Cognitive and clinical dysfunction, altered MEG resting-state networks and thalamic atrophy in multiple sclerosis.

Prejaas Tewarie,Marieke L Van Der Meer,Chris H Polman,Cornelis J Stam,Frederik Barkhof,Menno M Schoonheim,Bob W Van Dijk,Arjan Hillebrand,Gareth Robert Barnes

doi:10.1371/journal.pone.0069318

Prejaas Tewarie, Marieke L Van Der Meer + Show 7 more

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https://doi.org/10.1371/journal.pone.0069318

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Abstract

The relation between pathological findings and clinical and cognitive decline in Multiple Sclerosis remains unclear. Here, we tested the hypothesis that altered functional connectivity could provide a missing link between structural findings, such as thalamic atrophy and white matter lesion load, and clinical and cognitive dysfunction. Resting-state magnetoencephalography recordings from 21 MS patients and 17 gender- and age matched controls were projected onto atlas-based regions-of–interest using beamforming. Average functional connectivity was computed for each ROI and literature-based resting-state networks using the phase-lag index. Structural measures of whole brain and thalamic atrophy and lesion load were estimated from MRI scans. Global analyses showed lower functional connectivity in the alpha2 band and higher functional connectivity in the beta band in patients with Multiple Sclerosis. Additionally, alpha2 band functional connectivity was lower for the patients in two resting-state networks, namely the default mode network and the visual network. Higher beta band functional connectivity was found in the default mode network and in the temporo-parietal network. Lower alpha2 band functional connectivity in the visual network was related to lower thalamic volumes. Beta band functional connectivity correlated positively with disability scores, most prominently in the default mode network, and correlated negatively with cognitive performance in this network. These findings illustrate the relationship between thalamic atrophy, altered functional connectivity and clinical and cognitive dysfunction in MS, which could serve as a bridge to understand how neurodegeneration is associated with altered functional connectivity and subsequently clinical and cognitive decline.

Highlights

Multiple Sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease leading to clinical and cognitive decline to varying degree
Changes in whole brain, and thalamic atrophy was related to altered functional connectivity (FC) in the visual network and the temporo-parietal network in respectively the alpha2 and beta band
Most strikingly and clinically relevant was the observed correlation between higher beta band FC in the default mode network (DMN) and higher Expanded Disability Status Scale (EDSS) scores and poorer cognition

Summary

Introduction

Multiple Sclerosis (MS) is an inflammatory demyelinating and neurodegenerative disease leading to clinical and cognitive decline to varying degree. The discrepancy between classical MRI findings such as white matter lesion load on the one hand and clinical decline on the other hand has been called the clinico-radiological paradox [1]. To overcome this paradox the emphasis of research has shifted from white matter pathology to gray matter pathology [2]. Gray matter pathology such as atrophy and cortical lesions seem to correlate better with physical disability and cognitive impairment than white matter pathology [3,4]. Thalamic atrophy in particular seems to be present even in the earlier phases of the disease and is a strong predictor of cognitive decline [3,4,5,6,7]

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