Altered Brain Network in Amyotrophic Lateral Sclerosis: A Resting Graph Theory-Based Network Study at Voxel-Wise Level

Amyotrophic lateral sclerosis (ALS) is a rare degenerative disorder characterized by loss of upper and lower motor neurons. Neuroimaging has provided noticeable evidence that ALS is a complex disease, and shown that anatomical and functional lesions extend beyond precentral cortices and corticospinal tracts, to include the corpus callosum; frontal, sensory, and premotor cortices; thalamus; and midbrain. The aim of this study is to investigate graph theory-based functional network abnormalities at voxel-wise level in ALS patients on a whole brain scale. Forty-three ALS patients and 44 age- and sex-matched healthy volunteers were enrolled. The voxel-wise network degree centrality (DC), a commonly employed graph-based measure of network organization, was used to characterize the alteration of whole brain functional network. Compared with the controls, the ALS patients showed significant increase of DC in the left cerebellum posterior lobes, bilateral cerebellum crus, bilateral occipital poles, right orbital frontal lobe, and bilateral prefrontal lobes; significant decrease of DC in the bilateral primary motor cortex, bilateral sensory motor region, right prefrontal lobe, left bilateral precuneus, bilateral lateral temporal lobes, left cingulate cortex, and bilateral visual processing cortex. The DC's z-scores of right inferior occipital gyrus were significant negative correlated with the ALSFRS-r scores. Our findings confirm that the regions with abnormal network DC in ALS patients were located in multiple brain regions including primary motor, somatosensory and extra-motor areas, supporting the concept that ALS is a multisystem disorder. Specifically, our study found that DC in the visual areas was altered and ALS patients with higher DC in right inferior occipital gyrus have more severity of disease. The result demonstrated that the altered DC value in this region can probably be used to assess severity of ALS.