Although Social Anxiety Disorder (SAD) is one of the most prevalent mental disorders, still little is known about its development and maintenance. Cognitive models assume that deviations in attentional as well as associative learning processes play a role in the etiology of SAD. Amongst others, deficits in inhibitory attentional control as well as aberrations during fear generalization, which have already been observed in other anxiety disorders, are two candidate mechanisms that might contribute to the onset and retention of SAD. However, a review of the literature shows that there is a lack of research relating to these topics. Thus, the aim of the present thesis was to examine in which way individuals with SAD differ from healthy controls regarding attentional control and generalization of acquired fear during the processing of social stimuli. Study 1 tested whether impairment in the inhibitory control of attention is a feature of SAD, and how it might be influenced by emotional expression and gaze direction of an interactional partner. For this purpose, individuals with SAD and healthy controls (HC) participated in an antisaccade task with faces displaying different emotional expressions (angry, neutral and happy) and gaze directions (direct and averted) serving as target stimuli. While the participants performed either pro- or antisaccades in response to the peripherally presented faces, their gaze behavior was recorded via eye-tracking, and ratings of valence and arousal were obtained. Results revealed that both groups showed prolonged latencies and increased error rates in trials with correct anti- compared to prosaccades. However, there were no differences between groups with regard to response latency or error rates, indicating that SAD patients did not exhibit impairment on inhibitory attentional control in comparison to HC during eye-tracking. Possible explanations for this finding could be that reduced inhibitory attentional control in SAD only occurs under certain circumstances, for example, when these individuals currently run the risk of being negatively evaluated by others and not in the mere presence of phobic stimuli, or when the cognitive load of a task is so high that it cannot be unwound by compensatory strategies, such as putting more effort into a task. As not only deviations in attentional, but also associative learning processes might be pathogenic markers of SAD, these mechanisms were further addressed in the following experiments. Study 2 is the first that attempted to investigate the generalization of conditioned fear in patients with SAD. To this end, patients with SAD and HC were conditioned to two neutral female faces serving as conditioned stimuli (CS+: reinforced; CS-: non-reinforced) and a fearful face paired with a loud scream serving as unconditioned stimulus (US). Fear generalization was tested by presenting morphs of the two faces (GS: generalization stimuli), which varied in their similarity to the original faces. During the whole experiment, self-report ratings, heart rate (HR) and skin conductance responses (SCR) were recorded. Results demonstrated that SAD patients rated all stimuli as less pleasant and more arousing, and overestimated the occurrence of the US compared to HC, indicating a general hyperarousal in individuals with SAD. In addition, ratings and SCR indicated that both groups generalized their acquired fear from the CS+ to intermediate GSs as a function of their similarity to the CS+. However, except for the HR data, which indicated that only SAD patients but not HC displayed a generalization response in this measure, most of the results did not support the hypothesis that SAD is characterized by overgeneralization. A plausible reason for this finding could be that overgeneralization is just a key characteristic of some anxiety disorders and SAD is not one of them. Still, other factors, such as comorbidities in the individuals with SAD, could also have had an influence on the results, which is why overgeneralization was further examined in study 3. The aim of study 3 was to investigate fear generalization on a neuronal level. Hence, high (HSA) and low socially anxious participants (LSA) underwent a conditioning paradigm, which was an adaption of the experimental design used study 2 for EEG. During the experiment, steady-state visually evoked potentials (ssVEPs) and ratings of valence and arousal were recorded. Analyses revealed significant generalization gradients in all ratings with highest fear responses to the CS+ and a progressive decline of these reactions with increasing similarity to the CS-. In contrast, the generalization gradient on a neuronal level showed highest amplitudes for the CS+ and a reduction in amplitude to the most proximal, but not distal GSs in the ssVEP signal, which might be interpreted as lateral inhibition in the visual cortex. The observed dissociation among explicit and implicit measures points to different functions of behavioral and sensory cortical processes during fear generalization: While the ratings might reflect an individual’s consciously increased readiness to react to threat, the lateral inhibition pattern in the occipital cortex might serve to maximize the contrast among stimuli with and without affective value and thereby improve adaptive behavior. As no group differences could be observed, the finding of study 2 that overgeneralization does not seem to be a marker of SAD is further consolidated. In sum, the conducted experiments suggest that individuals with SAD are characterized by a general hyperarousal during the exposition to disorder-relevant stimuli as indicated by enhanced arousal and reduced valence ratings of the stimuli compared to HC. However, the hypotheses that reduced inhibitory attentional control and overgeneralization of conditioned fear are markers of SAD were mostly not confirmed. Further research is required to elucidate whether they only occur under certain circumstances, such as high cognitive load (e.g. handling two tasks simultaneously) or social stress (e.g. before giving a speech), or whether they are not characteristics of SAD at all. With the help of these findings, new interventions for the treatment of SAD can be developed, such as attentional bias modification or discrimination learning.

The perception of pain can be modulated by a variety of factors such as biological/pharmacological treatments as well as potent cognitive and emotional manipulations. Placebo and nocebo effects are among the most prominent examples for such manipulations. Placebo and nocebo manipulations cause reliable psychological and physiological changes, although the administered agent or treatment is inert. The present dissertation aimed at investigating the role of cognitive and emotional influences in the generation of placebo and nocebo effects on pain perception. In addition, the feasibility of solely psychological placebo manipulations to alter the perception of pain was tested. Two commonly discussed preconditions for the generation of placebo and nocebo effects are prior experiences (i.e., past encounter of drug effects) and expectations (i.e., positive or negative attitudes towards an intervention). So far, research on placebo and nocebo effects relied on the administration of sham interventions, which resembled medical treatments like inert pills, creams or injections. However, such experimental procedures deal with confounds due to earlier experiences and expectations resulting from the individual’s history with medical interventions. Accordingly, the implementation of a placebo manipulation that is completely new to an individual, seems necessary to disentangle the contribution of experience and expectation for the induction of placebo and nocebo effects. To this end, in Experiment 1 the level of experience and expectation regarding a placebo-nocebo treatment was stepwise manipulated across three different experimental groups. To avoid any resemblances to earlier experiences and individual expectations, a mere psychological placebo-nocebo treatment was chosen that was new to all participants. They were instructed that visual black and white stripe patterns had been found to reliably alter the perception of pain. One group of participants received only the placebo-nocebo instruction (expectation), a second group experienced a placebo-nocebo treatment within a conditioning phase (experience) but no instruction, and a third group received the combination of both that is a placebo-nocebo instruction and a placebo-nocebo conditioning (experience + expectation). It was shown that only the experience + expectation group revealed significantly higher pain ratings and physiological responses during nocebo, compared to placebo trials of the succeeding test phase. These findings demonstrate that the induction of a mere psychological placebo-nocebo effect on pain is in principle possible. Most important, results indicate that such effects most likely rely on both, a positive treatment experience, due to the encounter of an effective intervention (placebo conditioning), and a positive expectation about the intervention (placebo instruction).Besides experience and expectation, the current mood state has been shown to modulate pain and to impact the induction of placebo and nocebo effects. In this vein it has been demonstrated that placebo effects come along with positive affect, while nocebo effects often occur together with elevated feelings of anxiety. To clarify the interaction of emotions and placebo-nocebo manipulations on pain perception, in Experiment 2 the paradigm of Experiment 1 was modified. Instead of black and white stripe patterns, positive and negative emotional pictures were presented, which either cued pain increase (nocebo) or pain decrease (placebo). Two experimental groups were compared, which differed with regard to the instructed contingency of positive pictures serving as placebo and negative pictures serving as nocebo cues or vice versa (congruent vs. incongruent). Results indicate that the differentiation of placebo and nocebo trials (behaviorally and physiologically) was more pronounced for the congruent compared to the incongruent group. However, in the incongruent group, affective pain ratings were also significantly higher for nocebo (positive pictures) than placebo (negative pictures) trials, similar to the congruent group. These findings demonstrate that a placebo-nocebo manipulation is capable to dampen and even reverse the originally pain augmenting effect of negative emotions. The results of Experiment 2 were further corroborated in Experiment 3, when the design was adapted to the fMRI scanner, and again a congruent and an incongruent experimental group were compared. Behavioral, physiological and neurophysiological markers of pain processing revealed a differentiation between nocebo and placebo conditions that was present irrespective of the experimental group. In addition, the fMRI analysis revealed an increased engagement of prefrontal areas for the incongruent group only, supposedly reflecting the reinterpretation or appraisal process when positive pictures were cueing negative outcomes. Taken together, the results of the present studies showed (a) that it is possible to induce a placebo-nocebo effect on pain solely by a psychological manipulation, (b) that both, prior experiences and positive expectation, are necessary preconditions for this placebo-nocebo effect, (c) that the impact of negative emotion on pain can be dampened and even reversed by placebo-nocebo manipulations, and (d) that most likely a cognitive top-down process is crucial for the induction of (psychological) placebo-nocebo effects. These results significantly enhance our understanding of psychological mechanisms involved in the induction of placebo-nocebo effects. Further, a fruitful foundation for future studies is provided, which will need to determine the contributions of primarily nocebo or placebo responses mediating the effects as demonstrated in the present studies. In a long-term perspective, the present findings may also help to exploit placebo effects and prevent from nocebo effect in clinical contexts by further elucidating crucial psychological factors that contribute to the placebo and nocebo response.

Virtual reality exposure therapy (VRET) is an effective cognitive-behavioral treatment for anxiety disorders that comprises systematic confrontations to virtual representations of feared stimuli and situations. However, not all patients respond to VRET, and some patients relapse after successful treatment. One explanation for this limitation of VRET is that its underlying mechanisms are not yet fully understood, leaving room for further improvement. On these grounds, the present thesis aimed to investigate two major research questions: first, it explored how virtual stimuli induce fear responses in height-fearful participants, and second, it tested if VRET outcome could be improved by incorporating techniques derived from two different theories of exposure therapy. To this end, five studies in virtual reality (VR) were conducted. Study 1 (N = 99) established a virtual environment for height exposure using a Computer Automatic Virtual Environment (CAVE) and investigated the effects of tactile wind simulation in VR. Height-fearful and non-fearful participants climbed a virtual outlook, and half of the participants received wind simulation. Results revealed that height-fearful participants showed stronger fear responses, on both a subjective and behavioral level, and that wind simulation increased subjective fear. However, adding tactile wind simulation in VR did not affect presence, the user's sense of 'being there' in the virtual environment. Replicating previous studies, fear and presence in VR were correlated, and the correlation was higher in height-fearful compared to non-fearful participants. Study 2 (N = 43) sought to corroborate the findings of the first study, using a different VR system for exposure (a head-mounted display) and measuring physiological fear responses. In addition, the effects of a visual cognitive distractor on fear in VR were investigated. Participants' fear responses were evident on both a subjective and physiological level---although much more pronounced on skin conductance than on heart rate---but the virtual distractor did not affect the strength of fear responses. In Study 3 (N = 50), the effects of trait height-fearfulness and height level on fear responses were investigated in more detail. Self-rated level of acrophobia and five different height levels in VR (1 m--20 m) were used as linear predictors of subjective and physiological indices of fear. Results showed that subjective fear and skin conductance responses were a function of both trait height-fearfulness and height level, whereas no clear effects were visible for heart rate. Study 4 (N = 64 + N = 49) aimed to advance the understanding of the relationship between presence and fear in VR. Previous research indicates a positive correlation between both measures, but possible causal mechanisms have not yet been identified. The study was the first to experimentally manipulate both presence (via the visual and auditive realism of the virtual environment) and fear (by presenting both height and control situations). Results indicated a causal effect of fear on presence, i.e., experiencing fear in a virtual environment led to a stronger sense of `being there' in the virtual environment. However, conversely, presence increased by higher scene realism did not affect fear responses. Nonetheless, presence seemed to have some effects on fear responding via another pathway, as participants whose presence levels were highest in the first safe context were also those who had the strongest fear responses in a later height situation. This finding indicated the importance of immersive user characteristics in the emergence of presence and fear in VR. The findings of the first four studies were integrated into a model of fear in VR, extending previous models and highlighting factors that lead to the emergence of both fear and presence in VR. Results of the studies showed that fear responses towards virtual heights were affected by trait height-fearfulness, phobic elements in the virtual environment, and, at least to some degree, on presence. Presence, on the other hand, was affected by experiencing fear in VR, immersion---the characteristics of the VR system---and immersive user characteristics. Of note, the manipulations of immersion used in the present thesis, visual and auditory realism of the virtual environment and tactile wind simulation, were not particularly effective in manipulating presence. Finally, Study 5 (N = 34) compared two different implementations of VRET for acrophobia to investigate mechanisms underlying its efficacy. The first implementation followed the Emotional Processing Theory, assuming that fear reduction during exposure is crucial for positive treatment outcome. In this condition, patients were asked to focus on their fear responses and on the decline of fear (habituation) during exposures. The second implementation was based on the inhibitory learning model, assuming that expectancy violation is the primary mechanism underlying exposure therapy efficacy. In this condition, patients were asked to focus on the non-occurrence of feared outcomes (e.g., 'I could fall off') during exposure. Based on predictions of the inhibitory learning model, the hypothesis for the study was that expectancy-violation-based exposure would outperform habituation-based exposure. After two treatment sessions in VR, both treatment conditions effectively reduced the patients' fear of heights, but the two conditions did not differ in their efficacy. The study replicated previous studies by showing that VRET is an effective treatment for acrophobia; however, contrary to the assumption, explicitly targeting the violation of threat expectancies did not improve outcome. This finding adds to other studies failing to provide clear evidence for expectancy violation as the primary mechanism underlying exposure therapy. Possible explanations for this finding and clinical implications are discussed, along with suggestions for further research.