Stimulus-Dependent, Not Resting-State, Neural Dysfunction Underlies the Neurobiology of Delayed Ejaculation: A
1Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.
Introduction:
Delayed ejaculation (DE) is a common sexual dysfunction with unclear neurobiological mechanisms. Few studies have explored its neural substrates using functional magnetic resonance imaging (fMRI), especially combining resting-state and task-state paradigms.
Methods:
Forty-two DE patients and 36 healthy controls (HCs) were enrolled. Clinical data (demographics, IIEF-5, GAD-7, PHQ-9, serum testosterone) and fMRI data (resting-state and visual sexual stimulation-induced task-state) were collected. Data were analyzed using regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuations (fALFF), independent component analysis (ICA), and functional connectivity assessments.
Results:
Demographically, DE patients and HCs showed no differences in height, weight, or BMI (all p > 0.05), but DE patients had lower serum total testosterone, reduced IIEF-5 scores, and higher GAD-7/PHQ-9 ratings (all p < 0.05), with higher comorbidity of erectile dysfunction, anxiety, and depression. Resting-state fMRI revealed no significant voxel-wise differences in ReHo or fALFF between groups (all p > 0.05). However, during visual sexual stimulation, the two groups exhibited diametrically opposite responses in sensorimotor network regions. For ReHo, the bilateral precentral gyrus, postcentral gyrus, and rolandic operculum exhibited significant inhibition in DE patients (e.g., PoCG.L: T = -6.56) and robust activation in HCs (e.g., PoCG.L: T = 7.57). For fALFF, DE patients showed inhibition in these regions, including the supplementary motor area and the middle cingulate gyrus, whereas HCs activated them; post-correction, DE patients still showed significant inhibition in the left precentral/postcentral gyrus compared with the HC group. (e.g., PoCG.L: T = -4.44). ICA identified the parahippocampal gyrus (PHG) as a dual-functional hub-core node of the default mode network and cross-network connector-with disrupted functional connectivity to supplementary motor area, inferior parietal lobule, and temporal regions in DE patients.
Conclusions:
DE is associated with stimulus-dependent neural dysregulation rather than inherent resting-state abnormalities. Inhibition of the sensorimotor network and PHG-centered connectivity disruption underlie DE's neurobiological basis, providing potential targets for clinical interventions.
