Localised grey matter atrophy in multiple sclerosis is network-based: a coordinate-based meta-analysis

Abstract

To test the network degeneration hypothesis in multiple sclerosis (MS) with a two-stage coordinate-based meta-analysis by: (1) characterising regional selectivity of grey matter (GM) atrophy and (2) testing for functional connectivity involving these regions. Meta-analytic sources included 33 journal articles (1,666 MS patients and 1,269 healthy controls) with coordinate-based results from voxel-based morphometry analysis demonstrating GM atrophy. Mass univariate and multivariate coordinate-based meta-analyses were performed to identify a convergent pattern of GM atrophy and determine inter-regional co-activation (as a surrogate of functional connectivity), with anatomical likelihood estimation and functional meta-analytic connectivity modelling, respectively. Localised GM atrophy was demonstrated in the thalamus, putamen, caudate, sensorimotor cortex, insula, superior temporal gyrus, and cingulate gyrus. This convergent pattern of atrophy displayed significant inter-regional functional co-activations. In MS, GM atrophy was regionally selective, and these regions were functionally connected. The meta-analytic model-based results of this study are intended to guide future development of quantitative neuroimaging markers for diagnosis, evaluating disease progression, and monitoring treatment response.