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Adv."],"published-print":{"date-parts":[[2026,8,7]]},"abstract":"<jats:p>\n                    We investigated how patients with Parkinson\u2019s disease (PD) manage the explore-exploit trade-off in a structured reward-learning task. Patients were tested either on (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a034) or off (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a034) dopaminergic medication (levodopa), with age-matched polyneuropathy patients serving as controls (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u00a0=\u00a035). 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\u2013upper 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.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee6556","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T18:01:42Z","timestamp":1785952902000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Dopamine depletion in Parkinson\u2019s increases directed but not random exploration"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9326-400X","authenticated-orcid":true,"given":"Bj\u00f6rn","family":"Meder","sequence":"first","affiliation":[{"name":"Institute for Mind, Brain, and Behavior, Health and Medical University, Olympischer Weg 1, 14471 Potsdam, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha","family":"Sterf","sequence":"additional","affiliation":[{"name":"Institute for Mind, Brain, and Behavior, Health and Medical University, Olympischer Weg 1, 14471 Potsdam, Germany."},{"name":"Medical School Berlin, R\u00fcdesheimer Str. 50, 14197 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charley M.","family":"Wu","sequence":"additional","affiliation":[{"name":"Human and Machine Cognition Lab, University of T\u00fcbingen, Maria-von-Linden-Str. 6, 72074 T\u00fcbingen, Germany."},{"name":"Institute of Psychology, Technical University of Darmstadt, Karolinenplatz 5, 64289 Darmstadt, Germany."},{"name":"Hessian.AI, Landwehrstra\u00dfe 50A, 64293 Darmstadt, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0139-4123","authenticated-orcid":true,"given":"Matthias","family":"Guggenmos","sequence":"additional","affiliation":[{"name":"Institute for Mind, Brain, and Behavior, Health and Medical University, Olympischer Weg 1, 14471 Potsdam, Germany."},{"name":"Bernstein Center for Computational Neuroscience Berlin, Philippstra\u00dfe 13, 10115 Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"9","article-title":"The discovery of dopamine deficiency in the parkinsonian brain","volume":"70","author":"Hornykiewicz O.","year":"2006","unstructured":"O. 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