Funding agencies: This research was funded by a Canadian Institutes of Health Research Clinician-Scientist Phase I Scholarship.
Parkinson's disease duration determines effect of dopaminergic therapy on ventral striatum function
Article first published online: 19 NOV 2012
Copyright © 2012 Movement Disorders Society
Volume 28, Issue 2, pages 153–160, February 2013
How to Cite
MacDonald, A. A., Monchi, O., Seergobin, K. N., Ganjavi, H., Tamjeedi, R. and MacDonald, P. A. (2013), Parkinson's disease duration determines effect of dopaminergic therapy on ventral striatum function. Mov. Disord., 28: 153–160. doi: 10.1002/mds.25152
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue published online: 23 FEB 2013
- Article first published online: 19 NOV 2012
- Manuscript Accepted: 28 JUN 2012
- Manuscript Revised: 22 JUN 2012
- Manuscript Received: 9 APR 2012
- Parkinson's disease;
- basal ganglia
We investigated the hypothesis that variation in endogenous dopamine (DA) across brain regions explains dissimilar effects of dopaminergic therapy on aspects of cognition in early Parkinson's disease (PD). Extensive degeneration of DA-producing cells in the substantia nigra cause dorsal striatum (DS) DA deficiency and movement abnormalities. Particularly in early PD, this contrasts with relative sparing of the dopaminergic cells of the ventral tegmental area (VTA). The hypothesis predicts that DS-mediated cognitive functions are deficient at baseline and improved by DA replacement, whereas functions depending upon VTA-innervated brain regions are normal off medication and worsen with treatment. The latter pattern presumably owes to overdose of relatively DA-replete VTA-supplied brain regions with medication levels titrated to DS-mediated motor symptoms.[2, 3] As PD progresses, however, VTA degeneration increases. Impairment in cognitive operations performed by VTA-innervated brain regions, such as the ventral striatum (VS), is expected. We compared the performance of early and late PD patients, on and off dopaminergic medication, relative to age-matched controls, on reward learning, previously shown to implicate the VS. As expected, in early PD, stimulus-reward learning was normal off medication, but worsened with DA replacement. At more advanced disease stages, PD patients learned stimulus-reward contingencies more poorly than controls and early PD patients off medication. Furthermore, dopaminergic medication did not worsen reward learning in late PD patients, in line with the dopamine overdose hypothesis. Unlike its effect on DS-mediated functions, however, DA-replacement therapy did not improve reward learning in late PD patients. © 2012 Movement Disorder Society