{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T21:30:22Z","timestamp":1782509422728,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,8,1]],"date-time":"2016-08-01T00:00:00Z","timestamp":1470009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005725","name":"CHDI Foundation Inc.","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005725","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"the Wellcome Trust","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>While the <jats:italic>HTT<\/jats:italic> CAG\u2010repeat expansion mutation causing Huntington's disease (HD) is highly correlated with the rate of pathogenesis leading to disease onset, considerable variance in age\u2010at\u2010onset remains unexplained. Therefore, other factors must influence the pathogenic process. We asked whether these factors were related to natural biological variation in the sensory\u2010motor system. In 243 participants (96 premanifest and 35 manifest HD; 112 controls), sensory\u2010motor structural MRI, tractography, resting\u2010state fMRI, electrophysiology (including SEP amplitudes), motor score ratings, and grip force as sensory\u2010motor performance were measured. Following individual modality analyses, we used principal component analysis (PCA) to identify patterns associated with sensory\u2010motor performance, and manifest versus premanifest HD discrimination. We did not detect longitudinal differences over 12 months. PCA showed a pattern of loss of caudate, grey and white matter volume, cortical thickness in premotor and sensory cortex, and disturbed diffusivity in sensory\u2010motor white matter tracts that was connected to CAG repeat length. Two further major principal components appeared in controls and HD individuals indicating that they represent natural biological variation unconnected to the HD mutation. One of these components did not influence HD while the other non\u2010CAG\u2010driven component of axial versus radial diffusivity contrast in white matter tracts were associated with sensory\u2010motor performance and manifest HD. The first component reflects the expected CAG expansion effects on HD pathogenesis. One non\u2010CAG\u2010driven component reveals an independent influence on pathogenesis of biological variation in white matter tracts and merits further investigation to delineate the underlying mechanism and the potential it offers for disease modification. <jats:italic>Hum Brain Mapp 37:4615\u20134628, 2016<\/jats:italic>. \u00a9 <jats:bold>2016 Wiley Periodicals, Inc.<\/jats:bold><\/jats:p>","DOI":"10.1002\/hbm.23332","type":"journal-article","created":{"date-parts":[[2016,8,2]],"date-time":"2016-08-02T17:04:42Z","timestamp":1470157482000},"page":"4615-4628","source":"Crossref","is-referenced-by-count":22,"title":["Natural variation in sensory\u2010motor white matter organization influences manifestations of Huntington's disease"],"prefix":"10.1002","volume":"37","author":[{"given":"Michael","family":"Orth","sequence":"first","affiliation":[{"name":"Department of Neurology Ulm University Hospital Ulm 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Biophysics Section UCL Institute of Child Health London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Boyd","sequence":"additional","affiliation":[{"name":"Centre for Brain Health University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Borowsky","sequence":"additional","affiliation":[{"name":"CHDI Foundation Inc Princeton New Jersey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Reilmann","sequence":"additional","affiliation":[{"name":"George\u2010Huntington\u2010Institute, Technology\u2010Park Muenster Muenster Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Bernhard Landwehrmeyer","sequence":"additional","affiliation":[{"name":"Department of Neurology Ulm University Hospital Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blair R","family":"Leavitt","sequence":"additional","affiliation":[{"name":"Center for Molecular Medicine and Therapeutics and Department of Medical Genetics Child and Family Research Institute, University of British Columbia Vancouver Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymund AC","family":"Roos","sequence":"additional","affiliation":[{"name":"Department of Neurology Leiden University Medical Centre Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Durr","sequence":"additional","affiliation":[{"name":"APHP Department of Genetics Groupe Hospitalier Piti\u00e9\u2010Salp\u00eatri\u00e8re, and Institut Du Cerveau Et De La Moelle, INSERM U1127, CNRS UMR7225, UPMC Universit\u00e9 Paris VI UMR_S1127 Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraint","family":"Rees","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Neuroimaging University College 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