Dopamine is associated with prioritization of reward-associated memories in Parkinson’s disease

Author:

Sharp Madeleine E1,Duncan Katherine2,Foerde Karin3,Shohamy Daphna456

Affiliation:

1. Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada

2. Department of Psychology, University of Toronto, Toronto, Canada

3. New York State Psychiatric Institute and Department of Psychiatry, Columbia University, New York, NY, USA

4. Department of Psychology, Columbia University, New York, NY, USA

5. Zuckerman Mind, Brain, Behavior Institute, Columbia University, New York, NY, USA

6. Kavli Institute for Brain Science, Columbia University, New York, NY, USA

Abstract

Abstract Patients with Parkinson’s disease have reduced reward sensitivity related to dopaminergic neuron loss, which is associated with impairments in reinforcement learning. Increasingly, however, dopamine-dependent reward signals are recognized to play an important role beyond reinforcement learning. In particular, it has been shown that reward signals mediated by dopamine help guide the prioritization of events for long-term memory consolidation. Meanwhile, studies of memory in patients with Parkinson’s disease have focused on overall memory capacity rather than what is versus what isn’t remembered, leaving open questions about the effect of dopamine replacement on the prioritization of memories by reward and the time-dependence of this effect. The current study sought to fill this gap by testing the effect of reward and dopamine on memory in patients with Parkinson’s disease. We tested the effect of dopamine modulation and reward on two forms of long-term memory: episodic memory for neutral objects and memory for stimulus-value associations. We measured both forms of memory in a single task, adapting a standard task of reinforcement learning with incidental episodic encoding events of trial-unique objects. Objects were presented on each trial at the time of feedback, which was either rewarding or not. Memory for the trial-unique images and for the stimulus-value associations, and the influence of reward on both, was tested immediately after learning and 2 days later. We measured performance in Parkinson’s disease patients tested either ON or OFF their dopaminergic medications and in healthy older control subjects. We found that dopamine was associated with a selective enhancement of memory for reward-associated images, but that it did not influence overall memory capacity. Contrary to predictions, this effect did not differ between the immediate and delayed memory tests. We also found that while dopamine had an effect on reward-modulated episodic memory, there was no effect of dopamine on memory for stimulus-value associations. Our results suggest that impaired prioritization of cognitive resource allocation may contribute to the early cognitive deficits of Parkinson’s disease.

Funder

NIH

Parkinson Foundation

Canadian Institutes of Health Research Fellowship

Publisher

Oxford University Press (OUP)

Subject

Clinical Neurology

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