Dysfunction of human brain network hierarchy in Parkinson's disease patients with freezing of gait

Introduction Hierarchy has been identified as a principle underlying the organization of human brain networks. In Parkinson's disease with freezing of gait (PD-FOG), it remains unclear whether and how the network hierarchy is disrupted. Additionally, the associations between changes in the brain network hierarchy of PD patients with FOG and clinical scales remain unclear. The aim of this study was to explore alterations in the network hierarchy of PD-FOG and their clinical relevance. Methods In this study, the brain network hierarchy of each group was described through a connectome gradient analysis among 31 PD-FOG, 50 PD patients without FOG (PD-NFOG), and 38 healthy controls (HC). Changes in the network hierarchy were assessed by comparing different gradient values of each network between the PD-FOG, PD-NFOG and HC groups. We further examined the relationship between dynamically changing network gradient values and clinical scales. Results For the second gradient, Salience/ventral attention network-A (SalVentAttnA) network gradient of PD-FOG group was significantly lower than that of PD-NFOG, while both PD subgroups had a Default mode network-C gradient that was significantly lower than that of the HC group. In the third gradient, somatomotor network-A gradient of PD-FOG patients was significantly lower than the PD-NFOG group. Moreover, reduced SalVentAttnA network gradient values were associated with more severe gaits, fall risk, and frozen gait in PD-FOG patients. Conclusions The brain network hierarchy in PD-FOG is disturbed, this dysfunction is related to the severity of frozen gait. This study provides novel evidence for the neural mechanisms of FOG.