{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:15:45Z","timestamp":1787008545073,"version":"build-2736575974"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T00:00:00Z","timestamp":1676505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"European Union\u2019s Horizon 2020","award":["826421"],"award-info":[{"award-number":["826421"]}]},{"name":"European Union\u2019s Horizon 2020","award":["945539"],"award-info":[{"award-number":["945539"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Structural grey and white matter changes precede the manifestation of clinical signs of Huntington\u2019s disease by many years. Conversion to clinically manifest disease therefore likely reflects not merely atrophy but a more widespread breakdown of brain function. Here, we investigated the structure\u2013function relationship close to and after clinical onset, in important regional brain hubs, particularly caudate nucleus and putamen, which are central to maintaining normal motor behaviour. In two independent cohorts of patients with premanifest Huntington\u2019s disease close to onset and very early manifest Huntington\u2019s disease (total n = 84; n = 88 matched controls), we used structural and resting state functional MRI.<\/jats:p>\n                  <jats:p>We show that measures of functional activity and local synchronicity within cortical and subcortical regions remain normal in the premanifest Huntington\u2019s disease phase despite clear evidence of brain atrophy. In manifest Huntington\u2019s disease, homeostasis of synchronicity was disrupted in subcortical hub regions such as caudate nucleus and putamen, but also in cortical hub regions, for instance the parietal lobe. Cross-modal spatial correlations of functional MRI data with receptor\/neurotransmitter distribution maps showed that Huntington\u2019s disease-specific alterations co-localize with dopamine receptors D1 and D2, as well as dopamine and serotonin transporters. Caudate nucleus synchronicity significantly improved models predicting the severity of the motor phenotype or predicting the classification into premanifest Huntington\u2019s disease or motor manifest Huntington\u2019s disease.<\/jats:p>\n                  <jats:p>Our data suggest that the functional integrity of the dopamine receptor-rich caudate nucleus is key to maintaining network function. The loss of caudate nucleus functional integrity affects network function to a degree that causes a clinical phenotype. These insights into what happens in Huntington\u2019s disease could serve as a model for what might be a more general relationship between brain structure and function in neurodegenerative diseases in which other brain regions are vulnerable.<\/jats:p>","DOI":"10.1093\/brain\/awad043","type":"journal-article","created":{"date-parts":[[2023,2,16]],"date-time":"2023-02-16T12:10:51Z","timestamp":1676549451000},"page":"3319-3330","source":"Crossref","is-referenced-by-count":20,"title":["Local synchronicity in dopamine-rich caudate nucleus influences Huntington\u2019s disease motor phenotype"],"prefix":"10.1093","volume":"146","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2542-4347","authenticated-orcid":false,"given":"Jan","family":"Kasper","sequence":"first","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre J\u00fclich , 52428 J\u00fclich , Germany"},{"name":"Institute of Systems Neuroscience, Medical Faculty & University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf , 40225 D\u00fcsseldorf , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon B","family":"Eickhoff","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre J\u00fclich , 52428 J\u00fclich , Germany"},{"name":"Institute of Systems Neuroscience, Medical Faculty & University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf , 40225 D\u00fcsseldorf , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Caspers","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine (INM-1), Research Centre J\u00fclich , 52428 J\u00fclich , Germany"},{"name":"Institute of Anatomy I, Medical Faculty & University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf , 40225 D\u00fcsseldorf , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Peter","sequence":"additional","affiliation":[{"name":"University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern , 3000 Bern 60 , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imis","family":"Dogan","sequence":"additional","affiliation":[{"name":"Department of Neurology, RWTH Aachen University , 52056 Aachen , Germany"},{"name":"JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Research Centre J\u00fclich GmbH , 52425 J\u00fclich Germany"},{"name":"RWTH Aachen University , 52056 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5358-5212","authenticated-orcid":false,"given":"Robert Christian","family":"Wolf","sequence":"additional","affiliation":[{"name":"Center for Psychosocial Medicine, Department of General Psychiatry, Heidelberg University , 69047 Heidelberg , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9730-9228","authenticated-orcid":false,"given":"Kathrin","family":"Reetz","sequence":"additional","affiliation":[{"name":"Department of Neurology, RWTH Aachen University , 52056 Aachen , Germany"},{"name":"JARA-BRAIN Institute Molecular Neuroscience and Neuroimaging, Research Centre J\u00fclich GmbH , 52425 J\u00fclich Germany"},{"name":"RWTH Aachen University , 52056 Aachen , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0492-5644","authenticated-orcid":false,"given":"Juergen","family":"Dukart","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain & Behaviour (INM-7), Research Centre J\u00fclich , 52428 J\u00fclich , Germany"},{"name":"Institute of Systems Neuroscience, Medical Faculty & University Hospital D\u00fcsseldorf, Heinrich Heine University D\u00fcsseldorf , 40225 D\u00fcsseldorf , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0817-8431","authenticated-orcid":false,"given":"Michael","family":"Orth","sequence":"additional","affiliation":[{"name":"University Hospital of Old Age Psychiatry and Psychotherapy, University of Bern , 3000 Bern 60 , Switzerland"},{"name":"Neurozentrum Siloah , 3073 G\u00fcmligen , Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,16]]},"reference":[{"key":"2023080120154013800_awad043-B1","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/S1474-4422(14)70238-8","article-title":"Prediction of manifest Huntington\u2019s disease with clinical and imaging measures: A prospective observational study","volume":"13","author":"Paulsen","year":"2014","journal-title":"Lancet 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