Walter Everaerd

Salivary alpha amylase as marker for adrenergic activity during stress: Effect of betablockade

Free salivary cortisol is an established non-invasive marker of hypothalamus pituitary adrenal (HPA) axis activity. In contrast, such a well-characterized salivary marker for activity of the sympatho-adrenal medullar (SAM) system is still missing. As one potential candidate salivary alpha amylase (sAA) has been suggested. In humans increases in sAA levels have been observed in response to physiological and psychological stress. The present study aimed at exploring the effects of a pharmacological manipulation (betablockade) on sAA in the context of a stressful fMRI experiment on emotional information processing. Thirty young healthy subjects participated in a double blind group comparison study and received 80 mg of the betablocker (BB) propranolol or a placebo (PL). Salivary samples were obtained before and 90 min (pre-scan) and 135 min (post-scan) after drug application. In addition heart rate and blood pressure were assessed. During rest a significant drug by time interaction was observed, lowering sAA levels as well as heart rate and systolic blood pressure in the betablocker treatment group. During the scanning procedure, in which participants were confronted with highly negative emotional pictures, the significant increase in sAA levels in the PL group compared to the BB group persisted. No additional change was noticed in heart rate or blood pressure during scanning in the PL or BB group. The current pharmacological study in the human provides direct evidence for the sensitivity of sAA to changes in adrenergic activation, specifically in reaction to psychological stress.

Automatic processes and the appraisal of sexual stimuli: Toward an information processing model of sexual arousal

A model of sexual arousal is presented that highlights the interaction between automatic and controlled cognitive processes and proposes that different levels of cognitive processing can differentially affect subjective and physiological sexual arousal. In addition, two studies are presented in which the role of automatic processes was explored using a priming paradigm. Subjects were sexually functional men. In the first study an effect of priming was found on penile erection. Unexpectedly, responses were lower in sexual than in neutral trials. In the second study support was found, using a behavioral measure (decision time), for the notion that the meaning of sexual stimuli can be perceived in a fast, automatic manner. Priming was most successful at lower levels of stimulus accessibility. The model and experimental approach presented in this article render starting points for new research on response discordance, gender differences in the processing of sexual stimuli, and inhibition of sexual response.

Psychosocial stress impairs working memory at high loads: An association with cortisol levels and memory retrieval

Stress and cortisol are known to impair memory retrieval of well-consolidated declarative material. The effects of cortisol on memory retrieval may in particular be due to glucocorticoid (GC) receptors in the hippocampus and prefrontal cortex (PFC). Therefore, effects of stress and cortisol should be observable on both hippocampal-dependent declarative memory retrieval and PFC-dependent working memory (WM). In the present study, it was tested whether psychosocial stress would impair both WM and memory retrieval in 20 young healthy men. In addition, the association between cortisol levels and cognitive performance was assessed. It was found that stress impaired WM at high loads, but not at low loads in a Sternberg paradigm. High cortisol levels at the time of testing were associated with slow WM performance at high loads, and with impaired recall of moderately emotional, but not of highly emotional paragraphs. Furthermore, performance at high WM loads was associated with memory retrieval. These data extend previous results of pharmacological studies in finding WM impairments after acute stress at high workloads and cortisol-related retrieval impairments.

Memory for emotional events: differential effects of centrally versus peripherally acting β-blocking agents

Abstract Substantial evidence from animal research indicates that enhanced memory associated with emotional experiences involves activation of the β-adrenergic system. This hypothesis is further supported by the finding in human subjects that blockade of β-adrenergic receptors with propranolol selectively reduced memory for emotional events. In the present study, we compared the effects of propranolol, a lipid soluble drug which crosses the blood-brain barrier easily, with those of nadolol, a water soluble drug which crosses the blood-brain barrier to a considerably lesser extent, to determine whether the effect involved peripheral or central β-adrenergic receptors. The effects of these drugs, taken before subjects watched a slide show that was either emotionally arousing or relatively neutral in content, were tested 1 week later with a surprise memory test. Consistent with previous results, propranolol impaired memory (recall and recognition) in the subjects who saw the emotional version of the slide show. In contrast, nadolol did not impair memory of the emotional slide show. These results indicate that the blockade of central β-adrenergic receptors is responsible for the reduction in storage of emotional events. The results support the view that memory of a mild emotional event involves activation of central, but not necessarily peripheral β-adrenergic receptors.

Women's sexual and emotional responses to male- and female-produced erotica

Whether erotic films made by women are more arousing for women than erotic films made by men was studied. Forty-seven subjects were exposed to both a woman-made, female-initiated, and female-centered, erotic film excerpt and a man-made, male-initiated, and male-centered erotic film excerpt. Photoplethysmographic vaginal pulse amplitude was recorded continuously. Self-report ratings of sexual arousal and affective reactions were collected after each stimulus presentation. Contrary to expectation, genital arousal did not differ between films, although genital response to both films was substantial. Subjective experience of sexual arousal was significantly higher during the woman-made film. The man-made film evoked more feelings of shame, guilt, and aversion. Correlations between subjective experience of sexual arousal and photoplethysmographic measures of sexual arousal were nonsignificant. The largest contribution to female sexual excitement might result from the processing of stimulus-content and stimulus-meaning and not from peripheral vasocongestive feedback.

Noradrenaline mediates amygdala activation in men and women during encoding of emotional material

The amygdala is a pivotal structure in humans for encoding of emotional information, as shown by recent imaging studies. It is unknown which neurotransmitters are specifically involved in the human amygdala, although in animal studies noradrenaline was shown to be essential. In our study, participants received the betablocker propranolol (which blocks the noradrenergic response) or placebo when watching neutral to highly negative arousing pictures. Amygdala activation, monitored with functional magnetic resonance imaging (fMRI), increased with emotional intensity of the pictures under placebo condition. Betablockade selectively decreased amygdala activation for emotional pictures of the second highest category, but not for the highest or lower (neutral) category pictures. Two findings add to the existing knowledge in this area. First, the activation pattern in the amygdala under placebo condition shows a nonlinearity related to the emotional categories of the pictures. Second, propranolol disturbs this activation pattern in the amygdala. Explorations with respect to gender show a similar effect of betablockade on amygdala activation in both men and women, but a difference in its effect on long-term memory for emotional pictures. This study supports the hypothesis that the neurotransmitter noradrenaline also mediates amygdala activity in humans when processing emotional stimuli and that betablockers can disrupt the normal activation pattern in the amygdala.

Endogenous cortisol level interacts with noradrenergic activation in the human amygdala

Animal studies show that high cortisol levels exert their effect on stressful task performance via modulation of the amygdala. Availability of noradrenaline in this brain region appears to be a critical prerequisite for this effect. This relationship between noradrenaline and cortisol is explained by an animal model where the amygdala constitutes a crucial region for this interaction. In humans this model has not been extensively tested so far. In a previously reported study human subjects (aged 20.93+/-2.38) were scanned using fMRI when watching sets of emotional and neutral pictures after taking the beta-adrenergic antagonist propranolol or placebo. Stimulus sets consisted of 92 pictures, divided in four emotional categories that ranged from neutral scenes of domestic objects (CAT1) to extremely negative scenes of mutilation or accidents (CAT4). Confrontation with arousing emotional pictures, accompanied by increased noradrenaline levels, evoked increased amygdala activation under placebo but not under betablocker condition. This new and additional analysis of this data set was carried out to determine the effect of differential endogenous cortisol levels on amygdala activation. Cortisol levels during scanning were determined using salivary samples and subjects were post hoc divided in a High (n=14) and Low cortisol group (n=14). When subjects were watching emotional stimuli, presumably associated with enhanced noradrenaline (NA) levels, amygdala activation was contrasted between the two cortisol groups. We hypothesized that emotional stimuli would elicit more amygdala activation in the High than in the Low cortisol group. Here we demonstrate indeed a significant interaction effect of the endogenous cortisol level with increasing activation in the amygdala under placebo but not under betablocker condition, thereby extending the rodent based model of a synergistic effect of the two stress hormones to the human.

The enhancement of vaginal vasocongestion by sildenafil in healthy premenopausal women.

OBJECTIVE This study examined the effect of a single oral dose of sildenafil citrate (Viagra, Pfizer, Inc., New York, NY) on vaginal vasocongestion and subjective sexual arousal in healthy premenopausal women. METHODS Twelve women without sexual dysfunction were randomly assigned to receive either a single oral 50 mg dose of sildenafil or matching placebo in a first session and the alternate medication in a second session. Subjective measures of sexual arousal were assessed after participants had been exposed to erotic stimulus conditions. Vaginal vasocongestion was recorded continuously during baseline, neutral, and erotic stimulus conditions. At the end of each session, subjects were also asked to specify which treatment they suspected they had received. RESULTS Significant increases in vaginal vasocongestion were found with sildenafil treatment compared with placebo. There were no differences between treatments on subjective sexual arousal experience. Analyses by suspected treatment received found that significantly stronger sexual arousal and vaginal wetness were reported for the treatment that was believed to be sildenafil vs. the treatment that was believed to be placebo. The suspected treatment sequence was incorrect for half of the women. Sildenafil was well tolerated, with no evidence of significant adverse events. CONCLUSIONS Sildenafil was found to be effective in enhancing vaginal engorgement during erotic stimulus conditions in healthy women without sexual dysfunction but was not associated with an effect on subjective sexual arousal.

Performance demand and sexual arousal in women

Up to now, no experimental studies have inquired into the possible role of performance demand in female sexuality. The objective of this study is to investigate the effects of performance demand on sexual arousal in functional women, using explicit instructions. Forty-eight female subjects were asked to respond with maximum sexual arousal within 2 min, both during sexual fantasy and while watching an erotic film excerpt. Photoplethysmographic pulse amplitude was continuously recorded and self-report ratings of sexual arousal and affective reactions were collected after each erotic condition. Subjects were also instructed to continuously indicate their subjective sexual excitement during the conditions by means of a lever. Performance demand resulted in higher genital responses and was most effective in the fantasy condition. These results corroborate the findings for functional men. Although for both measures of subjective experience of sexual arousal performance demand yielded significantly higher ratings, this was conditioned by the order in which subjects were exposed to conditions. Women who masturbate with a mean frequency of 4 times a month reported higher subjective sexual arousal during performance demand conditions as compared with women who masturbate substantially more or who do not masturbate. Genital vasocogestion did not differ between masturbation-groups. Continuous subjective monitoring yielded lower correlations with vasocongestion than discrete ratings of sexual arousal and appears to be more sensitive to order effects.

Vaginismus, a component of a general defensive reaction. an investigation of pelvic floor muscle activity during exposure to emotion-inducing film excerpts in women with and without vaginismus

Abstract: This study investigates the mechanism underlying vaginismus, which may be part of a general defense mechanism. Exposure to a threatening situation will evoke an increase in muscle activity. This muscle reaction will not be restricted to the pelvic floor but will also occur in postural muscles, such as in the trapezius region. Women with and without vaginismus were exposed to four stimuli: excerpts from threatening, erotic, neutral and sexual-threatening films. Subjects were 45 physician- or self-referred patients with vaginismus and 32 controls with no sexual or pelvic floor complaints. The activity of the pelvic floor muscles and of the muscles in the trapezius region was recorded with surface electrodes. There were no differences between women with and without vaginistic reactions. EMG measurement of both the pelvic floor muscles and the trapezius muscle showed an increase in muscle activity during the threatening and sexual-threatening excerpts in women with and without vaginismus. This increase of involuntary pelvic floor muscle activity is part of a general defense mechanism that occurs during exposure to threatening situations. This reaction is not restricted to a situation with a sexual content. The results of this study shed new light on the concept of vaginismus as a primarily sexual dysfunction.