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Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model
Published on: January 7, 2019
Dopamine depletion in Parkinson's increases directed but not random exploration
Björn Meder1, Martha Sterf1,2, Charley M Wu3,4,5
1Institute for Mind, Brain, and Behavior, Health and Medical University, Olympischer Weg 1, 14471 Potsdam, Germany.
None:
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 patients with PD 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 affects reward learning under uncertainty, suggesting a key role of dopamine in exploration and generalization.
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