prediction: Behavior

Probabilistic Classification Task:Classification > Baseline

Basal ganglia and hippocampus

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Right caudate(head)

R medialtemporal

Competition between MTL and striatal learning systems

Poldrack et al. 2001

Probabilistic classification task (yellow, triangles)Paired associates task (blue, circles)

Outstanding questions

Reason for recruitment of striatum Actual engram location? Executive functioning?

• Feedback

• Uncertainty / Probabilistic nature of task Modulatory system related to reward?

Nature of competition between MTL and striatal learning systems

Study 1: Feedback and Stimulus - outcome contingencies

Manipulate degree of probabilistic relationships from deterministic to random

Examine negative vs. positive feedback. Requires a post hoc analysis, which is possible due to the event related design.

Examine basal ganglia and medial temporal lobe interrelationships

Trial procedure

Correct0 ms

2500 ms…

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While stimulus is on the screen, participants press key for rain or sun

Stimulus - outcome relationships

Stimulus Relationship P ( rain)1 Deterministic 1002 Deterministic 03 Probabilistic 904 Probabilistic 105 Probabilistic 806 Probabilistic 207 Random 508 Random 50

Baseline NA

Participants: 15 young adults Conditions analyzed

Stimulus type• Det, Prob, Ran

Correctness• C and I

Feedback received• P and N

Examples• Det-CP Det-IN• Ran-P Ran-N• Prob-CP Prob-IN Prob-CN• Baseline

Comparisons

Areas associated with classification: Conjunction analysis Det-CP > baseline and Prob-CP > baseline

Areas associated with processing feedback: Ran-P < > Ran-N Prob-CP < > Prob-CN

Learning across blocks

1 2 3 Block

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DeterministicProbabilisticRandom

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Right body / tail caudate

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Det-CPProb-CPBaseline

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Left body / tail caudate

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Successful classification versusBaseline(Det-CP > base) and (Prob-CP > base)

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Areas associated with feedback: Head of the caudate

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Prob-CN >Prob-IN

Ran-P > Ran-N

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Ran-NRan-P

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Interrelationships between hippocampal and caudate activity

Ran-P > Ran-N Det-CP HippocampusRight caudate .47 #Left caudate .63 *

Prob-CPRight caudate .00Left caudate .04

Ran-P:Right caudate .33Left caudate -.10

#: p < .1; *: p < .05

Right caudate-B1 Left caudate-B1Accuracy .61 * .57 *

Correlations between blood flow and successful learning

Right hippocampusAccuracy-B1 -.59 *

*: p < .05

Study 2: Observational and Feedback learning

Basal ganglia play important role in learning via feedback Feedback leads to better learning than observe

in normal subjects on complex categorization tasks.

Learning via feedback is impaired in PD Could be due to the DA reward circuits in the

basal ganglia.

Stimulus set 1 (length-angle)

Category A Category B

Baseline

Ashby, Maddox, & Bohil (2002)

Category A Category B

Baseline

Set 2: Length-width

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Observational Learning

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Feedback Learning

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Training portion

Test trials: Observe and Feedback

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Methods

12 participants Within subjects design: Each participant did

both observe and feedback, counterbalanced, with different stimulus set.

Block design Alternated task blocks with baseline blocks Every 6th task block was a test block.

Classification performance on test trials

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Observe Feedback

PercentageCorrect

Common classification activity: body and tail of caudate.

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Obs > Base Feed C > base

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Head of caudate

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PercentSignal change

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Hippocampus / MTL

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Obs > Base

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Feed C > Base

Tentative conclusions from in-progress studies

Role of the head of the caudate differs from that of the body/tail of the caudate Tail-body: stimulus-outcome mapping.

• Consistent with the “visual” corticostriatal loop Head: related to processing feedback,

expectancy, executive functioning.• Consistent with the “cognitive” corticostriatal loop

Hippocampal - striatal antagonism not straightforward