Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles.

INTRODUCTION: Sexual health, an integral component of overall well-being, is frequently compromised by common yet underdiagnosed sexual dysfunctions. Traditional interventions encompass pharmaceutical and psychological treatments. Unconventional therapies, like MDMA, offer hope for sexual dysfunction. This review delves into MDMA's effects on sexual responsiveness and its potential role in treating sexual dysfunction. OBJECTIVES: The purpose of this review is to elucidate effects of MDMA on different domains of the female and male sexual response cycles. METHODS: We conducted a systematic review on the effects of MDMA on each domain of the female and male sexual response cycles. PubMed, MEDLINE, and EMBASE were queried, and results were screened using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Search terms utilized were "MDMA" or "ecstasy" in combination with "desire," "arousal," "lubrication," "orgasm," "pleasure," "libido," "erection," and "ejaculation." Inclusion criteria for this review were MDMA use by study subjects and sexual outcomes in at least 1 domain of the female and/or male sexual response cycles were described and measured. Randomized controlled trials, cohort studies (both prospective and retrospective), surveys, and literature reviews published between January 2000 and June 2022 were included. Case reports and studies that did not address conditions of interest were excluded from analysis. Duplicated search results were screened out. The remaining studies were then read in full text to ensure they met inclusion and exclusion criteria for analysis. RESULTS: We identified 181 studies, of which 6 met criteria for assessment of the female sexual response cycle and 8 met criteria for assessment of the male sexual response cycle. Four of 6 studies reported increased sexual desire with MDMA use among women. Arousal and lubrication were improved with MDMA use in 3 of 4 studies, but they were not affected in 1 randomized control study. In men, 7 studies evaluated the effects of MDMA on desire and/or arousal, 5 studies measured impact on erection, 3 on orgasm, and 2 on ejaculation. Sixty percent of interview-based studies reported increased sexual desire in men, while 40% reported mixed or no effect. Two studies reported impairment of erection, 2 reported mixed effects, and 1 reported fear of erection impairment. In both men and women, all studies evaluating orgasm reported delay in achieving orgasm but increased intensity and pleasure if achieved. Primary outcome measures were variable and largely qualitative. CONCLUSION: Our findings suggest that MDMA generally increases sexual desire and intensifies orgasm when achieved. While producing conflicting evidence on sexual arousal in both sexes, MDMA may impair erectile and ejaculatory function in men.

Lumbar endoscopic spine surgery for persistent genital arousal disorder/genitopelvic dysesthesia resulting from lumbosacral annular tear-induced sacral radiculopathy.

BACKGROUND: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is characterized by distressing, abnormal genitopelvic sensations, especially unwanted arousal. In a subgroup of patients with PGAD/GPD, cauda equina Tarlov cyst-induced sacral radiculopathy has been reported to trigger the disorder. In our evaluation of lumbosacral magnetic resonance images in patients with PGAD/GPD and suspected sacral radiculopathy, some had no Tarlov cysts but showed lumbosacral disc annular tear pathology. AIM: The aims were 2-fold: (1) to utilize a novel multidisciplinary step-care management algorithm designed to identify a subgroup of patients with PGAD/GPD and lumbosacral annular tear-induced sacral radiculopathy who could benefit from lumbar endoscopic spine surgery (LESS) and (2) to evaluate long-term safety and efficacy of LESS. METHODS: Clinical data were collected on patients with PGAD/GPD who underwent LESS between 2016 and 2020 with at least 1-year follow-up. LESS was indicated because all had lumbosacral annular tear-induced sacral radiculopathy confirmed by our multidisciplinary management algorithm that included the following: step A, a detailed psychosocial and medical history; step B, noninvasive assessments for sacral radiculopathy; step C, targeted diagnostic transforaminal epidural spinal injections resulting in a temporary, clinically significant reduction of PGAD/GPD symptoms; and step D, surgical intervention with LESS and postoperative follow-up. OUTCOMES: Treatment outcome was based on the validated Patient Global Impression of Improvement, measured at postoperative intervals. RESULTS: Our cohort included 15 cisgendered women and 5 cisgendered men (mean ± SD age, 40.3 ± 16.8 years) with PGAD/GPD who fulfilled the criteria of lumbosacral annular tear-induced sacral radiculopathy based on our multidisciplinary management algorithm. Patients were followed for an average of 20 months (range, 12-37) post-LESS. Lumbosacral annular tear pathology was identified at multiple levels, the most common being L4-L5 and L5-S1. Twenty-two LESS procedures were performed in 20 patients. Overall, 80% (16/20) reported improvement on the Patient Global Impression of Improvement; 65% (13/20) reported improvement as much better or very much better. All patients were discharged the same day. There were no surgical complications. CLINICAL IMPLICATIONS: Among the many recognized triggers for PGAD/GPD, this subgroup exhibited lumbosacral annular tear-induced sacral radiculopathy and experienced long-term alleviation of symptoms by LESS. STRENGTHS AND LIMITATIONS: Strengths include long-term post-surgical follow-up and demonstration that LESS effectively treats patients with PGAD/GPD who have lumbosacral annular tear-induced sacral radiculopathy, as established by a multidisciplinary step-care management algorithm. Limitations include the small study cohort and the unavailability of a clinical measure specific for PGAD/GPD. CONCLUSION: LESS is safe and effective in treating patients with PGAD/GPD who are diagnosed with lumbosacral annular tear-induced sacral radiculopathy.

Hiding in plain sight? A review of post-convulsive leukocyte elevations.

During physiological stress responses such as vigorous exercise, emotional states of fear and rage, and asphyxia, the nervous system induces a massive release of systemic catecholamines that prepares the body for survival by increasing cardiac output and redirecting blood flow from non-essential organs into the cardiopulmonary circulation. A curious byproduct of this vital response is a sudden, transient, and redistributive leukocytosis provoked mostly by the resultant shear forces exerted by rapid blood flow on marginated leukocytes. Generalized convulsive seizures, too, result in catecholamine surges accompanied by similar leukocytoses, the magnitude of which appears to be rooted in semiological factors such as convulsive duration and intensity. This manuscript reviews the history, kinetics, physiology, and clinical significance of post-convulsive leukocyte elevations and discusses their clinical utility, including a proposed role in the scientific investigation of sudden unexpected death in epilepsy (SUDEP).

Orgasm and Related Disorders Depend on Neural Inhibition Combined With Neural Excitation.

INTRODUCTION: Prevalent models of sexual desire, arousal and orgasm postulate that they result from an excitatory process, whereas disorders of sexual desire, arousal and orgasm result from an inhibitory process based on psychosocial, pharmacological, medical, and other factors. But neuronal excitation and active neuronal inhibition normally interact at variable intensities, concurrently and continuously. We propose herein that in conjunction with neuronal excitation, neuronal inhibition enables the generation of the intense, non-aversive pleasure of orgasm. When this interaction breaks down, pathology can result, as in disorders of sexual desire, arousal, and orgasm, and in anhedonia and pain. For perspective, we review some fundamental behavioral and (neuro-) physiological functions of neuronal excitation and inhibition in normal and pathological processes. OBJECTIVES: To review evidence that the variable balance between neuronal excitation and active neuronal inhibition at different intensities can account for orgasm and its disorders. METHODS: We selected studies from searches on PubMed, Google Scholar, Dialnet, and SciELO for terms including orgasm, neuronal development, Wallerian degeneration, prenatal stress, parental behavior, sensorimotor, neuronal excitation, neuronal inhibition, sensory deprivation, anhedonia, orgasmic disorder, hypoactive sexual desire disorder, persistent genital arousal disorder, sexual pain. RESULTS: We provide evidence that the intensity of neuronal inhibition dynamically covaries concurrently with the intensity of neuronal excitation. Differences in these relative intensities can facilitate the understanding of orgasm and disorders of orgasm. CONCLUSION: Neuronal excitation and neuronal inhibition are normal, continuously active processes of the nervous system that are necessary for survival of neurons and the organism. The ability of genital sensory stimulation to induce concurrent neuronal inhibition enables the stimulation to attain the pleasurable, non-aversive, high intensity of excitation characteristic of orgasm. Excessive or deficient levels of neuronal inhibition relative to neuronal excitation may account for disorders of sexual desire, arousal and orgasm. Komisaruk BR, Rodriguez del Cerro MC. Orgasm and Related Disorders Depend on Neural Inhibition Combined With Neural Excitation. Sex Med Rev 2022;10:481-492.

Threshold for copulation-induced analgesia varies according to the ejaculatory endophenotypes in rats.

Analgesia may be modulated by multiple internal and external factors. In prior studies, copulatory-induced analgesia was demonstrated using the vocalization threshold to tail shock (VTTS) in male and female rats. Three ejaculatory endophenotypes have been characterized in male Wistar rats based upon their ejaculation latency (EL). Since intromissions and ejaculations produce analgesia, and these copulatory patterns are performed with different frequency depending on the male's ejaculatory endophenotype, we hypothesized that copulation-induced analgesia would vary in relation to these endophenotypes. In the present study, we used three groups according to the EL (medians): rapid ejaculators (236 s; n = 21), intermediate ejaculators (663.2 s; n = 20) and sluggish ejaculators (1582.2 s; n = 8). Our aim was to evaluate whether copulation-induced analgesia is related to the ejaculatory endophenotypes during two consecutive ejaculatory series (EJS). In the first EJS, the VTTS of the rapid ejaculators was significantly higher than that of intermediate and sluggish rats. At the onset of the second EJS, the VTTS of the rapid and intermediate ejaculators was significantly higher than that of the sluggish rats. No differences in VTTS were observed during the first or second post-ejaculatory intervals among the three groups. These findings provide evidence that the more intromissions that occurred per unit time, the higher was the level of analgesia.

Vagus nerve afferent stimulation: Projection into the brain, reflexive physiological, perceptual, and behavioral responses, and clinical relevance.

The afferent vagus nerves project to diverse neural networks within the brainstem and forebrain, based on neuroanatomical, neurophysiological, and functional (fMRI) brain imaging evidence. In response to afferent vagal stimulation, multiple homeostatic visceral reflexes are elicited. Physiological stimuli and both invasive and non-invasive electrical stimulation that activate the afferent vagus elicit perceptual and behavioral responses that are of physiological and clinical significance. In the present review, we address these multiple roles of the afferent vagus under normal and pathological conditions, based on both animal and human evidence.

Orgasm and Related Disorders Depend on Neural Inhibition Combined With Neural Excitation.

INTRODUCTION: Prevalent models of sexual desire, arousal and orgasm postulate that they result from an excitatory process, whereas disorders of sexual desire, arousal and orgasm result from an inhibitory process based on psychosocial, pharmacological, medical, and other factors. But neuronal excitation and active neuronal inhibition normally interact at variable intensities, concurrently and continuously. We propose herein that in conjunction with neuronal excitation, neuronal inhibition enables the generation of the intense, non-aversive pleasure of orgasm. When this interaction breaks down, pathology can result, as in disorders of sexual desire, arousal, and orgasm, and in anhedonia and pain. For perspective, we review some fundamental behavioral and (neuro-) physiological functions of neuronal excitation and inhibition in normal and pathological processes. OBJECTIVES: To review evidence that the variable balance between neuronal excitation and active neuronal inhibition at different intensities can account for orgasm and its disorders. METHODS: We selected studies from searches on PubMed, Google Scholar, Dialnet, and SciELO for terms including orgasm, neuronal development, Wallerian degeneration, prenatal stress, parental behavior, sensorimotor, neuronal excitation, neuronal inhibition, sensory deprivation, anhedonia, orgasmic disorder, hypoactive sexual desire disorder, persistent genital arousal disorder, sexual pain. RESULTS: We provide evidence that the intensity of neuronal inhibition dynamically covaries concurrently with the intensity of neuronal excitation. Differences in these relative intensities can facilitate the understanding of orgasm and disorders of orgasm. CONCLUSION: Neuronal excitation and neuronal inhibition are normal, continuously active processes of the nervous system that are necessary for survival of neurons and the organism. The ability of genital sensory stimulation to induce concurrent neuronal inhibition enables the stimulation to attain the pleasurable, non-aversive, high intensity of excitation characteristic of orgasm. Excessive or deficient levels of neuronal inhibition relative to neuronal excitation may account for disorders of sexual desire, arousal and orgasm.

The Use of Pramipexole to Treat Persistent Genital Arousal Disorder: A Case Report.

INTRODUCTION: Persistent Genital Arousal Disorder (PGAD) is defined as "spontaneous, intrusive, and unwanted genital arousal (tingling, throbbing, pulsating) in the absence of sexual interest and desire" and traditionally causes marked distress, embarrassment and shame. PGAD may be caused by starting, discontinuing, or making adjustments in certain antidepressants or other medications. AIM: To report the case of a 36- year- old woman with PGAD, likely due to changes in her psychiatric medications, who was treated with pramipexole and experienced improvement in her PGAD symptoms. METHODS: Patient self-report and literature review. Written informed consent was obtained from the patient. MAIN OUTCOME MEASURE: Improvement in PGAD symptoms. RESULTS: Patient reported improvement in her symptoms by "90%" on a low dose of pramipexole, although higher doses exacerbated her symptoms. CONCLUSIONS: It is likely that an effective treatment window exists for the treatment of PGAD with drugs that possess the ability to exert their control of dopaminergic transmission. This includes direct acting receptor agonists like pramipexole, which produce feedback inhibition. Limitations to their efficacy then involve co-treatments that counteract their ability to exert a dampening effect on hyperstimulated dopamine transmission. It is recommended that clinicians be aware of drugs taken by patients to treat psychiatric disorders that could induce PGAD symptoms, drugs recently discontinued where a rebound effect could lead to PGAD symptoms, and drug mechanisms that could counteract the effect of treatments for PGAD. Lynn BK, Grabenhorst C, Komisaruk BR, et al. The Use of Pramipexole to Treat Persistent Genital Arousal Disorder: A Case Report. Sex Med 2021;9:100372.

International Society for the Study of Women's Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD).

BACKGROUND: Persistent genital arousal disorder (PGAD), a condition of unwanted, unremitting sensations of genital arousal, is associated with a significant, negative psychosocial impact that may include emotional lability, catastrophization, and suicidal ideation. Despite being first reported in 2001, PGAD remains poorly understood. AIM: To characterize this complex condition more accurately, review the epidemiology and pathophysiology, and provide new nomenclature and guidance for evidence-based management. METHODS: A panel of experts reviewed pertinent literature, discussed research and clinical experience, and used a modified Delphi method to reach consensus concerning nomenclature, etiology, and associated factors. Levels of evidence and grades of recommendation were assigned for diagnosis and treatment. OUTCOMES: The nomenclature of PGAD was broadened to include genito-pelvic dysesthesia (GPD), and a new biopsychosocial diagnostic and treatment algorithm for PGAD/GPD was developed. RESULTS: The panel recognized that the term PGAD does not fully characterize the constellation of GPD symptoms experienced by patients. Therefore, the more inclusive term PGAD/GPD was adopted, which maintains the primacy of the distressing arousal symptoms and acknowledges associated bothersome GPD. While there are diverse biopsychosocial contributors, there is a common underlying neurologic basis attributable to spontaneous intense activity of the genito-pelvic region represented in the somatosensory cortex and its projections. A process of care diagnostic and treatment strategy was developed to guide the clinician, whenever possible, by localizing the symptoms as originating in any of five regions: (i) end organ, (ii) pelvis/perineum, (iii) cauda equina, (iv) spinal cord, and (v) brain. Psychological treatment strategies were considered critical and should be performed in conjunction with medical strategies. Pharmaceutical interventions may be used based on their site and mechanism of action to reduce patients' symptoms and the associated bother and distress. CLINICAL IMPLICATIONS: The process of care for PGAD/GPD uses a personalized, biopsychosocial approach for diagnosis and treatment. STRENGTHS AND LIMITATIONS: Strengths and Limitations: Strengths include characterization of the condition by consensus, analysis, and recommendation of a new nomenclature and a rational basis for diagnosis and treatment. Future investigations into etiology and treatment outcomes are recommended. The main limitations are the dearth of knowledge concerning this condition and that the current literature consists primarily of case reports and expert opinion. CONCLUSION: We provide, for the first time, an expert consensus review of the epidemiology and pathophysiology and the development of a new nomenclature and rational algorithm for management of this extremely distressing sexual health condition that may be more prevalent than previously recognized. Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women's Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med 2021;18:665-697.

How Does Our Brain Generate Sexual Pleasure?

We present herein an exploratory essay on sexual pleasure, in support of the objective of developing an evidence base of knowledge for the WAS Declaration of Sexual Rights. We have attempted to account for the feeling of erotic sexual pleasure, in terms of what is known about neuronal function. The brain regions that are activated during women's orgasm, and their perceptual and physiological roles, are compared with brain regions related to chemically induced euphoria and craving. The brain regions that are activated at orgasm match those that are activated by both euphoria and craving. Based on these findings, we propose that erotic, sensual feeling is a simultaneous activation of euphoria plus craving. The importance of sensory stimulation, proprioception, sensations, and feelings is emphasized by evidence that their disruption leads to pathologies. The process of buildup of excitation to a peak and then resolution is proposed as a basic "orgasmic" property of the nervous system shared by multiple systems, as in a sneeze, which we consider to be a non-genital orgasm. We postulate a process by which an excitation pattern feels pleasurable and - at higher intensity - euphoric, if it is congruent with an unconscious dynamic "template," but aversive and at higher intensity painful, to the extent that it is incongruent with the template. Under this formulation, peak neuronal excitation that is congruent with the unconscious, simultaneously "getting what is craved," generates orgasmic, erotic, sexual pleasure.

Brain Activity Unique to Orgasm in Women: An fMRI Analysis.

BACKGROUND: Although the literature on imaging of regional brain activity during sexual arousal in women and men is extensive and largely consistent, that on orgasm is relatively limited and variable, owing in part to the methodologic challenges posed by variability in latency to orgasm in participants and head movement. AIM: To compare brain activity at orgasm (self- and partner-induced) with that at the onset of genital stimulation, immediately before the onset of orgasm, and immediately after the cessation of orgasm and to upgrade the methodology for obtaining and analyzing functional magnetic resonance imaging (fMRI) findings. METHODS: Using fMRI, we sampled equivalent time points across female participants' variable durations of stimulation and orgasm in response to self- and partner-induced clitoral stimulation. The first 20-second epoch of orgasm was contrasted with the 20-second epochs at the beginning of stimulation and immediately before and after orgasm. Separate analyses were conducted for whole-brain and brainstem regions of interest. For a finer-grained analysis of the peri-orgasm phase, we conducted a time-course analysis on regions of interest. Head movement was minimized to a mean less than 1.3 mm using a custom-fitted thermoplastic whole-head and neck brace stabilizer. OUTCOMES: Ten women experienced orgasm elicited by self- and partner-induced genital stimulation in a Siemens 3-T Trio fMRI scanner. RESULTS: Brain activity gradually increased leading up to orgasm, peaked at orgasm, and then decreased. We found no evidence of deactivation of brain regions leading up to or during orgasm. The activated brain regions included sensory, motor, reward, frontal cortical, and brainstem regions (eg, nucleus accumbens, insula, anterior cingulate cortex, orbitofrontal cortex, operculum, right angular gyrus, paracentral lobule, cerebellum, hippocampus, amygdala, hypothalamus, ventral tegmental area, and dorsal raphe). CLINICAL TRANSLATION: Insight gained from the present findings could provide guidance toward a rational basis for treatment of orgasmic disorders, including anorgasmia. STRENGTHS AND LIMITATIONS: This is evidently the first fMRI study of orgasm elicited by self- and partner-induced genital stimulation in women. Methodologic solutions to the technical issues posed by excessive head movement and variable latencies to orgasm were successfully applied in the present study, enabling identification of brain regions involved in orgasm. Limitations include the small sample (N = 10), which combined self- and partner-induced stimulation datasets for analysis and which qualify the generalization of our conclusions. CONCLUSION: Extensive cortical, subcortical, and brainstem regions reach peak levels of activity at orgasm. Wise NJ, Frangos E, Komisaruk BR. Brain Activity Unique to Orgasm in Women: An fMRI Analysis. J Sex Med 2017;14:1380-1391.

A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts.

INTRODUCTION: Since 14 years of age, the patient had experienced extreme penile pain within seconds of initial sexual arousal through masturbation. Penile pain was so severe that he rarely proceeded to orgasm or ejaculation. After 7 years of undergoing multiple unsuccessful treatments, he was concerned for his long-term mental health and for his future ability to have relationships. AIM: To describe a novel collaboration among specialists in sexual medicine, neurophysiology, and spine surgery that led to successful management. METHODS: Collaborating health care providers conferred with the referring physician, patient, and parents and included a review of all medical records. MAIN OUTCOME MEASURE: Elimination of postpubertal intense penile pain during sexual arousal. RESULTS: The patient presented to our sexual medicine facility at 21 years of age. The sexual medicine physician identifying the sexual health complaint noted a pelvic magnetic resonance imaging report of an incidental sacral Tarlov cyst. A subsequent sacral magnetic resonance image showed four sacral Tarlov cysts, with the largest measuring 18 mm. Neuro-genital testing result were abnormal. The neurophysiologist hypothesized the patient's pain at erection was produced by Tarlov cyst-induced neuropathic irritation of sensory fibers that course within the pelvic nerve. The spine surgeon directed a diagnostic injection of bupivacaine to the sacral nerve roots and subsequently morphine to the conus medullaris of the spinal cord. The bupivacaine produced general penile numbness; the morphine selectively decreased penile pain symptoms during sexual arousal without blocking penile skin sensation. The collaboration among specialties led to the conclusion that the Tarlov cysts were pathophysiologically mediating the penile pain symptoms during arousal. Long-term follow-up after surgical repair showed complete symptom elimination at 18 months after treatment. CONCLUSION: This case provides evidence that (i) Tarlov cysts can cause sacral spinal nerve root radiculitis through sensory pelvic nerve and (ii) there are management benefits from collaboration among sexual medicine, neurophysiology, and spine surgery subspecialties. Goldstein I, Komisaruk BR, Rubin RS, et al. A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts. Sex Med 2017;5:e203-e211.

Access to Vagal Projections via Cutaneous Electrical Stimulation of the Neck: fMRI Evidence in Healthy Humans.

BACKGROUND: Stimulation of the vagus nerve via implanted electrodes is currently used to treat refractory epilepsy and depression. Recently, a non-invasive approach to vagal stimulation has demonstrated similar beneficial effects, but it remains unclear whether these effects are mediated via activation of afferent vagal fibers. OBJECTIVE: The present study was designed to ascertain whether afferent vagal projections can be accessed non-invasively by transcutaneous electrical stimulation of the antero-lateral surface of the neck, which overlies the course of the vagus nerve. METHODS: Thirteen healthy subjects underwent 2 fMRI scans in one session. Transcutaneous electrical stimulation was applied for 2 min to the right postero-lateral surface of the neck during scan #1 (control condition, sternocleidomastoid stimulation: "SCM") and to the right antero-lateral surface of the neck during scan #2 (experimental condition, non-invasive vagus nerve stimulation: "nVNS"). Two analyses were conducted using FSL (whole-brain and brainstem; corrected, p < 0.01) to determine whether nVNS activated vagal projections in the brainstem and forebrain, compared to baseline and SCM stimulation. RESULTS: Compared to baseline and control (SCM) stimulation, nVNS significantly activated primary vagal projections including: nucleus of the solitary tract (primary central relay of vagal afferents), parabrachial area, primary sensory cortex, and insula. Regions of the basal ganglia and frontal cortex were also significantly activated. Deactivations were found in the hippocampus, visual cortex, and spinal trigeminal nucleus. CONCLUSION: The present findings provide evidence in humans that cervical vagal afferents can be accessed non-invasively via transcutaneous electrical stimulation of the antero-lateral surface of the neck, which overlies the course of the nerve, suggesting an alternative and feasible method of stimulating vagal afferents.

Commentary on "The Evolutionary Origin of Female Orgasm" by M. Pavlicev and G. Wagner, 2016, J. Exp. Zool. (Mol. Dev. Evol.) 326(6):326-337.

Evidence is presented as an alternative to the authors' claims that in the course of evolution, a link between orgasm and ovulation has been lost in women, that evolutionary changes in clitoral anatomy underlie this loss, and that women's orgasm plays no significant role in reproduction.

Activation of sensory cortex by imagined genital stimulation: an fMRI analysis.

BACKGROUND: During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. OBJECTIVE: This study extends our previous findings by further characterizing how the brain differentially processes physical 'touch' stimulation and 'imagined' stimulation. DESIGN: Eleven healthy women (age range 29-74) participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions - imagined dildo self-stimulation and imagined speculum stimulation - were included to characterize the effects of erotic versus non-erotic imagery. RESULTS: Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex) and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region), and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. CONCLUSION: The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the 'reward system'. In addition, these results suggest a mechanism by which some individuals may be able to generate orgasm by imagery in the absence of physical stimulation.