Disruption of structural and functional networks in long-standing multiple sclerosis

Abstract

Both gray matter atrophy and disruption of functional networks are important predictors for physical disability and cognitive impairment in multiple sclerosis (MS), yet their relationship is poorly understood. Graph theory provides a modality invariant framework to analyze patterns of gray matter morphology and functional coactivation. We investigated, how gray matter and functional networks were affected within the same MS sample and examined their interrelationship. Magnetic resonance imaging and magnetoencephalography (MEG) were performed in 102 MS patients and 42 healthy controls. Gray matter networks were computed at the group-level based on cortical thickness correlations between 78 regions across subjects. MEG functional networks were computed at the subject level based on the phase-lag index between time-series of regions in source-space. In MS patients, we found a more regular network organization for structural covariance networks and for functional networks in the theta band, whereas we found a more random network organization for functional networks in the alpha2 band. Correlation analysis revealed a positive association between covariation in thickness and functional connectivity in especially the theta band in MS patients, and these results could not be explained by simple regional gray matter thickness measurements. This study is a first multimodal graph analysis in a sample of MS patients, and our results suggest that a disruption of gray matter network topology is important to understand alterations in functional connectivity in MS as regional gray matter fails to take into account the inherent connectivity structure of the brain.

Structure‐function relationships in the visual system in multiple sclerosis: an MEG and OCT study

“…In total, 102 MS patients were included for analysis based on a previous study, and the MEG data used in this study have been published in another context,16 separately from the OCT data 8. Patients were recruited from the Amsterdam MS cohort, at the VUmc MS center.…”

“…The study protocol was approved by Medical Ethical Review Committee of the VU University Medical Center, whose ethics review criteria conformed to the Helsinki declaration. All subjects gave written informed consent prior to participation (protocol number ethics 2010/336, R&D CWO/10‐25D) 8, 16. A detailed description of the full cohort, recruitment, and eligibility procedure can be found elsewhere 16…”

“…Data acquisition is described in detail in previous work 16. The MEG data were recorded using a 306‐channel whole‐head MEG system (Elekta Neuromag, Oy, Helsinki, Finland).…”

“…The exact beamforming procedure has been described in previous work16 and can also be found in the Data S1. For every subject this procedure results in one time‐series for every cortical region of interest (ROI) in the automated anatomical labeling (AAL) atlas.…”

“…The PLI is a phase synchronization metric that quantifies the asymmetry of the distribution of the phase differences between the time‐series and is relatively insensitive to signal leakage. The rationale to use this functional connectivity metric is that it has proven to be a very sensitive metric to distinguish between healthy subjects and MS patients in a clinically meaningful way 16, 24. PLI values between visual regions were averaged in order to obtain a single PLI value per subject.…”