The Role of Network Connectivity and Transcriptomic Vulnerability in Shaping Grey Matter Atrophy in Multiple Sclerosis
This study highlights the importance of network connectivity in understanding grey matter atrophy in multiple sclerosis, suggesting that it may help predict future atrophy progression.
Where it sits
this study against the rest of the bam-15 corpusSummary and findings
This study investigated the relationship between network connectivity and grey matter atrophy in multiple sclerosis (MS) using MRIs from 2,187 participants. The research aimed to understand the mechanisms driving atrophy progression and variability among individuals. No therapeutic claims are made.
Abstract
Clinical progression is strongly linked to grey matter atrophy in multiple sclerosis (MS), detectable early on MRI and progressing non-randomly across the brain. However, the mechanisms driving its spatio-temporal progression and individual variability remain unclear. Using MRIs from 2,187 participants, alongside normative data, we systematically investigated network-based mechanisms underlying MS-related atrophy. Regional atrophy colocalised with functional cortical hubs, supporting the nodal stress hypothesis, and propagated along anatomical and functional connections, consistent with transneuronal degeneration. Lesional disconnection and transcriptomic vulnerability played marginal roles. Patient- and subgroup-level analyses revealed that network-based mechanisms are specifically linked to MS-related neurodegeneration and may operate differently in distinct subtypes or disease phases. Atrophy patterns were anchored to the connectivity profiles of disease epicentres involving the visual, sensorimotor, and temporal cortices, and the hippocampi and thalami. Network-based measures enhanced the prediction of future atrophy progression in individual with MS, providing a mechanistic framework to understand neurodegeneration in MS.