Hanneke E Hulst

Background: Cognitive training elicits mild-to-moderate improvements in cognitive functioning in people with multiple sclerosis (PwMS), although response heterogeneity limits overall effectiveness. Objective: To identify patient characteristics associated with response and non-response to cognitive training. Methods: Eighty-two PwMS were randomized into a 7-week attention training ( n = 58, age = 48.4 ± 10.2 years) or a waiting-list control group ( n = 24, age = 48.5 ± 9.4 years). Structural and functional magnetic resonance imaging (MRI) was obtained at baseline and post-intervention. Twenty-one healthy controls (HCs, age = 50.27 ± 10.15 years) were included at baseline. Responders were defined with a reliable change index of 1.64 on at least 2/6 cognitive domains. General linear models and logistic regression were applied. Results: Responders ( n = 36) and non-responders ( n = 22) did not differ on demographics, clinical variables and baseline cognition and structural MRI. However, non-responders exhibited a higher baseline functional connectivity (FC) between the default-mode network (DMN) and the ventral attention network (VAN), compared with responders ( p = 0.018) and HCs ( p = 0.001). Conversely, responders exhibited no significant baseline differences in FC compared with HCs. Response to cognitive training was predicted by lower DMN-VAN FC ( p = 0.004) and DMN-frontoparietal FC ( p = 0.029) (Nagelkerke R 2 = 0.25). Conclusion: An intact pre-intervention FC is associated with cognitive training responsivity in pwMS, suggesting a window of opportunity for successful cognitive interventions.