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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.

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.

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.

Two correlates of outcome processing in the orbitofrontal cortex (OFC) have been proposed in the literature: One hypothesis suggests that the lateral/medial division relates to representation of outcome valence (negative vs. positive), and the other suggests that the medial OFC maintains steady stimulus-outcome associations, whereas the lateral OFC represents changing (unsteady) outcomes to prepare for response shifts. These two hypotheses were contrasted by comparing the original with the inverted version of the Iowa Gambling Task in an event-related functional magnetic resonance imaging experiment. Results showed (1) that (caudo) lateral OFC was indeed sensitive to the steadiness of the outcomes and not merely to outcome valence and (2) that the original and the inverted tasks, although both designed to measure sensitivity for future outcomes, were not equivalent as they enacted different behaviors and brain activation patterns. Results are interpreted in terms of Kahneman and Tversky's prospect theory suggesting that cognitions and decisions are biased differentially when probabilistic future rewards are weighed against consistent punishments relative to the opposite scenario [Kahneman, D., & Tversky, A. Choices, values, and frames. American Psychologist, 39, 341-350, 1984]. Specialized processing of unsteady rewards (involving caudolateral OFC) may have developed during evolution in support of goal-related thinking, prospective planning, and problem solving.

Recent work has demonstrated the feasibility of simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Virtually no systematic comparisons between EEG recorded inside and outside the MR scanner have been conducted, and it is unknown if different kinds of frequency mix, topography, and domain-specific processing are uniformly recordable within the scanner environment. The aim of the study was to investigate several typical EEG waveforms in the same subjects inside the magnet during fMRI and outside the MR examination room. We examined whether uniform artifact subtraction allows the extraction of these different EEG waveforms inside the scanner during EPI scanning to the same extent as outside the scanner. Three well-established experiments were conducted, eliciting steady state visual evoked potentials (SSVEP), lateralized readiness potentials (LRP), and frontal theta enhancement induced by mental addition. All waveforms could be extracted from the EEG recorded during fMRI. Substantially no differences in these waveforms of interest were found between gradient-switching and intermediate epochs during fMRI (only the SSVEP-experiment was designed for a comparison of gradient-with intermediate epochs), or between waveforms recorded inside the scanner during EPI scanning and outside the MR examination room (all experiments). However, non-specific amplitude differences were found between inside and outside recorded EEG at lateral electrodes, which were not in any interaction with the effects of interest. The source of these differences requires further exploration. The high concordance of activation patterns with published results demonstrates that EPI-images could be acquired during EEG recording without significant distortion.