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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.

The effects of sex and stress hormones on classical fear conditioning have been subject of recent experimental studies. A correlation approach between basal cortisol concentrations and neuronal activation in fear-related structures seems to be a promising alternative approach in order to foster our understanding of how cortisol influences emotional learning. In this functional magnetic resonance imaging study, participants with varying sex hormone status (20 men, 15 women taking oral contraceptives, 15 women tested in the luteal phase) underwent an instructed fear conditioning protocol with geometrical figures as conditioned stimuli and an electrical stimulation as unconditioned stimulus. Salivary cortisol concentrations were measured and afterwards correlated with fear conditioned brain responses. Results revealed a positive correlation between basal cortisol levels and differential activation in the amygdala in men and OC women only. These results suggest that elevated endogenous cortisol levels are associated with enhanced fear anticipation depending on current sex hormone availability.

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.

Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ventromedial prefrontal cortex was observed. Furthermore, phobia-specific effortful regulation within phobics was associated with altered activity in medial prefrontal cortex areas. Altogether, these results suggest that spider phobic subjects are indeed characterized by a deficit in the automatic as well as the effortful regulation of emotions elicited by phobic compared with aversive stimuli. These two forms of phobic emotion regulation deficits are associated with altered activity in different medial prefrontal cortex subregions.

OBJECTIVE: The quality of averaged gradient artifact subtraction from EEG recorded during fMRI is highly dependent on the accuracy of gradient artifact sampling. Even small sampling shifts (e.g. a single datapoint at 5kHz) increase the variance of the sampled gradient artifacts because of very steep slopes in the signal time course. Hence, although principally gradient artifacts are invariant signals because of their technical origin, variance attributed to sampling errors attenuates the effect of artifact removal. Recently, it has been shown that synchronizing the EEG-amplifier clock to the MR-scanner control-device clock improves artifact reduction by subtraction. METHODS: In order to investigate the synchronized measurement of combined EEG-fMRI, we used simulated EEG by measuring function generator signals in the MR-scanner. Only the usage of known signals allows an assessment of the improvement in accuracy of artifact recording by synchronized compared to non-synchronized measurement, since the signal is identical in both conditions. RESULTS: After averaged gradient artifact subtraction synchronized recorded signals were apparently less distorted than non-synchronized recorded signals. Spectral analyses revealed that especially artifact frequencies above 50Hz had less power in restored synchronized compared to restored non-synchronized recorded signals. Computed total signal variances were not always less in restored synchronized compared to restored non-synchronized recorded signals. CONCLUSIONS: Taken together, synchronizing simultaneous EEG-fMRI measurement is a useful enhancement for averaged gradient artifact subtraction although post-correction filtering is still necessary. SIGNIFICANCE: Our results support the recent finding that synchronization improves the quality of averaged gradient artifact subtraction. However, quantitatively we could not verify a systematic benefit of recording electrical signals during fMRI synchronously rather than non-synchronously to the MR-scanner control-device clock.

The simulation concept suggested by Jeannerod (Neuroimage 14:S103-S109, 2001) defines the S-states of action observation and mental simulation of action as action-related mental states lacking overt execution. Within this framework, similarities and neural overlap between S-states and overt execution are interpreted as providing the common basis for the motor representations implemented within the motor system. The present brain imaging study compared activation overlap and differential activation during mental simulation (motor imagery) with that while observing gymnastic movements. The fMRI conjunction analysis revealed overlapping activation for both S-states in primary motor cortex, premotor cortex, and the supplementary motor area as well as in the intraparietal sulcus, cerebellar hemispheres, and parts of the basal ganglia. A direct contrast between the motor imagery and observation conditions revealed stronger activation for imagery in the posterior insula and the anterior cingulate gyrus. The hippocampus, the superior parietal lobe, and the cerebellar areas were differentially activated in the observation condition. In general, these data corroborate the concept of action-related S-states because of the high overlap in core motor as well as in motor-related areas. We argue that differential activity between S-states relates to task-specific and modal information processing.

Mindfulness meditators practice the non-judgmental observation of the ongoing stream of internal experiences as they arise. Using voxel-based morphometry, this study investigated MRI brain images of 20 mindfulness (Vipassana) meditators (mean practice 8.6 years; 2 h daily) and compared the regional gray matter concentration to that of non-meditators matched for sex, age, education and handedness. Meditators were predicted to show greater gray matter concentration in regions that are typically activated during meditation. Results confirmed greater gray matter concentration for meditators in the right anterior insula, which is involved in interoceptive awareness. This group difference presumably reflects the training of bodily awareness during mindfulness meditation. Furthermore, meditators had greater gray matter concentration in the left inferior temporal gyrus and right hippocampus. Both regions have previously been found to be involved in meditation. The mean value of gray matter concentration in the left inferior temporal gyrus was predictable by the amount of meditation training, corroborating the assumption of a causal impact of meditation training on gray matter concentration in this region. Results suggest that meditation practice is associated with structural differences in regions that are typically activated during meditation and in regions that are relevant for the task of meditation.

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.

This study investigated differences in brain activation during meditation between meditators and non-meditators. Fifteen Vipassana meditators (mean practice: 7.9 years, 2h daily) and fifteen non-meditators, matched for sex, age, education, and handedness, participated in a block-design fMRI study that included mindfulness of breathing and mental arithmetic conditions. For the meditation condition (contrasted to arithmetic), meditators showed stronger activations in the rostral anterior cingulate cortex and the dorsal medial prefrontal cortex bilaterally, compared to controls. Greater rostral anterior cingulate cortex activation in meditators may reflect stronger processing of distracting events. The increased activation in the medial prefrontal cortex may reflect that meditators are stronger engaged in emotional processing.

Findings from several functional magnetic resonance imaging (fMRI) studies implicate the existence of a distinct neural disgust substrate, whereas others support the idea of distributed and integrative brain systems involved in emotional processing. In the present fMRI experiment 12 healthy females viewed pictures from four emotion categories. Two categories were disgust-relevant and depicted contamination or mutilation. The other scenes showed attacks (fear) or were affectively neutral. The two types of disgust elicitors received comparable ratings for disgust, fear and arousal. Both were associated with activation of the occipitotemporal cortex, the amygdala, and the orbitofrontal cortex; insula activity was nonsignificant in the two disgust conditions. Mutilation scenes induced greater inferior parietal activity than contamination scenes, which might mirror their greater capacity to capture attention. Our results are in disagreement with the idea of selective disgust processing at the insula. They point to a network of brain regions involved in the decoding of stimulus salience and the regulation of attention.