Abstract
INTRODUCTION: Multiple sclerosis (MS) affects different cognitive domains, including social cognition. Immersive Virtual Reality (VR) may provide a novel rehabilitative approach to treat motor and cognitive symptoms of MS. This exploratory pilot study evaluated the effects of immersive VR rehabilitation on social cognition in MS patients and explored related cortical neurophysiological signatures. METHODS: Seven MS patients underwent immersive VR rehabilitation with the CAREN system (3 sessions/week, approximately 45 min of active training per session, about 1 h including preparation, 8 weeks), while seven healthy controls (HC) did not undergo any intervention. Patients were evaluated at baseline (T0) and post-treatment (T1) with standardized measures of cognitive, emotional, and motor functioning. EEG data were acquired from all participants, and, after artifact removal, spectral parameterization decomposed signals into aperiodic (exponent, offset) and periodic oscillatory components (alpha and beta power). Power spectral density was analyzed using group comparisons and Pearson correlations with neuropsychological measures. RESULTS: Compared with HC, MS patients showed reduced alpha-band power, mainly over frontal and parieto-occipital regions, whereas aperiodic parameters did not differ between groups. In patients, alpha and beta power correlated with the Positive Emotions Self-Efficacy Scale (alpha: r = 0.92, p = 0.003; beta: r = 0.83, p = 0.020). Alpha power is also correlated with RAO SRT-LTS (r = 0.85, p = 0.016), and beta with EQ-CE (r = 0.82, p = 0.023). Overall, alpha and beta power were correlated with emotional self-efficacy, balance, memory, and empathy, suggesting that oscillatory markers are potential indicators of clinical outcomes. DISCUSSION: Rehabilitation via immersive VR has shown promising clinically significant effects in the cognitive, emotional, and motor domains, supported by convergent EEG spectral signatures. Future studies employing predictive modeling approaches will be required to assess their prognostic value.