The effect of dopamine therapy on ventral and dorsal striatum-mediated cognition in Parkinson's disease: support from functional MRI
Identifieur interne : 001909 ( Main/Exploration ); précédent : 001908; suivant : 001910The effect of dopamine therapy on ventral and dorsal striatum-mediated cognition in Parkinson's disease: support from functional MRI
Auteurs : Penny A. Macdonald [Canada] ; Alex A. Macdonald [Canada] ; Ken N. Seergobin [Canada] ; Ruzbeh Tamjeedi [Canada] ; Hooman Ganjavi [Canada] ; Jean-Sebastien Provost [Canada] ; Oury Monchi [Canada]Source :
- Brain [ 0006-8950 ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
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.
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Seergobin</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Centre for Biological Timing and Cognition, University of Toronto</s1><s2>Toronto, Ontario, M5S 3G3</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Tamjeedi, Ruzbeh" sort="Tamjeedi, Ruzbeh" uniqKey="Tamjeedi R" first="Ruzbeh" last="Tamjeedi">Ruzbeh Tamjeedi</name><affiliation wicri:level="4"><inist:fA14 i1="05"><s1>Department of Philosophy, McGill University</s1><s2>Montreal, Quebec, H3A 2T7</s2><s3>CAN</s3><sZ>4 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Ganjavi, Hooman" sort="Ganjavi, Hooman" uniqKey="Ganjavi H" first="Hooman" last="Ganjavi">Hooman Ganjavi</name><affiliation wicri:level="4"><inist:fA14 i1="06"><s1>Department of Psychiatry, McGill University</s1><s2>Montreal, Quebec, H3A 1A1</s2><s3>CAN</s3><sZ>5 aut.</sZ></inist:fA14><country>Canada</country><placeName><settlement type="city">Montréal</settlement><region type="state">Québec</region></placeName><orgName type="university">Université McGill</orgName></affiliation></author><author><name sortKey="Provost, Jean Sebastien" sort="Provost, Jean Sebastien" uniqKey="Provost J" first="Jean-Sebastien" last="Provost">Jean-Sebastien Provost</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Functional Neuroimaging Unit, Centre de Recherche, Institut Universitaire de Gériatrie de Montréal</s1><s2>Montreal, Quebec, H3W 1W4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec, H3W 1W4</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Radiology, University of Montreal</s1><s2>Montreal, Quebec, H3C 3J7</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec, H3C 3J7</wicri:noRegion></affiliation></author><author><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Functional Neuroimaging Unit, Centre de Recherche, Institut Universitaire de Gériatrie de Montréal</s1><s2>Montreal, Quebec, H3W 1W4</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec, H3W 1W4</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Radiology, University of Montreal</s1><s2>Montreal, Quebec, H3C 3J7</s2><s3>CAN</s3><sZ>6 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Montreal, Quebec, H3C 3J7</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Cognition</term><term>Cognitive disorder</term><term>Dopamine</term><term>Nervous system diseases</term><term>Nuclear magnetic resonance imaging</term><term>Parkinson disease</term><term>Treatment</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Trouble cognitif</term><term>Pathologie du système nerveux</term><term>Dopamine</term><term>Traitement</term><term>Cognition</term><term>Imagerie RMN</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li><li>Québec</li></region><settlement><li>Montréal</li><li>Toronto</li></settlement><orgName><li>Université McGill</li><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><region name="Québec"><name sortKey="Macdonald, Penny A" sort="Macdonald, Penny A" uniqKey="Macdonald P" first="Penny A." last="Macdonald">Penny A. Macdonald</name></region><name sortKey="Ganjavi, Hooman" sort="Ganjavi, Hooman" uniqKey="Ganjavi H" first="Hooman" last="Ganjavi">Hooman Ganjavi</name><name sortKey="Macdonald, Alex A" sort="Macdonald, Alex A" uniqKey="Macdonald A" first="Alex A." last="Macdonald">Alex A. Macdonald</name><name sortKey="Macdonald, Penny A" sort="Macdonald, Penny A" uniqKey="Macdonald P" first="Penny A." last="Macdonald">Penny A. Macdonald</name><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><name sortKey="Provost, Jean Sebastien" sort="Provost, Jean Sebastien" uniqKey="Provost J" first="Jean-Sebastien" last="Provost">Jean-Sebastien Provost</name><name sortKey="Provost, Jean Sebastien" sort="Provost, Jean Sebastien" uniqKey="Provost J" first="Jean-Sebastien" last="Provost">Jean-Sebastien Provost</name><name sortKey="Seergobin, Ken N" sort="Seergobin, Ken N" uniqKey="Seergobin K" first="Ken N." last="Seergobin">Ken N. Seergobin</name><name sortKey="Tamjeedi, Ruzbeh" sort="Tamjeedi, Ruzbeh" uniqKey="Tamjeedi R" first="Ruzbeh" last="Tamjeedi">Ruzbeh Tamjeedi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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