The role of network connectivity and transcriptomic vulnerability in shaping gray matter atrophy in multiple sclerosis.

Network connectivity explains MS-related gray matter atrophy progression in 2187 participants, with atrophy constrained by anatomical and functional connections and anchored to disease epicenters.

• Why it matters: Gray matter loss in MS is linked to clinical progression and appears early on MRI, but the spatiotemporal mechanisms and why individuals differ are unclear.
• What they did: Using MRIs from 2187 participants plus normative data, the study tested whether cortical hubness, connection constraints, lesional disconnection, and transcriptomic vulnerability predict regional and future atrophy.
• The result: Atrophy aligned with functional cortical hubness and was consistent with transneuronal degeneration, while lesional disconnection and transcriptomic vulnerability played marginal roles, and network measures improved prediction of future progression.

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