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Cognitive reappraisal and expressive suppression, two major emotion regulation strategies, are differentially related to emotional well-being. The aim of this study was to test the association of individual differences in these two emotion regulation strategies with gray matter volume of brain regions that have been shown to be involved in the regulation of emotions. Based on high-resolution magnetic resonance images of 96 young adults voxel-based morphometry was used to analyze the gray matter volumes of the a priori regions of interest, including amygdala, insula, dorsal anterior cingulate and paracingulate cortex, medial and lateral prefrontal cortex (PFC) and their association with cognitive reappraisal and expressive suppression usage as well as neuroticism. A positive association of cognitive reappraisal with right and tendentially left amygdala volume and of neuroticism with left amygdala volume (marginally significant) was found. Expressive suppression was related to dorsal anterior cingulate/paracingulate cortex and medial PFC gray matter volume. The results of this study emphasize the important role of the amygdala in individual differences in cognitive reappraisal usage as well as neuroticism. Additionally, the association of expressive suppression usage with larger volumes of the medial PFC and dorsal anterior/paracingulate cortex underpins the role of these regions in regulating emotion-expressive behavior.

Cocaine-dependent individuals show altered brain activation during decision making. It is unclear, however, whether these activation differences are related to relapse vulnerability. This study tested the hypothesis that brain-activation patterns during reinforcement learning are linked to relapse 1 year later in individuals entering treatment for cocaine dependence. Subjects performed a Paper-Scissors-Rock task during functional magnetic resonance imaging (fMRI). A year later, we examined whether subjects had remained abstinent (n=15) or relapsed (n=15). Although the groups did not differ on demographic characteristics, behavioral performance, or lifetime substance use, abstinent patients reported greater motivation to win than relapsed patients. The fMRI results indicated that compared with abstinent individuals, relapsed users exhibited lower activation in (1) bilateral inferior frontal gyrus and striatum during decision making more generally; and (2) bilateral middle frontal gyrus and anterior insula during reward contingency learning in particular. Moreover, whereas abstinent patients exhibited greater left middle frontal and striatal activation to wins than losses, relapsed users did not demonstrate modulation in these regions as a function of outcome valence. Thus, individuals at high risk for relapse relative to those who are able to abstain allocate fewer neural resources to action-outcome contingency formation and decision making, as well as having less motivation to win on a laboratory-based task.

There is some evidence that neuroimaging can be used to predict relapse among abstinent methamphetamine-dependent (MD) individuals. However, it remains unclear what cognitive and neural processes contribute to relapse. This investigation examined whether insula activation during risk-taking decisions-a process shown to be disrupted in MD-is able to predict susceptibility for relapse. Sixty-eight MD enrolled in a treatment program during early abstinence completed a risk-taking task during functional magnetic resonance imaging. Sixty-three of the sixty-eight individuals were followed up 1 year after the study. Of these, 18 MD reported relapse. The 45 abstinent MD showed patterns of insula activation during risky decisions that resembled those found in prior studies of healthy controls, consisting of lower insula activation during safe decisions paired with higher activation during risky decisions. In contrast, the 18 relapsed MD showed similar insula activation during safe and risky decisions. An increase in one standard deviation in the difference in insula activation between risky and safe choices was associated with a 0.34 odds ratio for relapse at any given time. A median split of insula activation (difference between risky and safe) showed that individuals in the bottom half were two times more likely to relapse. In addition, a model that included several other brain regions increased prediction accuracy compared with insula-based model alone. These results suggest that failure to differentially activate the insula as a function of risk is a part of an altered risk-processing network associated with an increased susceptibility to relapse.

The belief in free will has been frequently challenged since Benjamin Libet published his famous experiment in 1983. Although Libet's experiment is highly dependent upon subjective reports, no study has been conducted that focused on a first-person or introspective perspective of the task. We took a neurophenomenological approach in an N=1 study providing reliable and valid measures of the first-person perspective in conjunction with brain dynamics. We found that a larger readiness potential (RP) is attributable to more frequent occurrences of self-initiated movements during negative deflections of the slow cortical potentials (SCP). These negative deflections occur in parallel with an inner impulse reported by an expert meditator which may in turn lead to a voluntary act. We demonstrate in this proof-of-principle approach that the first-person perspective obtained by an expert meditator in conjunction with neural signal analysis can contribute to our understanding of the neural underpinnings of voluntary acts.

This study addresses the controversy over how motor maps are organized during action simulation by examining whether action simulation states, that is, motor imagery and action observation, run on either effector-specific and/or action-specific motor maps. Subjects had to observe or imagine three types of movements effected by the right hand or the right foot with different action goals. The functional magnetic resonance imaging results showed an action-specific organization within premotor and posterior parietal areas of both hemispheres during action simulation, especially during action observation. There were also less pronounced effector-specific activation sites during both simulation processes. It is concluded that the premotor and parietal areas contain multiple motor maps rather than a single, continuous map of the body. The forms of simulation (observation, imagery), the task contexts (movements related to an object, with usual/unusual effector), and the underlying reason for performing the simulation (rate your subjective success afterwards) lead to the specific use of different representational motor maps within both regions. In our experimental setting, action-specific maps are dominant especially, during action observation, whereas effector-specific maps are recruited to only a lesser degree.

Data from three experiments on serial perception of temporal intervals in the supra-second domain are reported. Sequences of short acoustic signals ("pips") separated by periods of silence were presented to the observers. Two types of time series, geometric or alternating, were used, where the modulus 1+δ of the inter-pip series and the base duration Tb (range from 1.1 to 6s) were varied as independent parameters. The observers had to judge whether the series were accelerating, decelerating, or uniform (3 paradigm), or to distinguish regular from irregular sequences (2 paradigm). "Intervals of subjective uniformity" (isus) were obtained by fitting Gaussian psychometric functions to individual subjects' responses. Progression towards longer base durations (Tb=4.4 or 6s) shifts the isus towards negative δs, i.e., accelerating series. This finding is compatible with the phenomenon of "subjective shortening" of past temporal intervals, which is naturally accounted for by the lossy integration model of internal time representation. The opposite effect observed for short durations (Tb=1.1 or 1.5s) remains unexplained by the lossy integration model, and presents a challenge for further research.

We investigated the impact of sexual stimuli and the influence of sexual motivation on the performance in a dot-probe task and a line-orientation task in a large sample of males and females. All pictures (neutral, erotic) were rated on the dimensions of valence, arousal, disgust, and sexual arousal. Additionally, questionnaires measuring sexual interest/desire/motivation were employed. The ratings of the sexual stimuli point to a successful picture selection because sexual arousal did not differ between the sexes. The stimuli were equally arousing for men and women. Higher scores in the employed questionnaires measuring sexual interest/desire/motivation led to higher sexual arousal ratings of the sex pictures. Attentional bias towards sex pictures was observed in both experimental tasks. The attentional biases measured by the dot-probe and the line-orientation task were moderately intercorrelated suggesting attentional bias as a possible marker for a sex-attention trait. Finally, only the sexual sensation seeking score correlated with the attentional biases of the two tasks. Future research is needed to increase the predictive power of these indirect measures of sexual interest.

BACKGROUND: Asperger Autism is a lifelong psychiatric condition with highly circumscribed interests and routines, problems in social cognition, verbal and nonverbal communication, and also perceptual abnormalities with sensory hypersensitivity. To objectify both lower-level visual and cognitive alterations we looked for differences in visual event-related potentials (EEG) between Asperger observers and matched controls while they observed simple checkerboard stimuli. METHODS: In a balanced oddball paradigm checkerboards of two checksizes (0.6° and 1.2°) were presented with different frequencies. Participants counted the occurrence times of the rare fine or rare coarse checkerboards in different experimental conditions. We focused on early visual ERP differences as a function of checkerboard size and the classical P3b ERP component as an indicator of cognitive processing. RESULTS: We found an early (100-200 ms after stimulus onset) occipital ERP effect of checkerboard size (dominant spatial frequency). This effect was weaker in the Asperger than in the control observers. Further a typical parietal/central oddball-P3b occurred at 500 ms with the rare checkerboards. The P3b showed a right-hemispheric lateralization, which was more prominent in Asperger than in control observers. DISCUSSION: The difference in the early occipital ERP effect between the two groups may be a physiological marker of differences in the processing of small visual details in Asperger observers compared to normal controls. The stronger lateralization of the P3b in Asperger observers may indicate a stronger involvement of the right-hemispheric network of bottom-up attention. The lateralization of the P3b signal might be a compensatory consequence of the compromised early checksize effect. Higher-level analytical information processing units may need to compensate for difficulties in low-level signal analysis.

Ambiguous figures attract observers because perception alternates between different interpretations while the sensory information stays unchanged. Understanding the underlying processes is difficult because the precise time instant of this endogenous reversal event needs to be known but is difficult to measure. Presenting ambiguous figures discontinuously and using stimulus onset as estimation of the reversal event increased temporal resolution and provided a series of well-confirmed EEG signatures. In the current EEG study we used this 'onset paradigm' for the first time with Boring's old/young woman stimulus. We found an early occipital event-related potential (ERP) correlate of reversals between the perception of the old woman and the perception of the young woman that fits well with previous ERP findings. This component was not followed by the often-reported occipito-parietal Reversal Negativity at 260 ms, but instead by an occipito-temporal N170, that is typically reported with face stimuli. We interpret our results as follows: ambiguity conflicts take place during processing of stimulus elements in early visual areas roughly 130 ms after stimulus onset. The disambiguation of these elements and their assembly to object 'gestalts' result from an interplay between early visual and object-specific brain areas in a temporal window between 130 and 260 ms after stimulus onset. In the particular case of Boring's old/young woman the processes of element disambiguation and gestalt construction are already finished at 170 ms and, thus, 90 ms earlier than in the case of ambiguous geometric figures (eg Necker cube or Schroeder staircase) or of binocular rivalrous gratings.

Temporally distributed ("spaced") learning can be twice as efficient as massed learning. This "spacing effect" occurs with a broad spectrum of learning materials, with humans of different ages, with non-human vertebrates and also invertebrates. This indicates, that very basic learning mechanisms are at work ("generality"). Although most studies so far focused on very narrow spacing interval ranges, there is some evidence for a non-monotonic behavior of this "spacing effect" ("nonlinearity") with optimal spacing intervals at different time scales. In the current study we focused both the nonlinearity aspect by using a broad range of spacing intervals and the generality aspect by using very different learning/practice domains: Participants learned German-Japanese word pairs and performed visual acuity tests. For each of six groups we used a different spacing interval between learning/practice units from 7 min to 24 h in logarithmic steps. Memory retention was studied in three consecutive final tests, one, seven and 28 days after the final learning unit. For both the vocabulary learning and visual acuity performance we found a highly significant effect of the factor spacing interval on the final test performance. In the 12 h-spacing-group about 85% of the learned words stayed in memory and nearly all of the visual acuity gain was preserved. In the 24 h-spacing-group, in contrast, only about 33% of the learned words were retained and the visual acuity gain dropped to zero. The very similar patterns of results from the two very different learning/practice domains point to similar underlying mechanisms. Further, our results indicate spacing in the range of 12 hours as optimal. A second peak may be around a spacing interval of 20 min but here the data are less clear. We discuss relations between our results and basic learning at the neuronal level.

The perception of time is a fundamental part of human experience. Recent research suggests that the experience of time emerges from emotional and interoceptive (bodily) states as processed in the insular cortex. Whether there is an interaction between the conscious awareness of interoceptive states and time distortions induced by emotions has rarely been investigated so far. We aimed to address this question by the use of a retrospective time estimation task comparing two groups of participants. One group had a focus on interoceptive states and one had a focus on exteroceptive information while watching film clips depicting fear, amusement and neutral content. Main results were that attention to interoceptive processes significantly affected subjective time experience. Fear was accompanied with subjective time dilation that was more pronounced in the group with interoceptive focus, while amusement led to a quicker passage of time which was also increased by interoceptive focus. We conclude that retrospective temporal distortions are directly influenced by attention to bodily responses. These effects might crucially interact with arousal levels. Sympathetic nervous system activation affecting memory build-up might be the decisive factor influencing retrospective time judgments. Our data substantially extend former research findings underscoring the relevance of interoception for the effects of emotional states on subjective time experience.

It has been repeatedly shown that specific brain activity related to planning movement develops before the conscious intention to act. This empirical finding strongly challenges the notion of free will. Here, we demonstrate that in the Libet experiment, spontaneous fluctuations of the slow electro-cortical potentials (SCPs) account for a significant fraction of the readiness potential (RP). The individual potential shifts preceding self-initiated movements were classified as showing a negative or positive shift. The negative and positive potential shifts were analyzed in a self-initiated movement condition and in a no-movement condition. Comparing the potential shifts between both conditions, we observed no differences in the early part of the potential. This reveals that the apparently negative RP emerges through an unequal ratio of negative and positive potential shifts. These results suggest that ongoing negative shifts of the SCPs facilitate self-initiated movement but are not related to processes underlying preparation or decision to act.

Stress and fear conditioning processes are both important vulnerability factors in the development of psychiatric disorders. In behavioral studies considerable sex differences in fear learning have been observed after increases of the stress hormone cortisol. But neuroimaging experiments, which give insights into the neurobiological correlates of stress × sex interactions in fear conditioning, are lacking so far. In the current functional magnetic resonance imaging (fMRI) study, we tested whether a psychosocial stressor (Trier Social Stress Test) compared to a control condition influenced subsequent fear conditioning in 48 men and 48 women taking oral contraceptives (OCs). One of two pictures of a geometrical figure was always paired (conditioned stimulus, CS+) or never paired (CS-) with an electrical stimulation (unconditioned stimulus). BOLD responses as well as skin conductance responses were assessed. Sex-independently, stress enhanced the CS+/CS- differentiation in the hippocampus in early acquisition but attenuated conditioned responses in the medial frontal cortex in late acquisition. In early acquisition, stress reduced the CS+/CS- differentiation in the nucleus accumbens in men, but enhanced it in OC women. In late acquisition, the same pattern (reduction in men, enhancement in OC women) was found in the amygdala as well as in the anterior cingulate. Thus, psychosocial stress impaired the neuronal correlates of fear learning and expression in men, but facilitated them in OC women. A sex-specific modulation of fear conditioning after stress might contribute to the divergent prevalence of men and women in developing psychiatric disorders.

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.

Disgust extinction is an important mechanism relevant for the treatment of psychiatric disorders. However, only a few studies have investigated disgust extinction. Moreover, because disgust sensitivity (DS) is considered as a relevant factor for learning processes, this study also investigated the potential relationship between DS and disgust extinction learning. The aim of this study was to explore the neuronal correlates of disgust extinction, as well as changes in skin conductance responses (SCRs) and evaluative conditioning. Twenty subjects were exposed to a differential extinction paradigm, in which a previous conditioned, and now unreinforced, stimulus (conditioned stimulus, CS+) was compared to a second stimulus (CS-), which was previously not associated with the unconditioned stimulus (UCS). Extinction learning was measured on three different response levels (BOLD responses, SCRs, and evaluative conditioning). Regarding evaluative conditioning, the CS+ was rated as more unpleasant than the CS-. Interestingly, significantly increased amygdala responses and SCRs toward to the CS- were observed. Finally, a (negative) trend was found between DS scores and BOLD responses of the prefrontal cortex. The present findings showed a dissociation of different response levels. The increased CS- responses could be explained by the assumption that the increased amygdala activity may reflect a safety learning signal during the first extinction trials and the subjective focus may therefore shift from the CS+ to the CS-. The correlation finding supports previous studies postulating that DS hampers extinction processes. The present results point toward dissociations between the response levels in context of extinction processes.

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.

Fear learning is a crucial process in the pathogeneses of psychiatric disorders, which highlights the need to identify specific factors contributing to interindividual variation. We hypothesized variation in the serotonin transporter gene (5-HTTLPR) and stressful life events (SLEs) to be associated with neural correlates of fear conditioning in a sample of healthy male adults (n = 47). Subjects were exposed to a differential fear conditioning paradigm after being preselected regarding 5-HTTLPR genotype and SLEs. Individual differences in brain activity as measured by functional magnetic resonance imaging (fMRI), skin conductance responses and preference ratings were assessed. We report significant variation in neural correlates of fear conditioning as a function of 5-HTTLPR genotype. Specifically, the conditioned stimulus (CS(+)) elicited elevated activity within the fear-network (amygdala, insula, thalamus, occipital cortex) in subjects carrying two copies of the 5-HTTLPR S' allele. Moreover, our results revealed preliminary evidence for a significant gene-by-environment interaction, such as homozygous carriers of the 5-HTTLPR S' allele with a history of SLEs demonstrated elevated reactivity to the CS(+) in the occipital cortex and the insula. Our findings contribute to the current debate on 5-HTTLPR x SLEs interaction by investigating crucial alterations on an intermediate phenotype level which may convey an elevated vulnerability for the development of psychopathology.

Aversive social learning experiences might play a significant role in the aetiology of social anxiety disorder. Therefore, we investigated emotional learning and unlearning processes in healthy humans using a social conditioning paradigm. Forty-nine healthy subjects participated in a 2-day fMRI differential conditioning protocol. Acquisition and extinction were conducted on Day 1 and extinction recall on Day 2. BOLD responses, ratings and skin conductance responses were collected. Our data indicate successful conditioning and extinction on the neural and subjective level. As a main result, we observed a positive correlation of social anxiety and conditioning responses on the subjective level (valence and fear) as well as on the neural level with significant CS(+)/CS(-) differentiation in the left amygdala and the left hippocampus. Further, significant CS(+)/CS(-) differentiation in the left amygdala was found during extinction and was associated with lower scores in social anxiety. During extinction recall, we found a tendentially negative correlation of social anxiety and CS(+)/CS(-) differentiation in the vmPFC. In sum, we were able to show that social anxiety is related to conditionability with socially threatening stimuli. This could point to an important aspect in the aetiology of social anxiety disorder.

A large number of competing models exist for how the brain creates a representation of time. However, several human and animal studies point to 'climbing neural activation' as a potential neural mechanism for the representation of duration. Neurophysiological recordings in animals have revealed how climbing neural activation that peaks at the end of a timed interval underlies the processing of duration, and, in humans, climbing neural activity in the insular cortex, which is associated with feeling states of the body and emotions, may be related to the cumulative representation of time.

Jeannerod (2001) hypothesized that action execution, imagery, and observation are functionally equivalent. This led to the major prediction that these motor states are based on the same action-specific and even effector-specific motor representations. The present study examined whether hand and foot movements are represented in a somatotopic manner during action execution, imagery, and action observation. The experiment contained ten conditions: three execution conditions, three imagery conditions, three observation conditions, and one baseline condition. In the nine experimental conditions, participants had to execute, observe, or imagine right-hand extension/flexion movements or right-foot extension/flexion movements. The fMRI results showed a somatotopic organization within the contralateral premotor and primary motor cortex during motor imagery and motor execution. However, there was no clear somatotopic organization of action observation in the given regions of interest within the contralateral hemisphere, although observation of these movements activated these areas significantly.