Multiple sclerosis (MS) is characterized by large-scale brain network dysfunctions. EEG microstate analysis may track these dynamics. We investigated whether microstates could distinguish patients with MS from healthy volunteers, and cognitively impaired from cognitively preserved (CP) patients. For this cross-sectional observational study, we recruited participants from the Policlinico Umberto I Multiple Sclerosis Center (Rome). We compared microstates of patients with relapsing-remitting MS (Expanded Disability Status Scale [EDSS] score <3, no relapses within 30 days) with those of age-matched and sex-matched healthy volunteers. We also compared cognitively impaired and preserved patients. Group comparisons were performed on microstate temporal parameters and topographies (topographic analysis of variance). Classification used stepwise linear discriminant analysis (LDA). We enrolled 88 patients with MS (60 women, mean age 42.75 years) and 46 healthy volunteers (23 women, mean age 33.7 years). Compared with healthy volunteers (n = 45, 23 women, mean age 33.7 years), patients with MS (n = 46, 25 women, mean age 34.6 years) showed greater explained variance (p < 0.001), occurrence (p < 0.001), and coverage (p < 0.001) of class B (visual network) and reduced mean duration (MD) of classes F (salience network, p = 0.014) and G (sensorimotor network, p = 0.009). Topographic differences were found between cognitively impaired (n = 57, 20 women, mean age 35.5 years) and preserved (n = 31, 40 women, mean age 46.7 years) patients for classes C, F, and G (p < 0.05). Patients with cognitive impairment exhibited significantly reduced explained variance of class F (p = 0.003). Class A was associated with longer disease duration (explained variance, p = 0.006; MD, p = 0.042; coverage, p = 0.007), higher EDSS scores (MD, p = 0.013), and poorer ambulation (explained variance, p = 0.049). Class D inversely correlated with EDSS scores (occurrence, p = 0.011; coverage, p = 0.036), whereas class B inversely correlated with information processing speed (explained variance, p = 0.025; occurrence, p = 0.018; coverage, p = 0.028). Stepwise LDA identified classes B and D as discriminators between patients with MS and healthy volunteers (77% accuracy, p < 0.001), and class F as a discriminator between CP and impaired participants (64.8% accuracy, p = 0.007). EEG microstates reveal behaviorally relevant alterations in patients with MS, supporting their utility as sensitive markers of large-scale functional network reorganization associated with clinical disability.

Background/Objectives: Blepharospasm (BSP) is a focal dystonia characterized by involuntary, bilateral spasms of the orbicularis oculi muscle. While botulinum toxin (BoNT) is the standard treatment, cognitive tasks such as reading and writing may exert transient modulatory effects on spontaneous blinking and dystonic spasms. This study investigates the potential of cognitive training, including reading and writing tasks, as a complementary therapeutic approach to BoNT in BSP patients. Methods: A total of 16 BSP patients were randomly assigned to two groups: Group A (n = 6) received cognitive training alongside BoNT, while Group B (n = 10) received only BoNT. Cognitive training included structured reading and writing exercises over three months. Blink rate (BR) and dystonic spasms were assessed at baseline (T0), one month (T1), and three months (T2) post-treatment. Results: Both groups exhibited a significant reduction in BR at T1 (p = 0.001), but Group A exhibited a greater improvement in BR (45.4%) compared to that of Group B (12.6%, p = 0.04). Reading and writing tasks were the most effective in reducing BR and dystonic spasms (p < 0.001). No significant correlation was found between the clinical and demographic features (p > 0.05). Conclusions: Cognitive training significantly enhances the therapeutic effects of BoNT on BR in BSP patients, suggesting its potential as a non-invasive complementary intervention. These preliminary findings warrant further investigation using larger cohorts and employing neurophysiological assessments.