{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T02:28:30Z","timestamp":1786328910476,"version":"build-2736575974"},"reference-count":72,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T00:00:00Z","timestamp":1786233600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["223082\/Z\/21\/Z"],"award-info":[{"award-number":["223082\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Longitudinal studies of seed\u2010based functional connectivity (SBFC) in young adult\u00a0Huntington's disease gene\u2010expanded (HDGE) individuals are rare, and none, to our knowledge, have examined adult cohorts decades from predicted clinical motor diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine longitudinal functional connectivity (FC) changes over ~4.8\u2009years in adult HDGE individuals before clinical motor diagnosis compared with matched controls, all selected from the HD Young Adult Study (HD\u2010YAS) cohort, focusing on bilateral caudate and putamen as seeds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A subset of 71 right\u2010handed individuals (43 HDGEs and 28 controls) from the HD\u2010YAS underwent resting\u2010state functional magnetic resonance imaging (fMRI) at two visits ~4.8\u2009years apart. SBFC analyses focused on bilateral caudate and putamen seeds. Mixed\u2010effects analysis of variance (ANOVA) tested main effects of group, time, and group \u00d7 time interactions, with false discovery rate (FDR) correction. Post hoc tests explored significant findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HDGEs showed reduced FC between the putamen and cerebellar vermis\/lobules and brainstem (\n                      <jats:italic>P<\/jats:italic>\n                      \u2010FDR\u2009\u2264\u20090.01), alongside increased connectivity with precuneus (\n                      <jats:italic>P<\/jats:italic>\n                      \u2010FDR\u2009=\u20090.04), supramarginal, and angular gyri (\n                      <jats:italic>P<\/jats:italic>\n                      \u2010FDR\u2009=\u20090.04). Over ~4.8\u2009years, HDGEs exhibited different FC trajectories compared with controls, displaying FC reductions between the right caudate and paracingulate, frontal (\n                      <jats:italic>P<\/jats:italic>\n                      \u2010FDR\u2009=\u2009&lt;\u20090.001), occipital (\n                      <jats:italic>P<\/jats:italic>\n                      \u2010FDR\u2009=\u2009&lt;\u20090.01), and striatal regions (\n                      <jats:italic>P<\/jats:italic>\n                      \u2010FDR\u2009=\u2009\u2264 0.03).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These findings provide the first longitudinal evidence of early cortico\u2010striatal and cerebellar functional network changes in adult HDGEs decades before clinical motor diagnosis, alongside possible compensatory processes in key hubs of the default mode network. These early FC changes likely reflect a dynamic interplay between neurodegenerative processes and adaptive reorganization, a balance that may ultimately fail as pathology progresses. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70461","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:41:50Z","timestamp":1786326110000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Early Longitudinal Brain Network Changes in Huntington's Disease Before Clinical Motor Onset"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7321-6054","authenticated-orcid":false,"given":"Michela","family":"Leocadi","sequence":"first","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Z.","family":"Hobbs","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0679-0117","authenticated-orcid":false,"given":"Mena","family":"Farag","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Fayer","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Thackeray","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry","family":"Knights","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7216-8679","authenticated-orcid":false,"given":"James B.","family":"Rowe","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences University of Cambridge, Cambridge Biomedical Campus  Cambridge UK"},{"name":"Cambridge University Hospitals NHS Foundation Trust  Cambridge UK"},{"name":"Medical Research Council Cognition and Brain Sciences Unit University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor W.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Department of Psychology University of Cambridge  Cambridge UK"},{"name":"Behavioural and Clinical Neuroscience Institute University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7352-1745","authenticated-orcid":false,"given":"Barbara J.","family":"Sahakian","sequence":"additional","affiliation":[{"name":"Behavioural and Clinical Neuroscience Institute University of Cambridge  Cambridge UK"},{"name":"Department of Psychiatry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraint","family":"Rees","sequence":"additional","affiliation":[{"name":"UCL Institute of Cognitive Neuroscience University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael I.","family":"Scahill","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Tabrizi","sequence":"additional","affiliation":[{"name":"Huntington's Disease Centre, Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-2820","authenticated-orcid":false,"given":"Christelle","family":"Langley","sequence":"additional","affiliation":[{"name":"Behavioural and Clinical Neuroscience Institute University of Cambridge  Cambridge UK"},{"name":"Department of Psychiatry University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-198511000-00003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(14)70238-8"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.30992"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e318249f683"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40734-018-0069-3"},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/S0072-9752(07)01256-0","article-title":"Neuropathology of Huntington's disease","volume":"89","author":"Vonsattel JPG","year":"2008","journal-title":"Handb Clin Neurol"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(11)70263-0"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70088-7"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30143-5"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-03424-6"},{"issue":"7","key":"e_1_2_10_12_1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/S1474-4422(22)00120-X","article-title":"A biological classification of Huntington's disease: the integrated staging system","volume":"21","author":"Tabrizi SJ","year":"2022","journal-title":"Lancet Neurol"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000617"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/B978-0-12-801893-4.00020-1","article-title":"Structural imaging in premanifest and manifest Huntington disease","volume":"144","author":"Scahill RI","year":"2017","journal-title":"Handb Clin Neurol"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2014.24"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2018.03.013"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.24790"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22616"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2011.06.011"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.08.105"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43841"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2013.03.001"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.120226"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2012.02.095"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2020-324104"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70944"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000501616"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/mdc3.70010"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.384"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.08.002"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy122"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx022"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/WCO.0000000000000469"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410521"},{"key":"e_1_2_10_35_1","doi-asserted-by":"crossref","DOI":"10.56441\/hilbertpress.2207.6598","volume-title":"Handbook of Functional Connectivity Magnetic Resonance Imaging Methods in CONN","author":"Nieto\u2010Castanon A","year":"2020"},{"key":"e_1_2_10_36_1","doi-asserted-by":"crossref","DOI":"10.56441\/hilbertpress.2207.6598","volume-title":"Handbook of Functional Connectivity Magnetic Resonance Imaging Methods in CONN","author":"Nieto\u2010Castanon A","year":"2020"},{"issue":"1","key":"e_1_2_10_37_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/(SICI)1097-0193(1996)4:1<58::AID-HBM4>3.0.CO;2-O","article-title":"A unified statistical approach for determining significant signals in images of cerebral activation","volume":"4","author":"Worsley KJ","year":"1996","journal-title":"Hum Brain Mapp"},{"key":"e_1_2_10_38_1","doi-asserted-by":"crossref","DOI":"10.56441\/hilbertpress.2207.6598","volume-title":"Handbook of Functional Connectivity Magnetic Resonance Imaging Methods in CONN","author":"Nieto\u2010Castanon A","year":"2020"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.10.090"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2012.00629.x"},{"key":"e_1_2_10_41_1","volume-title":"Principles of Neural Science","author":"Cerebellum T","year":"2014"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0959-4388(00)00153-7"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1544"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000496107"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2023.1019239"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-020-01198-4"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25984"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.2009.190702"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-015-7642-6"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jocn.2025.111073"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1355617707071214"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1212\/wnl.0000000000009364"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2025.1453025"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.1996.01830070053009"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2002.4.4\/fxcastellanos"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.11.003"},{"issue":"1","key":"e_1_2_10_57_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4103\/AOMD.AOMD_24_21","article-title":"Evolution of eye movement abnormalities in Huntington's disease","volume":"5","author":"Patel K","year":"2022","journal-title":"Ann Mov Disord"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2011.09.035"},{"issue":"24","key":"e_1_2_10_59_1","doi-asserted-by":"crossref","first-page":"3639","DOI":"10.1016\/S0042-6989(96)00169-1","article-title":"Ocular motor abnormalities in Huntington's disease","volume":"37","author":"Lasker AG","year":"1997","journal-title":"Vis Res"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0072159"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12701"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.22351"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2012.06.014"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhh004"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq047"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2008.02253.x"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn025"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510x(76)90114-3"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03411.x"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.70062"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.27046"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24669"},{"key":"e_1_2_10_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-01907-4"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70461","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70461","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70461","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T01:41:53Z","timestamp":1786326113000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70461"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,9]]},"references-count":72,"alternative-id":["10.1002\/mds.70461"],"URL":"https:\/\/doi.org\/10.1002\/mds.70461","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,9]]},"assertion":[{"value":"2026-03-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"mds.70461"}}