Topological differences of striato-thalamo-cortical circuit in functional brain network between premature ejaculation patients with and without depression.

INTRODUCTION: Premature ejaculation (PE), a common male sexual dysfunction, often accompanies by abnormal psychological factors, such as depression. Recent neuroimaging studies have revealed structural and functional brain abnormalities in PE patients. However, there is limited neurological evidence supporting the comorbidity of PE and depression. This study aimed to explore the topological changes of the functional brain networks of PE patients with depression. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 60 PE patients (30 with depression and 30 without depression) and 29 healthy controls (HCs). Functional brain networks were constructed for all participants based on rs-fMRI data. The nodal parameters including nodal centrality and efficiency were calculated by the method of graph theory analysis and then compared between groups. In addition, the results were corrected for multiple comparisons by family-wise error (FWE) (p < .05). RESULTS: PE patients with depression had increased degree centrality and global efficiency in the right pallidum, as well as increased degree centrality in the right thalamus when compared with HCs. PE patients without depression showed increased degree centrality in the right pallidum and thalamus, as well as increased global efficiency in the right precuneus, pallidum, and thalamus when compared with HCs. PE patients with depression demonstrated decreased degree centrality in the right pallidum and thalamus, as well as decreased global efficiency in the right precuneus, pallidum, and thalamus when compared to those without depression. All the brain regions above survived the FWE correction. CONCLUSION: The results suggested that increased and decreased functional connectivity, as well as the capability of global integration of information in the brain, might be related to the occurrence of PE and the comorbidity depression in PE patients, respectively. These findings provided new insights into the understanding of the pathological mechanisms underlying PE and those with depression.

Glans penis volume is associated with lifelong premature ejaculation.

BACKGROUND: Although premature ejaculation (PE) is the most common male sexual dysfunction, the underlying mechanisms are not fully understood. AIM: The study sought to evaluate the possible associations among glans penis volume and tissue stiffness measured using penile ultrasonography and penile shear wave elastography (SWE) with PE. METHODS: Men 18 to 65 years of age with normal International Index of Erectile Function scores (>25) and who were diagnosed with PE between June 2021 and June 2022 were enrolled. The Premature Ejaculation Diagnostic Tool score and intravaginal ejaculation latency times were recorded. Healthy volunteers constituted the control group. The study group was divided into lifelong PE (LLPE) and acquired PE (AqPE) subgroups. In all groups, the glans penis volume was measured via penile ultrasonography and tissue stiffness of the glans penis, penile frenulum, postcircumcision mucosal cuff, and penile shaft were measured via SWE. The findings of the groups were compared using appropriate statistical methods. OUTCOMES: The outcomes included ultrasonographic and elastographic measurements of the glans penis. RESULTS: Data on 140 men, including 70 PE patients and 70 healthy volunteers, were evaluated. Of the patients, 20 had LLPE and 50 had AqPE. The median glans penis volume was significantly greater in the LLPE group (14.1 [range, 6.6-19] mm3) compared with the AqPE group (11.7 [range, 5.1-27] mm3) and control group (11.4 [range, 6.1-32] mm3) (P = .03). According to the Youden index, the best cutoff value for glans penis volume in LLPE compared with non-LLPE (AqPE + control) was 12.65 mm3 (area under the curve, 0.684; 95% confidence interval, 0.556-0.812; P = .009). The risk of having LLPE in those with a glans penis volume ≥12.65 mm3 was 3.326 (95% confidence interval, 1.234-8.965) times higher than the non-LLPE group (P = .014). There were no significant differences between the groups in the SWE evaluation of glans penis, penile frenulum, mucosal cuff, and penile shaft tissue stiffness. CLINICAL IMPLICATIONS: The high incidence of PE in those with high glans penis volume may make glans penis volume a predictor for the development of LLPE. STRENGTHS AND LIMITATIONS: This was the first study to show that PE is more common in individuals with a high glans penis volume. It was also the first to perform a penile elastographic evaluation in patients with PE. The most important limitation was that we did not evaluate glans penile nerve function with a test, but rather we made an indirect inference about the density of free nerve endings based on increased glans penile volume. CONCLUSION: Glans penis volume was a significant predictor for LLPE. However, there are no associations between PE and the glans penis, postcircumcision mucosal cuff, penile frenulum, or penile shaft tissue stiffness and development.

Tarlov Cysts and Premature Ejaculation.

Tarlov cysts adjacent to the spinal cord are usually asymptomatic and found incidentally via magnetic resonance imaging. On rare occasions, they increase in size to produce symptoms resembling disk herniation. We report a rare case of a sacral cyst resulting in premature ejaculation in a 32-year-old man who presented with pelvic pain and acquired premature ejaculation. Spinal nerve root decompression, excision of intraspinal Tarlov cyst, and spinal nerve root adhesion release surgery significantly improved his pain and premature ejaculation at a six-month follow-up.

Decreased grey matter volume in dorsolateral prefrontal cortex and thalamus accompanied by compensatory increases in middle cingulate gyrus of premature ejaculation patients.

INTRODUCTION: The prefrontal-cingulate-thalamic areas are associated with ejaculation control. Functional abnormalities of these areas and decreased grey matter volume (GMV) in the subcortical areas have been confirmed in premature ejaculation (PE) patients. However, no study has explored the corresponding GMV changes in the prefrontal-cingulate-thalamic areas, which are considered as the important basis for functional abnormalities. This study aimed to investigated whether PE patients exhibited impaired GMV in the brain, especially the prefrontal-cingulate-thalamic areas, and whether these structural deficits were associated with declined ejaculatory control. METHODS: T1-weighted structural magnetic resonance imaging (MRI) data were acquired from 50 lifelong PE patients and 50 age-, and education-matched healthy controls (HCs). The PE diagnostic tool (PEDT) was applied to assess the subjective symptoms of PE. Based on the method of voxel-based morphometry (VBM), GMV were measured and compared between groups. In addition, the correlations between GMV of brain regions showed differences between groups and PEDT scores were evaluated in the patient group. RESULTS: PE patients showed decreased GMV in the right dorsolateral superior frontal gyrus (clusters = 13, peak T-values = -4.30) and left thalamus (clusters = 47, T = -4.33), and increased GMV in the left middle cingulate gyrus (clusters = 12, T = 4.02) when compared with HCs. In the patient group, GMV of the left thalamus were negatively associated with PEDT scores (r = -0.35; P = 0.01). Receiver operating characteristic (ROC) analysis showed that GMV of the right dorsolateral superior frontal gyrus (AUC = 0.71, P < 0.01, sensitivity = 60%, specificity = 78%), left thalamus (AUC = 0.72, P < 0.01, sensitivity = 92%, specificity = 46%) and middle cingulate gyrus (AUC = 0.69, P < 0.01, sensitivity = 50%, specificity = 90%), and the combined model (AUC = 0.84, P < 0.01, sensitivity = 78%, specificity = 80%) all had the ability to distinguish PE patients from HCs. CONCLUSION: Disturbances in GMV were revealed in the prefrontal-cingulate-thalamic areas of PE patients. The findings implied that decreased GMV in the dorsolateral prefrontal cortex and thalamus might be associated with the central pathological neural mechanism underlying the declined ejaculatory control while increased GMV in the middle cingulate gyrus might be the compensatory mechanism underlying PE.

Changes of insular function in lifelong premature ejaculation patients before and after SSRI administration.

OBJECTIVE: Lifelong premature ejaculation (PE) is regarded as one of the most common male sexual dysfunction. We aimed to detect whether insula-related brain functional networks are altered in lifelong PE patients and whether such alterations are "normalised" after selective serotonin reuptake inhibitors (SSRI) administration. METHODS: Twenty-three drug-naive lifelong PE patients and 30 healthy controls (HC) were recruited in current study. All subjects underwent resting-state functional magnetic resonance imaging (fMRI) scan at first. One hour after dapoxetine administration, all patients underwent fMRI scanning again. The degree centrality (DC), amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) analysis, and ROI-based functional connectivity (FC) analysis were applied to calculate the abnormalities in insula-related functions among three groups. RESULTS: Compared to HC group, PE patients at baseline showed significantly altered DC, ALFF, and ReHo value of the bilateral insula, which subsequently showed a "normalised" trend after dapoxetine administration. Additionally, compared to HC group, PE patients at baseline showed significantly decreased FC between insula and precentral gyrus, inferior frontal gyrus, middle/inferior temporal gyrus, and caudate, while patients after dapoxetine administration showed increased insula-related FC in anterior cingulate cortex and decreased FC in thalamus and middle/inferior temporal gyrus. The main effects of dapoxetine were located in precentral gyrus, inferior frontal gyrus, caudate, and limbic system. CONCLUSIONS: Our findings report altered brain mechanism of insula in lifelong PE patients and also indicate that dapoxetine can "normalise" the abnormal function of the insula to certain extent in lifelong PE patients.

Magnetic Resonance Imaging-Based Structural Covariance Changes of the Striatum in Lifelong Premature Ejaculation Patients.

BACKGROUND: The striatum has been reported to be implicated in various neurological diseases, including lifelong premature ejaculation (LPE). Altered striatum-related functional connectivity was investigated in LPE patients in previous studies; however, structural abnormalities in the striatum have been less studied in LPE. PURPOSE: To identify the gray matter volume (GMV) and structural covariance patterns of the striatum between LPE patients and healthy controls (HCs). STUDY TYPE: Prospective. SUBJECTS: Forty-three LPE patients and 31 male HCs. FIELD STRENGTH/SEQUENCE: 3.0 T magnetic resonance imaging (MRI) scanner; T1-weighted imaging using a spoiled gradient recalled echo sequence. ASSESSMENT: Preprocessing of structural MRI data and the striatum-seeded GMV computation were conducted using SPM12. STATISTICAL TESTS: Two sample t-test was used to compare differences in GMV of the striatum between patients and HCs. Regions showing altered between-group GMV were considered as seeds for structural covariance analysis in two groups. Additionally, correlations between GMV findings and clinical features were assessed with age and total intracranial volume (TIV) as covariates and with age, TIV, anxiety, and depression scores as covariates in the patient group, P < 0.05 was considered statistically significant. RESULTS: Compared to HCs, LPE patients had significantly decreased GMV in four regions located in the bilateral caudate and putamen. Distinct striatum-based structural covariance patterns in the two groups were mainly related to the thalamus, amygdala, insula, anterior cingulate cortex, middle cingulate cortex, medial prefrontal cortex, primary motor cortex, and precuneus/cuneus. LPE patients showed that GMV in the bilateral caudate negatively correlated with the premature ejaculation diagnostic tool (PEDT) scores (r = -0.369, r = -0.377, respectively). DATA CONCLUSION: Our findings indicated that LPE patients had altered GMV and structural covariance patterns in the striatum compared to HCs. The correlations between abnormal GMV and PEDT were also shown in the present findings. These findings may contribute to enhancing the understanding of the pathophysiology of LPE. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Smaller volume and altered functional connectivity of the amygdala in patients with lifelong premature ejaculation.

OBJECTIVES: To analyze the abnormal amygdala structure and function in lifelong premature ejaculation (PE) patients compared with healthy controls (HCs). METHODS: Forty-four lifelong PE patients and thirty-one HCs were enrolled in this study. Each subject was diagnosed with PE using a Premature Ejaculation Diagnostic Tool (PEDT) and intravaginal ejaculation latency time (IELT) score. Based on t-tests and Pearson correlation analysis, the voxel-based morphometry and functional connectivity (FC) analyses were applied to evaluate brain structural and functional changes by using T1-weighted and resting-state functional magnetic resonance imaging scans. RESULTS: Lifelong PE patients had decreased gray matter volume in the bilateral amygdala and increased FC between the amygdala and precuneus, posterior cingulate cortex (PCC), and middle temporal cortex (MTC), as well as decreased FC between the amygdala and precentral gyrus, insula, and inferior frontal gyrus. Moreover, significantly negative correlations between the IELT score and the mean z-score from amygdala-MTC (r = -0.49) and amygdala-PCC (r = -0.48) FC were found in lifelong PE patients. CONCLUSIONS: Our study investigated the abnormal amygdala-related structure and connectivity patterns in PE patients, which might provide novel perspective for understanding the crucial role of the amygdala in the neural mechanism of PE. KEY POINTS: • As one of the most common diseases in men, PE may be related to abnormal brain mechanisms. • Functional and structural magnetic resonance imaging used to explore amygdala abnormalities in PE patients. • The correlation between clinical scores and functional connectivity was used to assess the reasonability of the results.

Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation.

BACKGROUND: Although some recent neuroimaging studies have indicated the abnormal brain structure or function in patients with lifelong premature ejaculation (LPE), whether and how the abnormal thalamic function participates in processing sexual behavioral information are still unclear in patients with LPE. AIM: The aim of this study was to assess the changes in the thalamus metabolism and structural integrity in patients with LPE. METHODS: We performed a multimodal magnetic resonance approach in a 3.0 T system, including proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging, and volumetric analysis to detect the differences in thalamic metabolism and structure between 20 patients with LPE and 15 healthy controls. OUTCOMES: We analyzed and correlated the clinical symptoms of the subjects with significant 1H-MRS-based features. Peak areas of N-acetylaspartate, choline, creatine (Cr), and glutamate/glutamine (Glu) were calculated with the LCModel software. RESULTS: Diffusion tensor imaging and volumetric analysis of thalami showed no differences between the 2 groups. On the contrary, 1H-MRS study disclosed that both Glu concentrations and Glu/Cr ratio values in the thalami of patients with LPE were remarkably increased when compared with healthy controls (P < .01 for both variables). In addition, both the intravaginal ejaculatory latency time score and Chinese Index of Sexual Function for Premature Ejaculation-5 score were negatively related to increased Glu concentrations and Glu/Cr ratio values. CLINICAL IMPLICATIONS: Glutamatergic activity changes of thalamus may be an underlying indicator for evaluating sensory conduction efficiency in patients with LPE. STRENGTHS & LIMITATIONS: The present study first found the abnormal thalamic metabolism in patients with LPE and contributed to a better understanding of the LPE etiology. Limitations include a cross-sectional study design with small samples and no examination of other brain areas. CONCLUSION: Our findings show that the increase in glutamatergic activity of thalamus is related to LPE, suggesting that the increased Glu neurotransmission in the thalamus may contribute to the development of premature ejaculation. Xia J-D, Chen F, Zhang Q-J, et al. Abnormal Thalamic Metabolism in Patients With Lifelong Premature Ejaculation. J Sex Med 2021;18:275-283.

Aberrant default mode network and auditory network underlying the sympathetic skin response of the penis (PSSR) of patients with premature ejaculation: A resting-state fMRI study.

INTRODUCTION: Hyperactivity of the sympathetic nervous system is considered as an important component involved in the pathological mechanisms of premature ejaculation (PE). However, the neural mechanisms of PE with high sympathetic activity are still not well understood. METHODS: The activity of the sympathetic innervations in the penis was evaluated by the sympathetic skin response of the penis (PSSR) with an electromyograph and evoked potential equipment. Resting-state functional magnetic resonance imaging (fMRI) data were acquired from 18 PE patients with high sympathetic activity (sPE), 17 PE patients with normal sympathetic activity (nsPE), and 24 healthy controls (HC). We investigated the neural basis of sPE based on the measure of regional homogeneity (ReHo). Moreover, the correlations between brain regions with altered ReHo and PEDT scores and PSSR latencies in the patient group were explored. RESULTS: Altered ReHo values among three groups were found in the temporal, cingulated, and parietal cortex in the default mode network (DMN), as well as the temporal cortex in the auditory network (AUD). Compared with HC, Patients with sPE had increased ReHo values of brain regions in DMN, AUD, and decreased ReHo values of brain regions in DMN. In addition, increased ReHo values were found in DMN of patients with nsPE, while decreased ReHo values were found in DMN and the attention network (AN). Moreover, sPE patients had increased ReHo values in AUD and decreased ReHo values in DMN when compared with nsPE patients. Finally, altered ReHo values of brain regions in DMN and AUD were associated with PEDT scores and PSSR latencies in the patient group. CONCLUSION: Our results suggested that PE patients had abnormal ReHo values in DMN, AUD, and AN. Patients with sPE were characterized by increased neuronal activity in AUD and decreased activity in DMN. This highlighted the significances of DMN, AUD, and AN in the pathophysiology of PE and also provided potential neuroimaging biomarkers for distinguishing sPE from nsPE and HC.

Abnormal degree centrality in lifelong premature ejaculation patients: an fMRI study.

Lifelong premature ejaculation (PE) is one of the most prevalent male sexual dysfunctions. It is still not well known about the possible neural mechanisms of lifelong PE. This study tried to investigate the abnormal characteristics of brain functional networks of lifelong PE and to assess relationships of PE-related functional abnormalities with clinical symptoms. Functional magnetic resonance imaging (fMRI) data and clinical symptoms were collected from 45 lifelong PE patients and 37 healthy controls (HCs) since 2016, including disease and sexual life history, intravaginal ejaculatory latency time measured by stopwatch and other scales. The degree centrality (DC) approach were applied to distinguish altered brain functions between the two groups (p < 0.05, false discovery rate corrected). Correlation analysis was then performed to examine relationships between the imaging findings and clinical symptoms (p < 0.05, Bonferroni corrected). Results showed that compared with HCs, lifelong PE patients had increased DC value in the medial prefrontal cortex (mPFC), precuneus and primary somatosensory cortex (SI) as well as decreased DC value in the insula and orbitofrontal cortex. After controlling for anxiety and depression levels, the significant difference in the mPFC was not found. The DC value in the SI positively correlated with premature ejaculation diagnostic tool (PEDT) score in the patients. The present findings indicate that lifelong PE patients have altered DC in brain regions involved in sensation, motivation and inhibitory control processing. Our study may improve our understanding and provide a new sight into the further research of lifelong PE.

Brain Functional Biomarkers Distinguishing Premature Ejaculation From Anejaculation by ALFF: A Resting-State fMRI Study.

INTRODUCTION: Premature ejaculation (PE) and anejaculation (AJ) are 2 opposite disorders of male ejaculatory dysfunction. Recent studies have demonstrated that the process of ejaculation is mediated by certain neural circuits in the brain. However, different mechanisms between PE and AJ are still unclear. AIM: Therefore, we used resting-state functional magnetic resonance imaging (fMRI) to explore the underlying neural mechanisms in patients with PE and AJ by measuring the amplitude of low-frequency fluctuations (ALFF). METHODS: Resting-state fMRI data were acquired in 17 PE, 20 AJ patients and 23 matched healthy controls (HC). MAIN OUTCOME MEASURE: Differences of ALFF values among the 3 groups were compared. We also explored the correlations between brain regions showing altered ALFF values and scores of Premature Ejaculation Diagnostic Tool (PEDT) in the PE group. RESULTS: There were widespread differences of ALFF values among the 3 groups, which included left anterior cingulate gyrus, precentral and postcentral gyrus, paracentral lobule, superior temporal gyrus, calcarine fissure, putamen; right postcentral gyrus, paracentral lobule, middle temporal gyrus, putamen. Compared with HC, PE patients had greater ALFF in the right inferior frontal gyrus (opercular part), AJ patients had greater ALFF in the left postcentral gyrus. In addition, PE patients exhibited greater ALFF in the left Rolandic operculum, anterior cingulate gyrus, inferior frontal gyrus (orbital part), putamen, and right putamen when compared with AJ patients, as well as decreased ALFF in the right postcentral gyrus. Moreover, positive correlations were found between ALFF of left postcentral gyrus, inferior frontal gyrus (orbital part), right inferior frontal gyrus (opercular part), and PEDT scores. CLINICAL IMPLICATIONS: The differences in central pathophysiological mechanisms between PE and AJ might be useful for improving the clinical diagnosis of ejaculation dysfunction. STRENGTH & LIMITATIONS: Our results showed that the method of fMRI could identify the differences of ALFF between PE and AJ and that these alterations in ALFF were related to clinical function. However, this was a relatively small sample study, and further multimodal neuroimaging studies with large samples were needed. CONCLUSION: The findings demonstrated that altered ALFF of frontal, parietal cortex, and putamen might help distinguish premature ejaculation from anejaculation. Abnormal function of these brain regions might play a critical role in the physiopathology of ejaculatory dysfunction of patients. Chen J, Yang J, Huang X, et al. Brain Functional Biomarkers Distinguishing Premature Ejaculation From Anejaculation by ALFF: A Resting-State fMRI Study. J Sex Med 2020;17:2331-2340.

Selective Functional Hyperconnectivity in the Middle Temporal Gyrus Subregions in Lifelong Premature Ejaculation.

BACKGROUND: Lifelong premature ejaculation (LPE) has been linked to altered brain function and structure. Although the middle temporal gyrus (MTG) is consistently more affected in LPE, its functional and structural changes have yet to be determined at the subregional level. AIM: To explore the functional and structural changes of MTG in LPE at the subregional level based on a combined analysis of multimodal magnetic resonance imaging data. METHODS: 25 patients with LPE and 21 healthy controls underwent resting-state functional and structural magnetic resonance imaging scans. The MTG was parcellated into the anterior part of the MTG (aMTG), middle part of the MTG, posterior part of the MTG, and sulcus part of the MTG. Resting-state functional connectivity (rsFC) and gray matter volume (GMV) of each MTG subregion were calculated and compared between the 2 groups. OUTCOMES: The functional and structural changes of MTG at the subregional level were assessed in patients with LPE and controls, as well as the correlation of them with premature ejaculation diagnostic tool and Beck Depression Inventory. RESULTS: Despite similar rsFC patterns of each MTG subregion in both groups, quantitative comparison analyses revealed that patients with LPE showed increased rsFC between the left aMTG and the right cuneus (0.34 ± 0.12 vs 0.17 ± 0.17), between the right aMTG and the right parahippocampal gyrus (0.36 ± 0.16 vs 0.15 ± 0.10), and between the right middle MTG and the left MTG (0.40 ± 0.14 vs 0.18 ± 0.15) relative to controls (P < .05, cluster-level family-wise error corrected). Moreover, validation analyses revealed that these results remained significant after adjusting for depression. However, there were no significant group differences in GMV in all the MTG subregions (P > .05, Bonferroni corrected). In addition, no significant correlations between rsFC and GMV of the MTG subregions and the clinical variables were found in patients with LPE (P > .05, Bonferroni corrected). CLINICAL IMPLICATIONS: Functional hyperconnectivity in the MTG subregions may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE. STRENGTHS AND LIMITATIONS: There are no previous studies examining functional and structural changes in LPE at the MTG subregional level. The main limitation is the small sample size. CONCLUSIONS: We present evidence that individuals with LPE have a selective functional hyperconnectivity yet preserved structural integrity in the MTG subregions, which may facilitate a more sophisticated understanding of the neuropathological mechanism underlying LPE by highlighting the critical role of the MTG in this disorder. Zhang T, Tang D, Cai H, et al. Selective Functional Hyperconnectivity in the Middle Temporal Gyrus Subregions in Lifelong Premature Ejaculation. J Sex Med 2020;17:1457-1466.

Altered Functional Connectivity of Hypothalamus in Lifelong Premature Ejaculation Patients.

BACKGROUND: As one of the most prevalent sexual dysfunctions in men, lifelong premature ejaculation (PE) often leads to patient distress. The hypothalamus is implicated in the ejaculatory control of healthy males. However, we do not know whether the hypothalamus-related intrinsic connectivity is altered in lifelong PE patients. PURPOSE: To investigate abnormal intrinsic connectivity of the hypothalamus in lifelong PE patients compared with healthy controls (HCs). STUDY TYPE: Prospective pilot study using cross-sectional data of patients and HCs. SUBJECTS: Forty-seven lifelong PE patients and 30 HCs were included in this study. FIELD STRENGTH/SEQUENCE: 3.0T MRI scanner for T1 -weighted imaging using spoiled gradient recalled echo sequence and functional imaging using a single-shot gradient recalled echo sequence. ASSESSMENT: Preprocessing of MRI data and hypothalamus-seeded functional connectivity (FC) computation were performed using DPABI4.1. STATISTICAL TESTS: The two-sample t-test within SPM12 was adopted to examine possible alterations of intrinsic connectivity of hypothalamus in lifelong PE patients compared with HCs including anxiety and depression scores as covariates (false discovery rate-corrected, P < 0.05). The correlation analysis was then used to assess possible associations between the imaging findings and clinical features in the patient group (Bonferroni-corrected, P < 0.05). RESULTS: Compared with HCs, lifelong PE patients had decreased hypothalamus-seeded FC in the left orbitofrontal cortex, bilateral insula, superior temporal cortex, superior temporal pole, middle temporal cortex, left fusiform, right parahippocampal gyrus, and right cerebellum. The intravaginal ejaculatory latency time positively correlated with the mean z-score from the hypothalamus-insula (r = 0.45) and hypothalamus-cerebellum (r = 0.48) intrinsic connectivity, separately. DATA CONCLUSION: We have shown that hypothalamus-seeded FC alterations and the correlations between the aforementioned abnormal FC alterations and intravaginal ejaculatory latency time. The current findings may promote the understanding of the hypothalamus-related neural mechanisms involved in the abnormal ejaculatory information processing in lifelong PE patients. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 3 J. Magn. Reson. Imaging 2020;52:778-784.

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 ±â€¯4.52 years) and 15 normal controls (mean age: 27.87 ±â€¯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.

Perineal Ultrasound: a Review in the Context of Ejaculatory Dysfunction.

BACKGROUND: Ejaculation consists of the emission of semen from seminal vesicles and prostate, followed by expulsion. Ejaculatory dysfunction may take several forms including premature ejaculation, delayed or anejaculation, retrograde ejaculation, and painful ejaculation. Ejaculation is what we can see whereas orgasm is what we feel. The presence of ejaculate does not indicate the ability to experience orgasm. Hence, for the purpose of this work we consider orgasm and ejaculation as 2 separate neurobiological phenomena. AIM: To review the role of advanced investigative techniques such as perineal ultrasound in the diagnosis and management of ejaculation and ejaculatory dysfunction. METHODS: We performed a PubMed search for key words individually and in combination: "ejaculation," "ejaculatory dysfunction," "delayed ejaculation," "painful ejaculation," "retrograde ejaculation," "perineal ultrasound," and "transrectal ultrasound." We also share our local experience using perineal ultrasound in assessing ejaculation. OUTCOMES: Perineal ultrasound can be used as an aid in the investigation of ejaculatory dysfunction. RESULTS: Evaluation of ejaculatory function hinges on a detailed psychosexual history and appropriate physical examination. Function of the ejaculatory center in the spine is androgen dependent; thus, hormonal evaluation is an important aspect of the workup. Disorders of ejaculation and orgasm require evaluation of neuromuscular reflexes activated during sexual activity. Dynamic ultrasonographic (US) ejaculatory-orgasmic studies allow for reproducible and detailed descriptions of the sexual response. Transrectal ejaculatory studies are useful in uncovering reasons for lack of antegrade semen emission, especially in men with poor sperm production or after vasectomy. Dynamic US studies contribute clinical utility in its non-invasive nature and can provide insight to the dynamic processes surrounding pelvic floor functioning in men. CONCLUSIONS: Perineal US for men with delayed ejaculation or anejaculation, painful ejaculation, or retrograde ejaculation may be helpful in select cases. Further research using this modality may help advance our understanding of ejaculatory dysfunction. Forbes CM, Flannigan R, Paduch DA. Perineal Ultrasound: a Review in the Context of Ejaculatory Dysfunction. Sex Med Rev 2018;6:419-428.

Relation of size of seminal vesicles on ultrasound to premature ejaculation.

Myriad biological factors have been proposed to explain premature ejaculation (PE). However, data correlating PE with seminal vesicles (SVs) are sparse. The study aimed to evaluate the relationship between the size of SV and PE. The cross-sectional study included 44 outpatients with PE and 44 volunteers without PE, and the size of SV was compared. Self-estimated intravaginal ejaculatory latency time, the Premature Ejaculation Diagnostic Tool (PEDT), the International Index of Erectile Function-15, and the National Institutes of Health-Chronic Prostatitis Symptom Index were used for assessment of symptoms. Compared to the control group, the PE group had significantly higher mean anterior-posterior diameter (APD) of SV (P < 0.001). The optimal mean APD of SV cutoff level was 9.25 mm for PE. In the PE group, PEDT was also higher with a mean APD of SV ≥9.25 mm compared with mean APD of SV <9.25 mm. PEDT was significantly correlated with the mean APD of SV (r = 0.326, P = 0.031). The seminal plasma proteins were compared between six PE and six matched control cases by mass spectrometry and it was shown that 102 proteins were at least 1.5-fold up- or down-regulated. Among them, GGT1, LAMC1, and APP were significantly higher in the PE group. These results indicated that men with a larger mean APD of SV might have a higher PEDT score. Transrectal ultrasound of SV should be considered in the evaluation of patients with premature ejaculation. SV might be a potential target for the treatment of patients with PE and ultrasound change in SV.

Acquired premature ejaculation and male accessory gland infection: relevance of ultrasound examination.

We have previously demonstrated a high frequency of premature ejaculation (PE) among patients with male accessory gland infection (MAGI). The aim of this study was to evaluate the ultrasound (US) features of patients with MAGI and acquired premature ejaculation (APE) associated (MAGI-APEpos). US evaluation of 50 MAGI-APEpos patients compared to 50 patients with MAGI without PE (MAGI-PEneg) which represent the control group. The diagnosis of APE was made through the evaluation of Intravaginal ejaculation latency time (IELT) and confirmed with the questionnaire PEDT (Premature Ejaculation Diagnostic Tool). The main outcome measure was represented by the frequency of US criteria suggestive of P (prostatitis), V (vesiculitis), and E (epididymitis) in MAGI-APEpos and MAGI-PEneg patients. MAGI-APEpos patients showed a total number of US criteria significantly higher compared to MAGI-PEneg patients. MAGI-APEpos showed a higher frequency of US criteria of V and E (complicated forms of MAGI). Finally, in MAGI-APEpos group, it was found a positive relationship between the anteroposterior diameter (APD) of the caudal tract of the epididymis and the APD of the seminal vesicles, as well as between both diameters and the PEDT score. MAGI-APEpos patients have a peculiar US characterization compared to MAGI-PEneg patients. According to these results, US evaluation of the epididymal and of the prostato vesicular tract should be considered in the practical clinical approach of patients with MAGI and APE. In particular, it could be a support for a possible pathophysiological interpretation of this clinical problem in these patients.

Percutaneous CT-guided cryoablation of the dorsal penile nerve for treatment of symptomatic premature ejaculation.

PURPOSE: To evaluate expansion of image-guided interventional cryoablation techniques usually employed for pain management to address the feasibility, safety, and efficacy of treatment for a urologic condition with otherwise limited treatment options, premature ejaculation (PE). MATERIALS AND METHODS: Prospective institutional review board approval was obtained, and 24 subjects with PE were enrolled. All patients underwent unilateral percutaneous computed tomography-guided cryoablation of the dorsal penile nerve (DPN). Postprocedural intravaginal ejaculatory latency times (IELTs) and PE Profile (PEP) results served as outcome variables. In addition, subjects were asked whether they would have the procedure done again based on their experience at the 180- and 360-day marks. RESULTS: The technical success rate was 100%. Baseline average IELT was 54.7 seconds ± 7.8 (n = 24), which increased to a maximum of 256 seconds ± 104 (n = 11; P = .241) by day 7 and decreased to 182.5 seconds ± 87.8 (n = 6; P = .0342) by day 90. The mean IELT remained at 182.5 seconds ± 27.6 at day 180 (n = 23; P<.0001) and decreased to 140.9 seconds ± 83.6 by 1 year (n = 22; P<.001). PEP scores improved overall, IELTs significantly improved at 180 and 360 days, and 83% of subjects reported that they would undergo the procedure again if given the same opportunity. There were no procedure-related complications. CONCLUSIONS: CT-guided percutaneous unilateral cryoablation of the DPN is a feasible, safe, single-day outpatient procedure for the treatment of symptomatic PE.