Regional alterations in cortical thickness and white matter integrity in amyotrophic lateral sclerosis

Previous neuroimaging studies have revealed that both gray matter (GM) and white matter (WM) are altered in several morphological aspects in amyotrophic lateral sclerosis (ALS). However, the relations between GM and WM measures and their contributions to clinical features remain in doubt. In this study, we acquired high-resolution diffusion tensor imaging along with structural magnetic resonance imaging data on 20 patients with clinical evidence of ALS and 21 matched healthy controls. WM microstructural metrics and cortical thickness were measured to characterize the whole brain WM and GM degenerative patterns. Probabilistic diffusion tractography was used to reconstruct the tracts from the WM regions characterized by fractional anisotropy (FA) decrease in patients. Decreased FA and increased radial diffusivity was observed in WM regions of the bilateral corticospinal tracts (CST) and callosal motor fibers in the ALS patients, while the superior longitudinal fasciculus exhibited a changing trend. Cortical thinning was found in the anatomically congruent regions, including the motor-related cortices (i.e., bilateral precentral gyri, dorsal premotor cortices, and left supplementary motor area), prefrontal and occipito-parietal regions. However, there was no significant relationship between FA reduction and cortical thinning. Finally, patients with faster clinical progression showed more severe cortical thinning of the left precentral gyrus and FA reduction of the left CST. Together, these findings suggest that ALS is multisystem degeneration involving both the widespread cortices and the underlying WM fibers. GM and WM changes might play distinct roles in the disease progression.