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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.

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.

Pain can be modulated by several cognitive techniques, typically involving increased cognitive control and decreased sensory processing. Recently, it has been demonstrated that pain can also be attenuated by mindfulness. Here, we investigate the underlying brain mechanisms by which the state of mindfulness reduces pain. Mindfulness practitioners and controls received unpleasant electric stimuli in the functional magnetic resonance imaging scanner during a mindfulness and a control condition. Mindfulness practitioners, but not controls, were able to reduce pain unpleasantness by 22% and anticipatory anxiety by 29% during a mindful state. In the brain, this reduction was associated with decreased activation in the lateral prefrontal cortex and increased activation in the right posterior insula during stimulation and increased rostral anterior cingulate cortex activation during the anticipation of pain. These findings reveal a unique mechanism of pain modulation, comprising increased sensory processing and decreased cognitive control, and are in sharp contrast to established pain modulation mechanisms.

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.

An important feature of addiction is the high drug craving that may promote the continuation of consumption. Environmental stimuli classically conditioned to drug-intake have a strong motivational power for addicts and can elicit craving. However, addicts differ in the attitudes towards their own consumption behavior: some are content with drug taking (consonant users) whereas others are discontent (dissonant users). Such differences may be important for clinical practice because the experience of dissonance might enhance the likelihood to consider treatment. This fMRI study investigated in smokers whether these different attitudes influence subjective and neural responses to smoking stimuli. Based on self-characterization, smokers were divided into consonant and dissonant smokers. These two groups were presented smoking stimuli and neutral stimuli. Former studies have suggested differences in the impact of smoking stimuli depending on the temporal stage of the smoking ritual they are associated with. Therefore, we used stimuli associated with the beginning (BEGIN-smoking-stimuli) and stimuli associated with the terminal stage (END-smoking-stimuli) of the smoking ritual as distinct stimulus categories. Stimulus ratings did not differ between both groups. Brain data showed that BEGIN-smoking-stimuli led to enhanced mesolimbic responses (amygdala, hippocampus, insula) in dissonant compared to consonant smokers. In response to END-smoking-stimuli, dissonant smokers showed reduced mesocortical responses (orbitofrontal cortex, subcallosal cortex) compared to consonant smokers. These results suggest that smoking stimuli with a high incentive value (BEGIN-smoking-stimuli) are more appetitive for dissonant than consonant smokers at least on the neural level. To the contrary, smoking stimuli with low incentive value (END-smoking-stimuli) seem to be less appetitive for dissonant smokers than consonant smokers. These differences might be one reason why dissonant smokers experience difficulties in translating their attitudes into an actual behavior change.

In an fMRI study, effects of contingency awareness on conditioned responses were assessed in three groups comprising 118 subjects. A differential fear-conditioning paradigm with visual conditioned stimuli, an electrical unconditioned stimulus and two distractors was applied. The instructed aware group was informed about the contingencies, whereas the distractors prevented contingency detection in the unaware group. The third group (learned aware) was not informed about the contingencies, but learned them despite the distractors. Main effects of contingency awareness on conditioned responses emerged in several brain structures. Post hoc tests revealed differential dorsal anterior cingulate, insula and ventral striatum responses in aware conditioning only, whereas the amygdala was activated independent of contingency awareness. Differential responses of the hippocampus were specifically observed in learned aware subjects, indicating a role in the development of contingency awareness. The orbitofrontal cortex showed varying response patterns: lateral structures showed higher responses in instructed aware than unaware subjects, the opposite was true for medial parts. Conditioned subjective and electrodermal responses emerged only in the two aware groups. These results confirm the independence of conditioned amygdala responses from contingency awareness and indicate specific neural circuits for different aspects of fear acquisition in unaware, learned aware and instructed aware subjects.

Several studies provide empirical evidence for the association between impulsivity and time perception. However, little is known about the neural substrates underlying this function. This investigation examined the influence of impulsivity on neural activation patterns during the encoding and reproduction of intervals with durations of 3, 9 and 18s using event-related functional magnetic resonance imaging (fMRI). Twenty-seven subjects participated in this study, including 15 high impulsive subjects that were classified based on their self-rating. FMRI activation during the duration reproduction task was correlated with measures of two self-report questionnaires related to the concept of impulsivity (Barratt Impulsiveness Scale, BIS; Zimbardo Time Perspective Inventory, ZTPI). Behaviorally, those individuals who under-reproduced temporal intervals also showed lower scores on the ZTPI future perspective subscale and higher scores on the BIS. FMRI activation revealed an accumulating pattern of neural activity peaking at the end of the 9- and 18-s intervals within right posterior insula. Activations of brain regions during the reproduction phase of the timing task, such as those related to motor execution as well as to the 'core control network' - encompassing the inferior frontal and medial frontal cortices, the anterior insula as well as the inferior parietal cortex - were significantly correlated with reproduced duration, as well as with BIS and ZTPI subscales. In particular, the greater activation in these regions the shorter were the reproduced intervals, the more impulsive was an individual and the less pronounced the future perspective. Activation in the core control network, thus, may form a biological marker for cognitive time management and for impulsiveness.

Event-related functional magnetic resonance imaging was applied to identify cortical areas involved in maintaining target information in working memory used for an upcoming grasping action. Participants had to grasp with their thumb and index finger of the dominant right hand three-dimensional objects of different size and orientation. Reaching-to-grasp movements were performed without visual feedback either immediately after object presentation or after a variable delay of 2-12 s. The right inferior parietal cortex demonstrated sustained neural activity throughout the delay, which overlapped with activity observed during encoding of the grasp target. Immediate and delayed grasping activated similar motor-related brain areas and showed no differential activity. The results suggest that the right inferior parietal cortex plays an important functional role in working memory maintenance of grasp-related information. Moreover, our findings confirm the assumption that brain areas engaged in maintaining information are also involved in encoding the same information, and thus extend previous findings on working memory function of the posterior parietal cortex in saccadic behavior to reach-to-grasp movements.

Perceiving a first target stimulus (T1) in a rapid serial visual presentation stream results in a transient impairment in detecting a second target (T2). This "attentional blink" is modulated by the emotional relevance of T1 and T2. The present experiment examined the neural underpinnings of the emotional modulation of the attentional blink. Behaviorally, the attentional blink was reduced for emotional T2 while emotional T1 led to a prolonged attentional blink. Using functional magnetic resonance imaging, we observed amygdala activation associated with the reduced attentional blink for emotional T2 in the face of neutral T1. The prolonged attentional blink following emotional T1 was correlated with enhanced activity in a cortical network including the anterior cingulate cortex, the insula and the orbitofrontal cortex. These results suggest that brain areas previously implicated in rather reflexive emotional reactions are responsible for the reduced attentional blink for emotional T2 whereas neural structures previously related to higher level processing of emotional information mediate the prolonged attentional blink following emotional T1.

Neuroimaging studies on attention-deficit/hyperactivity disorder (ADHD) suggest dysfunctional reward processing, with hypo-responsiveness during reward anticipation in the reward system including the nucleus accumbens (NAcc). In this study, we investigated the association between ADHD related behaviors and the reward system using functional magnetic resonance imaging in a non-clinical sample. Participants were 31 healthy, female undergraduate students with varying levels of self-reported ADHD related behaviors measured by the adult ADHD self-report scale. The anticipation of different types of reward was investigated: monetary reward, punishment avoidance, and verbal feedback. All three reward anticipation conditions were found to be associated with increased brain activation in the reward system, with the highest activation in the monetary reward anticipation condition, followed by the punishment avoidance anticipation condition, and the lowest activation in the verbal feedback anticipation condition. Most interestingly, in all three conditions, NAcc activation was negatively correlated with ADHD related behaviors. In conclusion, our results from a non-clinical sample are in accordance with reported deficits in the reward system in ADHD patients: the higher the number and severity of ADHD related behaviors, the lower the neural responses in the dopaminergic driven reward anticipation task. Thus, our data support current aetiological models of ADHD which assume that deficits in the reward system might be responsible for many of the ADHD related behaviors.

Previously, we observed cortisol induced enhancement of neural fear acquisition in women. Yet, less is known about cortisol effects on neural fear extinction. Via differential fear conditioning, we explored cortisol effects on acquisition and extinction. Twenty contingency aware women taking monophasic oral contraceptives were included; 10 received placebo, 10 cortisol before conditioning. Group differences emerged in anterior cingulate cortex (ACC), hippocampus, and--as trend--in insula and thalamus during acquisition and in hippocampus, thalamus, and--as trend--in amygdala, insula, and ACC during extinction. During acquisition group differences were due to higher responses to the CS+ than to the CS- in the cortisol group. Notably, during extinction, group differences were due to higher responses to the CS- than to the CS+ in this group. Thus, cortisol induced a fear acquisition and extinction specific enhanced neural differentiation.

BACKGROUND: Action observation leads to neural activation of the human premotor cortex. This study examined how the level of motor expertise (expert vs. novice) in ballroom dancing and the visual viewpoint (internal vs. external viewpoint) influence this activation within different parts of this area of the brain. RESULTS: Sixteen dance experts and 16 novices observed ballroom dance videos from internal or external viewpoints while lying in a functional magnetic resonance imaging scanner. A conjunction analysis of all observation conditions showed that action observation activated distinct networks of premotor, parietal, and cerebellar structures. Experts revealed increased activation in the ventral premotor cortex compared to novices. An internal viewpoint led to higher activation of the dorsal premotor cortex. CONCLUSIONS: The present results suggest that the ventral and dorsal premotor cortex adopt differential roles during action observation depending on the level of motor expertise and the viewpoint.

Functional magnetic resonance imaging studies have examined neural correlates of disgust imagery, but have never taken into account the moderating effects of personality traits. Twenty-four women first viewed and subsequently visualized pictures with disgust-inducing and happiness-inducing content. Relative to the picture perception, disgust, and happiness imagery provoked activation of the insula, anterior cingulate cortex, and parietal cortex. Trait disgust was negatively correlated with localized brain activation (e.g. insula, amygdala, parietal cortex, anterior cingulate cortex) during disgust imagery. This study provides first evidence that disgust propensity is associated with brain activation during imagery of repulsive scenes.

Neurofunctional mechanisms underlying cognitive behavior therapy (CBT) are still not clearly understood. This functional magnetic resonance imaging (fMRI) study focused on changes in brain activation as a result of one-session CBT in patients suffering from spider phobia. Twenty-six female spider phobics and 25 non-phobic subjects were presented with spider pictures, generally disgust-inducing, generally fear-inducing and affectively neutral scenes in an initial fMRI session. Afterwards, the patients were randomly assigned to either a therapy group (TG) or a waiting list group (WG). The scans were repeated one week after the treatment or after a one-week waiting period. Relative to the non-phobic participants, the patients displayed increased activation in the amygdala and the fusiform gyrus as well as decreased activation in the medial orbitofrontal cortex (OFC) during the first exposure. The therapy effect consisted of increased medial OFC activity in the TG relative to the WG. Further, therapy-related reductions in experienced somatic anxiety symptoms were positively correlated with activation decreases in the amygdala and the insula. We conclude that successful treatment of spider phobia is primarily accompanied by functional changes of the medial OFC. This brain region is crucial for the self-regulation of emotions and the relearning of stimulus-reinforcement associations.

Inconsistent findings from several functional magnetic resonance imaging (fMRI) studies on fear and disgust raise the question which brain regions are relatively specialized and which are general in the processing of these basic emotions. Some of these inconsistencies could partially be due to inter-individual differences in the experience of the applied emotional stimuli. In the present study, we therefore correlated the participants' individual online reports of fear and disgust with their hemodynamic responses towards each of the fear- and disgust-inducing scenes. Sixty six participants (32 females) took part in the fMRI study. In an event-related design, they saw 50 pictures with different emotional impact (10 neutral, 20 disgust-inducing, 20 fear-inducing). Pictures were presented for 4 s and participants rated each picture online - just after the presentation - on the dimensions disgust and fear among others. The results indicate that the processing of disgust- and fear-inducing pictures involves similar as well as distinct brain regions. Both emotional stimulus categories resulted in activations in the extended occipital cortex, in the prefrontal cortex, and in the amygdala. However, insula activations were only significantly correlated with subjective ratings of disgust, pointing to a specific role of this brain structure in the processing of disgust.

Functional magnetic resonance imaging (fMRI) studies consistently demonstrate an enhanced activation of the visual cortex in reaction to emotionally salient visual stimuli. This increase of activation is probably modulated by top-down processes, that are initiated in emotion processing structures, specifically the amygdala and the orbitofrontal cortex. In the present fMRI study, a differential fear conditioning paradigm was applied to investigate this assumed modulation. Hemodynamic responses towards a neutral visual stimulus (CS+) predicting an electrical stimulation (UCS) were compared with responses towards a neutral and unpaired stimulus (CS-). Thereby, particularly the time courses of neural responses were considered. Skin conductance measures were concurrently recorded. Our results show that the differentiation between CS+ and CS- within the amygdala and the extended visual cortex was accomplished during a late acquisition phase. In the orbitofrontal cortex the differentiation occurred at an earlier stage and was then sustained throughout acquisition. It is suggested that these altering activation patterns are reflecting different phases of learning, integrating the analyzed regions to varying degrees. Additionally, the results indicate that statistical analyses comprising a temporal variation of hemodynamic responses are more likely to detect amygdala activation.

The majority of neuroimaging studies on affective processing have indicated that there are specific brain structures, which are selectively responsive to fear and disgust. Whereas the amygdala is assumed to be fear-related, the insular cortex is most likely involved in disgust processing. Since these findings are mainly a result of studies focusing exclusively either on fear, or on disgust, but rarely on both emotions together, the present experiment explored the neural effects of viewing disgusting and fear-inducing pictures in contrast to neutral pictures. This was done by means of functional magnetic resonance imaging (fMRI) with 19 subjects (nine males, ten females), who also gave affective ratings for the presented pictures. The fear and the disgust pictures were able to induce the target emotions and they received comparable valence and arousal ratings. The processing of both aversive picture types was associated with an increased brain activation in the occipital-temporal lobe, in the prefrontal cortex, and in the thalamus. The amygdala was significantly activated by disgusting, but not by fear-inducing, pictures. Thus, our data are in contrast with the idea of highly emotion-specific brain structures and rather suggest the existence of a common affective circuit.

Findings from animal as well as human neuroimaging studies suggest that reward delivery is associated with the activation of subcortical limbic and prefrontal brain regions, including the thalamus, the striatum, the anterior cingulate and the prefrontal cortex. The aim of the present study was to explore if these reward-sensitive regions are also activated during the anticipation of reinforcers that vary with regard to their motivational value. A differential conditioning paradigm was performed, with the presentation of a rewarded reaction time task serving as the unconditioned stimulus (US). Depending on their reaction time, subjects were given (or not given) a monetary reward, or were presented with a verbal feedback consisting of being fast or slow. In a third control condition no task needed to be executed. Each of the three conditions was introduced by a different visual cue (CS). Brain activation of 27 subjects was recorded using event-related functional magnetic resonance imaging. The results showed significant activation of the substantia nigra, thalamic, striatal, and orbitofrontal brain regions as well as of the insula and the anterior cingulate during the presentation of a CS signalling a rewarded task. The anticipation of a monetary reward produced stronger activation in these regions than the anticipation of positive verbal feedback. The results are interpreted as reflecting the motivation-dependent reactivity of the brain reward system with highly motivating stimuli (monetary reward) leading to a stronger activation than those less motivating ones (verbal reward).