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Our objective was to investigate changes and responsiveness of multimodal biomarkers in individuals with FMD undergoing multidisciplinary management. 34 patients with clinically definite FMD (mean age 42.76\u2009\u00b1\u200911.01 years; 85.7% female; mean disease duration 0.64\u2009\u00b1\u20091.52 years) underwent a standardized multimodal assessment at baseline and 3-month follow-up after a multidisciplinary program. The intervention included a 5-day intensive rehabilitation program (2\u00a0h\/day), followed by a 12-week phase of telemedicine (one session every 2 weeks) and home-based self-management (two sessions\/week). Multimodal biomarkers across motor, exteroceptive, interoceptive, and brain function domains were assessed using clinical, neurophysiological, and task-based functional MRI measures. Motor symptoms improved with concurrent gains in depressive symptoms, physical quality of life, and fatigue (all,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.047). Specific improvements were observed in motor performance, including reduced stride time variability during cognitive dual-tasking (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.018) and enhanced postural stability mainly in the eyes-closed condition (all,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.028), while neurophysiological and nociceptive measures remained unchanged. Patients showed altered baseline brain activity compared with controls; post-intervention changes were observed in motor, cerebellar, and fronto-insular regions (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001, uncorrected), without correlations with clinical outcomes. Multidisciplinary management in FMD was associated with improved clinical outcomes and specific motor and neural changes, suggesting domain-specific responsiveness and a potential role for multimodal biomarkers, requiring confirmation in larger controlled studies. Trial Registration number NCT06328790. Registered on 26 March 2024.\n                  <\/jats:p>","DOI":"10.1007\/s00702-026-03254-5","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T12:09:21Z","timestamp":1786018161000},"page":"2733-2743","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multimodal assessment of clinical and neural changes following multidisciplinary management in functional motor 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Sarasso, S. Basaia, and E. Canu have received research support from the Italian Ministry of Health. M. Filippi is Editor-in-Chief of the Journal of Neurology, Associate Editor of Human Brain Mapping, Neurological Sciences, and Radiology, received compensation for consulting services from Alexion, Almirall, Biogen, Merck, Novartis, Roche, Sanofi, speaking activities from Bayer, Biogen, Celgene, Chiesi Italia SpA, Eli Lilly, Genzyme, Janssen, Merck-Serono, Neopharmed Gentili, Novartis, Novo Nordisk, Roche, Sanofi, Takeda, and TEVA, participation in Advisory Boards for Alexion, Biogen, Bristol-Myers Squibb, Merck, Novartis, Roche, Sanofi, Sanofi-Aventis, Sanofi-Genzyme, Takeda, scientific direction of educational events for Biogen, Merck, Roche, Celgene, Bristol-Myers Squibb, Lilly, Novartis, Sanofi-Genzyme, he receives research support from Biogen Idec, Merck-Serono, Novartis, Roche, Italian Ministry of Health, the Italian Ministry of University and Research, and Fondazione Italiana Sclerosi Multipla. F. Agosta is Associate Editor of NeuroImage: Clinical, has received speaker honoraria from Biogen Idec, Italfarmaco, Roche, Zambon and Ely Lilli, and receives or has received research supports from the Italian Ministry of Health, the Italian Ministry of University and Research, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council, the EU Joint Programme \u2013 Neurodegenerative Disease Research (JPND), and Foundation Research on Alzheimer Disease (France). The other authors have declared that they have no competing interests. M. Gandolfi has received research support from Fondazione Italiana Sclerosi Multipla. M.T. Pellecchia has received research support from the Italian Ministry of Health and the Italian Ministry of University. M. Tinazzi has received research support from the Italian Ministry of Health. A. Fratucello received compensation for consulting services from Novartis.","order":1,"name":"Ethics","label":"<b>Conflict of interest<\/b>","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Local Ethics Committees approved the study (4201CESC -PNRR-MAD-2022-12376826), and all participants signed written informed consent.","order":2,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}}]}}