Investigating glymphatic function and bed nucleus of the stria terminalis-based functional connectivity in Parkinson’s disease with and without depression

Glymphatic activity and the bed nucleus of the stria terminalis (BNST) have been implicated in the pathogenesis of Parkinson’s disease (PD) with depression (PDD). This study aimed to investigate glymphatic function and BNST-based functional connectivity (FC) and potential biomarkers in PDD. The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index combined with BNST-based FC and support vector machine were applied to 24 PDD, 24 PD with non-depression (PDND), and 25 healthy controls. We found that (1) the DTI-ALPS indices (p < 0.001), the right BNST-based FC values (p < 0.001, FWE small volume correction) were significantly different among three groups; (2) the FC features in the right mPFC (mPFC_R), right MTG (MTG_R), and right ITG (ITG_R) can distinguish PDD from PDND; (3) the right BNST-based FC values, DTI-ALPS indices, and HAMD scores were correlated with each other (r = −0.620, p = 0.004; r = 0.651, p = 0.002; r = −0.53, p = 0.016). Impaired glymphatic function and altered BNST-based FC values are strongly associated with PD, and brain regions with differences in the right BNST-based FC values may serve as potential biomarkers for classifying clinical subtypes of PD. These findings provide new insights into the pathogenesis of depression in PD. This study protocol was registered on the Chinese Clinical Trial Registry (ChiCTR2000038411, September 22, 2020, https://www.chictr.org.cn/showproj.html?proj=56715).