Linking Microstructural Integrity and Motor Cortex Excitability in Multiple Sclerosis

Abstract

Motor skills are frequently impaired in multiple sclerosis (MS) patients following grey and white matter damage with cortical excitability abnormalities. We applied advanced diffusion imaging with 3T magnetic resonance tomography for neurite orientation dispersion and density imaging (NODDI), as well as diffusion tensor imaging (DTI) in 50 MS patients and 49 age-matched healthy controls to quantify microstructural integrity of the motor system. To assess excitability, we determined resting motor thresholds using non-invasive transcranial magnetic stimulation. As measures of cognitive-motor performance, we conducted neuropsychological assessments including the Nine-Hole Peg Test, Trail Making Test part A and B (TMT-A and TMT-B) and the Symbol Digit Modalities Test (SDMT). Patients were evaluated clinically including assessments with the Expanded Disability Status Scale. A hierarchical regression model revealed that lower neurite density index (NDI) in primary motor cortex, suggestive for axonal loss in the grey matter, predicted higher motor thresholds, i.e. reduced excitability in MS patients (p =.009, adjusted r² = 0.117). Furthermore, lower NDI was indicative of decreased cognitive-motor performance (p =.007, adjusted r² =.142 for TMT-A; p =.009, adjusted r² =.129 for TMT-B; p =.006, adjusted r² =.142 for SDMT). Motor WM tracts of patients were characterized by overlapping clusters of lowered NDI (p