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Extensive volume loss and altered diffusion metrics in the basal ganglia, cortex and white matter are seen when patients with Huntington's disease (HD) undergo structural imaging, suggesting that changes in basal ganglia\u2010cortical structural connectivity occur. The aims of this study were to characterise altered patterns of basal ganglia\u2010cortical structural connectivity with high anatomical precision in premanifest and early manifest HD, and to identify associations between structural connectivity and genetic or clinical markers of HD. 3\u2010Tesla diffusion tensor magnetic resonance images were acquired from 14 early manifest HD subjects, 17 premanifest HD subjects and 18 controls. Voxel\u2010based analyses of probabilistic tractography were used to quantify basal ganglia\u2010cortical structural connections. Canonical variate analysis was used to demonstrate disease\u2010associated patterns of altered connectivity and to test for associations between connectivity and genetic and clinical markers of HD; this is the first study in which such analyses have been used. Widespread changes were seen in basal ganglia\u2010cortical structural connectivity in early manifest HD subjects; this has relevance for development of therapies targeting the striatum. Premanifest HD subjects had a pattern of connectivity more similar to that of controls, suggesting progressive change in connections over time. Associations between structural connectivity patterns and motor and cognitive markers of disease severity were present in early manifest subjects. Our data suggest the clinical phenotype in manifest HD may be at least partly a result of altered connectivity. <jats:italic>Hum Brain Mapp 36:1728\u20131740, 2015<\/jats:italic>. \u00a9 <jats:bold>2015 Wiley Periodicals, Inc<\/jats:bold>.<\/jats:p>","DOI":"10.1002\/hbm.22733","type":"journal-article","created":{"date-parts":[[2015,1,30]],"date-time":"2015-01-30T17:19:12Z","timestamp":1422638352000},"page":"1728-1740","source":"Crossref","is-referenced-by-count":39,"title":["Basal ganglia\u2010cortical structural connectivity in Huntington's disease"],"prefix":"10.1002","volume":"36","author":[{"given":"Marianne J.U.","family":"Novak","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology  London United Kingdom"},{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiran K.","family":"Seunarine","sequence":"additional","affiliation":[{"name":"Developmental Imaging and Biophysics Section UCL Institute of Child Health  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clare R.","family":"Gibbard","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London United Kingdom"},{"name":"Developmental Imaging and Biophysics Section UCL Institute of Child Health  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"McColgan","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Draganski","sequence":"additional","affiliation":[{"name":"LREN D\u00e9partement des Neurosciences Cliniques CHUV Universit\u00e9 de Lausanne  Switzerland"},{"name":"Department of Cognitive Neurology Max\u2010Planck Institute for Human Cognitive and Brain Sciences Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Friston","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris A.","family":"Clark","sequence":"additional","affiliation":[{"name":"Developmental Imaging and Biophysics Section UCL Institute of Child Health  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"Department of Neurodegenerative Disease UCL Institute of Neurology  London United Kingdom"},{"name":"National Hospital for Neurology and Neurosurgery  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,1,30]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2007.07.007"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.44.5.823"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmrb.1994.1037"},{"key":"e_1_2_5_5_1","first-page":"82","volume-title":"Manual for the Beck Depression Inventory\u2010II, Vol. 1","author":"Beck ATS RA","year":"1996"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.02.010"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11682-011-9121-8"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awh622"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1176\/jnp.17.3.378"},{"key":"e_1_2_5_10_1","doi-asserted-by":"crossref","unstructured":"CookPA BaiY Nedjati\u2010GilaniS SeunarineKK HallMG ParkerGJ AlexanderDC(2006): Camino: Open source diffusion\u2010MRI reconstruction and processing. 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