MULTIMODAL STUDY OF BRAIN RECONFIGURATIONS IN AN EXPERIMENTAL MODEL OF MULTIPLE SCLEROSIS

Multiple sclerosis (MS) is an autoimmune disorder of the Central Nervous System (CNS) characterized by inflammation, demyelination, and neuronal loss. Pathological changes within the CNS disrupt structural and functional connectivity (FC) across brain networks, contributing to a spectrum of clinical manifestations, including motor and cognitive deficits. However, the link between FC disruptions and disease severity remains elusive, and no therapies exist to specifically preserve the connectome. FC changes observed in patients are incongruous, likely reflecting a complex interplay between structural and functional damage, as well as heterogeneity in MS expression, population and treatment. This variability can be addressed using experimental models.
Accordingly, this study aims to identify FC signatures of MS using resting-state fMRI in Experimental Autoimmune Encephalomyelitis (EAE) mice, and to explore their relationship with structural and molecular data collected from the same cohort. In parallel, we also test whether Cladribine, an MS-approved molecule modulating both immunity and synaptic transmission, could rescue pathological changes in FC networks.
Our current findings show stage specific alterations of FC in EAE, mainly within sensory-motor and thalamic networks. Glial activation and demyelination appear in regions supporting these circuits, together with axonal damage that remains stable despite FC deterioration with disease severity. Importantly, Cladribine exerts a protective effect on cortical network reorganization, as well as on concurrent demyelination and axonal destruction. Taken together, our results provide new insights into the relationship between functional and structural changes, and disease severity, and highlight the importance of targeting neuronal activity to protect network stability.