People with multiple sclerosis (MS) often present with cognitive deficits that cannot fully be attributed to focal brain alterations. Whole-brain network changes show stronger relations, but MS network insights have mostly focused on either structural or functional (single-layer) networks, while recent work has shown the importance of multilayer frontoparietal network integration for cognition. Here, we explored the cognitive relevance of multilayer integration of the frontoparietal network in relapsing-remitting MS (n = 780) using diffusion and resting-state fMRI. Cognitive relations were first assessed for nodal multilayer eigenvector centrality, averaged over frontoparietal network nodes as a measure of integration, and post hoc for mean eccentricity for both single layer and multilayers. Higher multilayer frontoparietal network centrality was associated with worse Symbol Digit Modalities Test (SDMT) performance (β = -.117, p = .005). Mean eccentricity of single-layer diffusion (β = -.123, p < .001) and multilayer networks (β = .085, p = .018) were associated with SDMT performance. However, results could not be replicated using a different anatomical parcellation. This study showed that cognition in MS is related to multilayer network parameters. Nevertheless, correlations were weak and atlas specific, suggesting that a binary structure-function multilayer network approach is not particularly relevant as a correlate of cognition in MS.
Keywords: Executive functioning; Functional connectivity; Graph theory; Multilayer networks; Structural connectivity.
Cognitive dysfunction is common in people with multiple sclerosis (MS). Although network approaches have revealed associations between network topology and such cognitive deficits, they mostly focus on structural or functional networks in isolation. Recent work has shown the importance of multiplex networks, combining structural and functional network information into a single model, for cognition. Here, we leverage a large multicenter dataset (n = 780) to explore the cognitive relevance of multiplex frontoparietal network integration in relapsing–remitting MS. We find evidence for a negative relation between multiplex frontoparietal network integration and cognitive performance. However, effect sizes are small and do not hold up to validation analyses, underscoring the importance of further exploring the complex interplay between structural and functional neuroimaging network dynamics and cognition.
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