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.

Many studies of brain networks have revealed densely connected regions forming the rich club and diverse club, which occupy the central position of the hierarchical brain system. Here, we explore the hierarchical topology in Parkinson’s disease (PD) and investigate the neural effect of levodopa on it. We show that within the core position of the hierarchical system, the function of the diverse club is preserved while the function of the rich club is impaired. Along the rich-club hierarchical system, the function of biologically costly rich-club and feeder subnetworks is disrupted, together with an increased function of peripheral nodes, which could be normalized by levodopa. Our study provides evidence of a disparity pattern between different levels of brain hierarchical systems under PD pathology.

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Author notes

Competing Interests: The authors have declared that no competing interests exist.


Tao Guo and Min Xuan should be considered joint first author.

Handling Editor: Mikail Rubinov

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