{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T23:11:36Z","timestamp":1784761896759,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T00:00:00Z","timestamp":1759104000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While structural and functional connectivity changes in multiple sclerosis (MS) are well documented, their complex interplay remains poorly understood. This study identifies co\u2010fluctuating patterns of structural and functional changes in MS using an MRI\u2010based multimodal fusion approach and assesses the added value to clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Linked independent component analysis (ICA) was applied to spatial maps of white matter (WM) lesions, fractional anisotropy (FA), gray matter (GM) volume, and functional network connectivity to detect regions with differential co\u2010fluctuations. Graph theory (GT) was then used to reveal clusters of interconnected brain regions. Linear mixed\u2010effect models targeted regions with significantly different co\u2010fluctuating patterns between MS and HC. Multivariate stepwise regressions analyzed the associations between co\u2010fluctuating patterns and disability and cognitive dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The study included 147 patients with MS and 57 HC. Significant co\u2010fluctuating patterns of decreased FA, increased lesion probability in the thalamic radiation and corpus callosum, GM atrophy in sensorimotor and thalamic areas, and enhanced functional connectivity in the temporal parietal network distinguished MS from HC (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). GT revealed eight brain sub\u2010networks of spatially connected clusters. Regional\u2010 and modality\u2010specific loadings and GT changes explained physical (adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.51,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) and cognitive (adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.44,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001) disability better than traditional MRI measures (adjusted\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090.12\u20130.33,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our multimodal MRI approach revealed co\u2010fluctuating regional patterns of lesions, structural disconnection, and functional hyperconnectivity in MS, offering a more comprehensive explanation of clinical outcomes than traditional MRI metrics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.70367","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T09:35:34Z","timestamp":1759138534000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Clinically Relevant Patterns of Co\u2010Fluctuating Structure and Function in Multiple Sclerosis"],"prefix":"10.1111","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8820-3248","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Battaglini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience University of Siena  Siena Italy"},{"name":"SIENA Imaging SRL  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Cortese","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Laura","family":"Stromillo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience University of Siena  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marzia","family":"Mortilla","sequence":"additional","affiliation":[{"name":"Radiology Anna Meyer Children's University Hospital\u2010 IRCCS  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ludovico","family":"Luchetti","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience University of Siena  Siena Italy"},{"name":"SIENA Imaging SRL  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giordano","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Neuroscience University of Siena  Siena Italy"},{"name":"SIENA Imaging SRL  Siena Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilio","family":"Portaccio","sequence":"additional","affiliation":[{"name":"Department of Neurofarba University of Florence  Florence Italy"},{"name":"IRCCS Fondazione Don Carlo Gnocchi  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Pia","family":"Amato","sequence":"additional","affiliation":[{"name":"Department of Neurofarba University of Florence  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