Glans penis electric stimulation modulates cerebral activity and functional connectivity in lifelong premature ejaculation revealed by functional MRI

Abstract

To compare brain activation in the dopaminergic reward system between 26 LPE patients and 16 normal controls (NCs) via glans penis electric stimulation task-fMRI and resting-state fMRI (rs-fMRI). The beta value, degree centrality (DC), and functional connectivity (FC) were calculated. The Pearson correlation was used to analyze the correlation between the fMRI measurements and disease severity. After task-fMRI, PE patients had significantly higher beta values in the dopaminergic reward system, including the bilateral thalamus and inferior frontal gyrus than NCs. In the rs-fMRI, higher DC values in the bilateral supplementary motor area (SMA) and lower DC values in the bilateral precuneus were found. Furthermore, our results showed enhanced FC between the right inferior frontal gyrus and the bilateral SMA and decreased FC between the bilateral precuneus and bilateral thalamus after electrical stimulation. The sensitivity was 80.77%, the specificity was 81.25%, and the AUC was 0.83 (p < 0.001) when differentiating the PE and NC using the FC between the inferior frontal gyrus and SMA. The sensitivity was 73.08%, the specificity was 75.00%, and the AUC was 0.82 (P = 0.002) when differentiating the two groups using the FC between the precuneus and thalamus.

Keywords: Degree centrality; Electrical stimulation; Premature ejaculation; Reward system; fMRI.

Fig. 1

Workflow of the experimental design and data analysis. (A) Paradigm of task-fMRI using electrical stimulation on the glans penis. The blue bars represent the rest state, and the green bars represent the electrical stimulation state. The participants received electrical stimulation on the glans penis. The stimuli intensity was 10.0 mA, the frequency was 3 Hz, and the duration of stimuli was 1 ms in each subject. The electric stimuli were given in 30-s blocks (green) separated by 30-s intervals of rest (blue). Each electric stimulation block and rest block were alternately presented six times. The paradigm lasted 360 s in total. (B) Brain regions with group differences in beta values under task-fMRI. (C) Calculation of the DC metric using the rs-fMRI dataset. (D) Brain regions with group differences in DC. (E) The abnormal functional connectivity within the brain regions founded based on the task and rest fMRI data. (F) Correlation between MRI parameters and IELT.

Fig. 2

Brain responses to electrical stimulation on the glans penis of subjects. The results of the independent samples t-test showed a significant increase in activation in the LPE patients compared to the NC group (A, axial view; B, coronal view. T maps threshold at p < 0.05, AlphaSim corrected); The 3-D render of the bilateral thalami and IFGtriang (C); The beta values for the bilateral thalami and IFGtriang (D, each dot represents the value of each subject, the shaded area represents the standard deviation, and the black horizontal line represents the mean value). **p < 0.01; IFGtriang: inferior frontal gyrus, triangulation area.

Fig. 3

The difference in DC from rs-fMRI between PE and NC. Independent sample t-test results showed that the patients with LPE exhibited significantly altered voxels of DC compared to the NC group (A, axial view; B, coronal view. T maps threshold at p < 0.05, AlphaSim corrected, red areas mean increased FC and blue areas mean decreased FC.); The 3-D render of the bilateral SMA and PCUN (C); The DC values for the bilateral SMA and PCUN (D, each dot represents the value of each subject, the shaded area represents the standard deviation, and the black horizontal line represents the mean value). **p < 0.01; SMA: SMA; PCUN: precuneus.

Fig. 4

Using the bilateral SMA and PCUN from the DC map as fingerprints, fMRI showed that FC was altered between groups. An independent sample t-test was performed between the LPE patients and NC groups (T maps threshold at p < 0.05, AlphaSim corrected). (A) The brain areas where FC was enhanced between the bilateral SMA and the right inferior frontal gyrus; (B) The brain areas where FC was dropped off between the bilateral PCUN and bilateral thalamus. (C) The ROC curves for distinguishing the two groups using the FC between the inferior frontal gyrus and SMA. The AUC was 0.82 (P = 0.002). (D) The ROC curves for distinguishing the two groups using the FC between the precuneus and thalamus. The AUC was 0.83 (p < 0.001). ROI: region-of-interest SMA: SMA; PCUN: precuneus.

Fig. 5

Correlation between clinical scale score and brain activity (beta values and DC). The DC value in SMA (A) and PCUN (B) correlated with the IELT. The beta value of the bilateral thalamus and IFGtriang correlated with the IELT (C–F). IELT: intravaginal ejaculatory latency time; SMA: SMA; PCUN: precuneus; IFGtriang: inferior frontal gyrus, triangulation area; DC: DC.