Linked structural-functional brain abnormalities in patients with multiple sclerosis

Multiple sclerosis (MS) is a widespread inflammatory, demyelinating and neurodegenerative disease of the central nervous system (CNS). Various lines of evidence from magnetic resonance image (MRI) have proven that MS results in multiple structural abnormalities, in terms of grey matter (GM) atrophy, white matter (WM) lesions and microstructural damage as well as in functional connectivity abnormalities. Recently, some studies suggested that WM damage may be spatially linked with subsequent cortical and deep GM atrophy in primary progressive and longstanding MS. Other studies showed that most of the cortical GM atrophy may be partially independent from the WM lesions in both early and progressive MS. Few recent studies have revealed in MS, at the level of “patterns” (i.e., co-varying structurally and/or functionally related regions of the human brain), the presence of GM atrophy or WM microstructural damage, through source-based morphometry (SBM), a novel model-free and data-driven multivariate MRI-based approach, allowing grouping brain structural abnormalities into spatial patterns, well beyond the traditional assessment of single brain regions. We used here SBM on MRI data of a MS patient cohort with relatively mild disability in order to assess whether and to what extent distinct spatial patterns of GM atrophy and WM microstructural damage exist and may be inter-related. Given the alterations found in both structural and functional MRI modalities in MS, integration across such modalities might provide a more comprehensive view of the pathogenic substrates, by revealing important “hidden” relationships that could not be detected from a single MRI modality. Despite the development of different MRI techniques has improved the evaluation of the relationship between structure and function in MS brain, there is still a need to bridge the gap in linking such structural/functional changes in order to better clarify the picture of the MS pathogenic mechanisms. Multimodal neuroimaging data-driven approach, by searching for common information across modalities, could identify co-occurring changes across various brain measures, and thus yield a more comprehensive picture of the multiple underlying pathogenic mechanisms of disease. In this regard, we aimed to uncover in MS the hidden relationships between brain structural damage and functional alterations and the shared pathophysiology across different MRI modalities from a system-level perspective, through the multivariate analysis of multimodal brain MRI data. Our results reinforce previous findings on single MRI modalities and, furthermore, allow to investigate more efficiently the intimate pathogenic mechanism of WM and GM damage in terms of coexisting structural and functional changes, even at early disease stage.