Probabilistic reversal learning is impaired in Parkinson's disease

• Published in: Neuroscience Vol. 163; no. 4; pp. 1092 - 1101
• Main Authors: Peterson, D.A., Elliott, C., Song, D.D., Makeig, S., Sejnowski, T.J., Poizner, H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 10.11.2009; Elsevier
• Subjects: Adaptation, Psychological; Aged; Aged, 80 and over; Algorithms; basal ganglia; Biological and medical sciences; computational modeling; Computer Simulation; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dopamine; Feedback, Psychological; Female; Fundamental and applied biological sciences. Psychology; Humans; Learning Disabilities - etiology; Male; Medical sciences; Middle Aged; Models, Psychological; Neurology; Neuropsychological Tests; Parkinson Disease - complications; Primates; Probability Learning; reinforcement learning; Reversal Learning; Reward; Vertebrates: nervous system and sense organs; basal ganglia; PD; BDI; MMSE; UPDRS; computational modeling; dopamine; reinforcement learning; United Parkinson's Disease Rating Scale; Parkinson's disease; Mini-Mental State Exam; Beck Depression Inventory; Nervous system diseases; Dopamine; Central nervous system; Parkinson disease; Basal ganglion; Catecholamine; Encephalon; Cerebral disorder; Learning; Acquisition process; Central nervous system disease; Neurotransmitter; Reinforcement; Degenerative disease; Extrapyramidal syndrome
• DOI: 10.1016/j.neuroscience.2009.07.033
• ISSN: 0306-4522; 1873-7544

In many everyday settings, the relationship between our choices and their potentially rewarding outcomes is probabilistic and dynamic. In addition, the difficulty of the choices can vary widely. Although a large body of theoretical and empirical evidence suggests that dopamine mediates rewarded learning, the influence of dopamine in probabilistic and dynamic rewarded learning remains unclear. We adapted a probabilistic rewarded learning task originally used to study firing rates of dopamine cells in primate substantia nigra pars compacta [Morris G, Nevet A, Arkadir D, Vaadia E, Bergman H (2006) Midbrain dopamine neurons encode decisions for future action. Nat Neurosci 9:1057–1063] for use as a reversal learning task with humans. We sought to investigate how the dopamine depletion in Parkinson's disease (PD) affects probabilistic reward learning and adaptation to a reversal in reward contingencies. Over the course of 256 trials subjects learned to choose the more favorable from among pairs of images with small or large differences in reward probabilities. During a subsequent otherwise identical reversal phase, the reward probability contingencies for the stimuli were reversed. Seventeen PD patients of mild to moderate severity were studied off of their dopaminergic medications and compared to 15 age-matched controls. Compared to controls, PD patients had distinct pre- and post-reversal deficiencies depending upon the difficulty of the choices they had to learn. The patients also exhibited compromised adaptability to the reversal. A computational model of the subjects' trial-by-trial choices demonstrated that the adaptability was sensitive to the gain with which patients weighted pre-reversal feedback. Collectively, the results implicate the nigral dopaminergic system in learning to make choices in environments with probabilistic and dynamic reward contingencies.