Reward processing abnormalities in Parkinson's disease§

Authors

  • Dimitrios Kapogiannis MD,

    1. Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    2. Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
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  • Eric Mooshagian PhD,

    1. Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    2. Center for Neuroscience and Regenerative Medicine, Uniformed Services University of Health Sciences, Henry M. Jackson Foundation, Rockville, Maryland, USA
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  • Paul Campion MD,

    1. Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Jordan Grafman PhD,

    1. Cognitive Neuroscience Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Trelawny J. Zimmermann MS,

    1. Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Kelsey C. Ladt BS,

    1. Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
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  • Eric M. Wassermann MD

    Corresponding author
    1. Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
    • 10 Center Dr., MSC 1440, Bethesda, MD 20892-1440, USA
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  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • Funding for this work came exclusively from the Clinical Neuroscience Program of the National Institute of Neurological Disorders and Stroke and the Intramural Research Program of the National Institute on Aging (to Dr. Kapogiannis), National Institutes of Health, and the Center for Neuroscience and Regenerative Medicine at the Uniformed Service University of the Health Sciences, via the Henry Jackson foundation (to Dr. Mooshagian).

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid–A–mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age-matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk-taking behavior on the Iowa Gambling Task. However, pramipexole increased risk-taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk-taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk-taking behavior in patients on agonist treatment. © 2011 Movement Disorder Society

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