Background and aims: Emotional processing deficits are common in neurological conditions and contribute to behavioral disorders such as depression, a frequent comorbidity in people with Multiple Sclerosis (pwMS). Effective rehabilitation treatments are needed, along with reliable measures to investigate the underlying neural plasticity mechanisms. Traditional fMRI analyses rely on group-level GLM approaches, which may not accurately capture individual neural patterns observed in both healthy and clinical…

Methods: Thirty healthy volunteers (HV) and thirteen pwMS with depression underwent two fMRI sessions, before and after EMDR rehabilitation, during an emotion-processing task using a 3T Siemens Prisma scanner. Data were preprocessed with SPM12, and subject-level contrasts were analyzed via GLM-based paired t-tests. Additionally, threshold-weighted overlap maps (OMth-w) assessed neural activation intersubject variability. …

Results: While GLM analyses did not detect significant treatment-related longitudinal changes, variability analysis showed decreased neural response consistency in HV, whereas pwMS exhibited increased consistency post-rehabilitation, alongside a significant reduction in depressive symptoms (p < 0.001). …

Conclusions: These findings highlight the relevance of inter-subject variability analysis in detecting rehabilitation-induced neural changes in pwMS, supporting its role in advancing personalized rehabilitation strategies. Funding: This study was funded by “MNESYS-A multiscale integrated approach to the study of the nervous system in health and disease CUP: B43D22000650006. PROJECT ID: PE00000006” … “