Cognitive and Clinical Associations with Lesion Load and EEG Microstate Alterations in Multiple Sclerosis

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system involving both inflammatory and neurodegenerative mechanisms leading to progressive neuronal loss. Growing evidence indicates that neurodegeneration plays a key role in long-term disability progression and contributes to cognitive decline, affecting up to 70% of individuals with MS. To compare resting-state EEG microstates between patients with MS (PwMS) and healthy controls (HC), as well as across cognitive status subgroups within the PwMS cohort, taking into account lesion load, cognitive performance, and clinical features. Data from 55 PwMS and 42 HC were analyzed. Features resulting from microstates analysis, brain lesion segmentation, and clinical evaluation were associated with the occurrence of the disease and cognitive state using univariate and multivariate statistical analysis. Microstates analysis revealed altered microstate D topography between PwMS and HC, and among PwMS cognitive subgroups. Microstate B differentiated the PwMS group from HC, with its dynamics linked to higher lesion load, reflecting greater disease severity. Correlation analysis revealed an association between microstate A, lesion load, and California Verbal Learning Test, whereas the relationship between microstate C and Benton Visual Retention Test was unrelated to lesion volume. Integrating structural and functional measures may offer a more comprehensive understanding of MS-related neurodegeneration. Microstate D appears to be a potential marker of cognitive control network dysfunction and MS-related cognitive decline. Temporal dynamics of microstate B may indicate adaptive brain network reorganization, whereas microstate C might provide an additional marker of cognitive impairment in PwMS. • EEG microstates abnormalities reflect functional deficits in multiple sclerosis • Structural and functional information fusion improves cognitive assessment in MS • Microstate B reflects lesion load and greater multiple sclerosis severity • Microstate D topography is associated with MS-related cognitive decline