Changes in functional connectivity in relapsing-remitting multiple sclerosis spinal cord measured via region-based and data-driven analyses

The clinical picture of persons with multiple sclerosis (pwMS), a neuroinflammatory disease characterized by demyelination, does not consistently correlate with pathology noted on clinical magnetic resonance imaging (MRI). Functional MRI (fMRI) is a valuable tool to understand neural network alterations resulting from structural damage, with studies in the brain employing both region-of-interest and data-driven assessment of functional connectivity. However, similar studies in the spinal cord (SC) remain limited given the challenge of imaging a small structure in an area with substantial physiologic noise. We sought to apply resting-state fMRI at 3T in the SC of healthy controls (HC) and persons with relapsing-remitting MS (pwRRMS) to assess differences in functional connectivity and relate functional markers to clinicial measures of disability. Consistent with prior SC studies, we determined strongest functional connectivity between ventral gray matter horns in both HCs and pwMS and diminished mobility associated with reduced functional connectivity. Using independent-component analysis, we observed a possible compensatory mechanism of increased connectivity in earlier compared with later stages of relapsing-remitting MS. Further exploration is warranted, and our findings support the notion of functional alterations in the SC of pwMS.