Prefrontal Dopaminergic Receptor Abnormalities and Executive Functions in Parkinson's Disease
Identifieur interne : 001052 ( Main/Exploration ); précédent : 001051; suivant : 001053Prefrontal Dopaminergic Receptor Abnormalities and Executive Functions in Parkinson's Disease
Auteurs : JI HYUN KO [Canada] ; Francesca Antonelli [Canada] ; Oury Monchi [Canada] ; Nicola Ray [Canada] ; Pablo Rusjan [Canada] ; Sylvain Houle [Canada] ; Anthony E. Lang [Canada] ; Leigh Christopher [Canada] ; Antonio P. Strafella [Canada]Source :
- Human brain mapping [ 1065-9471 ] ; 2013.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
The main pattern of cognitive impairments seen in early to moderate stages of Parkinson's disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [11C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [11C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [11C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [11C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD.
Affiliations:
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type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Centre de Recherche Institute Universitaire de Gériatrie de Montreal, Université de Montréal</s1><s2>Quebec</s2><s3>CAN</s3><sZ>3 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Ray, Nicola" sort="Ray, Nicola" uniqKey="Ray N" first="Nicola" last="Ray">Nicola Ray</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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="Rusjan, Pablo" sort="Rusjan, Pablo" uniqKey="Rusjan P" first="Pablo" last="Rusjan">Pablo Rusjan</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Movement Disorder Unit and E. J. Safra Program in Parkinson Disease, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 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="Christopher, Leigh" sort="Christopher, Leigh" uniqKey="Christopher L" first="Leigh" last="Christopher">Leigh Christopher</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>Division of Brain, Imaging and Behaviour-Systems Neuroscience, Toronto Western Research Institute, UHN, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>8 aut.</sZ><sZ>9 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><affiliation wicri:level="4"><inist:fA14 i1="04"><s1>Movement Disorder Unit and E. J. Safra Program in Parkinson Disease, Toronto Western Hospital, UHN, University of Toronto</s1><s2>Ontario</s2><s3>CAN</s3><sZ>7 aut.</sZ><sZ>9 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></analytic><series><title level="j" type="main">Human brain mapping</title><title level="j" type="abbreviated">Hum. brain mapp.</title><idno type="ISSN">1065-9471</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Human brain mapping</title><title level="j" type="abbreviated">Hum. brain mapp.</title><idno type="ISSN">1065-9471</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biological receptor</term><term>Cognition</term><term>Dopamine</term><term>Emission tomography</term><term>Executive function</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Positron emission tomography</term><term>Radiodiagnosis</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Récepteur biologique</term><term>Fonction exécutive</term><term>Tomoscintigraphie</term><term>Tomographie par émission de positons</term><term>Cognition</term><term>Dopamine</term><term>Radiodiagnostic</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The main pattern of cognitive impairments seen in early to moderate stages of Parkinson's disease (PD) includes deficits of executive functions. These nonmotor complications have a significant impact on the quality of life and day-to-day activities of PD patients and are not effectively managed by current therapies, a problem which is almost certainly due to the fact that the disease extends beyond the nigrostriatal system. To investigate the role of extrastriatal dopamine in executive function in PD, PD patients and a control group were studied with positron-emission-tomography using a high-affinity dopamine D2/D3 receptor tracer, [<sup>11</sup>C]FLB-457. All participants were scanned twice while performing an executive task and a control task. Patients were off medication for at least 12 h. The imaging analysis revealed that parkinsonian patients had lower [<sup>11</sup>C]FLB-457 binding than control group independently of task conditions across different brain regions. Cognitive assessment measures were positively correlated with [<sup>11</sup>C]FLB-457 binding in the bilateral dorsolateral prefrontal cortex and anterior cingulate cortex only in control group, but not in PD patients. Within the control group, during the executive task (as compared to control task), there was evidence of reduced [<sup>11</sup>C]FLB-457 binding (indicative of increased dopamine release) in the right orbitofrontal cortex. In contrast, PD patients did not show any reduction in binding during the executive task (as compared with control task). These findings suggest that PD patients present significant abnormalities in extrastriatal dopamine associated with executive processing. These observations provide important insights on the pathophysiology of cognitive dysfunction in PD.</div></front></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"><region name="Ontario"><name sortKey="Ji Hyun Ko" sort="Ji Hyun Ko" uniqKey="Ji Hyun Ko" last="Ji Hyun Ko">JI HYUN KO</name></region><name sortKey="Antonelli, Francesca" sort="Antonelli, Francesca" uniqKey="Antonelli F" first="Francesca" last="Antonelli">Francesca Antonelli</name><name sortKey="Antonelli, Francesca" sort="Antonelli, Francesca" uniqKey="Antonelli F" first="Francesca" last="Antonelli">Francesca Antonelli</name><name sortKey="Christopher, Leigh" sort="Christopher, Leigh" uniqKey="Christopher L" first="Leigh" last="Christopher">Leigh Christopher</name><name sortKey="Christopher, Leigh" sort="Christopher, Leigh" uniqKey="Christopher L" first="Leigh" last="Christopher">Leigh Christopher</name><name sortKey="Houle, Sylvain" sort="Houle, Sylvain" uniqKey="Houle S" first="Sylvain" last="Houle">Sylvain Houle</name><name sortKey="Ji Hyun Ko" sort="Ji Hyun Ko" uniqKey="Ji Hyun Ko" last="Ji Hyun Ko">JI HYUN KO</name><name sortKey="Lang, Anthony E" sort="Lang, Anthony E" uniqKey="Lang A" first="Anthony E." last="Lang">Anthony E. Lang</name><name sortKey="Monchi, Oury" sort="Monchi, Oury" uniqKey="Monchi O" first="Oury" last="Monchi">Oury Monchi</name><name sortKey="Ray, Nicola" sort="Ray, Nicola" uniqKey="Ray N" first="Nicola" last="Ray">Nicola Ray</name><name sortKey="Ray, Nicola" sort="Ray, Nicola" uniqKey="Ray N" first="Nicola" last="Ray">Nicola Ray</name><name sortKey="Rusjan, Pablo" sort="Rusjan, Pablo" uniqKey="Rusjan P" first="Pablo" last="Rusjan">Pablo Rusjan</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</name><name sortKey="Strafella, Antonio P" sort="Strafella, Antonio P" uniqKey="Strafella A" first="Antonio P." last="Strafella">Antonio P. Strafella</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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