Effects of dopamine on reinforcement learning in Parkinson’s disease depend on motor phenotype
| Autor: | Hanneke E. M. den Ouden, Rick C. Helmich, Roshan Cools, Michiel F. Dirkx, Heidemarie Zach, Annelies J van Nuland, Ivan Toni |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Parkinson's disease Dopamine Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] Striatum Disease 240 Systems Neurology Antiparkinson Agents Levodopa Benserazide Neural Pathways Tremor 111 000 Intention & Action AcademicSubjects/SCI01870 Dopaminergic Neurodegeneration Cognition Parkinson Disease Middle Aged Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3] humanities Drug Combinations Phenotype Dopamine Agonists Female medicine.drug medicine.medical_specialty reinforcement learning Physical medicine and rehabilitation Punishment Reward medicine Learning Humans Computer Simulation Aged Motivation Neuro- en revalidatiepsychologie business.industry Action intention and motor control Neuropsychology and rehabilitation psychology Original Articles medicine.disease nervous system diseases Parkinson’s disease Conditioning Operant AcademicSubjects/MED00310 Neurology (clinical) business 170 000 Motivational & Cognitive Control |
| Zdroj: | Brain Brain, 143, 11, pp. 3422-3434 Brain, 143, 3422-3434 |
| ISSN: | 1460-2156 0006-8950 |
| Popis: | See Manohar (doi:10.1093/brain/awaa363) for a scientific commentary on this article. Parkinson’s disease is complicated by great variability in symptoms. Van Nuland et al. report that the well-established effects of levodopa on reinforcement learning apply only to patients without tremor symptoms, suggesting a need to revisit neurocognitive models of dopaminergic function in Parkinson’s disease. Parkinson’s 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’s 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’s 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 ‘Go/NoGo’ 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’s 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’s disease patients, and highlights the importance of considering motor phenotype in future work. |
| Databáze: | OpenAIRE |
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