L-Dopa Medication in Parkinson's Disease Restores Activity in the Motor Cortico-Striatal Loop but Does Not Modify the Cognitive Network
Identifieur interne : 001E29 ( Main/Exploration ); précédent : 001E28; suivant : 001E30L-Dopa Medication in Parkinson's Disease Restores Activity in the Motor Cortico-Striatal Loop but Does Not Modify the Cognitive Network
Auteurs : Thomas Jubault [Canada] ; Laura Monetta [Canada] ; Antonio P. Strafella [Canada] ; Anne-Louise Lafontaine [Canada] ; Oury Monchi [Canada]Source :
- PLoS ONE [ 1932-6203 ] ; 2009.
English descriptors
- KwdEn :
- MESH :
- chemical , pharmacology : Levodopa.
- drug effects : Cognition, Corpus Striatum.
- drug therapy : Parkinson Disease.
- physiopathology : Parkinson Disease.
- chemical , therapeutic use : Levodopa.
- Aged, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged.
Abstract
The goal of this study was to evaluate the effects of L-Dopa medication in Parkinson's disease (PD) on brain activation during the performance of a set-shifting task. Using fMRI, we have previously studied the patterns of activity observed in patients with PD after overnight removal of dopaminergic medication compared with control participants during the performance of different stages of the Wisconsin Card Sorting Task (WCST). The results revealed decreased cortical activity in the PD group compared to controls in the conditions that significantly required striatum, while increased cortical activity was observed when striatum was not involved. However, the effect of dopaminergic medication in PD patients on those patterns of activity has not yet been studied.
Here, eleven PD patients at early stage of the disease taking L-Dopa medication were recruited and underwent two fMRI sessions while performing the WCST: one session while taking their normal dose of medication and the other following overnight dopaminergic medication withdrawal. We found that L-dopa medication helped restoring a normal pattern of activity when matching and not planning was required, by increasing cortical activity in the premotor cortex. This effect was even stronger in the motor loop, i.e. when the putamen was required for controls, when matching following negative feedback. However, the medication did not change the pattern of activity in conditions relying primarily on a cognitive loop, i.e. when the caudate nucleus was required.
These studies provide explanation at the neural level regarding the relatively poor effects of L-Dopa on the cognitive deficits observed in PD.
Url:
DOI: 10.1371/journal.pone.0006154
PubMed: 19584921
PubMed Central: 2702753
Affiliations:
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Jubault</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Unité de Neuroimagerie Fonctionnelle, Institut Universitaire de Gériatrie de Montréal, Montreal, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Unité de Neuroimagerie Fonctionnelle, Institut Universitaire de Gériatrie de Montréal, Montreal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Radiology, University of Montreal, Montreal, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Radiology, University of Montreal, Montreal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Monetta, Laura" sort="Monetta, Laura" uniqKey="Monetta L" first="Laura" last="Monetta">Laura Monetta</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Unité de Neuroimagerie Fonctionnelle, Institut Universitaire de Gériatrie de Montréal, Montreal, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Unité de Neuroimagerie Fonctionnelle, Institut Universitaire de Gériatrie de Montréal, Montreal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Radiology, University of Montreal, Montreal, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Radiology, University of Montreal, Montreal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation wicri:level="4"><nlm:aff id="aff3"><addr-line>Toronto Western Hospital/Research Institute & CAMH-PET Imaging Centre, University of Toronto, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Toronto Western Hospital/Research Institute & CAMH-PET Imaging Centre, University of Toronto, Toronto, Ontario</wicri:regionArea><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Lafontaine, Anne Louise" sort="Lafontaine, Anne Louise" uniqKey="Lafontaine A" first="Anne-Louise" last="Lafontaine">Anne-Louise Lafontaine</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Movement Disorders Unit, McGill University Health Centre, Toronto, Ontario, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Movement Disorders Unit, McGill University Health Centre, Toronto, Ontario</wicri:regionArea><wicri:noRegion>Ontario</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"><nlm:aff id="aff1"><addr-line>Unité de Neuroimagerie Fonctionnelle, Institut Universitaire de Gériatrie de Montréal, Montreal, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Unité de Neuroimagerie Fonctionnelle, Institut Universitaire de Gériatrie de Montréal, Montreal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Radiology, University of Montreal, Montreal, Québec, Canada</addr-line></nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Radiology, University of Montreal, Montreal, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Cognition (drug effects)</term><term>Corpus Striatum (drug effects)</term><term>Female</term><term>Humans</term><term>Levodopa (pharmacology)</term><term>Levodopa (therapeutic use)</term><term>Magnetic Resonance Imaging</term><term>Male</term><term>Middle Aged</term><term>Parkinson Disease (drug therapy)</term><term>Parkinson Disease (physiopathology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cognition</term><term>Corpus Striatum</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Levodopa</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Humans</term><term>Magnetic Resonance Imaging</term><term>Male</term><term>Middle Aged</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>The goal of this study was to evaluate the effects of L-Dopa medication in Parkinson's disease (PD) on brain activation during the performance of a set-shifting task. Using fMRI, we have previously studied the patterns of activity observed in patients with PD after overnight removal of dopaminergic medication compared with control participants during the performance of different stages of the Wisconsin Card Sorting Task (WCST). The results revealed decreased cortical activity in the PD group compared to controls in the conditions that significantly required striatum, while increased cortical activity was observed when striatum was not involved. However, the effect of dopaminergic medication in PD patients on those patterns of activity has not yet been studied.</p></sec><sec><title>Methodology/Principal Findings</title><p>Here, eleven PD patients at early stage of the disease taking L-Dopa medication were recruited and underwent two fMRI sessions while performing the WCST: one session while taking their normal dose of medication and the other following overnight dopaminergic medication withdrawal. We found that L-dopa medication helped restoring a normal pattern of activity when matching and not planning was required, by increasing cortical activity in the premotor cortex. This effect was even stronger in the motor loop, i.e. when the putamen was required for controls, when matching following negative feedback. However, the medication did not change the pattern of activity in conditions relying primarily on a cognitive loop, i.e. when the caudate nucleus was required.</p></sec><sec><title>Conclusions/Significance</title><p>These studies provide explanation at the neural level regarding the relatively poor effects of L-Dopa on the cognitive deficits observed in PD.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Emre, M" uniqKey="Emre M">M Emre</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, Ae" uniqKey="Taylor A">AE Taylor</name></author><author><name sortKey="Saint Cyr, Ja" uniqKey="Saint Cyr J">JA Saint-Cyr</name></author><author><name sortKey="Lang, Ae" uniqKey="Lang A">AE Lang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lees, Aj" uniqKey="Lees A">AJ Lees</name></author><author><name sortKey="Smith, E" uniqKey="Smith E">E 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E">E Stefanova</name></author><author><name sortKey="Barker, Ra" uniqKey="Barker R">RA Barker</name></author><author><name sortKey="Robbins, Tw" uniqKey="Robbins T">TW Robbins</name></author><author><name sortKey="Owen, Am" uniqKey="Owen A">AM Owen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mattay, Vs" uniqKey="Mattay V">VS Mattay</name></author><author><name sortKey="Tessitore, A" uniqKey="Tessitore A">A Tessitore</name></author><author><name sortKey="Callicott, Jh" uniqKey="Callicott J">JH Callicott</name></author><author><name sortKey="Bertolino, A" uniqKey="Bertolino A">A Bertolino</name></author><author><name sortKey="Goldberg, Te" uniqKey="Goldberg T">TE Goldberg</name></author><author><name sortKey="Chase, Tn" uniqKey="Chase T">TN Chase</name></author><author><name sortKey="Hyde, Tm" uniqKey="Hyde T">TM Hyde</name></author><author><name sortKey="Weinberger, Dr" uniqKey="Weinberger D">DR Weinberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gotham, Am" uniqKey="Gotham A">AM Gotham</name></author><author><name sortKey="Brown, Rg" uniqKey="Brown R">RG Brown</name></author><author><name sortKey="Marsden, Cd" uniqKey="Marsden C">CD Marsden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cools, R" uniqKey="Cools R">R Cools</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lange, Kw" uniqKey="Lange K">KW Lange</name></author><author><name sortKey="Paul, Gm" uniqKey="Paul G">GM Paul</name></author><author><name sortKey="Naumann, M" uniqKey="Naumann M">M Naumann</name></author><author><name sortKey="Gsell, W" uniqKey="Gsell W">W Gsell</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Canada</li></country><region><li>Ontario</li></region><settlement><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Canada"><noRegion><name sortKey="Jubault, Thomas" sort="Jubault, Thomas" uniqKey="Jubault T" first="Thomas" last="Jubault">Thomas Jubault</name></noRegion><name sortKey="Jubault, Thomas" sort="Jubault, Thomas" uniqKey="Jubault T" first="Thomas" last="Jubault">Thomas Jubault</name><name sortKey="Lafontaine, Anne Louise" sort="Lafontaine, Anne Louise" uniqKey="Lafontaine A" first="Anne-Louise" last="Lafontaine">Anne-Louise Lafontaine</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="Monetta, Laura" sort="Monetta, Laura" uniqKey="Monetta L" first="Laura" last="Monetta">Laura Monetta</name><name sortKey="Monetta, Laura" sort="Monetta, Laura" uniqKey="Monetta L" first="Laura" last="Monetta">Laura Monetta</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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