Normalization effect of levodopa on hierarchical brain function in Parkinson’s disease

AbstractHierarchical brain organization, in which rich-club and diverse-club situates in core position, is critical for global information integration in human brain network. Parkinson’s disease (PD), a common movement disorder, has been conceptualized as a network disorder. Levodopa is an effective treatment for PD. Whether a functional divergence between hierarchical brain system under PD pathology, and how this divergence is regulated by immediate levodopa therapy, remains unknown. We constructed functional network in 61 PD patients and 89 normal controls, and graph theoretical analyses were applied to examine the neural mechanism of levodopa short response from the perspective of brain hierarchical configuration. The results revealed that: (1) PD patients exhibited disrupted function within rich-club organization, while the diverse-club remained preserved function, indicating a differentiated brain topology organization in PD; (2) along the rich-club derivate hierarchical system, PD patients showed impaired network properties within rich-club and feeder subnetwork, and decreased nodal degree centrality in rich-club and feeder nodes, along with increased nodal degree in peripheral nodes, suggesting the distinct functional patterns in different types of nodes; and (3) levodopa could normalize the abnormal network architecture of rich-club system. This study provides evidence for levodopa effects on hierarchical brain system with divergent function.