Abnormal topological organization of structural covariance networks in amyotrophic lateral sclerosis

Abstract Neuroimaging studies of patients with amyotrophic lateral sclerosis (ALS) have shown widespread alterations in structure, function, and connectivity in both motor and non-motor brain regions, suggesting multi-systemic neurobiological abnormalities that might impact large-scale brain networks. Here, we examined the alterations in the topological organization of structural covariance networks of ALS patients ( N  = 60) compared with normal controls ( N  = 60). We found that structural covariance networks of ALS patients showed a consistent rearrangement towards a regularized architecture evidenced by increased path length, clustering coefficient, small-world index, and modularity, as well as decreased global efficiency, suggesting inefficient global integration and increased local segregation. Locally, ALS patients showed decreased nodal degree and betweenness in the gyrus rectus and/or Heschl's gyrus, and increased betweenness in the supplementary motor area, triangular part of the inferior frontal gyrus, supramarginal gyrus and posterior cingulate cortex. In addition, we identified a different number and distribution of hubs in ALS patients, showing more frontal and subcortical hubs than in normal controls. In conclusion, we reveal abnormal topological organization of structural covariance networks in ALS patients, and provide network-level evidence for the concept that ALS is a multisystem disorder with a cerebral involvement extending beyond the motor areas.