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This study assessed whether joint-ICA of GM and WM features better explained\u00a0cognitive function compared to single-tissue ICA. 89 people with MS underwent cognitive testing and magnetic resonance imaging. Structural T1 and diffusion-weighted images were used to measure GM volumes and WM connectomes (based on fractional anisotropy weighted by the number of streamlines). ICA was performed for each tissue type separately and as joint-ICA. For each tissue type and joint-ICA, 20 components were extracted. In stepwise linear regression models, joint-ICA components were significantly associated with all cognitive domains. Joint-ICA showed the highest variance explained for executive function (Adjusted <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\u2009=\u20090.35) and visual memory (Adjusted <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\u2009=\u20090.30), while WM-ICA explained the highest variance for working memory (Adjusted <jats:italic>R<\/jats:italic>\n            <jats:sup>2<\/jats:sup>\u2009=\u20090.23). No significant differences were found between joint-ICA and single-tissue ICA in information processing speed or verbal memory. This is the first MS study to explore GM and WM features in a joint-ICA approach and shows that joint-ICA outperforms single-tissue analysis in some, but not all cognitive domains. This highlights that cognitive domains are differentially affected by tissue-specific features in MS and that processes spanning GM and WM should be considered when explaining cognition.<\/jats:p>","DOI":"10.1007\/s00415-024-12795-2","type":"journal-article","created":{"date-parts":[[2025,1,15]],"date-time":"2025-01-15T13:28:49Z","timestamp":1736947729000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Explaining cognitive function in multiple sclerosis through networks of grey and white matter features: a joint independent component analysis"],"prefix":"10.1007","volume":"272","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8516-7429","authenticated-orcid":false,"given":"Senne B.","family":"Lageman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7413-9772","authenticated-orcid":false,"given":"Amy","family":"Jolly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0403-916X","authenticated-orcid":false,"given":"Nitin","family":"Sahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7872-0142","authenticated-orcid":false,"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2443-8800","authenticated-orcid":false,"given":"Baris","family":"Kanber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6652-3512","authenticated-orcid":false,"given":"Arman","family":"Eshaghi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-3184","authenticated-orcid":false,"given":"Carmen","family":"Tur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9942-676X","authenticated-orcid":false,"given":"Cyrus","family":"Eierud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9058-0747","authenticated-orcid":false,"given":"Vince D.","family":"Calhoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-6959","authenticated-orcid":false,"given":"Menno M.","family":"Schoonheim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3076-2682","authenticated-orcid":false,"given":"Declan T.","family":"Chard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,15]]},"reference":[{"issue":"12","key":"12795_CR1","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1016\/S1474-4422(08)70259-X","volume":"7","author":"ND Chiaravalloti","year":"2008","unstructured":"Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. 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D.C. is a consultant for Hoffmann-La Roche. In the last 3\u00a0years, he has been a consultant for Biogen, has received research funding from Hoffmann-La Roche, the International Progressive MS Alliance, the MS Society, the Medical Research Council, and the National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, and has been a speaker\u2019s honorarium from Novartis. He co-supervises a clinical fellowship at the National Hospital for Neurology and Neurosurgery, London, which is supported by Merck.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study had research ethics committee approval (09\/H0716\/77).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent"}},{"value":"All participants in the study gave written informed consent.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}],"article-number":"142"}}