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

Abstract

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.

Disrupted Modular Architecture of Cerebellum in Schizophrenia: A Graph Theoretic Analysis

“…However, the present work is in line with several previous studies investigating intracerebellar connections using fiber tractography. 21,56,57 In this study, we hypothesized that schizophrenia patients would show disturbed cerebellar structural network topology, supporting evidence of previous structural network studies on the cortical level 46,47 and underlying cerebellar abnormalities in schizophrenia. We also hypothesized that the schizophrenia patients would show abnormal microstructural integrity in the cerebellum and that these abnormalities would be associated with measures of cerebellar network topology and neuropsychiatric symptom scores.…”

“…Recent fiber tractography studies indicate progress in this regard. 21,56,57 Nevertheless, the present connectivity findings must be cautiously interpreted until their specific neuroanatomical substrates can be elucidated. Third, compared with recent cerebellar connectivity studies using higher angular resolution diffusion imaging 94 and probabilistic tractography, [95][96][97] the method we used in this study is based on the conventional deterministic approach using a streamline technique.…”

Primary motor cortex long‐term plasticity in multiple system atrophy

“…TBS disclosed no M1 plasticity differences in MSA‐P and MSA‐C nor did clinical variables correlate with neurophysiological measures. Compared with MSA‐P, MSA‐C implies disrupted cerebellar‐to‐thalamus connectivity, possibly eliciting additive effects on M1 plasticity . However, the similar responses to TBS in MSA‐P and MSA‐C suggest that reduced plasticity reflects common pathophysiological M1 abnormalities, probably secondary to altered thalamocortical inputs.…”

An update on the cerebellar subtype of multiple system atrophy

“…Many authors described cognitive impairment, involving executive functions and verbal learning in MSA-C [ 81 - 86 ] . These deficits are probably due to frontal atrophy [ 82 , 84 ] and white matter networks disruption [ 81 , 87 ].…”