Impairments of White Matter Tracts and Connectivity Alterations in Five Cognitive Networks of Patients with Multiple Sclerosis

Abstract Introduction MS is associated with structural and functional brain alterations leading to cognitive impairments across multiple domains including attention, memory, and speed of information processing. Here, we analyzed the white matter damage and topological organization of white matter tracts in specific brain regions responsible for cognition in MS. Methods Brain DTI, rs-fMRI, T1, T2, and T2-FLAIR were acquired for 22 MS subjects and 22 healthy controls. Automatic brain parcellation was performed on T1-weighted images. Skull-stripped T1-weighted intensity inverted images were co-registered to the b0 image. Diffusion-weighted images were processed to perform whole brain tractography. The rs-fMRI data were processed, and the connectivity matrixes were analyzed to identify significant differences in the network of nodes between the two groups using NBS analysis. In addition, diffusion entropy maps were produced from DTI data sets using in-house software. Results MS subjects exhibited significantly reduced mean FA and entropy in 38 and 34 regions, respectively, out of a total of 54 regions. The connectivity values in both structural and functional analyses were decreased in most regions of the default mode network and in four other cognitive networks in MS subjects compared to healthy controls. MS also induced significant reduction in the normalized hippocampus and corpus callosum volumes; the normalized hippocampus volume was significantly correlated with EDSS scores. Conclusion MS subjects have significant white matter damage and reduction of FA and entropy in various brain regions involved in cognitive networks. Structural and functional connectivity within the default mode network and an additional four cognitive networks exhibited significant changes compared with healthy controls.