Sabine Kagerer

Influence of the stress hormone cortisol on fear conditioning in humans: Evidence for sex differences in the response of the prefrontal cortex

The stress hormone cortisol is known to influence declarative memory and associative learning. In animals, stress has often been reported to have opposing effects on memory and learning in males and females. In humans, the effects of cortisol have mainly been studied at the behavioral level. The aim of the present experiment was to characterize the effects of a single cortisol dose (30 mg) on the hemodynamic correlates of fear conditioning. In a double-blind group comparison study subjects (17 females and 17 males) received 30 mg cortisol or placebo orally before participating in a discriminative fear conditioning paradigm. Results revealed that cortisol impaired electrodermal signs of learning (the first interval response) in males, while no conditioned SCRs emerged for the females independent of treatment. fMRI results showed that cortisol reduced activity for the CS+ > CS- comparison in the anterior cingulate, the lateral orbitofrontal cortex and the medial prefrontal cortex in males. Opposite findings (increase in these regions under cortisol) were detected in females. In addition, cortisol reduced the habituation in the CS+ > CS- contrast in the dorsolateral prefrontal cortex independent of sex. Finally, cortisol also modified the response to the electric shock (the UCS) by enhancing the activity of the anterior as well as the posterior cingulate. In sum, these findings demonstrate that in humans cortisol mostly influences prefrontal brain activation during fear conditioning and that these effects appear to be modulated by sex.

Neural Activations of the Acquisition of Conditioned Sexual Arousal: Effects of Contingency Awareness and Sex

INTRODUCTION Learning processes like classical conditioning are involved in mediating sexual behavior. Yet, the neural bases underlying these processes have not been investigated so far. AIM The aim of this study was to explore neural activations of classical conditioning of sexual arousal with respect to sex differences and contingency awareness. METHODS In the acquisition phase, a geometric figure (CS+) was presented for 8 seconds and was followed by highly sexual arousing pictures (UCS), whereas another figure (CS-) predicted neutral pictures. Ratings and contingency awareness were assessed after the entire conditioning procedure. Forty subjects (20 females) were classified into one of four groups according to their sex and the development of contingency awareness (aware females, aware males, unaware females, and unaware males). MAIN OUTCOME MEASURES Blood oxygen level dependent (BOLD) responses measured by functional magnetic resonance imaging (fMRI), skin conductance responses (SCRs), and subjective ratings. RESULTS fMRI analysis showed two effects (awareness and sex) when comparing CS+ with CS-: (i) aware compared to unaware subjects showed enhanced differentiation (e.g., ventral striatum, orbitofrontal cortex, occipital cortex); and (ii) men showed increased activity compared to women in the amygdala, thalamus, and brainstem. CS+ and CS- ratings differed in aware subjects only. However, no conditioned SCRs occurred in any group. CONCLUSION The increased activity in men is in line with theories postulating that men are generally more prone to conditioning of sexual arousal. Further, contingency awareness seems to be an important factor in appetitive learning processes, which facilitates conditioning processes.

Neural, electrodermal and behavioral response patterns in contingency aware and unaware subjects during a picture-picture conditioning paradigm.

One way of investigating affective learning is the use of aversive pictures as unconditioned stimuli (UCS) in conditioning paradigms. In the last decades, there has been a heated debate on the influence of contingency awareness on conditioned responses (CRs). Only a few studies found CRs in contingency unaware subjects whereas other studies only reported conditioned reactions in contingency aware participants. However, as a shortcoming, most studies employing picture-picture paradigms only investigated one response level (e.g. changes in subjective ratings). Further, changes in brain activity have so far been neglected in this field of research. The aim of the present study was to investigate different response levels with respect to contingency awareness: brain activity measured by functional magnetic resonance imaging (fMRI), skin conductance responses (SCRs) and valence ratings. A neutral geometric shape (conditioned stimulus, CS+) was followed by aversive pictures, whereas another shape (CS-) preceded neutral pictures. Unaware participants showed CRs in brain activity (e.g. the insula). Generally more activity was observed in the fear network (e.g. the amygdala, the lateral orbitofrontal cortex) in aware participants and in the nucleus accumbens (NAcc). Investigation of SCRs and valence ratings revealed that only aware participants showed conditioned reactions. Our results point toward dissociations between response levels (e.g. brain activity) not affected by contingency awareness and more cognitive response levels (e.g. subjective ratings and SCRs) which are affected by contingency awareness. As a unique finding in human aversive conditioning, we discuss the role of the nucleus accumbens as well as practical implications for affective learning models.

Contingency Learning in Human Fear Conditioning Involves the Ventral Striatum

The ability to detect and learn contingencies between fearful stimuli and their predictive cues is an important capacity to cope with the environment. Contingency awareness refers to the ability to verbalize the relationships between conditioned and unconditioned stimuli. Although there is a heated debate about the influence of contingency awareness on conditioned fear responses, neural correlates behind the formation process of contingency awareness have gained only little attention in human fear conditioning. Recent animal studies indicate that the ventral striatum (VS) could be involved in this process, but in human studies the VS is mostly associated with positive emotions. To examine this question, we reanalyzed four recently published classical fear conditioning studies (n = 117) with respect to the VS at three distinct levels of contingency awareness: subjects, who did not learn the contingencies (unaware), subjects, who learned the contingencies during the experiment (learned aware) and subjects, who were informed about the contingencies in advance (instructed aware). The results showed significantly increased activations in the left and right VS in learned aware compared to unaware subjects. Interestingly, this activation pattern was only found in learned but not in instructed aware subjects. We assume that the VS is not involved when contingency awareness does not develop during conditioning or when contingency awareness is unambiguously induced already prior to conditioning. VS involvement seems to be important for the transition from a contingency unaware to a contingency aware state. Implications for fear conditioning models as well as for the contingency awareness debate are discussed. Hum Brain Mapp, 2009.

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.

Neural correlates of disgust and fear conditioned responses

The understanding of individual differences in responses to disgusting stimuli is important to gain more insight into the development of certain psychiatric disorders. The aim of this study was to investigate conditioned disgust responses, its potential overlap with conditioned fear responses (CRs) and the influence of disgust sensitivity on blood oxygen level-dependent responses. Yet even though current studies report evidence that disgust sensitivity is a vulnerability factor, the knowledge about the underlying neural mechanisms remains very limited. Two groups were exposed either to a disgust- or a fear-conditioning paradigm. Using functional magnetic resonance imaging, we identified a conjoint activated network including the cingulate cortex, the nucleus accumbens, the orbitofrontal cortex, and the occipital cortex within the disgust- and the fear-conditioning group. Moreover, we report evidence of increased insula activation in the disgust-conditioning group. In addition, functional connectivity analysis revealed increased interconnections, most pronounced within the insula in the high disgust sensitivity group compared with the low disgust sensitivity group. The conjunction results suggest that the conditioned responses in disgust and fear conditioning recruit the same neural network, implicating that different conditioned responses of aversive learning depend on a common neural network. Increased insula activation within the disgust-conditioning group might be attributable to heightened interoceptive processes, which might be more pronounced in disgust. Finally, the findings regarding disgust sensitivity are discussed with respect to vulnerability factors for certain psychiatric disorders.

Effects of inpatient psychotherapy on the stability of alexithymia characteristics

BACKGROUND Although alexithymia is associated with several psychiatric disorders, there has been little research into the effects of psychodynamic psychotherapies on this condition. Here, the influence of inpatient multimodal psychodynamic psychotherapy on alexithymia and symptom load was evaluated in a large sample of patients. METHODS Alexithymia [measured with the Toronto Alexithymia Scale (TAS)-26] and psychological stress and depression [measured with the Symptom Checklist 90 Revised (SCL-90-R)] were evaluated at admission and after inpatient multimodal psychotherapy in patients with various psychosomatic and psychiatric disorders admitted to this unit between 2002 and 2005. Patients undergoing both short-term (up to 4 weeks) and long-term treatment (8-12 weeks) were studied. Analyses of covariance were used to analyse the data on depression (SCL-90-R) and psychological stress (SCL-90-R), and correlations between admission and discharge scores for the TAS-26 were computed to evaluate mean and relative stability of alexithymia. RESULTS Data on 397 of the 568 patients admitted were analysed. Psychological stress and depression (SCL-90-R) decreased significantly during the study across all diagnostic groups. The TAS-26 total score also decreased significantly, showing that there was no mean stability of alexithymic characteristics. However, the significance of decrease was lost when psychological stress and depression were controlled for. Highly significant correlations between TAS-26 sores before and after treatment reflected high relative stability of alexithymia. CONCLUSIONS During inpatient multimodal psychodynamic treatment, the symptom load and alexithymia in our patients decreased. The high relative stability of alexithymia shown supports the view that alexithymia is a relative stable personality trait.

Neural Activation Toward Erotic Stimuli in Homosexual and Heterosexual Males

INTRODUCTION Studies investigating sexual arousal exist, yet there are diverging findings on the underlying neural mechanisms with regard to sexual orientation. Moreover, sexual arousal effects have often been confounded with general arousal effects. Hence, it is still unclear which structures underlie the sexual arousal response in homosexual and heterosexual men. AIM Neural activity and subjective responses were investigated in order to disentangle sexual from general arousal. Considering sexual orientation, differential and conjoint neural activations were of interest. METHODS The functional magnetic resonance imaging (fMRI) study focused on the neural networks involved in the processing of sexual stimuli in 21 male participants (11 homosexual, 10 heterosexual). Both groups viewed pictures with erotic content as well as aversive and neutral stimuli. The erotic pictures were subdivided into three categories (most sexually arousing, least sexually arousing, and rest) based on the individual subjective ratings of each participant. MAIN OUTCOME MEASURES Blood oxygen level-dependent responses measured by fMRI and subjective ratings. RESULTS A conjunction analysis revealed conjoint neural activation related to sexual arousal in thalamus, hypothalamus, occipital cortex, and nucleus accumbens. Increased insula, amygdala, and anterior cingulate gyrus activation could be linked to general arousal. Group differences emerged neither when viewing the most sexually arousing pictures compared with highly arousing aversive pictures nor compared with neutral pictures. CONCLUSION Results suggest that a widespread neural network is activated by highly sexually arousing visual stimuli. A partly distinct network of structures underlies sexual and general arousal effects. The processing of preferred, highly sexually arousing stimuli recruited similar structures in homosexual and heterosexual males.

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.

Can you hear a difference? Neuronal correlates of melodic deviance processing in children

Many studies investigating music processing in adult musicians and nonmusicians point towards pronounced behavioral and neurophysiological differences between the two groups. Recent studies indicate that these differences can already be found in early childhood. Further, electro-encephalography studies using musical discrimination tasks have demonstrated that differences in music processing become more pronounced when explicitly rather than implicitly trained musical abilities are required. Exploring the functional neuroanatomy underlying the processing of different expectation violations in children and its association with musical training, we investigated neural responses to different melodic deviances in musically trained and untrained children. Using functional magnetic resonance imaging, children (aged 11-14 years) were examined while comparing pairs of short melodies that were either identical or differed with respect to four notes. The implemented deviances were either subtle (by inserting plausible in-key notes) or obvious (by inserting implausible out-of-key notes). Our results indicate a strong association between musical training and functional neuroanatomy of the brain. Similar to research on music processing in adults, the processing of obvious melodic deviances activated a network involving inferior frontal, premotor and anterior insula regions in musically trained and untrained children. By contrast, subtle deviances led to activation in the inferior frontal and premotor cortex, the anterior insula, the superior temporal gyrus, and the supramarginal gyrus in musically trained children only. Our work provides further insights into the functional neuroanatomy of melody processing and its association with musical training in children, providing the basis for further studies specifying distinct musical processes (e.g. contour and interval processing).