Corrélats neuraux de l’attirance sexuelle pédophile

The high frequency of sexual offenses against children and the severity of psychiatric disturbances that they contribute to generate warrant studying the mechanisms of pedophilic attraction to children, in order to improve therapeutic and preventive approaches. Emerging research based on functional neuroimaging techniques suggests that some brain regions are more activated in pedophilic patients than in healthy controls in response to non-pornographic images representing children. These regions include the cerebellum, the right orbital gyrus, the right inferior frontal gyrus, the left fusiform gyrus, the left anterior cingulate gyrus, the right and left insulae. By contrast, in response to these images, the activation of the right middle temporal gyrus is higher in controls. To help interpret these results, we present a neurophenomenological model of sexual arousal. This model comprises four coordinated components, i.e., cognitive, emotional, motivational, and physiological (autonomic and endocrinological). The cognitive component comprises a process of appraisal through which a stimulus is categorized as a sexual incentive and quantitatively evaluated as such. The emotional component includes the specific hedonic quality of sexual arousal, i.e., the pleasure associated with rising arousal and with the perception of specific bodily changes, such as penile tumescence. The motivational component comprises the processes that direct behavior to a sexual goal, including the perceived urge to express overt sexual behavior. The autonomic and endocrinological components include various responses (i.e., cardiovascular, respiratory, genital) leading the subject to a state of physiological readiness for sexual behavior. These four components are conceived as closely interrelated and coordinated. Finally, inhibitory processes comprise: 1) processes that are active between periods of sexual arousal and that prevent its emergence; we have suggested that this type of inhibitory control is exerted by regions of the temporal lobes where activity decreases in response to visual sexual stimuli; 2) cognitive processes that may – at least in patients with decreased sexual desire – devalue the sexual relevance of visual sexual stimuli; we have proposed that this type of control is mediated by the medial orbitofrontal cortex; and 3) processes that control the overt behavioral expression of sexual arousal, once it has begun to develop; we have proposed that the head of the right caudate nucleus participates in this function. It is likely that advances in functional neuroimaging studies of pedophilia will lead to relevant results regarding judicial issues and cases. These studies should be better organized through setting up a platform dedicated to clinical and research work in this area.     

Brain processing of visual sexual stimuli in men with hypoactive sexual desire disorder

Although hypoactive sexual desire disorder (HSDD) is a common condition and has long been hypothesized to result from malfunctions of the cerebral control mechanisms that adjust the level of sexual motivation, very little is known about the pathophysiology of this disorder. The primary objective was to identify in patients with HSDD brain regions where functional perturbations disrupt the regulation of sexual motivation. We used positron emission tomography to compare seven male patients with HSDD with eight healthy men on their regional cerebral blood flow responses to visual sexual stimuli (VSS) of graded intensity. Statistical Parametric Mapping was used to locate brain regions that demonstrated a differential activation (or deactivation) across the groups. Whereas in control subjects the medial orbitofrontal cortex showed a deactivation in response to VSS, in HSDD patients there was an abnormally maintained activity of this region, which has been implicated in the inhibitory control of motivated behavior. By contrast, the reverse pattern-activation in control subjects, deactivation or unchanged activity in patients-was found in the secondary somatosensory cortex and inferior parietal lobules, regions mediating emotional and motor imagery processes, as well as in those areas of the anterior cingulate gyrus and of the frontal lobes that are involved in premotor processes.     

Bioavailable Testosterone as a Correlate of Cognition, Psychological Status, Quality of Life, and Sexual Function in Aging Males: Implications for Testosterone Replacement Therapy

Andropause is a syndrome described in aging males, is composed of a constellation of physical, sexual, and emotional symptoms, and is thought to be related to declining concentrations of serum testosterone. Numerous studies of testosterone replacement therapy in elderly hypogonadal males have documented the physical benefits of such treatment, but have failed to assess cognition, psychological functioning, and quality of life. Male outpatients greater or equal to 55 years of age completed cognitive, psychological, sexual, and quality of life assessments. A serum sample was provided for bioavailable testosterone assay. The associations between bioavailable testosterone concentrations and neuropsychological testing were assessed using Spearman rank correlation. Overall, bioavailable testosterone was not an important determinant of cognitive, psychological, or sexual functioning or of quality of life. The implications for future studies involving testosterone replacement therapy are discussed.     

Neuroimaging studies of mood disorders.

Neuroimaging studies of major depression have identified neurophysiologic abnormalities in multiple areas of the orbital and medial prefrontal cortex, the amygdala, and related parts of the striatum and thalamus. Some of these abnormalities appear mood state-dependent and are located in regions where cerebral blood flow increases during normal and other pathologic emotional states. These neurophysiologic differences between depressives and control subjects may thus implicate areas where physiologic activity changes to mediate or respond to the emotional, behavioral, and cognitive manifestations of major depressive episodes. Other abnormalities persist following symptom remission, and are found in orbital and medial prefrontal cortex areas where postmortem studies demonstrate reductions in cortex volume and histopathologic changes in primary mood disorders. These areas appear to modulate emotional behavior and stress responses, based upon evidence from brain mapping, lesion analysis, and electrophysiologic studies of humans and/or experimental animals. Dysfunction involving these regions is thus hypothesized to play a role in the pathogenesis of depressive symptoms. Taken together, these findings implicate interconnected neural circuits in which pathologic patterns of neurotransmission may result in the emotional, motivational, cognitive, and behavioral manifestations of primary and secondary affective disorders.     

Neural correlates of emotional recognition memory in schizophrenia: effects of valence and arousal

Schizophrenia patients are often impaired in their memory for emotional events compared with healthy subjects. Investigations of the neural correlates of emotional memory in schizophrenia patients are scarce in the literature. The present study aimed to compare cerebral activations in schizophrenia patients and healthy controls during memory retrieval of emotional images that varied in both valence and arousal. In a study with functional magnetic resonance imaging, 37 schizophrenia patients were compared with 37 healthy participants while performing a yes/no recognition paradigm with positive, negative (differing in arousal intensity) and neutral images. Schizophrenia patients performed worse than healthy controls in all experimental conditions. They showed less cerebral activation in limbic and prefrontal regions than controls during retrieval of negatively valenced stimuli, but had a similar pattern of brain activation compared with controls during retrieval of positively valenced stimuli (particularly in the high arousal condition) in the cerebellum, temporal lobe and prefrontal cortex. Both groups demonstrated increased brain activations in the high relative to low arousing conditions. Our results suggest atypical brain function during retrieval of negative pictures, but intact functional circuitry of positive affect during episodic memory retrieval in schizophrenia patients. The arousal data revealed that schizophrenia patients closely resemble the control group at both the behavioral and neurofunctional level.     

Monoamines and neurosteroids in sexual function during induced hypogonadism in healthy men

CONTEXT: Although the behavioral effects of high-dose androgen administration may involve alterations in serotonergic activity, few studies have investigated the impact of androgen withdrawal on the central nervous system in humans. OBJECTIVE: To examine the effects of pharmacologically induced hypogonadism on several cerebrospinal fluid (CSF) systems that could mediate the behavioral concomitants of hypogonadism. DESIGN: Double-blind assessment of the effects of the short-term induction of hypogonadism and subsequent replacement with testosterone and placebo in a crossover design. SETTING: National Institutes of Health, Bethesda, Md. PARTICIPANTS: Twelve healthy male volunteers. INTERVENTIONS: We administered the gonadotropin-releasing hormone agonist leuprolide acetate (7.5 mg intramuscularly every 4 weeks) to the healthy male volunteers, creating a hypogonadal state, and then either replaced testosterone (200 mg intramuscularly) or administered a placebo every 2 weeks for 1 month. MAIN OUTCOME MEASURES: Mood and behavioral symptoms were monitored with daily self-ratings, and lumbar punctures were performed during both hypogonadal (placebo) and testosterone-replaced conditions for CSF levels of steroids and monoamine metabolites. RESULTS: The CSF testosterone, dihydrotestosterone, and androsterone levels were significantly lower during hypogonadism (P=.002, .04, and .046, respectively), but no significant changes were observed in CSF measures of 5-hydroxyindoleacetic acid, homovanillic acid, dehydroepiandrosterone, or pregnenolone. Decreased sexual interest was observed during the hypogonadal state compared with both baseline and testosterone replacement (P=.009) and correlated significantly with CSF measures of androsterone during both hypogonadism and testosterone replacement (r = -0.76 and -0.81, respectively; P<.01). Moreover, the change in severity of decreased sexual interest correlated significantly with the change in CSF androsterone levels between testosterone replacement and hypogonadism (r = -0.68; P<.05). The CSF 5-hydroxyindoleacetic acid and homovanillic acid levels did not correlate significantly with any behavioral or CSF measure. CONCLUSION: These data suggest that the neurosteroid androsterone contributes to the regulation of sexual function in men.     

Self-related processing in the sexual domain: a parametric event-related fMRI study reveals neural activity in ventral cortical midline structures

Self-related processing, reflecting the evaluation of environmental signals with regard to personal relevance, is fundamental for decision-making and subsequent behavioral responses. While self-related processing has already been investigated in several domains, one important domain, the sexual domain, has been spared so far. Recent imaging studies suggest that self-related processing in different domains involves common regions in medial orbitofrontal and prefrontal cortex, the so-called ventral cortical midline structures (CMS). However, the same regions have also been implicated in sexual arousal, especially with regard to emotional processing in sexual arousal. Therefore it remains unclear whether this involvement of ventral cortical midline regions reflects emotional processing in sexual arousal or associated self-relatedness. We here report data from a parametric event-related fMRI study that investigated the neural correlates of self-related processing in sexual arousal, using erotic pictures from the International Affective Picture System. It was found that self-related activity associated with sexual arousal showed neural activity in ventral CMS regions such as the venteromedial prefrontal cortex (VMPFC) and the perigenual anterior cingulate cortex (PACC), while self-related activity not associated with sexual arousal showed neural activity in the dorsomedial prefrontal cortex (DMPFC). Our study indicates that self-relatedness may be considered a crucial component in sexual arousal that is mediated by neural activity in ventral cortical midline structures.     

Brain processing of visual sexual stimuli in human males

Despite its critical sociobiological importance, the brain processing of visual sexual stimuli has not been characterized precisely in human beings. We used Positron Emission Tomography (PET) to investigate responses of regional cerebral blood flow (rCBF) in nine healthy males presented with visual sexual stimuli of graded intensity. Statistical Parametric Mapping was used to locate brain regions whose activation was associated with the presentation of the sexual stimuli and was correlated with markers of sexual arousal. The claustrum, a region whose function had been unclear, displayed one of the highest activations. Additionally, activations were recorded in paralimbic areas (anterior cingulate gyrus, orbito-frontal cortex), in the striatum (head of caudate nucleus, putamen), and in the posterior hypothalamus. By contrast, decreased rCBF was observed in several temporal areas. Based on these results, we propose a model of the brain processes mediating the cognitive, emotional, motivational, and autonomic components of human male sexual arousal.     

The functional neuroanatomy of male psychosexual and physiosexual arousal: A quantitative meta‐analysis

Reproductive behavior is mandatory for conservation of species and mediated by a state of sexual arousal (SA), involving both complex mental processes and bodily reactions. An early neurobehavioral model of SA proposes cognitive, emotional, motivational, and autonomic components. In a comprehensive quantitative meta‐analysis on previous neuroimaging findings, we provide here evidence for distinct brain networks underlying psychosexual and physiosexual arousal. Psychosexual (i.e., mental sexual) arousal recruits brain areas crucial for cognitive evaluation, top‐down modulation of attention and exteroceptive sensory processing, relevance detection and affective evaluation, as well as regions implicated in the representation of urges and in triggering autonomic processes. In contrast, physiosexual (i.e., physiological sexual) arousal is mediated by regions responsible for regulation and monitoring of initiated autonomic processes and emotions and for somatosensory processing. These circuits are interconnected by subcortical structures (putamen and claustrum) that provide exchange of sensorimotor information and crossmodal processing between and within the networks. Brain deactivations may imply attenuation of introspective processes and social cognition, but be necessary to release intrinsic inhibition of SA. Hum Brain Mapp 35:1404–1421, 2014. © 2013 Wiley Periodicals, Inc.     

Self-related processing in the sexual domain: A parametric event-related fMRI study reveals neural activity in ventral cortical midline structures

Abstract

Self-related processing, reflecting the evaluation of environmental signals with regard to personal relevance, is fundamental for decision-making and subsequent behavioral responses. While self-related processing has already been investigated in several domains, one important domain, the sexual domain, has been spared so far.

Recent imaging studies suggest that self-related processing in different domains involves common regions in medial orbitofrontal and prefrontal cortex, the so-called ventral cortical midline structures (CMS). However, the same regions have also been implicated in sexual arousal, especially with regard to emotional processing in sexual arousal. Therefore it remains unclear whether this involvement of ventral cortical midline regions reflects emotional processing in sexual arousal or associated self-relatedness. We here report data from a parametric event-related fMRI study that investigated the neural correlates of self-related processing in sexual arousal, using erotic pictures from the International Affective Picture System. It was found that self-related activity associated with sexual arousal showed neural activity in ventral CMS regions such as the venteromedial prefrontal cortex (VMPFC) and the perigenual anterior cingulate cortex (PACC), while self-related activity not associated with sexual arousal showed neural activity in the dorsomedial prefrontal cortex (DMPFC). Our study indicates that self-relatedness may be considered a crucial component in sexual arousal that is mediated by neural activity in ventral cortical midline structures.     

The male menopause and mood: testosterone decline and depression in the aging male--is there a link?

The objective of this study was to review the literature on the hormonal changes that occur in aging males in order to determine if testosterone declines in relation to depressed mood and if testosterone might prove useful in treatment of depression. Pertinent articles were identified through a MEDLINE search from 1966 to 1999 and by careful review of the bibliographies of articles most relevant to the topic. There is a moderate decline of total testosterone and more significant decline of bioavailable testosterone in aging males. Elderly males who are depressed appear to have the lowest testosterone levels. In eugonadal males, testosterone replacement does not have a significant effect on mood; in hypogonadal males, some studies show an effect whereas others do not. In several small studies of depressed hypogonadal males, testosterone was effective in alleviating depression. Major side effects of testosterone include increased hematocrit and potential effects on the prostate and lipid metabolism. Testosterone replacement as primary or adjuvant treatment of depression may prove useful in elderly, hypogonadal males who fail to respond to conventional antidepressants. Further studies are needed to confirm these initial impressions.     

Relationship between physical and psychosocial dysfunction in Mexican patients with vertigo: a cross-cultural validation of the vertigo symptom scale

The Vertigo Symptom Scale (VSS) was designed to assess and differentiate symptoms of: (a) balance disorder; and (b) somatic anxiety and autonomic arousal in patients complaining of dizziness and vertigo. Although it has been translated for use in countries other than the UK, where it was originally developed, its validity in different languages and cultures has not previously been evaluated. This study examined the structure, reliability, and discriminative power of a Spanish translation of the VSS administered to a Mexican sample of 172 dizzy patients and 40 healthy controls. Scores on the two subscales of the VSS not only discriminated between patients and controls, but were also sensitive to differences between patient groups classified on the basis of diagnosis, test results, and occupational disability. The pattern of intercorrelations between symptoms, anxiety, depression, and handicap in the Mexican sample was almost identical to that observed in the original UK sample.     

Categorization and evaluation of emotional faces in psychopathic women

Psychopathic individuals have been shown to respond less strongly than normal controls to emotional stimuli. Data about their ability to judge emotional facial expressions are inconsistent and limited to males. To measure categorical and dimensional evaluations of emotional facial expressions in psychopathic and non-psychopathic women, 13 female psychopathic forensic inpatients, 15 female non-psychopathic forensic inmates and 16 female healthy participants were tested in an emotion-categorizing task. Emotional facial expressions were presented briefly (33 ms) or until buttonpress. Participants were to classify emotional expressions, and to rate their valence and arousal. Group differences in categorization were observed at both presentation times. Psychopathic patients performed worst with briefly presented sad expressions. Moreover, their dimensional evaluation resulted in less positive ratings for happy expressions and less arousal for angry expressions compared with the responses of non-psychopathic and normal subjects. Results shed light on the mechanism possibly underlying the emotional deficits in psychopathic women.     

Hormonal and genetic influences on arousal--sexual and otherwise.

Genetic influences on lordosis, a mammalian social behavior, are amenable for study because of the relative simplicity of both stimuli and response. The neural circuit for lordosis involves a supraspinal loop, which is controlled by an estrogen- and progesterone-dependent signal from the medial hypothalamus and results in heightened sexual motivation. In turn, this involves elevated states of arousal, defined by increased sensory alertness, motor activity and emotional reactivity. Mice in which the gene encoding the alpha form of the estrogen receptor (ERalpha) has been knocked out show that ERalpha is crucial for lordosis behavior. Comparing ERalpha-, ERbeta- and double knockouts reveals that different patterns of sexual behaviors in mice require different patterns of ER activity. Understanding how hormonal and genetic effects on deep motivational and arousal processes contribute to their effects on specific sexual and aggressive behaviors pose significant challenges for mouse functional genomics.     

Endocrine, psychological and genital response to sexual arousal in men

The endocrine, genital, and cognitive--affective responses of sexually functional men were compared under sexually arousing and non-arousing conditions. Sexually aroused subjects showed significantly higher serum luteinizing hormone concentrations than non-aroused subjects. Testosterone concentration was correlated with higher levels of penile response, but it did not prime further sexual arousal. Cortisol and prolactin concentrations decreased in both groups, more in the non-aroused group, and appeared to both inhibit and facilitate sexual response, depending on the level of anxiety reported by the subjects. Cortisol was correlated with self-reported worry, and testosterone with relaxation. These results support a multidimensional approach to the endocrine study of sexual arousal that includes both cognitive and genital response components.     

Social and motivational functioning is not critically dependent on feedback of autonomic responses: neuropsychological evidence from patients with pure autonomic failure

Social, emotional and motivational behaviours are associated with production of automatic bodily responses. Re-representation in the brain through feedback of autonomic and skeletomuscular arousal is proposed to underlie “feeling states”. These influence emotional judgments and bias motivational decision-making and guide social interactions. Consistent with this hypothesis, dissocial behaviour and deficits on emotional and motivation tasks are associated with blunted bodily responses in patients with orbitofrontal brain lesions or developmental psychopathy. To determine the critical dependence of social and emotional behaviours on bodily responses mediated by the autonomic nervous system, we examined patients with pure autonomic failure (PAF), a peripheral denervation of autonomic neurons with onset in middle age.

Compared to healthy subjects, PAF patients were unimpaired on tests of motivational decision-making (Iowa Gambling Task), recognition of emotional facial expressions, Theory of Mind Tasks and tests of social cognition. Only on a test of emotional attribution, which is perhaps more sensitive to subjective feeling states, did PAF patients score worse than the comparison group, though there was no evidence that this deficit was specific to a discrete emotion and requires further validation.

These findings suggest that emotional and social functioning is not critically tied to on-going experience of autonomic arousal state, Acquisition of autonomic failure late in life may protect against maladaptive social behaviour through established behavioural responses that may be associated with central “as if” representations.     

Neural mechanisms of autonomic, affective, and cognitive integration

Influential theoretical models propose a central role for afferent information from the body in the expression of emotional feeling states. Feedback representations of changing states of bodily arousal influence learning and facilitate concurrent and prospective decision-making. Functional neuroimaging studies have increased understanding of brain mechanisms that generate changes in autonomic arousal during behavior and those which respond to internal feedback signals to influence subjective feeling states. In particular, anterior cingulate cortex is implicated in generating autonomic changes, while insula and orbitofrontal cortices may be specialized in mapping visceral responses. Independently, ventromedial prefrontal cortex is recognized to support processes of internal (self-) reference that predominate in states of rest and disengagement and which putatively serve as a benchmark for dynamic interactions with the environment. Lesion data further highlight the integrated role of these cortical regions in autonomic and motivational control. In computational models of control, forward (efference copies) and inverse models are proposed to enable prediction and correction of action and, by extension, the interpretation of the behavior of others. It is hypothesized that the neural substrate for these processes during motivational and affective behavior lies within the interactions of anterior cingulate, insula, and orbitofrontal cortices. Generation of visceral autonomic correlates of control reinforce experiential engagement in simulatory models and underpin concepts such as somatic markers to bridge the dualistic divide.     

Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial

BACKGROUND: Symptoms of male hypogonadism include low libido, fatigue, and dysphoria and are alleviated with testosterone replacement. The prevalence of major depressive disorder (MDD) in hypogonadal men is not known, nor is the antidepressant efficacy of testosterone replacement in depressed, hypogonadal men. METHOD: A 6-week double-blind, placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: Thirty patients were randomly assigned to an intervention; 13 received testosterone, and 17 received placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/-50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received testosterone achieved normalization of their testosterone levels. The HAM-D scores decreased in both testosterone and placebo groups, and there were no significant between-group differences: reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo. Response rate, defined as a 50% or greater reduction in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in sexual function (p = .02). CONCLUSION: In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.     

Effects of dialectic-behavioral-therapy on the neural correlates of affective hyperarousal in borderline personality disorder

BACKGROUND: Affective hyperarousal is the hallmark of borderline personality disorder (BPD) and the main target for dialectic-behavioral-therapy (DBT). This pilot study examined whether improved regulation of affective arousal following DBT translates into changes in relevant neural systems. METHODS: We applied five sequential fMRI scans over a 12-week in-patient treatment program. Six female BPD patients and six controls were included in an event-related fMRI design which induced emotional arousal through standardized images. In addition to analyzing valence-based stimulus categories over time, the study assessed the modulation of hemodynamic responses through emotional arousal by means of parametric HRF modulation with self-ratings of stimulus dependent arousal. RESULTS: BPD data revealed a decreasing hemodynamic response to negative stimuli in the right-sided anterior cingulate, temporal and posterior cingulate cortices as well as in the left insula. In addition, these areas displayed a continuous decrease in HRF modulation through individual arousal in BPD patients. Moreover the four DBT responders displayed reduction of HRF modulation in the left amygdala and both hippocampi. CONCLUSIONS: fMRI designs that use multiple repeated measures are suitable for application in therapy research. In our pilot study DBT treatment was accompanied by neural changes in limbic and cortical regions resembling those reported on psychotherapy effects in other mental disorders.