Local brain network alterations in prodromal and De Novo Parkinson's disease: basal ganglia functional connectivity mediates the association between regional homogeneity and motor manifestations.
BACKGROUND AND OBJECTIVE Recently, three motor phases of Parkinson's disease (PD) have been proposed (a silent period when nigrostriatal loss begins, a prodromal motor period with subtle focal manifestations, and clinical PD) accompanying the early loss of nigrostriatal dopaminergic pathways and the dysfunction of the basal ganglia (BG) loop, which produce vital network alterations that impact motor coordination. However, the relationships among local brain abnormalities, BG-based functional connectivity (FC) and motor performance in early PD remain unclear. Thus, our study aims to characterize local brain activity dysfunction and large-scale network disorganization, and further explore the potential neural pathway from local dysrhythmia to network-level dysfunction ultimately to clinical motor deficits. METHODS We enrolled 32 healthy controls (HC), 20 prodromal PD (pPD) patients without mild motor signs (pPD-NMMS), 42 pPD patients with MMS (pPD-MMS), and 58 de novo PD (dPD) patients. We calculated the regional homogeneity (ReHo) and FC values of BG subregions and differences among groups. Furthermore, correlation analyses between ReHo, FC values, and motor sub-scores were analyzed. Additionally, a mediation analysis was conducted to investigate the mediating function of FC-distinct brain regions between ReHo values and motor performance. RESULTS Compared with the other groups, pPD-NMMS patients had increased ReHo values in the right lingual gyrus (LING). However, the pPD-MMS group had increased FC values in the left globus pallidus (GP), the bilateral ventromedial putamen (vmPu) to sensorimotor regions, and the left vmPu, the left dorsal caudate (dCa) to visual cortex regions. Both ReHo values in the right LING and FC values of the left GP and the left vmPu were correlated with tremor scores. Eventually, mediation analyses revealed that FC values between the left GP and the right postcentral gyrus (PoCG), and between the left vmPu and the right inferior occipital gyrus (IOG) mediated the relationship between ReHo values in the right LING and tremor scores. CONCLUSION Along with the transition from the prodromal to the manifested period and the development of motor signs, network alterations of BG loop may play an important mediating role between local alterations in occipital-related brain regions and tremor performance.