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Increased flexibility of brain dynamics in patients with multiple sclerosis

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Item Type:Article
Title:Increased flexibility of brain dynamics in patients with multiple sclerosis
Creators Name:von Schwanenflug, N. and Koch, S.P. and Krohn, S. and Broeders, T.A.A. and Lydon-Staley, D.M. and Bassett, D.S. and Schoonheim, M.M. and Paul, F. and Finke, C.
Abstract:Patients with multiple sclerosis consistently show widespread changes in functional connectivity. Yet, alterations are heterogeneous across studies, underscoring the complexity of functional reorganization in multiple sclerosis. Here, we aim to provide new insights by applying a time-resolved graph-analytical framework to identify a clinically relevant pattern of dynamic functional connectivity reconfigurations in multiple sclerosis. Resting-state data from 75 patients with multiple sclerosis (N = 75, female:male ratio of 3:2, median age: 42.0 ± 11.0 years, median disease duration: 6 ± 11.4 years) and 75 age- and sex-matched controls (N = 75, female:male ratio of 3:2, median age: 40.2 ± 11.8 years) were analyzed using multilayer community detection. Local, resting-state functional system, and global levels of dynamic functional connectivity reconfiguration were characterized using graph theoretical measures including flexibility, promiscuity, cohesion, disjointedness, and entropy. Moreover, we quantified hypo- and hyperflexibility of brain regions and derived the flexibility reorganization index as a summary measure of whole-brain reorganization. Lastly, we explored the relationship between clinical disability and altered functional dynamics. Significant increases in global flexibility (t = 2.38, P(FDR) = 0.024), promiscuity (t = 1.94, P(FDR) = 0.038), entropy (t = 2.17, P(FDR) = 0.027), and cohesion (t = 2.45, P(FDR) = 0.024) were observed in patients and were driven by pericentral, limbic, and subcortical regions. Importantly, these graph metrics were correlated with clinical disability such that greater reconfiguration dynamics tracked greater disability. Moreover, patients demonstrate a systematic shift in flexibility from sensorimotor areas to transmodal areas, with the most pronounced increases located in regions with generally low dynamics in controls. Together, these findings reveal a hyperflexible reorganization of brain activity in multiple sclerosis that clusters in pericentral, subcortical, and limbic areas. This functional reorganization was linked to clinical disability, providing new evidence that alterations of multi-layer temporal dynamics play a role in the manifestation of multiple sclerosis.
Keywords:Time-Varying Functional Connectivity, Functional Reorganization, Temporal Core-Periphery, EDSS
Source:Brain Communications
Publisher:Oxford University Press
Page Range:fcad143
Date:3 May 2023
Official Publication:https://doi.org/10.1093/braincomms/fcad143
PubMed:View item in PubMed

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