Functional Brain Network Changes Linked to Cognitive Decline in Multiple Sclerosis

Background: Cognitive decline in multiple sclerosis (MS) is common and is increasingly studied using resting-state functional MRI (rs-fMRI) and network neuroscience approaches. Functional brain network reorganization may reflect both compensatory and maladaptive processes that relate to cognition over time.Objective: To present a complete original-paper workflow evaluating whether longitudinal changes in functional brain network metrics are associated with cognitive decline in MS using a dataset of 34 participants with baseline and 12-month follow-up measures.Methods: Thirty-four participants with MS phenotype criteria underwent baseline and 12-month cognitive testing (Symbol Digit Modalities Test [SDMT]) and rs-fMRI–derived network metrics, including global efficiency, modularity, default mode network–frontoparietal network (DMN–FPN) connectivity, and thalamo-cortical connectivity. The primary outcome was 12-month SDMT change. Multivariable linear regression tested associations between SDMT change and network changes, adjusting for age, education, disability (EDSS), lesion volume, and baseline SDMT.Results: Participants demonstrated heterogeneous SDMT trajectories over 12 months. Decline in global efficiency and thalamo-cortical connectivity was associated with greater SDMT decline in adjusted models. Baseline-to-follow-up SDMT values showed expected within-subject variability.Conclusions: In this longitudinal study of individuals with multiple sclerosis, declines in resting-state functional brain network integration were associated with worsening cognitive performance over 12 months.