Disrupted Paraventricular Hypothalamic Nucleus Functional Connectivity in Parkinson's Disease With Constipation

Background: Constipation is one of the most common non-motor symptoms in patients with Parkinson's disease (PD), which could manifest during the early stage of the disease. However, the etiology of constipation in PD remains largely unknown. Previous studies supported that gastrointestinal dysfunction may be associated with functional connectivity alterations in paraventricular hypothalamic nucleus (PVN). Therefore, this study aimed to investigate the potential contribution of the PVN to the pathogenesis of constipation in a cohort of early-stage patients with PD and to compare brain network organization between PD patients with and without constipation.

Methods: A total of 66 PD patients (PD with constipation and without constipation) and 30 healthy controls were prospectively enrolled. All participants acquired T1-weighted and resting-state fMRI scans. Then we employed voxel-based morphometry analysis and functional connectivity analysis.

Results: We observed a decreased functional connectivity in the PVN-pontine tegmentum pathway in PD patients with constipation compared to the patients without constipation (p = 0.006, t = 5.37), while we did not find any changes in basal ganglia circuitry between these two groups. In addition, we found that the functional connectivity between PVN and pontine tegmentum was negatively associated with the UPDRS I, II, III and NMSS scores (p < 0.05). Meanwhile, these two types of patients also showed substantial differences in functional connections linking the inferior frontal gyrus and cerebellum with multiple brain regions. We discovered no statistical difference in gray matter volume among these two groups.

Conclusions: Our study provides further insights into the dysfunctional mechanisms of constipation, suggesting that abnormal PVN functional connectivity may be related to the mechanism of constipation in PD. Meanwhile, the inferior frontal gyrus and cerebellum may be involved in the occurrence of constipation in PD patients.