Linking microstructural integrity and motor cortex excitability in multiple sclerosis

Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey (GM) and white matter (WM) damage with cortical excitability abnormalities. We performed advanced diffusion imaging for neurite orientation dispersion and density modeling and diffusion tensor imaging within the motor system of 50 MS patients and 49 age-matched healthy controls. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. A hierarchical regression model revealed that lower neurite density index (NDI), suggestive for axonal loss in the GM, predicted higher motor thresholds, i.e. reduced excitability in MS patients. Furthermore, lower NDI was indicative of decreased cognitive-motor performance. Interconnected motor WM tracts of patients were characterized by overlapping clusters of lowered fractional anisotropy and NDI, with NDI exclusively capturing a higher amount of abnormally appearing voxels. Our work outlines the potential of microstructure imaging using advanced biophysical models to forecast neurodegeneration and excitability alterations in neuroinflammation.