Abstract
BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) is associated with pathological α-synuclein deposition and may have different damage directions due to α-synuclein spreading orientations. Recent functional imaging studies of Parkinson's disease (PD) with RBD have identified abnormalities in connectivity, but effective connectivity (EC) for this altered orientation is understudied. Here, we aimed to explore altered intrinsic functional connectivity (FC) and EC in PD patients with probable RBD (pRBD). METHODS: This was a cross-sectional study. A total of 31 PD patients with pRBD (PD-pRBD), 35 PD without pRBD (PD-npRBD), and 32 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (RS-fMRI) scans. The voxel-wise degree centrality (DC) calculation was first performed to investigate the inherent connectivity of the PD-pRBD patients. Subsequently, we applied Granger causality analysis (GCA) to probe the causal effects of anomalous brain regions. Finally, the support vector machine (SVM) method was executed to evaluate the DC values in identifying PD-pRBD. RESULTS: PD-pRBD patients exhibited reduced z-DC values in the right precentral gyrus relative to PD-npRBD (voxel-level P<0.001, cluster-level P<0.05), as well as decreased z-DC values in the right postcentral gyrus and the superior parietal lobule compared to HCs. Then, our GCA revealed that decreased EC was located predominantly from the right precentral gyrus to the right caudate nucleus in the PD-pRBD group. Additionally, the SVM results revealed that the z-DC values of the right precentral gyrus could discriminate PD-pRBD from the PD-npRBD group [area under the curve (AUC) =0.905]. CONCLUSIONS: The altered z-DC in the right precentral gyrus and the anomaly causal effects from the precentral motor cortex to the ipsilateral striatum represented by the caudate nucleus might play vital roles in the pathogenesis of PD-pRBD. It was speculated that the attenuation of FC from the precentral motor cortex to the subcortical striatum might be associated with nocturnal muscle dyskinesia and behavioral abnormalities in PD-pRBD patients. This disruption pattern may be a prospective imaging marker in the characterization of PD with pRBD.