Multimodal assessment of clinical and neural changes following multidisciplinary management in functional motor disorders

: Functional motor disorders (FMD) are common and disabling conditions, but objective biomarker changes following multidisciplinary management remain limited. 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 ± 11.01 years; 85.7% female; mean disease duration 0.64 ± 1.52 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 h/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, p < 0.047). Specific improvements were observed in motor performance, including reduced stride time variability during cognitive dual-tasking (p = 0.018) and enhanced postural stability mainly in the eyes-closed condition (all, p < 0.028), 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 (p < 0.001, 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.