Fuchs TA, et al. - In this study involving 176 individuals with MS and 47 healthy controls with MR imaging at baseline and 5 years later, the cross-sectional and longitudinal characterization of the unique influence of focal WM damage on the atrophy of connected subcortical gray matter regions, beyond what is explainable by global disease progression, was attempted. For 14 subcortical gray matter regions, atrophy and lesion-based disruption of connected WM tracts were assessed. Controlling for age, sex, disease duration, whole-brain volume, and T2-lesion volume, hierarchic regressions were applied, predicting regional atrophy from focal WM disruption. They found that, when controlling for overall disease burden, WM tract disruption was responsible for a small percentage of atrophy in connected subcortical gray matter and was not the primary driver in most cases.