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Fox Foundation for Parkinson\u2019s Research","doi-asserted-by":"publisher","award":["#15581"],"award-info":[{"award-number":["#15581"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018044","name":"Verily Life Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018044","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health \u223c Holland"},{"DOI":"10.13039\/100013301","name":"Parkinson\u2019s Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013301","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006209","name":"Radboudumc","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006209","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001722","name":"Royal Netherlands Academy of Arts and Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001722","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","award":["453-14-015"],"award-info":[{"award-number":["453-14-015"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003246","name":"Dutch Research Council","doi-asserted-by":"publisher","award":["09150172010044"],"award-info":[{"award-number":["09150172010044"]}],"id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Dopaminergic medication is well established to boost reward- versus punishment-based learning in Parkinson\u2019s disease. However, there is tremendous variability in dopaminergic medication effects across different individuals, with some patients exhibiting much greater cognitive sensitivity to medication than others. We aimed to unravel the mechanisms underlying this individual variability in a large heterogeneous sample of early-stage patients with Parkinson\u2019s disease as a function of comorbid neuropsychiatric symptomatology, in particular impulse control disorders and depression.<\/jats:p>\n                  <jats:p>One hundred and ninety-nine patients with Parkinson\u2019s disease (138 ON medication and 61 OFF medication) and 59 healthy controls were scanned with functional MRI while they performed an established probabilistic instrumental learning task. Reinforcement learning model-based analyses revealed medication group differences in learning from gains versus losses, but only in patients with impulse control disorders. Furthermore, expected-value related brain signalling in the ventromedial prefrontal cortex was increased in patients with impulse control disorders ON medication compared with those OFF medication, while striatal reward prediction error signalling remained unaltered.<\/jats:p>\n                  <jats:p>These data substantiate the hypothesis that dopamine\u2019s effects on reinforcement learning in Parkinson\u2019s disease vary with individual differences in comorbid impulse control disorder and suggest they reflect deficient computation of value in medial frontal cortex, rather than deficient reward prediction error signalling in striatum.<\/jats:p>\n                  <jats:p>See Michael Browning (https:\/\/doi.org\/10.1093\/brain\/awad248) for a scientific commentary on this article.<\/jats:p>","DOI":"10.1093\/brain\/awad162","type":"journal-article","created":{"date-parts":[[2023,5,16]],"date-time":"2023-05-16T14:24:36Z","timestamp":1684247076000},"page":"3676-3689","source":"Crossref","is-referenced-by-count":22,"title":["Impulse control disorder in Parkinson\u2019s disease is associated with abnormal frontal value signalling"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6450-2304","authenticated-orcid":false,"given":"Jorryt G","family":"Tichelaar","sequence":"first","affiliation":[{"name":"Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging , 6525EN Nijmegen , The Netherlands"},{"name":"Radboud University Medical Center, Department of Neurology, Centre of Expertise for Parkinson and Movement Disorders , 6525GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3420-5499","authenticated-orcid":false,"given":"Ceyda","family":"Sayal\u0131","sequence":"additional","affiliation":[{"name":"The Johns Hopkins University School of Medicine, Center for Psychedelic and Consciousness Research , Baltimore, MD 21224 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-6573","authenticated-orcid":false,"given":"Rick C","family":"Helmich","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging , 6525EN Nijmegen , The Netherlands"},{"name":"Radboud University Medical Center, Department of Neurology, Centre of Expertise for Parkinson and Movement Disorders , 6525GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8994-5534","authenticated-orcid":false,"given":"Roshan","family":"Cools","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging , 6525EN Nijmegen , The Netherlands"},{"name":"Radboud University Medical Center, Department of Psychiatry , 6525GA Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,16]]},"reference":[{"key":"2023090117353171300_awad162-B1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The emerging evidence of the Parkinson pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J Parkinsons 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