Functional Magnetic Resonance Imaging Detects Between-Group Differences in Neural Activation Among Men with Delayed Orgasm Compared with Normal Controls: Preliminary Report

Background: Mechanisms underlying delayed orgasm (DO) are poorly understood; however, known effects of psychotropic medications on sexual function provides a rationale for aberrant central nervous system signaling as a cause. Aim: To compare brain activation between men with normal orgasm and those with lifelong DO during sexual stimulation using brain fMRI algorithms. Methods: 3 subjects with self-reported life-long DO and 6 normal controls were included in this study. The International Index of Erectile Function, Male Sexual Health Questionnaire, and self-reported time to orgasm were used to assess sexual function. Subjects underwent a 3-T fMRI study while viewing 3 video clips: a neutral control (NC), a positive emotional control (EC), and a sexual condition (SC). Each video sequence was repeated 5 times, with 50-second clips presented in a randomized fashion. fMRI data were analyzed in a block design manner to determine areas of differential brain activation between groups. The Allen Brain Atlas of gene expression in the human brain was used to identify signaling pathways in the areas of differential fMRI activation between the DO and control groups. Outcomes: The primary outcome was differential activation of fMRI neural activation between groups. Results: Analysis of differential activation in the SC compared with the NC and EC revealed increased activation in the right frontal operculum (P = .003), right prefrontal gyrus (P = .003), and inferior occipital gyrus (P = .003). Increased activation in the right fusiform gyrus of the occipital lobe and the right hippocampus (P = .0004) was seen in the DO group compared with controls. Using the Allen Atlas of Human Brain Expression, we identified corresponding neurotransmitter receptors to this region, including adenosine receptors, muscarinic and nicotinic cholinergic receptors, cannabinoid receptors, and dopamine receptors, among others. Clinical Implications: Lifelong DO in men may be due to abnormal neurotransmitter signaling leading to poor progression of arousal due to aberrant processing of sexual cues. Identification of neurotransmitter pathways by fMRI will aid the development of pharmacotherapeutic agents. Strengths & Limitations: Strengths of this study include the novel application of functional neuroimaging to investigate the pathogenesis of DO. Limitations include the small sample size, making this study exploratory in nature. Conclusion: This study revealed differences in brain activation on visualization of sexual stimuli in men with a history of DO compared with controls. Identified regions are rich in numerous neurotransmitter receptor subtypes and may be amenable to pharmacologic targeting to identify novel therapies for these men. Copyright (C) 2019, International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.