Topological disruption of high‐order functional networks in cognitively preserved Parkinson's disease

This study aimed to characterize the topological alterations and classification performance of high-order functional connectivity (HOFC) networks in cognitively preserved patients with Parkinson's disease (PD), relative to low-order FC (LOFC) networks.The topological metrics of the constructed networks (LOFC and HOFC) obtained from fifty-one cognitively normal patients with PD and 60 matched healthy control subjects were analyzed. The discriminative abilities were evaluated using machine learning approach.The HOFC networks in the PD group showed decreased segregation and integration. The normalized clustering coefficient and small-worldness in the HOFC networks were correlated to motor performance. The altered nodal centralities (distributed in the precuneus, putamen, lingual gyrus, supramarginal gyrus, motor area, postcentral gyrus and inferior occipital gyrus) and intermodular FC (frontoparietal and visual networks, sensorimotor and subcortical networks) were specific to HOFC networks. Several highly connected nodes (thalamus, paracentral lobule, calcarine fissure and precuneus) and improved classification performance were found based on HOFC profiles.This study identified disrupted topology of functional interactions at a high level with extensive alterations in topological properties and improved differentiation ability in patients with PD prior to clinical symptoms of cognitive impairment, providing complementary insights into complex neurodegeneration in PD.