Structure–function multilayer network integration and cognition in multiple sclerosis

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.

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Publication Details

Journal
Network Neuroscience
Published
2026-01-14
DOI
https://doi.org/10.1162/netn.a.545
Primary Topic
Functional Brain Connectivity Studies
Type
article
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article

Structure–function multilayer network integration and cognition in multiple sclerosis

Daniela Pinter, Einar August Høgestøl, Michael A. Foster, C. Vriend et al.
Network Neuroscience
Functional Brain Connectivity Studies
article

Structure–function multilayer network integration and cognition in multiple sclerosis

Daniela Pinter, Einar August Høgestøl, Michael A. Foster, C. Vriend, Elisabeth Solana, J. Palace, Marco Castellaro, Sara Collorone, Alvino Bisecco, Linda Douw, Antonio Gallo, Ferran Prados, Cortese Rosa, Marcello Moccia, Sara Llufriu, Fernando A. N. Santos, Alessandro Cagol, Olga Ciccarelli, Cristina Granziera, Giuseppe Pontillo, Nicola De Stefano, Christian Enzinger, Ahmed Toosy, Eloy Martinez-Heras, Gabriel Gonzalez-Escamilla, Silvia Messina, Eva M. Strijbis, Massimo Filippi, Gro O. Nygaard, Mara A. Rocca, Lucas Christian Breedt, Menno M. Schoonheim, Frederik Barkhof, Alle Meije Wink
article en

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.

Network Neuroscience
University of Siena (IT), University of Verona (IT), Oslo University Hospital (NO), University of Padua (IT), Universitat Oberta de Catalunya (ES), Vita-Salute San Raffaele University (IT), Queen Mary University of London (GB), University of Oslo (NO), University of Basel (CH), Johannes Gutenberg University Mainz (DE), University of Campania "Luigi Vanvitelli" (IT), Medical University of Graz (AT), University Hospital of Basel (CH), University of Oxford (GB), University Medical Center of the Johannes Gutenberg University Mainz (DE), Amsterdam Neuroscience (NL), Federico II University Hospital (IT), UK Dementia Research Institute (GB), National Hospital for Neurology and Neurosurgery (GB), Amsterdam University Medical Centers (NL), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), University College London (GB), Netherlands Institute for Advanced Study in the Humanities and Social Sciences (NL), University of Naples Federico II (IT), University of Genoa (IT), Vrije Universiteit Amsterdam (NL), University of Amsterdam (NL)
Openalex Percentile: Top 88%
Functional Brain Connectivity Studies
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