Evidence for Persistence of Sexual Evaluative Learning Effects.

INTRODUCTION: Several studies demonstrated that genital arousal and enhanced positive affect toward neutral stimuli due to sexual conditioning did not extinguish during a brief extinction phase, but other studies showed contrasting results. Possible resistance to extinction of conditioned human sexual response has, however, not been studied using extensive extinction trials. AIM: To study resistance to extinction of conditioned sexual response in men and women. METHODS: Healthy sexually functional men (N = 34) and women (N = 32) participated in a differential conditioning experiment, with neutral pictures as conditioned stimuli (CSs) and genital vibrostimulation as unconditioned stimulus. Only one CS (the CS+) was followed by the unconditioned stimulus during the acquisition phase. MAIN OUTCOME MEASURE: Penile circumference and vaginal pulse amplitude were assessed, and ratings of affective value and subjective sexual arousal were obtained. In addition, a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. RESULTS: Men and women rated the CS+ as more positive than the CS- during all 24 extinction trials and demonstrated a slight tendency to approach the CS+ directly after the extinction procedure. Participants rated the CS+ as more sexually arousing than the CS- during 20 extinction trials. No evidence was found for conditioned genital sexual response. CLINICAL IMPLICATIONS: Learned sexual evaluations may be difficult to modify through an extinction procedure; therefore, unwanted but persistent subjective sexual evaluations may be better targeted by interventions such as the deployment of emotion regulation strategies. STRENGTH & LIMITATIONS: Extensive extinction trials were used; however, only relatively short-term effects within one experimental session were studied and there was no (unpaired) control condition. CONCLUSION: The results provide evidence that conditioned sexual likes are relatively persistent, also at the behavioral level. Both S, Brom M, Laan E, et al. Evidence for Persistence of Sexual Evaluative Learning Effects. J Sex Med 2020;17:505-517.

Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials.

BACKGROUND: In women, low sexual desire and/or sexual arousal can lead to sexual dissatisfaction and emotional distress, collectively defined as female sexual interest/arousal disorder (FSIAD). Few pharmaceutical treatment options are currently available. AIM: To investigate the efficacy and safety of 2 novel on-demand pharmacologic treatments that have been designed to treat 2 FSIAD subgroups (women with low sensitivity for sexual cues and women with dysfunctional over-activation of sexual inhibition) using a personalized medicine approach using an allocation formula based on genetic, hormonal, and psychological variables developed to predict drug efficacy in the subgroups. METHODS: 497 women (21-70 years old) with FSIAD were randomized to 1 of 12 8-week treatment regimens in 3 double-blinded, randomized, placebo-controlled, dose-finding studies conducted at 16 research sites in the United States. Efficacy and safety of the following on-demand treatments was tested: placebo, testosterone (T; 0.5 mg), sildenafil (S; 50 mg), buspirone (B; 10 mg) and combination therapies (T 0.25 mg + S 25 mg, T 0.25 mg + S 50 mg, T 0.5 mg + S 25 mg, T 0.5 mg + S 50 mg, and T 0.25 mg + B 5 mg, T 0.25 mg + B 10 mg, T 0.5 mg + B 5 mg, T 0.5 mg + B 10 mg). OUTCOMES: The primary efficacy measure was the change in satisfying sexual events (SSEs) from the 4-week baseline to the 4-week average of the 8-week active treatment period after medication intake. For the primary end points, the combination treatments were compared with placebo and the respective monotherapies on this measure. RESULTS: In women with low sensitivity for sexual cues, 0.5 mg T + 50 mg S increased the number of SSEs from baseline compared with placebo (difference in change [Δ] = 1.70, 95% CI = 0.57-2.84, P = .004) and monotherapies (S: Δ = 1.95, 95% CI = 0.44-3.45, P = .012; T: Δ = 1.69, 95% CI = 0.58-2.80, P = .003). In women with overactive inhibition, 0.5 mg T + 10 mg B increased the number of SSEs from baseline compared with placebo (Δ = 0.99, 95% CI = 0.17-1.82, P = .019) and monotherapies (B: Δ = 1.52, 95% CI = 0.57-2.46, P = .002; T: Δ = 0.98, 95% CI = 0.17-1.78, P = .018). Secondary end points followed this pattern of results. The most common drug-related side effects were flushing (T + S treatment, 3%; T + B treatment, 2%), headache (placebo treatment, 2%; T + S treatment, 9%), dizziness (T + B treatment, 3%), and nausea (T + S treatment, 3%; T + B treatment, 2%). CLINICAL IMPLICATIONS: T + S and T + B are promising treatments for women with FSIAD. STRENGTHS AND LIMITATIONS: The data were collected in 3 well-designed randomized clinical trials that tested multiple doses in a substantial number of women. The influence of T + S and T + B on distress and the potentially sustained improvements after medication cessation were not investigated. CONCLUSIONS: T + S and T + B are well tolerated and safe and significantly increase the number of SSEs in different FSIAD subgroups. Tuiten A, van Rooij K, Bloemers J, et al. Efficacy and Safety of On-Demand Use of 2 Treatments Designed for Different Etiologies of Female Sexual Interest/Arousal Disorder: 3 Randomized Clinical Trials. J Sex Med 2018;15:201-216.

The Influence of Emotion Upregulation on the Expectation of Sexual Reward.

INTRODUCTION: Emotion regulation research has shown successful altering of unwanted aversive emotional reactions. Cognitive strategies can also downregulate expectations of reward arising from conditioned stimuli, including sexual stimuli. However, little is known about whether such strategies can also efficiently upregulate expectations of sexual reward arising from conditioned stimuli, and possible gender differences therein. AIM: The present study examined whether a cognitive upregulatory strategy could successfully upregulate sexual arousal elicited by sexual reward-conditioned cues in men and women. METHODS: Men (n = 40) and women (n = 53) participated in a study using a differential conditioning paradigm, with genital vibrostimulation as unconditioned stimulus (US) and sexually relevant pictures as conditional stimuli. MAIN OUTCOME MEASURES: Penile circumference and vaginal pulse amplitude were assessed and ratings of US expectancy, affective value, and sexual arousal value were obtained. Also a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. RESULTS: Evidence was found for emotion upregulation to increase genital arousal response in the acquisition phase in both sexes, and to enhance resistance to extinction of conditioned genital responding in women. In men, the emotion upregulatory strategy resulted in increased conditioned positive affect. CONCLUSION: The findings support that top-down modulation may indeed influence conditioned sexual responses. This knowledge may have implications for treating disturbances in sexual appetitive responses, such as low sexual arousal and desire.

d-Cycloserine reduces context specificity of sexual extinction learning.

BACKGROUND: d-Cycloserine (DCS) enhances extinction processes in animals. Although classical conditioning is hypothesized to play a pivotal role in the aetiology of appetitive motivation problems, no research has been conducted on the effect of DCS on the reduction of context specificity of extinction in human appetitive learning, while facilitation hereof is relevant in the context of treatment of problematic reward-seeking behaviors. METHODS: Female participants were presented with two conditioned stimuli (CSs) that either predicted (CS+) or did not predict (CS-) a potential sexual reward (unconditioned stimulus (US); genital vibrostimulation). Conditioning took place in context A and extinction in context B. Subjects received DCS (125mg) or placebo directly after the experiment on day 1 in a randomized, double-blind, between-subject fashion (Placebo n=31; DCS n=31). Subsequent testing for CS-evoked conditioned responses (CRs) in both the conditioning (A) and the extinction context (B) took place 24h later on day 2. Drug effects on consolidation were then assessed by comparing the recall of sexual extinction memories between the DCS and the placebo groups. RESULTS: Post learning administration of DCS facilitates sexual extinction memory consolidation and affects extinction's fundamental context specificity, evidenced by reduced conditioned genital and subjective sexual responses, relative to placebo, for presentations of the reward predicting cue 24h later outside the extinction context. CONCLUSIONS: DCS makes appetitive extinction memories context-independent and prevents the return of conditioned response. NMDA receptor glycine site agonists may be potential pharmacotherapies for the prevention of relapse of appetitive motivation disorders with a learned component.

Extinction of aversive classically conditioned human sexual response.

INTRODUCTION: Research has shown that acquired subjective likes and dislikes are quite resistant to extinction. Moreover, studies on female sexual response demonstrated that diminished genital arousal and positive affect toward erotic stimuli due to aversive classical conditioning did not extinguish during an extinction phase. Possible resistance to extinction of aversive conditioned sexual responses may have important clinical implications. However, resistance to extinction of aversive conditioned human sexual response has not been studied using extensive extinction trials. AIM: This article aims to study resistance to extinction of aversive conditioned sexual responses in sexually functional men and women. METHODS: A differential conditioning experiment was conducted, with two erotic pictures as conditioned stimulus (CSs) and a painful stimulus as unconditioned stimuli (USs). Only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase. MAIN OUTCOME MEASURE: Penile circumference and vaginal pulse amplitude were assessed, and ratings of affective value and subjective sexual arousal were obtained. Also, a stimulus response compatibility task was included to assess automatic approach and avoidance tendencies. RESULTS: Men and women rated the CS+ more negative as compared with the CS-. During the first trials of the extinction phase, vaginal pulse amplitude was lower in response to the CS+ than in response to the CS-, and on the first extinction trial women rated the CS+ as less sexually arousing. Intriguingly, men did not demonstrate attenuated genital and subjective sexual response. CONCLUSIONS: Aversive conditioning, by means of painful stimuli, only affects sexual responses in women, whereas it does not in men. Although conditioned sexual likes and dislikes are relatively persistent, conditioned affect eventually does extinguish.

Toward personalized sexual medicine (part 1): integrating the "dual control model" into differential drug treatments for hypoactive sexual desire disorder and female sexual arousal disorder.

In three related manuscripts we describe our drug development program for the treatment of Hypoactive Sexual Desire Disorder (HSDD). In this first theoretical article we will defend the hypothesis that different causal mechanisms are responsible for the emergence of HSDD: low sexual desire in women (with HSDD) could be due to either a relative insensitive brain system for sexual cues or to enhanced activity of sexual inhibitory mechanisms. This distinction in etiological background was taken into account when designing and developing new pharmacotherapies for this disorder. Irrespective of circulating plasma levels of testosterone, administration of sublingual 0.5 mg testosterone increases the sensitivity of the brain to sexual cues. The effects of an increase in sexual sensitivity of the brain depend on the motivational state of an individual. It might activate sexual excitatory mechanisms in low sensitive women, while it could evoke (or strengthen) sexual inhibitory mechanisms in women prone to sexual inhibition. Sexual stimulation in the brain is necessary for phosphodiesterase type 5 inhibitor (PDE5i)-mediated increase in genital sexual response. Accordingly, a single dose of T+PDE5i might enhance sexual responsiveness, especially in women with low sensitivity to sexual cues. In other women sexual stimulation might elicit a prefrontal cortex (PFC)-mediated phasic increase in sexual inhibition, in which activity of 5-hydroxytryptamine (5-HT, serotonin) is involved. We hypothesize that a single dose of 5-hydroxytryptamine receptor agonist (5-HT(1A)ra) will reduce the sexual-stimulation-induced PFC-mediated sexual inhibition during a short period after administration. Consequently, treatment with T+5-HT(1A)ra will be more effective, in particular in women exhibiting sexual inhibition. Based on the results of our efficacy studies described in parts 2 and 3 of the series, we conclude that tailoring on-demand therapeutics to different underlying etiologies might be a useful approach to treat common symptoms in subgroups of women with HSDD.

Toward personalized sexual medicine (part 3): testosterone combined with a Serotonin1A receptor agonist increases sexual satisfaction in women with HSDD and FSAD, and dysfunctional activation of sexual inhibitory mechanisms.

INTRODUCTION: Among other causes, low sexual desire in women may result from dysfunctional activation of sexual inhibition mechanisms during exposure to sex. Administration of sublingual 0.5 mg testosterone (T) increases the sensitivity of the brain to sexual cues, which might amplify sexual inhibitory mechanisms further in women already prone to sexual inhibition. Sexual stimulation might elicit a prefrontal cortex (PFC)-mediated phasic increase in sexual inhibition, in which activity of 5-hydroxytryptamine (5-HT, serotonin) is involved. A single dose of 5-HT receptor agonist (5-HT(1A)ra) might reduce the sexual stimulation induced PFC-mediated sexual inhibition during a short period after administration. Consequently, treatment with a single dose of T+5-HT(1A)ra might enhance sexual responsiveness, particularly in women exhibiting sexual inhibition. AIM: To investigate if treatment with a single dosage of T+5-HT(1A)ra will produce improvement in sexual functioning in women with Hypoactive Sexual Desire Disorder (HSDD) as the result of dysfunctional high sexual inhibition. METHODS: Fifty-four women were divided on the basis of their excitatory or inhibitory responses during T+phosphodiesterase type 5 inhibitor (PDE5i) in low (N = 26) and high inhibitors (N = 28). Physiological and subjective indices of sexual functioning were measured in a participant-controlled ambulatory psychophysiological experiment at home (the first week of each drug treatment). In a bedroom experiment (the subsequent 3 weeks), sexual functioning was evaluated by event, week, and monthly diaries. MAIN OUTCOME MEASURES: Subjective: sexual satisfaction, experienced genital arousal, sexual desire. Physiological: vaginal pulse amplitude. RESULTS: Women with high inhibition show a marked improvement in sexual function in response to treatment with T+5-HT ra relative to placebo and relative to T+PDE5i. CONCLUSIONS: The present study demonstrated that on-demand T+5-HT ra is a potentially promising treatment for women with HSDD, particularly for those women who are prone to sexual inhibition.

Toward personalized sexual medicine (part 2): testosterone combined with a PDE5 inhibitor increases sexual satisfaction in women with HSDD and FSAD, and a low sensitive system for sexual cues.

INTRODUCTION: Low sexual desire in women may result from a relative insensitivity of the brain for sexual cues. Administration of sublingual 0.5 mg testosterone (T) increases the sensitivity of the brain to sexual cues. Sexual stimulation in the brain is necessary for phosphodiesterase type 5 inhibitor (PDE5i)-mediated increase in genital sexual response. Accordingly, a single dose of T+PDE5i might enhance sexual responsiveness, especially in women with low sensitivity for sexual cues. AIM: To assess the hypothesis that treatment with on-demand use of T+PDE5i improves sexual functioning, particularly in women who suffer from Hypoactive Sexual Desire Disorder (HSDD) as the result of a relative insensitivity for sexual cues. METHODS: In a randomized, double-blind, placebo-controlled, crossover design, 56 women with HSDD underwent three medication treatment regimes (placebo, T+PDE5i, and T with a serotonin receptor agonist; see also parts 1 and 3), which lasted 4 weeks each. In a participant-controlled ambulatory psychophysiological experiment at home (the first week of each drug treatment), physiological and subjective indices of sexual functioning were measured. In a bedroom experiment (the subsequent 3 weeks), sexual functioning was evaluated following each sexual event after the self-administration of study medication. Subjective evaluation of sexual functioning was also measured by weekly and monthly reports. MAIN OUTCOME MEASURES: Subjective: sexual satisfaction, experienced genital arousal, sexual desire. Physiological: vaginal pulse amplitude. Cognitive: preconscious attentional bias. RESULTS: T+PDE5i, as compared with placebo, significantly improved physiological and subjective measures of sexual functioning during ambulatory psychophysiological lab conditions at home and during the sexual events, in women with low sensitivity for sexual cues. CONCLUSIONS: The present study demonstrated that on-demand T+PDE5i is a potentially promising treatment for women with HSDD, particularly in women with low sensitivity for sexual cues.

Focusing "hot" or focusing "cool": attentional mechanisms in sexual arousal in men and women.

INTRODUCTION: Knowledge about the regulation of sexual emotion may add to the understanding of sexual problems such as diminished sexual desire and hypersexuality. AIM: To investigate the regulation of sexual arousal by means of attentional focus in healthy sexually functional men and women. METHOD: Using a habituation design with attentional strategies, it was investigated whether a focus on hot, emotional information of sexual stimuli would sustain or amplify sexual responses, whereas a focus on cool, cognitive information would weaken sexual responses. MAIN OUTCOME MEASURES: Genital response (in women measured by vaginal photoplethysmography assessing vaginal pulse amplitude, and in men measured by mechanical penile strain gauge assessing penile circumference) and subjective report of sexual arousal and absorption. RESULTS: Attenuation of sexual feelings by attentional focus was observed, with stronger sexual feelings under the hot focus condition than under the cool focus condition. Also, sexual feelings diminished during repeated erotic stimulation, and increased with the introduction of novel stimulation, indicating habituation and novelty effects. Contrary to the expectations, the hot attentional focus did not preclude habituation of sexual arousal. CONCLUSIONS: Attentional focus has substantial regulatory effects on subjective sexual arousal. Taking a participant and emotion-oriented focus rather than a spectator and stimulus-oriented focus while viewing erotic stimuli, enhances feelings of sexual arousal. Implications for the treatment of hypoactive sexual desire, sexual arousal disorder, and hypersexuality are discussed, as well as future directions for studying regulation of sexual emotion.

Induction of sexual arousal in women under conditions of institutional and ambulatory laboratory circumstances: a comparative study.

INTRODUCTION: Measuring under naturally occurring circumstances increases ecological validity. We developed an ambulatory psychophysiological laboratory that allows experiments to be performed at home. AIMS: To compare institutional laboratory task measures with ambulatory laboratory task measures. MAIN OUTCOME MEASURES: Vaginal pulse amplitude (VPA), clitoral blood volume (CBV), subjective report of sexual arousal, preconscious attentional bias for erotic stimuli, subjective reports about feeling at ease, tense, anxious or inhibited. METHODS: VPA and CBV were measured in eight women with hypoactive sexual desire disorder (HSDD) and eight healthy controls while exposed to neutral and erotic film clips both in the institute's laboratory and at home. Before and after film clip presentations, subjects performed an emotional Stroop task and completed two questionnaires. RESULTS: In healthy controls, genital measures of sexual arousal were significantly increased at home compared with the institutional laboratory, whereas no differences were observed between the institutional laboratory and the at home measurements in women with HSDD. The responses at home were significantly higher in healthy controls compared with women with HSDD. Subjective experience of genital responding increased at home for both groups of women. Concordance between subjective experience and genital sexual arousal was more pronounced in the institutional laboratory setting. Preconscious attentional bias was stronger in the institutional laboratory for both groups of women. Healthy controls felt more at ease and less inhibited at home while subjects with HSDD did not. CONCLUSIONS: The use of an ambulatory laboratory is a valuable tool allowing psychophysiological (sex) research under more natural circumstances (e.g., a participant's home). In this study, the increase in ecological validity resulted in a qualitative differentiation between the healthy controls and the women with HSDD in the home setting, which is not apparent in the artificial setting of the institutional laboratory.

Immediate and prolonged effects of cortisol, but not propranolol, on memory retrieval in healthy young men.

BACKGROUND: While acute cortisol administration has been found to impair retrieval of emotional memories in healthy subjects, the duration of this memory impairment is still unknown. Propranolol, on the other hand, may impair the reconsolidation of emotional memories during reactivation, although human studies examining such effects are scarce. The present investigation was therefore undertaken to examine the immediate and prolonged effects of a single administered dose of cortisol or propranolol on memory retrieval in a double-blind placebo controlled design. METHODS: Eighty-five healthy male participants were asked to retrieve previously learned emotional and neutral information after ingestion of 35 mg cortisol, 80 mg propranolol or placebo. After a washout period of 1 week, recall was again tested. RESULTS: Memory retrieval of neutral and emotional information was impaired by a single dose of cortisol compared to placebo. The memory impairment due to cortisol remained, even after a washout period of 1 week. No immediate or prolonged effects of propranolol on memory retrieval were found, despite significant reductions in sympathetic arousal. CONCLUSIONS: These results lend support to the hypothesis that cortisol is able to attenuate (emotional) memory recall in men over longer time spans and may therefore augment the treatment of disorders like post-traumatic stress disorder and phobias, but do not clarify the mechanism(s) through which propranolol exerts its therapeutic effects.

Childhood sexual abuse, selective attention for sexual cues and the effects of testosterone with or without vardenafil on physiological sexual arousal in women with sexual dysfunction: a pilot study.

INTRODUCTION: Female sexual dysfunction (FSD) may be associated with reduced central sensitivity for sexual cues. A single dose of testosterone might induce an increase in sensitivity for sexual stimuli, which in turn allows a PDE5 inhibitor to be effective in boosting the physiological sexual response. Negative sexual experience-like childhood sexual abuse (CSA)-might be an important intervening factor in these drugs-induced alterations. AIM: To investigate if the combination of testosterone and vardenafil causes an increase in sensitivity for sexual cues and an increase in physiological sexual responding in women suffering from hypoactive sexual desire disorder (HSDD). METHODS: Thirteen women with HSDD underwent four different drug treatments: (i) placebo; (ii) vardenafil; (iii) testosterone; and (iv) combination of testosterone and vardenafil. During each treatment, they performed an emotional Stroop task and watched neutral and erotic film clips. MAIN OUTCOME MEASURES: A masked version of the emotional Stroop task, and the vaginal pulse amplitude (VPA). RESULTS: We found different effects in women who had reported CSA (N = 5) compared with those who had not (N = 8). In women without CSA, testosterone induced an increase in their originally low levels of preconscious attention for sexual cues, while women with CSA showed a decrease in their originally high levels of attention. In these groups, we also found different effects of the combination of testosterone and vardenafil on the VPA: women without CSA revealed a statistically significant increase in their VPA during treatment with the combination of testosterone and vardenafil as compared with placebo. Women with CSA, however, showed no alterations in their physiological sexual responding during this combined drug treatment. CONCLUSION: In women without CSA, testosterone appears to activate central sexual mechanisms resulting in higher VPA under the combination of testosterone and vardenafil. This effect did not occur in women with CSA.

The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction.

INTRODUCTION: Women with female sexual dysfunction have a reduced sensitivity to sexual stimuli. Activation of central mechanisms may open a window for phosphodiesterase type 5 inhibitors (PDE5) to be effective; as a consequence, the combination of testosterone and a PDE5 inhibitor will restore sexual function. AIM: To demonstrate that the combination of testosterone and vardenafil will increase the sensitivity for sexual stimuli and will improve the desire and arousal components of the sexual response. Methods. In a double-blind randomly assigned placebo-controlled crossover design, 28 women with desire and/or arousal disorder underwent four different drug treatments on four separate experimental days. A masked version of the emotional Stroop task with sexual and nonsexual words was used to measure sensitivity for sexual content. Neutral and erotic film fragments were used to determine genital-physiological and subjective reactions. MAIN OUTCOME MEASURES: A masked version of the emotional Stroop task, vaginal pulse amplitude. For subjective measurement, responses were collected continuously with a lever and two self-report measures were used. RESULTS: In two subgroups, which were differentiated on the basis of their initial preconscious attentional bias for sexual cues, a different sexual response profile was found. In an initially low-attention group, preconscious attentional bias for sexual cues increased under the testosterone condition. In these women, the combination of testosterone and vardenafil caused an improvement in genital response and subjective indices of sexual functioning. In the group that had initially a high attention for sexual cues, preconscious attentional bias for sexual cues decreased under the condition of testosterone. In these women, the combination of testosterone and vardenafil had no effect on any of the indices of their sexual functioning. CONCLUSION: In women suffering from low sexual desire-associated with low attention for sexual cues-the combination of testosterone and vardenafil may be a promising new treatment.

The clitoral photoplethysmograph: a new way of assessing genital arousal in women.

INTRODUCTION: In the present study, we introduce clitoral photoplethysmography as an instrument to assess clitoral blood volume (CBV). In research on female sexual functioning, vaginal pulse amplitude (VPA), as measured using vaginal photoplethysmography, has been used extensively as a measure of vaginal vasocongestion. Measurement of clitoral blood flow has thus far been problematic, mainly because of methodological constraints. AIM: To demonstrate that CBV is a valuable, easy to use complementary measure for the female sexual response, offering additional information to the VPA. METHODS: Thirty women with and without female sexual dysfunction (FSD) watched neutral and erotic film clips. At the end of the erotic clip, the session was interrupted to induce inhibition of the sexual response. Another neutral clip followed the interruption. VPA and CBV were measured simultaneously, as well as skin conductance levels (SCLs), to assess the amount of sympathetic activity. MAIN OUTCOME MEASURES: VPA, CBV, SCL. RESULTS: For both FSD and non-FSD women, VPA and CBV increased when sexually explicit material was presented. Changes in skin conductance significantly predicted changes in CBV (b = -0.61, t[27] = -3.88, P < 0.001), but not in VPA. A large increase in sympathetic activity was accompanied by a large decrease in CBV. Furthermore, a large increase in CBV at the end of the erotic film clip presentation, as compared with the neutral clip, was accompanied by a relatively small increase in VPA (b = -0.39, t[29] = -2.25, P < 0.033). CONCLUSION: CBV is a valid and sensitive tool to measure the female genital response. In the present study, it was particularly useful in investigating sexual inhibition, when used in combination with SCL. Furthermore, high CBV appeared to inhibit VPA, suggesting that VPA reflects an automatic preparatory response rather than genital arousal per se.

False heart rate feedback and the perception of heart symptoms in patients with congenital heart disease and anxiety.

BACKGROUND: Little is known about the mechanisms explaining an increased perception of heart symptoms in congenital heart disease (ConHD). In the present study, it was suggested that a combination of high trait anxiety and disease history increases the perception of heart symptoms. PURPOSE: It was tested whether false heart cues will result in an increased perception of heart symptoms in patients with ConHD and anxiety. METHOD: Thirty-six patients with ConHD and 44 healthy controls performed two exercise tasks. During one of the exercise tasks, participants were exposed to a false heart cue consisting of false heart rate feedback (regular or irregular). Perceived heart symptoms were assessed and heart rate, arterial partial pressure of CO(2), and respirator rate were monitored continuously. RESULTS: In line with the predictions, false heart rate feedback resulted in an increased perception of heart symptoms in high trait anxious patients with ConHD that could not be explained by acute heart dysfunction. However, unexpectedly, this effect was not observed immediately after the false heart rate feedback task but after a second exercise task without false feedback. CONCLUSION: The results suggest that not the sole presence of ConHD but ConHD in combination with high trait anxiety results in a vulnerability to overperceive heart symptoms.

Autobiographical memory after acute stress in healthy young men.

Autobiographical memories have been found to be less specific after hydrocortisone administration in healthy men, resembling memory deficits in, for example, depression. This is the first study to investigate the effects of stress-induced elevated cortisol levels on autobiographic memory specificity and experience in healthy young men. Autobiographical memories were elicited by neutral and negative cue words, with instructions to recall either recent or remote memories. No effect of psychosocial stress was found on memory specificity or experience, but cortisol increases tended to be related to less specific, recent memories elicited by neutral cue words, especially when participants were physically aroused during memory retrieval. These results indicate that autobiographical memories are fairly resistant to an acute stressor in healthy young men, but that endogenous cortisol increases might be related to autobiographical memory retrieval. More research into the relation between endogenous cortisol increases and autobiographic memory retrieval is needed, especially in stress-related disorders.

Interaction of endogenous cortisol and noradrenaline in the human amygdala.

Animal studies show that glucocorticoid effects on memory depend on noradrenergic activation within an intact amygdala. Testing this model in humans is the subject of the present fMRI study. Healthy subjects watched emotional and neutral stimuli after having received a betablocker or placebo. Cortisol levels of all subjects were determined and served as a marker of the subject's (endogenous) cortisol level during the experiment. Viewing emotional pictures resulted in increased amygdala activation compared to neutral pictures and this effect was enhanced in subjects with a high versus low cortisol level under placebo condition. Betablockade with propranolol, lowering the noradrenergic level in the amygdala, disrupted this effect and apparently the interaction with cortisol. These data support the hypothesis that high endogenous cortisol levels at the time of encoding interact with noradrenergic activation in the amygdala in man.

Long-term outcomes of memory retrieval under stress.

Previous studies have found impairing effects of stress hormones on memory retrieval. So far, it is unknown whether these impairments are temporary, persistent throughout time, or whether the strength of the memory trace changes after retrieval because of the effects of stress hormones on memory processes during retrieval. In the present study, delayed cued recall (6 months after initial learning) was compared between male participants who had retrieved previously learned word pairs during stress or a control condition. Retrieval (with or without stress) had taken place either 1 day or 5 weeks after initial encoding. The group that had retrieved words under stress 5 weeks after encoding performed worse on long-term recall than the comparable control group. However, when words were retrieved under stress 1 day after encoding, no long-term effect was found, although performance at 6 months in relation to performance under stress was slightly increased compared to the control group. These results support previous findings in animals that stress may affect memory during reactivation. It further suggests that time intervals between encoding and reactivation may play an important role.

Appetitive and aversive classical conditioning of female sexual response.

INTRODUCTION: There is only limited evidence for appetitive classical conditioning of female sexual response, and to date modulation of female sexual response by aversive conditioning has not been studied. AIM: The aim of this article is to study appetitive and aversive classical conditioning of sexual responses in women. MAIN OUTCOME MEASURES: Vaginal pulse amplitude was assessed by vaginal photoplethysmography and ratings of affective value were obtained. METHOD: Two differential conditioning experiments were conducted. In Experiment 1, on appetitive conditioning, neutral pictures served as conditional stimuli (CSs) and genital vibrotactile stimulation as the unconditional stimulus (US). In Experiment 2, on aversive conditioning, erotic pictures served as CSs and a pain stimulus as US. In both experiments, only one CS (the CS+) was followed by the US during the acquisition phase. Conditioned responses were assessed during the extinction phase. RESULTS: In Experiment 1, during the extinction phase, as expected vaginal pulse amplitude was higher in response to the CS+ than during the CS-. Also, the CS+ was rated as marginally more positive than the CS-. In Experiment 2, during the extinction phase, as expected vaginal pulse amplitude was lower in response to the CS+ than during the CS-, and the CS+ was rated as more negative than the CS-. CONCLUSIONS: The results provide evidence for appetitive classical conditioning of sexual response in women, and are the first to show attenuation of sexual response in women by aversive conditioning.