Disrupted cerebellar connectivity reduces whole-brain network efficiency in multiple system atrophy

Multiple system atrophy of the cerebellar type is a sporadic neurodegenerative disorder of the central nervous system. We hypothesized that the white matter degeneration of the cerebellum and pons in this disease may cause a breakdown of cerebellar structural networks and further reduce the network efficiency of cerebellar-connected cerebral regions. Diffusion tensor tractography was used to construct the structural networks of 19 cerebellar-type multiple system atrophy patients, who were compared with 19 age- and sex-matched controls. Graph theory was used to assess the small-world properties and topological organization of structure networks in both the control and patient groups. Our results showed that the cerebellar-type multiple system atrophy patients exhibited altered small-world architecture with significantly increased characteristic shortest path lengths and decreased clustering coefficients. We also found that white matter degeneration in the cerebellum was characterized by reductions in network strength (number and integrity of fiber connections) of the cerebellar regions, which further induced extensively decreased network efficiency for numerous cerebral regions. Finally, we found that the reductions in nodal efficiency of the cerebellar lobules and bilateral sensorimotor, prefrontal, and basal ganglia regions negatively correlated with the severity of ataxia for the cerebellar-type multiple system atrophy patients. This study demonstrates for the first time that the brains of cerebellar-type multiple system atrophy patients exhibit disrupted topological organization of white matter structural networks. Thus, this study provides structural evidence of the relationship between abnormalities of white matter integrity and network efficiency that occurs in cerebellar-type multiple system atrophy.