Short- and long-range synergism disorders in lifelong premature ejaculation evaluated using the functional connectivity density and network property

This study was aimed to investigate brain function connectivity in premature ejaculation (PE) patients using the functional connectivity density (FCD) and network property of resting-state functional magnetic resonance imaging. Twenty PE patients (mean age: 27.95 ± 4.52 years) and 15 normal controls (mean age: 27.87 ± 3.78 years) with no self-reported history of neurologic or psychiatric disease were enrolled in this study. International Index of Erectile Function-5 and Chinese Index of Sexual Function for Premature Ejaculation-5 questionnaires and self-reported intravaginal ejaculatory latency time (IELT) were obtained from each participant for symptom assessment. Two-sample t-tests (intergroup comparison) were applied in the short-range FCD (SFCD) analysis, long-range FCD (LFCD) analysis, region of interest–based analysis, and network topological organization analysis. Pearson correlation analysis was performed to correlate IELT with FCD or the network property. The patients with PE showed significantly decreased SFCD in the bilateral middle temporal gyrus, left orbitofrontal cortex, nucleus accumbens, fusiform, caudate, and thalamus (p < 0.05, AlphaSim-corrected). Notably, all these aforementioned brain areas are located in the dopamine pathway. In contrast, increased LFCD was observed in the left insula, Heschl's gyrus, putamen, bilateral precuneus, supplementary motor area, middle cingulate cortex, and anterior cingulate cortex in PE patients (p < 0.05, AlphaSim-corrected). In addition, the network topological analysis found reinforced network connectivity between several nodes. The degree of hub nodes increased in the patients with PE. IELT was positively correlated with SFCD and negatively correlated with LFCD or the degree of hub nodes (p < 0.05, Pearson correlation). In summary, our results are important for understanding the brain network in PE patients. The present findings indicate that PE patients have a significant synergism disorder across the region of dopamine pathway, which implied neuronal pathological changes might be related with the change of dopamine. The FCD and network property can serve as new disease severity biomarkers and therapeutic targets in PE. Keywords: Premature ejaculation, Functional connectivity density, The dopamine system, The rewarding syste