More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network. Physical disability and cognition were assessed with the Expanded Disability Status Scale (EDSS) and the symbol digit modalities test (SDMT), respectively. SMRI, dMRI, and resting-state fMRI data were parcellated into 100 cortical and 14 subcortical regions to obtain networks of morphological covariance, structural connectivity, and functional connectivity. Connectivity matrices were merged in a multiplex, from which regional coreness-the probability of a node being part of the multiplex core-and coreness disruption index (κ)-the global weakening of the core-periphery structure-were computed. The associations of κ with disease status (PwMS vs. healthy controls), clinical phenotype, level of physical disability (EDSS ≥ 4 vs. EDSS < 4), and cognitive impairment (SDMT z-score < -1.5) were tested within a linear model framework. Using random forest permutation feature importance, we assessed the relative contribution of κ in the multiplex and single-layer domains, in addition to conventional MRI measures (brain and lesion volumes), in predicting disease status, physical disability, and cognitive impairment. We studied 1048 PwMS (695F, mean ± SD age: 43.3 ± 11.4 years) and 436 healthy controls (250F, mean ± SD age: 38.3 ± 11.8 years). PwMS showed significant disruption of the multiplex core-periphery organization (κ = -0.14, Hedges' g = 0.49, p < 0.001), correlating with clinical phenotype (F = 3.90, p = 0.009), EDSS (Hedges' g = 0.18, p = 0.01), and SDMT (Hedges' g = 0.30, p < 0.001). Multiplex κ was the only connectomic measure adding to conventional MRI in predicting disease status and cognitive impairment, while physical disability also depended on single-layer contributions. In conclusion, we show that multilayer networks represent a biologically and clinically meaningful framework to model multimodal MRI data, with disruption of the core-periphery structure emerging as a potential connectomic biomarker for disease severity and cognitive impairment in PwMS.

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Journal
Human Brain Mapping
Published
2024-12-30
DOI
https://doi.org/10.1002/hbm.70107
Citations
2
Primary Topic
Advanced Neuroimaging Techniques and Applications
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article
Field-Weighted Citation Impact
0.81

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article

More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis

Daniela Pinter, Einar August Høgestøl, Massimo Filippi, James H. Cole et al.
2 citations
Human Brain Mapping
Advanced Neuroimaging Techniques and Applications
0.81
article

More Than the Sum of Its Parts: Disrupted Core Periphery of Multiplex Brain Networks in Multiple Sclerosis

Daniela Pinter, Einar August Høgestøl, Massimo Filippi, James H. Cole, Jacqueline Palace, Ahmed Toosy, Sara Llufriú, Gabriel González‐Escamilla, Michael A. Foster, Eloy Martínez‐Heras, Sergiu Groppa, Luigi Lorenzini, Alvino Bisecco, Eva M. M. Strijbis, Nicola De Stefano, Christian Enzinger, Giuseppe Pontillo, Paola Valsasina, Rosa Cortese, Marco Castellaro, Alessandro Cagol, Gro Owren Nygaard, Maria Petracca, Sara Collorone, Ferrán Prados, Tommy A.A. Broeders, Frederik Barkhof, Massimiliano Calabrese, Baris Kanber, Hugo Vrenken, Alle Meije Wink, Menno Michiel Schoonheim, Sirio Cocozza, Maria Assunta Rocca, Elisa Colato, Cristina Granziera, Marcello Moccia, Antonio Gallo, Linda Douw, Arturo Brunetti, Silvia Messina, Olga Ciccarelli, Hanne F. Harbo
article en
2 citations

Abstract

Disruptions to brain networks, measured using structural (sMRI), diffusion (dMRI), or functional (fMRI) MRI, have been shown in people with multiple sclerosis (PwMS), highlighting the relevance of regions in the core of the connectome but yielding mixed results depending on the studied connectivity domain. Using a multilayer network approach, we integrated these three modalities to portray an enriched representation of the brain's core-periphery organization and explore its alterations in PwMS. In this retrospective cross-sectional study, we selected PwMS and healthy controls with complete multimodal brain MRI acquisitions from 13 European centers within the MAGNIMS network. Physical disability and cognition were assessed with the Expanded Disability Status Scale (EDSS) and the symbol digit modalities test (SDMT), respectively. SMRI, dMRI, and resting-state fMRI data were parcellated into 100 cortical and 14 subcortical regions to obtain networks of morphological covariance, structural connectivity, and functional connectivity. Connectivity matrices were merged in a multiplex, from which regional coreness-the probability of a node being part of the multiplex core-and coreness disruption index (κ)-the global weakening of the core-periphery structure-were computed. The associations of κ with disease status (PwMS vs. healthy controls), clinical phenotype, level of physical disability (EDSS ≥ 4 vs. EDSS < 4), and cognitive impairment (SDMT z-score < -1.5) were tested within a linear model framework. Using random forest permutation feature importance, we assessed the relative contribution of κ in the multiplex and single-layer domains, in addition to conventional MRI measures (brain and lesion volumes), in predicting disease status, physical disability, and cognitive impairment. We studied 1048 PwMS (695F, mean ± SD age: 43.3 ± 11.4 years) and 436 healthy controls (250F, mean ± SD age: 38.3 ± 11.8 years). PwMS showed significant disruption of the multiplex core-periphery organization (κ = -0.14, Hedges' g = 0.49, p < 0.001), correlating with clinical phenotype (F = 3.90, p = 0.009), EDSS (Hedges' g = 0.18, p = 0.01), and SDMT (Hedges' g = 0.30, p < 0.001). Multiplex κ was the only connectomic measure adding to conventional MRI in predicting disease status and cognitive impairment, while physical disability also depended on single-layer contributions. In conclusion, we show that multilayer networks represent a biologically and clinically meaningful framework to model multimodal MRI data, with disruption of the core-periphery structure emerging as a potential connectomic biomarker for disease severity and cognitive impairment in PwMS.

Human Brain MappingVol. 46(1)
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), UK Dementia Research Institute (GB), Institute of Neuroimmunology of the Slovak Academy of Sciences (SK), National Hospital for Neurology and Neurosurgery (GB), 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), University of Naples Federico II (IT), Universitat de Barcelona (ES), Vrije Universiteit Amsterdam (NL), Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
Medical Research Council
Quality Education
Openalex Percentile: Top 23%
Advanced Neuroimaging Techniques and Applications
0.81
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