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Original Research ARTICLE

Front. Hum. Neurosci., 14 October 2010 | http://dx.doi.org/10.3389/fnhum.2010.00169

Differential influence of levodopa on reward-based learning in Parkinson’s disease

  • 1 Max Planck Institute for Human Development, Berlin, Germany
  • 2 Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
  • 3 Department of Psychology, University of Oslo, Oslo, Norway
  • 4 Department of Neurology, Charité, Campus Benjamin Franklin, Berlin, Germany

The mesocorticolimbic dopamine (DA) system linking the dopaminergic midbrain to the prefrontal cortex and subcortical striatum has been shown to be sensitive to reinforcement in animals and humans. Within this system, coexistent segregated striato-frontal circuits have been linked to different functions. In the present study, we tested patients with Parkinson’s disease (PD), a neurodegenerative disorder characterized by dopaminergic cell loss, on two reward-based learning tasks assumed to differentially involve dorsal and ventral striato-frontal circuits. 15 non-depressed and non-demented PD patients on levodopa monotherapy were tested both on and off medication. Levodopa had beneficial effects on the performance on an instrumental learning task with constant stimulus-reward associations, hypothesized to rely on dorsal striato-frontal circuits. In contrast, performance on a reversal learning task with changing reward contingencies, relying on ventral striato-frontal structures, was better in the unmedicated state. These results are in line with the “overdose hypothesis” which assumes detrimental effects of dopaminergic medication on functions relying upon less affected regions in PD. This study demonstrates, in a within-subject design, a double dissociation of dopaminergic medication and performance on two reward-based learning tasks differing in regard to whether reward contingencies are constant or dynamic. There was no evidence for a dose effect of levodopa on reward-based behavior with the patients’ actual levodopa dose being uncorrelated to their performance on the reward-based learning tasks.

Keywords: levodopa, decision-making, reinforcement learning, reversal learning, overdose hypothesis, PD, reward contingencies

Citation: Graef S, Biele G, Krugel LK, Marzinzik F, Wahl M, Wotka J, Klostermann F and Heekeren HR (2010) Differential influence of levodopa on reward-based learning in Parkinson’s disease. Front. Hum. Neurosci. 4:169. doi: 10.3389/fnhum.2010.00169

Received: 21 April 2010; Paper pending published: 07 May 2010;
Accepted: 08 August 2010; Published online: 14 October 2010

Edited by:

Francisco Barcelo, University of Illes Balears, Spain

Reviewed by:

Carme Junque, University of Barcelona, Spain
Esther Aarts, Radboud University, Netherlands
Ahmed A. Moustafa, Rutgers University, USA

Copyright: © 2010 Graef, Biele, Krugel, Marzinzik, Wahl, Wotka, Klostermann and Heekeren. This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence: Hauke R. Heekeren, Freie Universität Berlin, Habelschwerdter Allee 45, Raum JK 33/231, 14195 Berlin, Germany. e-mail: hauke.heekeren@fu-berlin.de;Susanne Graef, Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany. e-mail: graef@cbs.mpg.de