Dopamine depletion in Parkinson’s increases directed but not random exploration | Björn Meder

Dopamine depletion in Parkinson’s increases directed but not random exploration

Abstract

We investigated how patients with Parkinson’s disease (PD) manage the explore–exploit trade-off in a structured reward-learning task. Patients were tested either on (N=34) or off (N=34) dopaminergic medication (levodopa), with age-matched polyneuropathy patients serving as controls (N=35). Behaviorally, patients off medication showed marked learning and decision-making deficits, characterized by overexploration (excessive sampling of novel options) and insufficient exploitation (re-selection of previously rewarding options). To clarify the underlying mechanisms, we applied a Gaussian Process–Upper Confidence Bound (GP-UCB) model that combines generalization across spatially similar options with uncertainty-directed exploration (targeted sampling of uncertain options) and random exploration (undirected choice variability). Modeling results showed that patients off medication exhibited increased uncertainty-directed exploration compared to both controls and PD patients on medication, whereas random exploration did not differ across groups. Relative to controls, patients off medication also showed reduced generalization. In contrast, directed exploration and generalization in patients on medication were comparable to the control group. Our findings highlight how dopamine depletion in PD impacts reward learning under uncertainty, suggesting a key role of dopamine in exploration and generalization.

Publication
Science Advances

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