Topological alteration of the brain structural network in Parkinson's disease with apathy

Background: Apathy is a common neuropsychiatric manifestations in Parkinson's disease (PD), but neural network mechanisms still remain elusive. We aim to investigate the topological alteration of the brain structural network in PD with apathy. Method: In the present study, a total of 47 apathetic PD (aPD) patients, 37 non-apathetic PD (naPD) patients, and 40 healthy controls (HCs) were enrolled. Diffusion tensor imaging (DTI) in conjunction with graph-theoretic approaches were used to explore the alterations of topological properties of the WM structural network arising from apathy in PD. One-way analysis of covariance and post hoc analyses were performed to explore differences among the three groups. Correlations were ascertained to examine relationships between the Starkstein Apathy Scale (AS) scores and significantly different network metrics among the three groups. Results: Both aPD and naPD patients remained small-world topology. However, compared with the naPD patients, aPD patients showed increased clustering coefficient (Cp) at the global level. At the regional level, aPD exhibited decreased nodal properties, mainly in the right dorsolateral prefrontal cortex (DLPFC), the right caudate nucleus (CAU), the right hippocampus, and the right superior parietal gyrus. Further, AS scores were negatively correlated with degree centrality of the right DLPFC (r = -0.254, p = 0.020) and the right CAU ( r = -0.357, p = 0.001) in the pooled patients with PD. Conclusions: The findings suggested that apathy in PD presented relatively optimized global topological properties of the brain structural network and disrupted topological organization of the regional network, particularly involving the fronto-striatal-limbic circuits. The altered topological properties of abnormal brain regions might be used to understand the physiopathologic mechanism of the neural network in aPD patients.