Mapping Preclinical Compensation in Parkinson's Disease: An Imaging Genomics Approach
Identifieur interne : 002244 ( Main/Merge ); précédent : 002243; suivant : 002245Mapping Preclinical Compensation in Parkinson's Disease: An Imaging Genomics Approach
Auteurs : Bart F. L. Van Nuenen [Pays-Bas, Allemagne] ; Thilo Van Eimeren [Canada] ; Joyce P. M. Van Der Vegt [Pays-Bas, Allemagne] ; Carsten Buhmann [Allemagne] ; Christine Klein [Allemagne] ; Bastiaan R. Bloem [Pays-Bas] ; Hartwig R. Siebner [Allemagne, Danemark]Source :
- Movement disorders [ 0885-3185 ] ; 2009.
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- Pascal (Inist)
- Wicri :
- topic : Cartographie.
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Abstract
Mutations in the Parkin (PARK2) and PINK1 gene (PARK 6) can cause recessively inherited Parkinson's disease (PD). The presence of a single Parkin or PINK1 mutation is associated with a dopaminergic nigrostriatal dysfunction and conveys an increased risk to develop PD throughout lifetime. Therefore neuroimaging of non-manifesting individuals with a mutant Parkin or PINK1 allele opens up a window for the investigation of preclinical and very early phases of PD in vivo. Here we review how functional magnetic resonance imaging (fMRI) can be used to identify compensatory mechanisms that help to prevent development of overt disease. In two separate experiments, Parkin mutation carriers displayed stronger activation of rostral supplementary motor area (SMA) and right dorsal premotor cortex (PMd) during a simple motor sequence task and anterior cingulate motor area and left rostral PMd during internal movement selection as opposed to externally cued movements. The additional recruitment of the rostral SMA and right rostral PMd during the finger sequence task was also observed in a separate group of nonmanifesting mutation carriers with a single heterozygous PINK1 mutation. Because mutation carriers were not impaired at performing the task, the additional recruitment of motor cortical areas indicates a compensatory mechanism that effectively counteracts the nigrostriatal dysfunction. These first results warrant further studies that use these imaging genomics approach to tap into preclinical compensation of PD. Extensions of this line of research involve fMRI paradigms probing nonmotor brain functions. Additionally, the same fMRI paradigms should be applied to nonmanifesting mutation carriers in genes linked to autosomal dominant PD. This will help to determine how "generically" the human brain compensates for a preclinical dopaminergic dysfunction.
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Van Nuenen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurology, Christian-Albrechts-University</s1><s2>Kiel</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Van Eimeren, Thilo" sort="Van Eimeren, Thilo" uniqKey="Van Eimeren T" first="Thilo" last="Van Eimeren">Thilo Van Eimeren</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>CAMH-PET Centre, Toronto Western Research Institute and Movement Disorders Centre, University of Toronto</s1><s3>CAN</s3><sZ>2 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="Van Der Vegt, Joyce P M" sort="Van Der Vegt, Joyce P M" uniqKey="Van Der Vegt J" first="Joyce P. 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L." last="Van Nuenen">Bart F. L. Van Nuenen</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurology, Christian-Albrechts-University</s1><s2>Kiel</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Van Eimeren, Thilo" sort="Van Eimeren, Thilo" uniqKey="Van Eimeren T" first="Thilo" last="Van Eimeren">Thilo Van Eimeren</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>CAMH-PET Centre, Toronto Western Research Institute and Movement Disorders Centre, University of Toronto</s1><s3>CAN</s3><sZ>2 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="Van Der Vegt, Joyce P M" sort="Van Der Vegt, Joyce P M" uniqKey="Van Der Vegt J" first="Joyce P. M." last="Van Der Vegt">Joyce P. M. Van Der Vegt</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurology, Christian-Albrechts-University</s1><s2>Kiel</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation></author><author><name sortKey="Buhmann, Carsten" sort="Buhmann, Carsten" uniqKey="Buhmann C" first="Carsten" last="Buhmann">Carsten Buhmann</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neurology and Human Genetics, University Clinic Eppendorf</s1><s2>Hamburg</s2><s3>DEU</s3><sZ>4 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Neurology, University of Lübeck</s1><s2>Lübeck</s2><s3>DEU</s3><sZ>5 aut.</sZ></inist:fA14><country>Allemagne</country><wicri:noRegion>Lübeck</wicri:noRegion><wicri:noRegion>University of Lübeck</wicri:noRegion><wicri:noRegion>Lübeck</wicri:noRegion></affiliation></author><author><name sortKey="Bloem, Bastiaan R" sort="Bloem, Bastiaan R" uniqKey="Bloem B" first="Bastiaan R." last="Bloem">Bastiaan R. Bloem</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Nimègue</settlement><region type="province" nuts="2">Gueldre</region></placeName></affiliation></author><author><name sortKey="Siebner, Hartwig R" sort="Siebner, Hartwig R" uniqKey="Siebner H" first="Hartwig R." last="Siebner">Hartwig R. Siebner</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Department of Neurology, Christian-Albrechts-University</s1><s2>Kiel</s2><s3>DEU</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Allemagne</country><placeName><region type="land" nuts="2">Schleswig-Holstein</region><settlement type="city">Kiel</settlement></placeName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="06"><s1>Danish Research Centre for Magnetic Resonance, Hvidovre University Hospital, Copenhagen Medical School</s1><s2>Copenhagen</s2><s3>DNK</s3><sZ>7 aut.</sZ></inist:fA14><country>Danemark</country><placeName><settlement type="city">Copenhague</settlement><region type="région" nuts="2">Hovedstaden</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Asymptomatic</term><term>Cartography</term><term>Compensation</term><term>Functional imaging</term><term>Motor cortex</term><term>Nervous system diseases</term><term>Nuclear magnetic resonance imaging</term><term>Parkin</term><term>Parkinson disease</term><term>Parkinsonism</term><term>Surgical approach</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Parkinsonisme</term><term>Pathologie du système nerveux</term><term>Cartographie</term><term>Asymptomatique</term><term>Compensation</term><term>Voie abord</term><term>Imagerie fonctionnelle</term><term>Imagerie RMN</term><term>Cortex moteur</term><term>Parkine</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Cartographie</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Mutations in the Parkin (PARK2) and PINK1 gene (PARK 6) can cause recessively inherited Parkinson's disease (PD). The presence of a single Parkin or PINK1 mutation is associated with a dopaminergic nigrostriatal dysfunction and conveys an increased risk to develop PD throughout lifetime. Therefore neuroimaging of non-manifesting individuals with a mutant Parkin or PINK1 allele opens up a window for the investigation of preclinical and very early phases of PD in vivo. Here we review how functional magnetic resonance imaging (fMRI) can be used to identify compensatory mechanisms that help to prevent development of overt disease. In two separate experiments, Parkin mutation carriers displayed stronger activation of rostral supplementary motor area (SMA) and right dorsal premotor cortex (PMd) during a simple motor sequence task and anterior cingulate motor area and left rostral PMd during internal movement selection as opposed to externally cued movements. The additional recruitment of the rostral SMA and right rostral PMd during the finger sequence task was also observed in a separate group of nonmanifesting mutation carriers with a single heterozygous PINK1 mutation. Because mutation carriers were not impaired at performing the task, the additional recruitment of motor cortical areas indicates a compensatory mechanism that effectively counteracts the nigrostriatal dysfunction. These first results warrant further studies that use these imaging genomics approach to tap into preclinical compensation of PD. Extensions of this line of research involve fMRI paradigms probing nonmotor brain functions. Additionally, the same fMRI paradigms should be applied to nonmanifesting mutation carriers in genes linked to autosomal dominant PD. This will help to determine how "generically" the human brain compensates for a preclinical dopaminergic dysfunction.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Danemark</li><li>Pays-Bas</li></country><region><li>Gueldre</li><li>Hambourg</li><li>Hovedstaden</li><li>Ontario</li><li>Schleswig-Holstein</li></region><settlement><li>Copenhague</li><li>Hambourg</li><li>Kiel</li><li>Nimègue</li><li>Toronto</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Pays-Bas"><region name="Gueldre"><name sortKey="Van Nuenen, Bart F L" sort="Van Nuenen, Bart F L" uniqKey="Van Nuenen B" first="Bart F. L." last="Van Nuenen">Bart F. L. Van Nuenen</name></region><name sortKey="Bloem, Bastiaan R" sort="Bloem, Bastiaan R" uniqKey="Bloem B" first="Bastiaan R." last="Bloem">Bastiaan R. Bloem</name><name sortKey="Van Der Vegt, Joyce P M" sort="Van Der Vegt, Joyce P M" uniqKey="Van Der Vegt J" first="Joyce P. M." last="Van Der Vegt">Joyce P. M. Van Der Vegt</name></country><country name="Allemagne"><region name="Schleswig-Holstein"><name sortKey="Van Nuenen, Bart F L" sort="Van Nuenen, Bart F L" uniqKey="Van Nuenen B" first="Bart F. L." last="Van Nuenen">Bart F. L. Van Nuenen</name></region><name sortKey="Buhmann, Carsten" sort="Buhmann, Carsten" uniqKey="Buhmann C" first="Carsten" last="Buhmann">Carsten Buhmann</name><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name><name sortKey="Siebner, Hartwig R" sort="Siebner, Hartwig R" uniqKey="Siebner H" first="Hartwig R." last="Siebner">Hartwig R. Siebner</name><name sortKey="Van Der Vegt, Joyce P M" sort="Van Der Vegt, Joyce P M" uniqKey="Van Der Vegt J" first="Joyce P. M." last="Van Der Vegt">Joyce P. M. Van Der Vegt</name></country><country name="Canada"><region name="Ontario"><name sortKey="Van Eimeren, Thilo" sort="Van Eimeren, Thilo" uniqKey="Van Eimeren T" first="Thilo" last="Van Eimeren">Thilo Van Eimeren</name></region></country><country name="Danemark"><region name="Hovedstaden"><name sortKey="Siebner, Hartwig R" sort="Siebner, Hartwig R" uniqKey="Siebner H" first="Hartwig R." last="Siebner">Hartwig R. Siebner</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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