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This study investigates the effect of awareness of stimulus contingencies on BOLD responses within the amygdala, the orbitofrontal, and the occipital cortex, and on differential skin conductance responses (SCRs) during fear conditioning. Of two geometric figures, the paired conditioned stimulus (CS+) predicted an electrical stimulus (unconditioned stimulus = UCS), whereas the unpaired conditioned stimulus (CS-) was not followed by the UCS. Awareness of stimulus contingencies was manipulated experimentally, creating an aware and an unaware group: a distracter figure and a working memory task were introduced to conceal the stimulus contingencies of the conditioning paradigm, hence preventing contingency detection in the unaware group. The aware group was informed beforehand about the relation between CS+, CS-, and UCS. Differential SCRs were only obtained in the aware but not in the unaware group. Conversely, we observed enhanced responses of the amygdala, the orbitofrontal, and the occipital cortex to the CS+ in the unaware group only. Thus, we found a dissociation of SCR differentiation and the activation of a neural fear network depending on the presence or absence of awareness. These results support a model of fear conditioning that distinguishes between a more cognitive level of learning, reflected in contingency awareness and differential SCRs, and the awareness independent activation of a fear network.

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 cerebellum and the hippocampus are key structures for the acquisition of conditioned eyeblink responses. Whereas the cerebellum seems to be crucial for all types of eyeblink conditioning, the hippocampus appears to be involved only in complex types of learning. We conducted a differential conditioning study to explore the suitability of the design for magnetencephalography (MEG). In addition, we compared cerebellar and hippocampal activation during differential delay and trace conditioning. Comparable conditioning effects were seen in both conditions, but a greater resistance to extinction for trace conditioning. Brain activation differed between paradigms: delay conditioning provoked activation only in the cerebellum and trace conditioning only in the hippocampus. The results reflect differential brain activation patterns during the two types of eyeblink conditioning.

Priming tasks are used for investigating the deficits of selective attention in schizophrenia, which are thought to be related to the psychotic symptoms. Priming was assessed in acutely psychotic unmedicated (n = 22) and medicated (n = 36) schizophrenia patients and in control subjects (n = 42). The subjects had to indicate the location of a target stimulus in two consecutive stimulus displays (prime and probe). Each stimulus appeared together with a distractor on a screen. Negative Priming is characterized by an increase in reaction time, whenever a probe target is presented at a prime distractor location. Positive Priming is characterized by a decrease in reaction time, when the probe target is presented at the prime target location. Schizophrenia patients altogether showed no abnormalities in priming effects, neither in the acute phase of illness (medicated and unmedicated) nor in partial remission (one month later, medicated). In unmedicated patients however Negative Priming was inversely correlated with the severity of positive symptoms. This indicates a priming deficit in a small subgroup of severely ill patients. The data support the notion that automatic (implicit) mechanisms of learning are unimpaired in schizophrenia patients unless symptoms exceed a certain critical level.

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.

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.

Dopamine is known as the main neurotransmitter modulating the activation of the reward system of the brain. The DRD2 TaqIA polymorphism is associated with dopamine D2 receptor density which plays an important role in the context of reward. Persons carrying an A1 allele have a lower D2 receptor density and a higher risk to show substance abuse. The present study was designed to investigate the influence of the DRD2 TaqIA polymorphism and the selective D2 receptor agonist bromociptine on the activation of the reward system by means of functional magnetic resonance imaging (fMRI). In a double-blind crossover study with 24 participants we found an increase of reward system activation from placebo to bromocriptine only in subjects carrying the A1 allele. Furthermore, only A1 carrier showed an increase of performance under bromocriptine. The results are interpreted as reflecting a specific sensitivity for dopamine agonists in persons carrying an A1 allele and may complement actual data and theories of the development of addiction disorders postulating a higher genetic risk for substance abuse in carrier of the A1 allele.

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.

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.

In alexithymia a frontal dysfunction is supposed to be a neurobiological correlate. This study focuses on distorted patterns of neuronal activity evoked by emotional stimuli in alexithymics and controls. Out of hospitalised patients with psychosomatic diseases 8 patients with a high score (HA) and 8 with a low one (NA) on the TAS-20 were investigated with fMRI during emotional stimulation which included pictures evoking anxiety and disgust as well as neutral illustrations. As response to negative affect arousing visual stimulation HA in comparison to NA showed a lower activation in the right medial prefrontal cortex and in the right amygdala. The results were significant for the emotion disgust. The results support the existence of a complex central feedback circuit consisting of regions of the prefrontal cortex and limbic structures to process negative affects. Hypothetically a fundamental factor for the emergence of alexithymic traits is an inhibiting process between affect processing (e. g. medial prefrontal cortex, anterior cingulum) and affect generating structures (e. g. amygdala). Furthermore our findings confirm the hypothesis that alexithymia is a disorder of higher cerebral function.

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).

We investigated subjective and hemodynamic responses towards disgust-inducing, fear-inducing, and neutral pictures in a functional magnetic resonance imaging study. Within an interval of 1 week, 24 male subjects underwent the same block design twice in order to analyze possible response changes to the repeated picture presentation. The results showed that disgust-inducing and fear-inducing scenes provoked a similar activation pattern in comparison to neutral scenes. This included the thalamus, primary and secondary visual fields, the amygdala, the hippocampus, and various regions of the prefrontal cortex. During the retest, the affective ratings hardly changed. In contrast, most of the previously observed brain activations disappeared, with the exception of the temporo-occipital activation. An additional analysis, which compared the emotion-related activation patterns during the two presentations, showed that the responses to the fear-inducing pictures were more stable than the responses to the disgust-inducing ones.

The aim of this fMRI study was to explore brain structures that are involved in the processing of erotic and disgust-inducing pictures. The stimuli were chosen to trigger approach and withdrawal tendencies, respectively. By adding sadomasochistic (SM) scenes to the design and examining 12 subjects with and 12 subjects without sadomasochistic preferences, we introduced a picture category that induced erotic pleasure in one sample and disgust in the other sample. Since we also presented neutral pictures, all subjects viewed pictures of four different categories: neutral, disgust-inducing, erotic, and SM erotic pictures. The analysis indicated that several brain structures are commonly involved in the processing of disgust-inducing and erotic pictures (occipital cortex, hippocampus, thalamus, and the amygdala). The ventral striatum was specifically activated when subjects saw highly sexually arousing pictures. This indicates the involvement of the human reward system during the processing of visual erotica.