The effect of dopamine therapy on ventral and dorsal striatum-mediated cognition in Parkinson's disease: support from functional MRI.

Authors

Penny A MacDonald, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B5 Canada & Functional Neuroimaging Unit, Centre de Recherche, Institut Universitaire de Ge´ riatrie de Montre´ al, Montreal, Quebec, H3W 1W4 Canada
Alex A MacDonald, Department of Psychology, McGill University, Montreal, Quebec, H3A 1B1 Canada
Ken N Seergobin, Centre for Biological Timing and Cognition, University of Toronto, Toronto, Ontario, M5S 3G3 Canada
Ruzbeh Tamjeedi, Department of Philosophy, McGill University, Montreal, Quebec, H3A 2T7 Canada
Hooman Ganjavi, Department of Psychiatry, McGill University, Montreal, Quebec, H3A 1A1 Canada
Jean-Sebastien Provost, Functional Neuroimaging Unit, Centre de Recherche, Institut Universitaire de Ge´ riatrie de Montre´ al, Montreal, Quebec, H3W 1W4 Canada & Department of Radiology, University of Montreal, Montreal, Quebec, H3C 3J7 Canada
Oury Monchi, Functional Neuroimaging Unit, Centre de Recherche, Institut Universitaire de Ge´ riatrie de Montre´ al, Montreal, Quebec, H3W 1W4 Canada & Department of Radiology, University of Montreal, Montreal, Quebec, H3C 3J7 Canada

Document Type

Article

Publication Date

5-1-2011

Journal

Brain : a journal of neurology

Volume

134

Issue

Pt 5

First Page

1447

Last Page

1463

URL with Digital Object Identifier

10.1093/brain/awr075

Abstract

The central aim of our study was to elucidate functions mediated by the ventral and dorsal striatum, respectively, to better understand the cognitive effects of dopamine replacement in Parkinson's disease. We proposed that the ventral striatum underlies general learning of stimulus associations, whereas the dorsal striatum promotes integration of various influences on selecting. In Parkinson's disease, dopamine depletion is substantially less notable in the ventral relative to the dorsal striatum, and therefore greater improvements are expected for dorsal striatum-mediated functions with dopamine replacement. Using a simple selection task, we found that dopamine replacement impaired encoding and facilitation of consistent stimulus-stimulus relations across trials. This finding was in line with our contention that ventral striatum mediates learning stimulus associations, even when explicit feedback or reward is not provided. In contrast, dopamine replacement enhanced interference related to assimilating conflicting influences on selection across trials, consistent with our hypothesis that the dorsal striatum supports deciding in ambiguous contexts. We further confirmed these separable roles for the ventral and dorsal striatum in our selection task with healthy young volunteers using functional magnetic resonance imaging. In summary, we present a within-subject, double dissociation of the effects of dopamine replacement in patients with Parkinson's disease for ventral striatum-mediated facilitation and dorsal striatum-mediated interference, confirmed in a separate functional magnetic resonance imaging experiment. Defining the distinct functions of the ventral and dorsal striatum will have direct clinical implications. Titration of therapy in Parkinson's disease is generally geared towards optimizing dorsal striatum-mediated motor symptoms, possibly at the expense of ventral striatum operations, a consequence that is only beginning to be recognized. Enhanced awareness of these different processes will translate into medication strategies that take into account those symptoms that dopamine replacement might hinder, as well as improve. Here, we show impairments in learning new stimulus associations compared with improvements in integrating varied influences related to selection. Ultimately, this knowledge will lead clinicians to survey a broader range of symptoms in determining optimal therapy based on individual patient priorities.