Aberrant reward processing in Parkinson's disease is associated with dopamine cell loss |
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Authors: | Aarts Esther Helmich Rick C Janssen Marcel J R Oyen Wim J G Bloem Bastiaan R Cools Roshan |
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Institution: | a Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behavior, Kapittelweg 29, 6525 EN Nijmegen, The Netherlandsb Radboud University Nijmegen Medical Centre, Department of Psychiatry, Reinier Postlaan 10, 6525 GC Nijmegen, The Netherlandsc Radboud University Nijmegen Medical Centre, Department of Neurology, Parkinson Centre Nijmegen (ParC), Reinier Postlaan 4, 6525 GC Nijmegen, The Netherlandsd Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Geert Grooteplein 8, 6525 GA Nijmegen, The Netherlands |
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Abstract: | Dopamine has been implicated in reward-related impulsivity, but the exact relationship between dopamine, reward and impulsivity in humans remains unknown. We address this question in Parkinson's disease (PD), which is characterized by severe dopamine depletion. PD is associated primarily with motor and cognitive inflexibility, but can also be accompanied by reward-related impulsivity. This paradoxical symptom of PD has often been attributed to dopaminergic overstimulation by antiparkinson medication, which is necessary to relieve the motor and cognitive inflexibility. However, factors other than medication may also contribute to aberrant impact of reward. Here we assess whether cognitive inflexibility and aberrant reward impact in PD are two sides of the same coin, namely dopamine cell loss. To measure dopamine cell loss, we employed 123I-FP-CIT Single Photon Emission Computed Tomography (SPECT) in 32 PD patients (10 never-medicated patients and 22 patients after withdrawal of all medication for > 12 h) and related the values to behavior on a rewarded task-switching paradigm. Dopamine cell loss was associated not only with cognitive inflexibility (under low reward), but also with aberrant impact of reward. These effects could not be attributed to medication use. Relative to controls (n = 26), aberrant reward processing in PD was particularly expressed as reduced capacity to maintain (i.e., repeat) the current task-set under high reward. Our findings demonstrate that factors intrinsically related to PD may underlie the paradoxical symptoms of inflexibility and reward-related impulsivity in PD. The present results concur with observations that low baseline dopamine states predispose to drug and other addictions. |
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Keywords: | Impulsivity Dopamine SPECT Flexibility Reward Parkinson's disease |
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