Structure–function multilayer network integration and cognition in multiple sclerosis

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Authors: Lucas Christian Breedt, Giuseppe Pontillo, Fernando A. N. Santos, Chris Vriend, Ferran Prados, Alle Meije Wink, Alvino Bisecco, Alessandro Cagol, Massimiliano Calabrese, Marco Castellaro, Sara Collorone, Cortese Rosa
+26 more Nicola De Stefano, Christian Enzinger, Massimo Filippi, Michael A. Foster, Antonio Gallo, Gabriel Gonzalez-Escamilla, Cristina Granziera, Sergiu Groppa, Einar August Høgestøl, Sara Llufriú, Eloy Martinez-Heras, Elisabeth Solana, Silvia Messina, Marcello Moccia, Gro O. Nygaard, J. Palace, Daniela Pinter, Mara A. Rocca, Ahmed Toosy, Paola Valsasina, Olga Ciccarelli, Eva M. Strijbis, Frederik Barkhof, Menno M. Schoonheim, Linda Douw, MAGNIMS study group
Cited by: 1
References: 71

Abstract

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.

Fields of Study & Subjects

Functional Brain Connectivity Studies Multiple Sclerosis Research Studies Advanced Neuroimaging Techniques and Applications

Publication details

Journal / source
Network Neuroscience
Publisher
MIT Press
Volume
10
Issue
2
Pages
400–417
Publication date
1 January 2026
Language
EN