{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:53:18Z","timestamp":1793335998364,"version":"4.5.0"},"reference-count":65,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Netherlands Organization or Scientific Research","award":["175.450"],"award-info":[{"award-number":["175.450"]}]},{"DOI":"10.13039\/501100003246","name":"Netherlands Organisation for Scientific Research","doi-asserted-by":"crossref","award":["453-14-005"],"award-info":[{"award-number":["453-14-005"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dutch Brain Foundation","award":["F2013(1)\u201315"],"award-info":[{"award-number":["F2013(1)\u201315"]}]},{"name":"Netherlands Organization or Scientific Research","award":["91617077"],"award-info":[{"award-number":["91617077"]}]},{"DOI":"10.13039\/100013301","name":"Parkinson\u2019s Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Erwin Schroedinger grant of the Austrian Science Fund","award":["J3723-B27"],"award-info":[{"award-number":["J3723-B27"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease is clinically defined by bradykinesia, along with rigidity and tremor. However, the severity of these motor signs is greatly variable between individuals, particularly the presence or absence of tremor. This variability in tremor relates to variation in cognitive\/motivational impairment, as well as the spatial distribution of neurodegeneration in the midbrain and dopamine depletion in the striatum. Here we ask whether interindividual heterogeneity in tremor symptoms could account for the puzzlingly large variability in the effects of dopaminergic medication on reinforcement learning, a fundamental cognitive function known to rely on dopamine. Given that tremor-dominant and non-tremor Parkinson\u2019s disease patients have different dopaminergic phenotypes, we hypothesized that effects of dopaminergic medication on reinforcement learning differ between tremor-dominant and non-tremor patients. Forty-three tremor-dominant and 20 non-tremor patients with Parkinson\u2019s disease were recruited to be tested both OFF and ON dopaminergic medication (200\/50 mg levodopa-benserazide), while 22 age-matched control subjects were recruited to be tested twice OFF medication. Participants performed a reinforcement learning task designed to dissociate effects on learning rate from effects on motivational choice (i.e. the tendency to \u2018Go\/NoGo\u2019 in the face of reward\/threat of punishment). In non-tremor patients, dopaminergic medication improved reward-based choice, replicating previous studies. In contrast, in tremor-dominant patients, dopaminergic medication improved learning from punishment. Formal modelling showed divergent computational effects of dopaminergic medication as a function of Parkinson\u2019s disease motor phenotype, with a modulation of motivational choice bias and learning rate in non-tremor and tremor patients, respectively. This finding establishes a novel cognitive\/motivational difference between tremor and non-tremor Parkinson\u2019s disease patients, and highlights the importance of considering motor phenotype in future work.<\/jats:p>","DOI":"10.1093\/brain\/awaa335","type":"journal-article","created":{"date-parts":[[2020,9,15]],"date-time":"2020-09-15T23:25:24Z","timestamp":1600212324000},"page":"3422-3434","source":"Crossref","is-referenced-by-count":47,"title":["Effects of dopamine on reinforcement learning in Parkinson\u2019s disease depend on motor phenotype"],"prefix":"10.1093","volume":"143","author":[{"given":"Annelies J","family":"van Nuland","sequence":"first","affiliation":[{"name":"Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rick C","family":"Helmich","sequence":"additional","affiliation":[{"name":"Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, 6500 HB Nijmegen, The Netherlands"},{"name":"Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8763-8071","authenticated-orcid":false,"given":"Michiel F","family":"Dirkx","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidemarie","family":"Zach","sequence":"additional","affiliation":[{"name":"Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, 6500 HB Nijmegen, The Netherlands"},{"name":"Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, 6500 HB Nijmegen, The Netherlands"},{"name":"Department of Neurology, Medical University Vienna, Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Toni","sequence":"additional","affiliation":[{"name":"Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, 6500 HB Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Cools","sequence":"additional","affiliation":[{"name":"Radboud University, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, 6500 HB Nijmegen, The Netherlands"},{"name":"Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Department of Psychiatry, Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7039-5130","authenticated-orcid":false,"given":"Hanneke E M","family":"den Ouden","sequence":"additional","affiliation":[{"name":"Radboud 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