{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:06:50Z","timestamp":1788257210120,"version":"build-2803163510"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X005267\/1"],"award-info":[{"award-number":["MR\/X005267\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000381","name":"Multiple Sclerosis Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000381","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Brain Mapping"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Recent research suggests that individuals with multiple sclerosis (MS) and cognitive impairment exhibit more effortful and less efficient transitions in brain network activity. Previous studies further highlight the increased vulnerability of specific regions, particularly the thalamus, to disease\u2010related damage. This study investigates whether MS affects the controllability of specific brain regions in driving network activity transitions across the brain and examines the relationship between these changes and cognitive impairment in patients. Resting\u2010state functional MRI and neuropsychological data were collected from 102 MS and 27 healthy controls. Functional network controllability analysis was performed to quantify how specific regions influence transitions between brain activity patterns or states. Disease alterations in controllability were assessed in the main dataset and then replicated in an independent dataset of 95 MS and 45 healthy controls. Controllability metrics were then used to distinguish MS from healthy controls and predict cognitive status. MS\u2010specific controllability changes were observed in the subcortical network, particularly the thalamus, which were further confirmed in the replication dataset. Cognitively impaired patients showed significantly greater difficulty in the thalamus steering brain transitions towards difficult\u2010to\u2010reach states, which are typically associated with high\u2010energy\u2010cost cognitive functions. Thalamic network controllability proved more effective than thalamic volume in distinguishing MS from healthy controls (AUC\u2009=\u200988.3%), and in predicting cognitive status in MS (AUC\u2009=\u200980.7%). This study builds on previous research highlighting early thalamic damage in MS, aiming to demonstrate how this damage disrupts activity transitions across the cerebrum and may predict cognitive deficits. Our findings suggest that the thalamus in MS becomes less capable of facilitating broader brain activity transitions essential for high\u2010energy\u2010cost cognitive functions, implying a potential pathological mechanism that links thalamic functional changes to cognitive impairment in MS.<\/jats:p>","DOI":"10.1002\/hbm.70284","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T12:24:10Z","timestamp":1752150250000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Thalamic Network Controllability Predicts Cognitive Impairment in Multiple Sclerosis"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9738-4439","authenticated-orcid":false,"given":"Yuping","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Psychology, Communication and Human Neurosciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Woollams","sequence":"additional","affiliation":[{"name":"Division of Psychology, Communication and Human Neurosciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Lipp","sequence":"additional","affiliation":[{"name":"Department of Neurophysics Max Planck Institute for Human Cognitive and Brain Sciences  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6635-8705","authenticated-orcid":false,"given":"Zhizheng","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Tiantan Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3532-7575","authenticated-orcid":false,"given":"Marta Czime","family":"Litwi\u0144czuk","sequence":"additional","affiliation":[{"name":"Division of Psychology, Communication and Human Neurosciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Tomassini","sequence":"additional","affiliation":[{"name":"Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences University G. d'Annunzio of Chieti\u2010Pescara  Chieti Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Radiology Beijing Tiantan Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson J.","family":"Trujillo\u2010Barreto","sequence":"additional","affiliation":[{"name":"Division of Psychology, Communication and Human Neurosciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"},{"name":"School of Psychology, Faculty of Health and Education Manchester Metropolitan University  UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Muhlert","sequence":"additional","affiliation":[{"name":"Division of Psychology, Communication and Human Neurosciences, Faculty of Biology, Medicine and Health University of Manchester  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25150"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007447"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","unstructured":"Broeders T. 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