Cognition and motion dysfunction-associated brain functional network disruption in diabetic peripheral neuropathy

Neuroimaging studies have demonstrated extensive brain functional alterations in cognitive and motor functional areas in Type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN), suggesting potential alterations in large-scale brain networks related to DPN and associated cognition and motor dysfunction. In this study, using resting-state functional connectivity (FC) and graph theory computational approaches, we investigated the topological disruptions of brain functional networks in 28 DPN, 43 T2DM without DPN (NDPN), and 32 healthy controls (HCs) and examined the correlations between altered network topological metrics and cognitive/motor function parameters in T2DM. For global topology, NDPN exhibited a significantly decreased shortest path length compared with HCs, suggesting increased efficient global integration. For regional topology, DPN and NDPN had separated topological reorganization of functional hubs compared with HCs. In addition, DPN showed significantly decreased nodal efficiency (E_nodal ), mainly in the bilateral superior occipital gyrus (SOG), right cuneus, middle temporal gyrus (MTG), and left inferior parietal gyrus (IPL), compared with NDPN, whereas NDPN showed significantly increased E_nodal compared with HCs. Intriguingly, in T2DM patients, the E_nodal of the right SOG was significantly negatively correlated with Toronto Clinical Scoring System scores, while the E_nodal of the right postcentral gyrus (PoCG) and MTG were significantly positively correlated with Montreal Cognitive Assessment scores. Conclusively, DPN and NDPN patients had segregated disruptions in the brain functional network, which were related to cognition and motion dysfunctions. Our findings provide a theoretical basis for understanding the neurophysiological mechanism of DPN and its effective prevention and treatment in T2DM.