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.

Structure–function multilayer network integration and cognition in multiple sclerosis / Breedt, L. C.; Pontillo, G.; Santos, F. A. N.; Vriend, C.; Prados, F.; Wink, A. M.; Bisecco, A.; Cagol, A.; Calabrese, M.; Castellaro, M.; Collorone, S.; Cortese, R.; De Stefano, N.; Enzinger, C.; Filippi, M.; Foster, M. A.; Gallo, A.; Gonzalez-Escamilla, G.; Granziera, C.; Groppa, S.; Hogestol, E. A.; Llufriu, S.; Martinez-Heras, E.; Solana, E.; Messina, S.; Moccia, M.; Nygaard, G. O.; Palace, J.; Pinter, D.; Rocca, M. A.; Toosy, A.; Valsasina, P.; Ciccarelli, O.; Strijbis, E. M.; Barkhof, F.; Schoonheim, M. M.; Douw, L.. - In: NETWORK NEUROSCIENCE. - ISSN 2472-1751. - (2026). [Epub ahead of print] [10.1162/NETN.a.545]

Structure–function multilayer network integration and cognition in multiple sclerosis

Filippi M.;Messina S.;Rocca M. A.;
2026-01-01

Abstract

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.
2026
Executive functioning
Functional connectivity
Graph theory
Multilayer networks
Structural connectivity
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11768/200216
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