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

Hierarchical brain organization, in which the rich club and diverse club situate in core position, is critical for global information integration in the 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 there is a functional divergence in the hierarchical brain system under PD pathology, and how this divergence is regulated by immediate levodopa therapy, remains unknown. We constructed a functional network in 61 PD patients and 89 normal controls and applied graph theoretical analyses to examine the neural mechanism of levodopa short response from the perspective of brain hierarchical configuration. The results revealed the following: (a) PD patients exhibited disrupted function within rich-club organization, while the diverse club preserved function, indicating a differentiated brain topological organization in PD. (b) Along the rich-club derivate hierarchical system, PD patients showed impaired network properties within rich-club and feeder subnetworks, and decreased nodal degree centrality in rich-club and feeder nodes, along with increased nodal degree in peripheral nodes, suggesting distinct functional patterns in different types of nodes. And (c) levodopa could normalize the abnormal network architecture of the rich-club system. This study provides evidence for levodopa effects on the hierarchical brain system with divergent functions.