The impact of extinction timing on pre-extinction arousal and subsequent return of fear.

Exposure-based therapy is effective in treating anxiety, but a return of fear in the form of relapse is common. Exposure is based on the extinction of Pavlovian fear conditioning. Both animal and human studies point to increased arousal during immediate compared to delayed extinction (>+24 h), which presumably impairs extinction learning and increases the subsequent return of fear. Impaired extinction learning under arousal might interfere with psychotherapeutic interventions. The aim of the present study was to investigate whether arousal before extinction differs between extinction groups and whether arousal before extinction predicts the return of fear in a later (retention) test. As a highlight, both the time between fear acquisition and extinction (immediate vs. delayed) and the time between extinction and test (early vs. late test) were systematically varied. We performed follow-up analyses on data from 103 young, healthy participants to test the above hypotheses. Subjective arousal ratings and physiological arousal measures of sympathetic and hypothalamic pituitary adrenal axis activation (tonic skin conductance and salivary cortisol) were collected. Increased pre-extinction arousal in the immediate extinction group was only confirmed for subjective arousal. In linear regression analyses, none of the arousal measures predicted a significant return of fear in the different experimental groups. Only when we aggregated across the two test groups, tonic skin conductance at the onset of extinction predicted the return of fear in skin conductance responses. The overall results provide little evidence that pre-extinction arousal affects subsequent extinction learning and memory. In terms of clinical relevance, there is no clear evidence that exposure could be improved by reducing subjective or physiological arousal.

Appetitive conditioning with pornographic stimuli elicits stronger activation in reward regions than monetary and gaming-related stimuli.

Appetitive conditioning plays an important role in the development and maintenance of pornography-use and gaming disorders. It is assumed that primary and secondary reinforcers are involved in these processes. Despite the common use of pornography and gaming in the general population appetitive conditioning processes in this context are still not well studied. This study aims to compare appetitive conditioning processes using primary (pornographic) and secondary (monetary and gaming-related) rewards as unconditioned stimuli (UCS) in the general population. Additionally, it investigates the conditioning processes with gaming-related stimuli as this type of UCS was not used in previous studies. Thirty-one subjects participated in a differential conditioning procedure in which four geometric symbols were paired with either pornographic, monetary, or gaming-related rewards or with nothing to become conditioned stimuli (CS + porn, CS + game, CS + money, and CS-) in an functional magnetic resonance imaging study. We observed elevated arousal and valence ratings as well as skin conductance responses for each CS+ condition compared to the CS-. On the neural level, we found activations during the presentation of the CS + porn in the bilateral nucleus accumbens, right medial orbitofrontal cortex, and the right ventral anterior cingulate cortex compared to the CS-, but no significant activations during CS + money and CS + game compared to the CS-. These results indicate that different processes emerge depending on whether primary and secondary rewards are presented separately or together in the same experimental paradigm. Additionally, monetary and gaming-related stimuli seem to have a lower appetitive value than pornographic rewards.

Neural correlates of immediate versus delayed extinction when simultaneously varying the time of the test in humans.

Anxiety disorders are effectively treated with exposure therapy based on the extinction of Pavlovian fear conditioning. Animal research indicates that both the timing of extinction and test are important factors to reduce the return of fear. However, empirical evidence in humans is incomplete and inconsistent. In this neuroimaging study, we, therefore, tested 103 young, healthy participants in a 2-factorial between-subjects design with the factors extinction group (immediate, delayed) and test group (+1 day and +7 days). Immediate extinction led to greater retention of fear memory at the beginning of extinction training indicated by increased skin conductance responses. A return of fear was observed in both extinction groups, with a trend toward a greater return of fear in immediate extinction. The return of fear was generally higher in groups with an early test. Neuroimaging results show successful cross-group fear acquisition and retention, as well as activation of the left nucleus accumbens during extinction training. Importantly, the delayed extinction group showed a larger bilateral nucleus accumbens activation during test. This nucleus accumbens finding is discussed in terms of salience, contingency, relief, and prediction error processing. It may imply that the delayed extinction group benefits more from the test as a new learning opportunity.

Same same, but different: A psychometric examination of three frequently used experimental tasks for cognitive bias assessment in a sample of healthy young adults.

Cognitive bias research draws upon the notion that altered information processing is key for understanding psychological functioning and well-being. However, little attention has been paid to the question of whether the frequently used experimental paradigms hold adequate psychometric properties. The present study examined the psychometric properties of three widely used cognitive bias tasks: the Approach-Avoidance Task (AAT), the visual dot-probe-task, and the Implicit Association Test (IAT). Approach, attentional, and association biases towards valenced stimuli were repeatedly measured at five different time points in a sample of 79 healthy young adults. Two different devices were used for assessment: a personal computer (PC) and a touchscreen-based tablet. Reliability estimates included internal consistency and temporal stability. Validity was inferred from convergence across different behavioral tasks and correlations between bias scores and self-reported psychological traits. Reliability ranged widely amongst tasks, assessment devices, and measurement time points. While the dot-probe-task appeared to be completely unreliable, bias scores obtained from the PC-based version of the AAT and both (PC and touchscreen) versions of the IAT showed moderate reliability. Almost no associations were found across information processing tasks or between implicit and explicit measures. Cognitive bias research should adopt a standard practice to routinely estimate and report psychometric properties of experimental paradigms, investigate feasible ways to develop more reliable tools, and use tasks that are suitable to answer the precise research question asked.

Cross-paradigm integration shows a common neural basis for aversive and appetitive conditioning.

Sharing imaging data and comparing them across different psychological tasks is becoming increasingly possible as the open science movement advances. Such cross-paradigm integration has the potential to identify commonalities in findings that neighboring areas of study thought to be paradigm-specific. However, even the integration of research from closely related paradigms, such as aversive and appetitive classical conditioning is rare - even though qualitative comparisons already hint at how similar the 'fear network' and 'reward network' may be. We aimed to validate these theories by taking a multivariate approach to assess commonalities across paradigms empirically. Specifically, we quantified the similarity of an aversive conditioning pattern derived from meta-analysis to appetitive conditioning fMRI data. We tested pattern expression in three independent appetitive conditioning studies with 29, 76 and 38 participants each. During fMRI scanning, participants in each cohorts performed an appetitive conditioning task in which a CS+ was repeatedly rewarded with money and a CS- was never rewarded. The aversive pattern was highly similar to appetitive CS+ > CS- contrast maps across samples and variations of the appetitive conditioning paradigms. Moreover, the pattern distinguished the CS+ from the CS- with above-chance accuracy in every sample. These findings provide robust empirical evidence for an underlying neural system common to appetitive and aversive learning. We believe that this approach provides a way to empirically integrate the steadily growing body of fMRI findings across paradigms.

Addiction Research Unit: Affective and cognitive mechanisms of specific Internet-use disorders.

In the eleventh International Classification of Diseases (ICD-11) of the World Health Organization, gambling disorder and gaming disorder are included in the category 'disorders due to addictive behaviours', which can be specified further as occurring either predominantly offline or predominantly online. Other specific problematic behaviours may be considered for the category 'other specified disorders due to addictive behaviours'. The Research Unit FOR 2974, funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG), focuses on the most prominent online addictive behaviours: gaming, pornography use, buying-shopping and social-networks use. The main goal of the Research Unit is to contribute to a better understanding of the common and differential psychological as well as neurobiological mechanisms involved in these specific types of Internet-use disorders. We aim to investigate theoretically argued (bio)psychological processes with a focus on concepts coming from research of substance-use disorders, for example, cue reactivity and craving, executive functions and specific inhibitory control, coping, implicit cognitions, and decision making. One central characteristic of the Research Unit is that we will investigate all participants using a comprehensive core battery of experimental paradigms, neuropsychological tasks, questionnaires, biomarkers, ambulatory assessment, and a 6-month follow-up survey. Beyond the anticipated contributions to the scientific understanding of the mechanisms involved in the development and maintenance of respective online addictive behaviours, we also expect contributions to clinical practice by showing which affective and cognitive mechanisms may be addressed more intensively to optimize treatment.

Amygdala and nucleus accumbens involvement in appetitive extinction.

Extinction of appetitive conditioning is regarded as an important model for the treatment of psychiatric disorders like addiction. However, very few studies have investigated its neural correlates. Therefore, we investigated neural correlates of appetitive extinction in a large human sample including all genders (N = 76, 40 females) to replicate and extend results from a previous study. During differential appetitive conditioning, one stimulus (CS+) was paired with the chance to win a monetary reward, whereas another stimulus (CS-) was not. During appetitive extinction on the next day, neither the CS+ nor the CS- were reinforced. After successful acquisition of appetitive conditioning, the extinction phase elicited significant reductions of valence and arousal ratings toward the CS+ and a significant reduction in skin conductance responses to the CS+ from early to late extinction. On a neural level, early extinction showed significant differential (CS+ - CS-) activation in dACC and hippocampus, whereas involvement of the vACC and caudate nucleus did not replicate. The differential activation of amygdala and nucleus accumbens during late extinction was replicated, with the amygdala displaying significantly higher differential activation during the late phase of extinction as compared to the early phase of extinction. We show discernible signals for reward learning and extinction in subregions of amygdala and nucleus accumbens after extinction learning. This successful replication underlines the role of nucleus accumbens and amygdala in neural models of appetitive extinction in humans that was previously only based on animal findings.

The relationship between neuroticism and appetitive conditioning.

Appetitive conditioning is considered a central mechanism for the vulnerability to psychiatric disorders. However, the investigation of individual differences that are related to altered appetitive learning has been almost neglected so far. The aim of this study was to investigate the link between neuroticism and appetitive conditioning processes. 79 subjects participated in a differential conditioning procedure in which a conditioned stimulus (CS+) was paired with a reward (money) after a fast behavioral response, while a second conditioned stimulus (CS-) was never followed by a reward, irrespective of the behavioral response. As a main result, neuroticism correlated negatively with the underlying neural processes of appetitive conditioning in females, but not in males. In detail, higher levels of neuroticism were associated with decreased neural responses in the left (p = .001) and right amygdala (p = .011), left (p = .063) and right (p = .019) nucleus accumbens, and left (p = .002) and right (p = .021) orbitofrontal cortex (all results are family-wise-error-corrected). The present results support previous findings, which also showed an inverse sex-specific effect in the context of neuroticism and emotional processing in females. In addition, the findings suggest that neuroticism is not solely linked to increased amygdala sensitivity during the processing of negative stimuli but also to decreased neural responses when processing rewarding stimuli. Possible explanations for the sex differences and implications are discussed.

Altered reward learning and hippocampal connectivity following psychosocial stress.

Acute stress has a profound influence on learning, as has been demonstrated in verbal learning or fear conditioning. However, its effect on appetitive conditioning is still unclear. Fear conditioning research suggests the possibility of overgeneralization of conditioning to the CS- under acute stress due to its effect on prefrontal and hippocampal processing. In this study, participants (N = 56 males) were subjected to the Trier Social Stress Test or a placebo version. After that, all participants underwent an appetitive conditioning paradigm in the fMRI, in which one neutral cue (CS+) was repeatedly paired with reward, while another (CS-) was not. Importantly, the stress-group revealed overgeneralization of conditioning to the CS- on the behavioral level. On the neural level, stressed participants showed increased connectivity between the hippocampus and amygdala, vACC, and OFC, which maintain specificity of conditioning and also showed reduced differential activation. The results indicate overgeneralization of appetitive conditioning promoted by maladaptive balancing of pattern separation and pattern completion in the hippocampus under acute stress and are discussed with respect to clinical implications.

Neural correlates of subjective CS/UCS association in appetitive conditioning.

Explicit knowledge of conditioned stimulus (CS)/unconditioned stimulus (UCS) associations is proposed as important factor in classical conditioning. However, while previous studies have focused on its roles in fear conditioning, it has been neglected in the context of appetitive conditioning. The present functional magnetic resonance study aimed to investigate neural activation and functional connectivity linked to subjective CS/UCS association in appetitive conditioning. In total, 85 subjects participated in an appetitive acquisition procedure in which a neutral stimulus (CS+) was paired with a monetary reward, while another neutral stimulus (CS-) was never paired with the reward. Directly afterwards, subjective CS/UCS association was assessed by measuring the extent to which the CS+ was thought to be associated with the UCS compared to the CS-. Close relationships were established between subjective CS/UCS association and activations in the primary visual cortex (V1) during the early phase of conditioning and in the striatum during the late conditioning phase. In addition, we observed inverse relationships between subjective CS/UCS association and both V1/ventromedial prefrontal cortex (vmPFC) and striatal/vmPFC connectivity. The results suggest the involvement of decoupling vmPFC connectivity in reward learning in general and the roles of attentional processes in the formation of the subjective CS/UCS association during the early phase and reward prediction during the late phase of appetitive conditioning.

Fearfulness, neuroticism/anxiety, and COMT Val158Met in long-term fear conditioning and extinction.

Individual differences in long-term stability of fear memories are of potential relevance for stable dispositions related to threat processing, such as neuroticism/anxiety and fearfulness. As previous research suggests a prominent role of dopamine for the retention of conditioned and extinguished fear, dopaminergic gene polymorphisms may also relate to individual differences in fear stability. While the COMT Val158Met polymorphism causes individual differences in prefrontal dopamine, its associations with human long-term fear extinction are currently unknown. Here, n = 30/29/28 healthy male Val/Val, Val/Met and Met/Met carriers, respectively, underwent a two-day differential conditioning paradigm with fear acquisition and extinction on Day 1 and a recall test on Day 2 with recordings of EEG and ECG. Fearfulness but not neuroticism/anxiety predicted fear bradycardia (i.e., heart period slowing) during Day 1 fear acquisition while it did not affect extinction or Day 2 fear recall. In contrast, COMT Val158Met significantly modulated Day 2 fear recall as evident in fear bradycardia and Late Positive Potential (LPP) amplitudes while it did not affect Day 1 fear or extinction learning. Furthermore, exploratory analyses revealed that individual differences in fear bradycardia during Day 2 extinction recall depended on Day 1 extinction success. Importantly, this contingency was (a) modulated by COMT Val158Met and (b) significantly reduced in high vs. low neuroticism/anxiety. The present study indicates that (a) individual differences in dopaminergic genotypes may affect the long-term stability of fear memories and (b) fearfulness vs. neuroticism/anxiety might play distinct roles in initial fear reactions vs. long-term stability of fear memories, respectively.

Neuroticism and extraversion moderate neural responses and effective connectivity during appetitive conditioning.

Classical appetitive conditioning constitutes a basic learning process through which environmental stimuli can be associated with reward. Previous studies showed that individual differences in neuroticism and extraversion influence emotional processing and have been shown to modulate neural activity in subcortical and prefrontal areas in response to emotional stimuli. However, the role of individual differences in appetitive conditioning has so far not been investigated in detail. The aim of this study was to assess the association between neuroticism and extraversion with neural activity and connectivity during appetitive conditioning. The conditioned stimulus (CS) was either a picture of a dish or a cup. One stimulus (CS+) was paired with a monetary reward and the other stimulus (CS-) was associated with its absence while hemodynamic activity was measured by means of functional magnetic resonance imaging. A significant negative correlation of neuroticism scores with amygdala activity was observed during appetitive conditioning. Further, extraversion was positively associated with responses in the hippocampus and the thalamus. In addition, effective connectivity between the amygdala as a seed region and the anterior cingulate cortex, the insula, and the thalamus was negatively correlated with neuroticism scores and positively correlated with extraversion scores. The results may indicate a neural correlate for the deficits in appetitive learning in subjects with high neuroticism scores and point to a facilitating effect of extraversion on reward-related learning. Hum Brain Mapp 37:2992-3002, 2016. © 2016 Wiley Periodicals, Inc.

Altered Appetitive Conditioning and Neural Connectivity in Subjects With Compulsive Sexual Behavior.

INTRODUCTION: There has been growing interest in a better understanding of the etiology of compulsive sexual behavior (CSB). It is assumed that facilitated appetitive conditioning might be an important mechanism for the development and maintenance of CSB, but no study thus far has investigated these processes. AIM: To explore group differences in neural activity associated with appetitive conditioning and connectivity in subjects with CSB and a healthy control group. METHODS: Two groups (20 subjects with CSB and 20 controls) were exposed to an appetitive conditioning paradigm during a functional magnetic resonance imaging experiment, in which a neutral stimulus (CS+) predicted visual sexual stimuli and a second stimulus (CS-) did not. MAIN OUTCOME MEASURES: Blood oxygen level-dependent responses and psychophysiologic interaction. RESULTS: As a main result, we found increased amygdala activity during appetitive conditioning for the CS+ vs the CS- and decreased coupling between the ventral striatum and prefrontal cortex in the CSB vs control group. CONCLUSION: The findings show that neural correlates of appetitive conditioning and neural connectivity are altered in patients with CSB. The increased amygdala activation might reflect facilitated conditioning processes in patients with CSB. In addition, the observed decreased coupling could be interpreted as a marker for impaired emotion regulation success in this group.

Impact of COMT Val158Met-polymorphism on appetitive conditioning and amygdala/prefrontal effective connectivity.

Appetitive conditioning is an important mechanism for the development, maintenance, and treatment of psychiatric disorders like substance abuse. Therefore, it is important to identify genetic variations, which impact appetitive conditioning. It has been suggested that the Val(158) Met-polymorphism in the Catechol-O-Methyl-Transferase (COMT) is associated with the alteration of neural processes of appetitive conditioning due to the central role of the dopaminergic system in reward processing. However, no study has so far investigated the relationship between variations in the COMT Val(158) Met-polymorphism and appetitive conditioning. In this fMRI study, an appetitive conditioning paradigm was applied, in which one neutral stimulus (CS+) predicted appetitive stimuli (UCS) while a second neutral stimulus (CS-) was never paired with the UCS. As a main result, we observed a significant association between the COMT Val(158) Met-genotype and appetitive conditioning: skin conductance responses (SCRs) revealed a significant difference between CS+ and CS- in Val/Val-allele carriers but not in the other genotype groups. Val/Val-allele carriers showed increased hemodynamic responses in the amygdala compared with the Met/Met-allele group in the contrast CS+ > CS-. In addition, psychophysiological-interaction analysis revealed increased effective amygdala/ventromedial prefrontal cortex connectivity in Met/Met-allele carriers. The increased amygdala activity points to facilitated appetitive conditioning in Val/Val-allele carriers while the amygdala/prefrontal connectivity results could be regarded as a marker for altered emotion regulation during conditioning, which potentially impacts appetitive learning sensitivity. The SCRs finding indicates a stronger conditioned response in the Val/Val-allele group and dovetails with the neural differences between the groups. These findings contribute to the current research on COMT in emotional processing.

Trait sexual motivation questionnaire: concept and validation.

INTRODUCTION: Trait sexual motivation defines a psychological construct that reflects the long-lasting degree of motivation for sexual activities, which is assumed to be the result of biological and sociocultural influences. With this definition, it shares commonalities with other sexuality-related constructs like sexual desire, sexual drive, sexual needs, and sexual compulsivity. AIM: The Trait Sexual Motivation Questionnaire (TSMQ) was developed in order to measure trait sexual motivation with its different facets. METHODS: Several steps were conducted: First, items were composed assessing sexual desire, the effort made to gain sex, as well as specific sexual behaviors. Factor analysis of the data of a first sample (n = 256) was conducted. Second, the factor solution was verified by a confirmatory factor analysis in a second sample (n = 498) and construct validity was demonstrated. Third, the temporal stability of the TSMQ was tested in a third study (n = 59). MAIN OUTCOME MEASURE: Questionnaire data. RESULTS: The exploratory and confirmatory factor analyses revealed that trait sexual motivation is best characterized by four subscales: Solitary Sexuality, Importance of Sex, Seeking Sexual Encounters, and Comparison with Others. It could be shown that the test quality of the questionnaire is high. Most importantly for the trait concept, the retest reliability after 1 year was r = 0.87. CONCLUSION: Our results indicate that the TSMQ is indeed a suitable tool for measuring long-lasting sexual motivation with high test quality and high construct validity. A future differentiation between trait and state sexual motivation might be helpful for clinical as well as forensic research.

At the second glance: stability of neural responses toward visual sexual stimuli.

INTRODUCTION: Studies investigating the neural responses toward sexual stimuli can provide an important basis for further understanding disorders of sexual functioning. Although our knowledge of the neural correlates of sexual stimulus processing has increased considerably in the last decade, the stability of the observed effects in studies on neural sexual responses has been rather neglected. AIMS: The current study aimed to test the stability of behavioral and neural responses to visual sexual stimuli in men and women over a time span of 1 to 1.5 years. To disentangle valence and arousal-related aspects of sexual stimulus processing, we employed not only sexual and neutral, but also positive and negative emotional stimuli. METHODS: A sample of 56 subjects (24 women) was assessed twice, with an interval of 1 to 1.5 years between assessments. During a functional magnetic resonance imaging (fMRI) session, participants passively viewed sexual, neutral, positive, and negative emotional pictures. Pictures were presented in 24 blocks of five pictures each. Every block was rated immediately after its presentation with respect to valence, arousal, and sexual arousal. MAIN OUTCOME MEASURES: Blood oxygen level dependent (BOLD) responses measured by fMRI and stimulus ratings. RESULTS: fMRI analyses revealed a distributed network involved in the processing of sexual stimuli, with large parts of this network being consistently activated at both assessment points. Nucleus accumbens, anterior cingulate, occipital and parietal cortex showed the most robust results with respect to group stability. Responses of anterior cingulate, orbitofrontal, parietal and occipital cortex showed interindividual stability. Gender differences were restricted to a few regions of interest. CONCLUSIONS: Our data indicate stability of neural responses toward sexual stimuli not only on the group but also on the individual level. Activation of parietal and occipital cortex might reflect a trait like character of attention related responses toward sexual stimuli.

The impact of past childhood adversity and recent life events on neural responses during fear conditioning.

BACKGROUND AND PURPOSE: Many studies have shown that exposure to life events can have a negative impact on mental health. Life events like the death of a spouse or the birth of a child pose a challenge and require temporal or permanent adjustments. Meta-analyses on brain stress responses found bilateral anterior insula activation in response to acute stress. Fear conditioning is assumed a crucial mechanism for the development of anxiety disorders associated with increased activation in the bilateral amygdala. Empirical evidence is lacking regarding the relationship of exposure to recent life events and past childhood adversity with neural processing during fear conditioning. METHODS: In the present study, we analyzed data from 103 young, healthy participants. Multiple linear regressions were performed on functional magnetic resonance imaging activation during fear conditioning with the Life Events Scale for Students and the Childhood Trauma questionnaire included as covariates in two separate models. RESULTS: We found a positive relationship between the number of life events in the last year and left amygdala activation to the conditioned stimulus. A second finding was a positive relationship between childhood adversity and right anterior insula response to the unconditioned stimulus. CONCLUSIONS: Many studies have shown increased amygdala activity after stressful life events. In addition, the anterior insula is activated during acute stress. The present study points to stressor-induced increased salience processing during fear conditioning. We suggest that this could be a potential mechanism for resilience versus mental illness.

Nicotine-related interpretation biases in cigarette smoking individuals.

Addictive behaviors are characterized by information processing biases, including substance-related interpretation biases. In the field of cigarette smoking, such biases have not been investigated yet. The present study thus adopted an open-ended scenario approach to measure smoking-related interpretation biases. Individuals who smoke, those who ceased smoking, and those without a smoking history (total sample N = 177) were instructed to generate spontaneous continuations for ambiguous, open-ended scenarios that described either a smoking-related or neutral context. Overall, people who smoke generated more smoking-related continuations in response to smoking-relevant situations than non-smoking individuals or people who had stopped smoking, providing evidence for a smoking-related interpretation bias. When differentiating for situation type within smoking-relevant scenarios, smoking individuals produced more smoking-related continuations for positive/social and habit/addictive situations compared to negative/affective ones. Additionally, the tendency to interpret habit/addictive situations in a smoking-related manner was positively associated with cigarette consumption and levels of nicotine dependence. Exploratory analyses indicated that other substance-related continuations were correlated with their respective behavioral counterparts (e.g., the level of self-reported alcohol or caffeine consumption). The present study is the first to demonstrate smoking-related interpretation biases in relation to current cigarette smoking. Future studies should investigate the causal role of such biases in the initiation and/or maintainance of nicotine addiction and the merit of Interpretation-Bias-Modification training to support smoking cessation.

The 5-HTTLPR polymorphism is associated with altered hemodynamic responses during appetitive conditioning.

BACKGROUND: Current models suggest that a variation in the promoter region of the serotonin transporter gene (5-HTTLPR) is associated with altered amygdala reactivity not only towards negative but also towards positive stimuli, which has been neglected in the past. This association may possibly convey an elevated vulnerability for psychopathology like abuse, craving, and relapses. Since appetitive conditioning is a crucial mechanism in the pathogenesis of these psychiatric disorders, the identification of specific factors contributing to interindividual variation is important. METHODS: In the present study (N = 86), an appetitive conditioning paradigm was conducted, in which a neutral stimulus (CS+) was associated with appetitive stimuli, while a second stimulus (CS-) predicted their absence. Subjects were genotyped according to the 5-HTTLPR genotype. RESULTS: As the main result, we report a significant association between the 5-HTTLPR genotype and hemodynamic responses. Individuals with the s-allele displayed elevated conditioned bilateral amygdala activity in contrast to l/l-allele carriers. Further, increased hemodynamic responses in s-allele carriers were also found in the extended emotional network including the orbitofrontal cortex, the thalamus, and the ventral striatum. CONCLUSION: The present findings indicate an association of the 5-HTTLPR and altered conditioned responses in appetitive conditioning. Further, the findings contribute to the ongoing debate on 5-HTTLPR dependent hemodynamic response patterns by emphasizing that s-allele carriers are not exclusively biased towards fearful, but also towards positive stimuli. In conclusion, our results imply that s-allele carriers might be better described as hyper-reactive towards salient stimuli, which may convey vulnerability for the development of psychiatric disorders.

Gender commonalities and differences in the neural processing of visual sexual stimuli.

INTRODUCTION: Few studies so far have directly compared the neural processing of visual sexual stimuli in men and women. Also, most of these studies only compared sexual with neutral stimuli, making it difficult to disentangle sexual stimulus processing from general emotional processing. AIM: The current study aimed to explore gender commonalities and differences in neural activity associated with the processing of visual sexual stimuli in a large sample of 50 men and 50 women. In order to disentangle effects of sexual processing from those of general emotional processing, we employed sexual, neutral, positive, and negative emotional pictures. METHODS: Subjects passively viewed sexual, neutral, positive, and negative emotional pictures during a functional magnetic resonance imaging (fMRI) session. Pictures were presented in 24 blocks of five pictures each. Every block was rated immediately after its presentation with respect to valence, arousal, and sexual arousal. MAIN OUTCOME MEASURES: Blood oxygen level dependent responses measured by fMRI and subjective ratings. RESULTS: fMRI analysis revealed a distributed network for the neural processing of sexual stimuli comprising the hypothalamus, the nucleus accumbens, as well as orbitofrontal, occipital, and parietal areas. This network could be identified (i) for both men and women, with men showing overall stronger activations than women and (ii) independent of general emotional arousal or valence effects. CONCLUSION: Our data speak in favor of a common neural network associated with the processing of visual sexual stimuli in men and women. Apart from the observed gender commonalities, overall stronger responses in men were observed that might indicate stronger sexual responsivity in men.