@phdthesis{Siminski2023,
  author    = {Siminski, Niklas},
  title     = {Temporal predictability of threat: Evaluation of differential involvement of amygdala and BNST, and relevance for therapy response prediction in spider phobia},
  doi       = {10.25972/OPUS-24664},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246643},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Predictability of threat is one of the key modulators of neural activity in fear and anxiety-related threat processes and there is a considerable number of studies focusing on the exact contribution of centromedial amygdala and Bed nucleus of stria terminalis (BNST) in animals as well as in humans. In this research field, some studies already investigated the differential involvement of both areas during temporally predictable and unpredictable threat processes in humans. However, these studies showed several limitations e.g. small sample size, no predictable threat conditions, no separation of anticipation and confrontation processes, which should be addressed in future studies. Furthermore, evidence for group-based inter-individual differences of amygdala and BNST activity during predictable and unpredictable threat processes have not been studied extensively. Several studies suggest a relevant role of the amygdala and BNST activity in phobic processes in patients with specific phobia, but no study so far has investigated the exact contribution of centromedial amygdala (CM) and BNST during temporally predictable and unpredictable threat processes in specific phobia. This thesis consisted of three studies and aimed to evaluate the exact contribution of CM and BNST during temporally predictable and unpredictable threat anticipation and confrontation with the use of an optimized functional magnetic resonance imaging (fMRI) paradigm, which aimed to solve methodological limitations of recent studies. Study 1 used a large sample of healthy participants who were grouped based on NPSR1 genotype, and study 2 and study 3 used a sample of patients with spider phobia. In sum, the results of all three studies indicated, that BNST is more relevant for anticipation processes as compared to the CM. Contrary, during the confrontation phase the CM displays a greater relevance for threat confrontation processes. In recent years, various studies have investigated the extent to which treatment success can be predicted in patients with anxiety disorders based on pre-treatment fMRI activity. Therefore, this was investigated for the first time in study 3 in patients with spider phobia during temporally predictable and unpredictable threat processes. Results indicated that independent of temporal predictability lower anterior cingulate cortex (ACC) activity during threat anticipation and engaged BNST during threat confrontation might be benefitting factors for successful therapy response in spider phobia.},
  subject      = {Amygdala},
  language  = {en}
}
@phdthesis{Ulrich2016,
  author    = {Ulrich, Natalie},
  title     = {Processing of Near Outcomes and Outcome Sequences in Gambling: Implications for the Biopsychological Basis of Problem Gambling},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139612},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2016},
  abstract  = {Gambling is a popular activity in Germany, with 40\% of a representative sample reporting having gambled at least once in the past year (Bundeszentrale f{\"u}r gesundheitliche Aufkl{\"a}rung, 2014). While the majority of gamblers show harmless gambling behavior, a subset develops serious problems due to their gambling, affecting their psychological well-being, social life and work. According to recent estimates, up to 0.8\% of the German population are affected by such pathological gambling. People in general and pathological gamblers in particular show several cognitive distortions, that is, misconceptions about the chances of winning and skill involvement, in gambling. The current work aimed at elucidating the biopsychological basis of two such kinds of cognitive distortions, the illusion of control and the gambler's and hot hand fallacies, and their modulation by gambling problems. Therefore, four studies were conducted assessing the processing of near outcomes (used as a proxy for the illusion of control) and outcome sequences (used as a proxy for the gambler's and hot hand fallacies) in samples of varying degrees of gambling problems, using a multimethod approach. The first study analyzed the processing and evaluation of near outcomes as well as choice behavior in a wheel of fortune paradigm using electroencephalography (EEG). To assess the influence of gambling problems, a group of problem gamblers was compared to a group of controls. The results showed that there were no differences in the processing of near outcomes between the two groups. Near compared to full outcomes elicited smaller P300 amplitudes. Furthermore, at a trend level, the choice behavior of participants showed signs of a pattern opposite to the gambler's fallacy, with longer runs of an outcome color leading to increased probabilities of choosing this color again on the subsequent trial. Finally, problem gamblers showed smaller feedback-related negativity (FRN) amplitudes relative to controls. The second study also targeted the processing of near outcomes in a wheel of fortune paradigm, this time using functional magnetic resonance imaging and a group of participants with varying degrees of gambling problems. The results showed increased activity in the bilateral superior parietal cortex following near compared to full outcomes. The third study examined the peripheral physiology reactions to near outcomes in the wheel of fortune. Heart period and skin conductance were measured while participants with varying degrees of gambling problems played on the wheel of fortune. Near compared to full outcomes led to increased heart period duration shortly after the outcome. Furthermore, heart period reactions and skin conductance responses (SCRs) were modulated by gambling problems. Participants with high relative to low levels of gambling problems showed increased SCRs to near outcomes and similar heart period reactions to near outcomes and full wins. The fourth study analyzed choice behavior and sequence effects in the processing of outcomes in a coin toss paradigm using EEG in a group of problem gamblers and controls. Again, problem gamblers showed generally smaller FRN amplitudes compared to controls. There were no differences between groups in the processing of outcome sequences. The break of an outcome streak led to increased power in the theta frequency band. Furthermore, the P300 amplitude was increased after a sequence of previous wins. Finally, problem gamblers compared to controls showed a trend of switching the outcome symbol relative to the previous outcome symbol more often. In sum, the results point towards differences in the processing of near compared to full outcomes in brain areas and measures implicated in attentional and salience processes. The processing of outcome sequences involves processes of salience attribution and violation of expectations. Furthermore, problem gamblers seem to process near outcomes as more win-like compared to controls. The results and their implications for problem gambling as well as further possible lines of research are discussed.},
  subject      = {Spielsucht},
  language  = {en}
}
@phdthesis{Seeger2023,
  author    = {Seeger, Fabian Reinhard},
  title     = {Moderators of exposure-based treatment outcome in anxiety disorders: an fMRI approach},
  doi       = {10.25972/OPUS-21435},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214356},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Even though exposure-based cognitive behavioral therapy (CBT) constitutes a first-line treatment for anxiety disorders, a substantial proportion of patients does not respond in a clinically significant manner. The identification of pre-treatment patient characteristics that are associated with treatment outcome might aid in improving response rates. Therefore, the present doctoral thesis aimed at investigating moderators of treatment outcome in anxiety disorders: first, we investigated the neural correlates of comorbidity among primary panic disorder/agoraphobia (PD/AG) and secondary social anxiety disorder (SAD) moderating treatment outcome towards exposure-based CBT. Second, pre-treatment functional resting-state connectivity signatures of treatment response in specific phobia were studied. Within the first study, we compared PD/AG patients with or without secondary SAD regarding their clinical and neurofunctional outcome towards a manualized CBT treatment focusing on PD/AG symptoms. Prior to treatment, PD/AG+SAD compared to PD/AG-SAD patients exhibited a specific neural signature within the temporal lobe, which was attenuated to the level of PD/AG-SAD patients afterwards. CBT was equally effective in both groups. Thus, comorbidity among those two anxiety disorders did not alter treatment outcome substantially. This might be due to the high overlap of shared pathophysiological features within both disorders. In the second study, we assessed pre-treatment functional resting-state connectivity within a sample of spider phobic patients that were treated with massed in virtuo exposure. We found responders already prior to treatment to be characterized by stronger inhibitory frontolimbic connectivity as well as heightened connectivity between the amygdala and regions related to the ventral visual stream. Furthermore, patients demonstrating high within-session extinction exhibited pronounced intrinsic prefrontal connectivity. Our results point to responders exhibiting a brain prepared for the mechanism of action of exposure. Taken together, results highlight the major impact of pre-treatment characteristics on treatment outcome. Both, PD/AG+SAD patients as well as responders within the SpiderVR study exhibited heightened activation or connectivity within the ventral visual pathway and the amygdala. Pronounced visual processing together with enhanced executive control and emotion regulation seem to constitute a fruitful soil for successful exposure. The results provide starting points for personalized treatment approaches in order to improve treatment success in the anxiety disorders. Future studies are needed to investigate the benefit of neuroscientifically informed CBT augmentation strategies such as repetitive transcranial magnetic stimulation.},
  subject      = {Angstst{\"o}rung},
  language  = {en}
}
@phdthesis{Ewald2014,
  author    = {Ewald, Heike},
  title     = {Influence of context and contingency awareness on fear conditioning - an investigation in virtual reality},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111226},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Fear conditioning is an efficient model of associative learning, which has greatly improved our knowledge of processes underlying the development and maintenance of pathological fear and anxiety. In a differential fear conditioning paradigm, one initially neutral stimulus (NS) is paired with an aversive event (unconditioned stimulus, US), whereas another stimulus does not have any consequences. After a few pairings the NS is associated with the US and consequently becomes a conditioned stimulus (CS+), which elicits a conditioned response (CR). The formation of explicit knowledge of the CS/US association during conditioning is referred to as contingency awareness. Findings about its role in fear conditioning are ambiguous. The development of a CR without contingency awareness has been shown in delay fear conditioning studies. One speaks of delay conditioning, when the US coterminates with or follows directly on the CS+. In trace conditioning, a temporal gap or "trace interval" lies between CS+ and US. According to existing evidence, trace conditioning is not possible on an implicit level and requires more cognitive resources than delay conditioning. The associations formed during fear conditioning are not exclusively associations between specific cues and aversive events. Contextual cues form the background milieu of the learning process and play an important role in both acquisition and the extinction of conditioned fear and anxiety. A common limitation in human fear conditioning studies is the lack of ecological validity, especially regarding contextual information. The use of Virtual Reality (VR) is a promising approach for creating a more complex environment which is close to a real life situation. I conducted three studies to examine cue and contextual fear conditioning with regard to the role of contingency awareness. For this purpose a VR paradigm was created, which allowed for exact manipulation of cues and contexts as well as timing of events. In all three experiments, participants were guided through one or more virtual rooms serving as contexts, in which two different lights served as CS and an electric stimulus as US. Fear potentiated startle (FPS) responses were measured as an indicator of implicit fear conditioning. To test whether participants had developed explicit awareness of the CS-US contingencies, subjective ratings were collected. The first study was designed as a pilot study to test the VR paradigm as well as the conditioning protocol. Additionally, I was interested in the effect of contingency awareness. Results provided evidence, that eye blink conditioning is possible in the virtual environment and that it does not depend on contingency awareness. Evaluative conditioning, as measured by subjective ratings, was only present in the group of participants who explicitly learned the association between CS and US. To examine acquisition and extinction of both fear associated cues and contexts, a novel cue-context generalization paradigm was applied in the second study. Besides the interplay of cues and contexts I was again interested in the effect of contingency awareness. Two different virtual offices served as fear and safety context, respectively. During acquisition, the CS+ was always followed by the US in the fear context. In the safety context, none of the lights had any consequences. During extinction, a additional (novel) context was introduced, no US was delivered in any of the contexts. Participants showed enhanced startle responses to the CS+ compared to the CS- in the fear context. Thus, discriminative learning took place regarding both cues and contexts during acquisition. This was confirmed by subjective ratings, although only for participants with explicit contingency awareness. Generalization of fear to the novel context after conditioning did not depend on awareness and was observable only on trend level. In a third experiment I looked at neuronal correlates involved in extinction of fear memory by means of functional magnetic resonance imaging (fMRI). Of particular interest were differences between extinction of delay and trace fear conditioning. I applied the paradigm tested in the pilot study and additionally manipulated timing of the stimuli: In the delay conditioning group (DCG) the US was administered with offset of one light (CS+), in the trace conditioning group (TCG) the US was presented 4s after CS+ offset. Most importantly, prefrontal activation differed between the two groups. In line with existing evidence, the ventromedial prefrontal cortex (vmPFC) was activated in the DCG. In the TCG I found activation of the dorsolateral prefrontal cortex (dlPFC), which might be associated with modulation of working memory processes necessary for bridging the trace interval and holding information in short term memory. Taken together, virtual reality proved to be an elegant tool for examining human fear conditioning in complex environments, and especially for manipulating contextual information. Results indicate that explicit knowledge of contingencies is necessary for attitude formation in fear conditioning, but not for a CR on an implicit level as measured by FPS responses. They provide evidence for a two level account of fear conditioning. Discriminative learning was successful regarding both cues and contexts. Imaging results speak for different extinction processes in delay and trace conditioning, hinting that higher working memory contribution is required for trace than for delay conditioning.},
  subject      = {Klassische Konditionierung},
  language  = {en}
}
@phdthesis{Schwarzmeier2023,
  author    = {Schwarzmeier, Hanna},
  title     = {From fear extinction to exposure therapy: neural mechanisms and moderators of extinction},
  doi       = {10.25972/OPUS-22330},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223304},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2023},
  abstract  = {Emotional-associative learning processes such as fear conditioning and extinction are highly relevant to not only the development and maintenance of anxiety disorders (ADs), but also to their treatment. Extinction, as the laboratory analogue to behavioral exposure, is assumed a core process underlying the treatment of ADs. Although exposure-based treatments are highly effective for the average patient suffering from an AD, there remains a gap in treatment efficacy with over one third of patients failing to achieve clinically significant symptom relief. There is ergo a pressing need for intensified research regarding the underlying neural mechanisms of aberrant emotional-associative learning processes and the neurobiological moderators of treatment (non-)response in ADs. The current thesis focuses on different applications of the fundamental principles of fear conditioning and extinction by using two example cases of ADs from two different multicenter trials. First, we targeted alterations in fear acquisition, extinction, and its recall as a function of psychopathology in panic disorder (PD) patients compared to healthy subjects using fMRI. Second, exposure-based therapy and pre-treatment patient characteristics exerting a moderating influence on this essential learning process later on (i.e. treatment outcome) were examined using multimodal functional and structural neuroimaging in spider phobia. We observed aberrations in emotional-associative learning processes in PD patients compared to healthy subjects indicated by an accelerated fear acquisition and an attenuated extinction recall. Furthermore, pre-treatment differences related to defensive, regulatory, attentional, and perceptual processes may exert a moderating influence on treatment outcome to behavioral exposure in spider phobia. Although the current results need further replication, on an integrative meta level, results point to a hyperactive defensive network system and deficient emotion regulation processes (including extinction processes) and top-down control in ADs. This speaks in favor of transdiagnostic deficits in important functional domains in ADs. Deficits in transdiagnostic domains such as emotion regulation processes could be targeted by enhancing extinction learning or by means of promising tools like neurofeedback. The detection of pre-treatment clinical response moderators, for instance via machine learning frameworks, may help in supporting clinical decision making on individually tailored treatment approaches or, respectively, to avoid ineffective treatment and its related financial costs. In the long run, the identification of neurobiological markers which are capable of detecting non-responders a priori represents an ultimate goal.},
  subject      = {Extinktion},
  language  = {en}
}
@phdthesis{Roesler2020,
  author    = {R{\"o}sler, Lara},
  title     = {Behavioral and Neural Mechanisms of Social Attention},
  doi       = {10.25972/OPUS-21609},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216092},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Humans in our environment are of special importance to us. Even if our minds are fixated on tasks unrelated to their presence, our attention will likely be drawn towards other people's appearances and their actions. While we might remain unaware of this attentional bias at times, various studies have demonstrated the preferred visual scanning of other humans by recording eye movements in laboratory settings. The present thesis aims to investigate the circumstances under and the mechanisms by which this so-called social attention operates. The first study demonstrates that social features in complex naturalistic scenes are prioritized in an automatic fashion. After 200 milliseconds of stimulus presentation, which is too brief for top-down processing to intervene, participants targeted image areas depicting humans significantly more often than would be expected from a chance distribution of saccades. Additionally, saccades towards these areas occurred earlier in time than saccades towards non-social image regions. In the second study, we show that human features receive most fixations even when bottom-up information is restricted; that is, even when only the fixated region was visible and the remaining parts of the image masked, participants still fixated on social image regions longer than on regions without social cues. The third study compares the influence of real and artificial faces on gaze patterns during the observation of dynamic naturalistic videos. Here we find that artificial faces, belonging to humanlike statues or machines, significantly predicted gaze allocation but to a lesser extent than real faces. In the fourth study, we employed functional magnetic resonance imaging to investigate the neural correlates of reflexive social attention. Analyses of the evoked blood-oxygenation level dependent responses pointed to an involvement of striate and extrastriate visual cortices in the encoding of social feature space. Collectively, these studies help to elucidate under which circumstances social features are prioritized in a laboratory setting and how this prioritization might be achieved on a neuronal level. The final experimental chapter addresses the question whether these laboratory findings can be generalized to the real world. In this study, participants were introduced to a waiting room scenario in which they interacted with a confederate. Eye movement analyses revealed that gaze behavior heavily depended on the social context and were influenced by whether an interaction is currently desired. We further did not find any evidence for altered gaze behavior in socially anxious participants. Alleged gaze avoidance or hypervigilance in social anxiety might thus represent a laboratory phenomenon that occurs only under very specific real-life conditions. Altogether the experiments described in the present thesis thus refine our understanding of social attention and simultaneously challenge the inferences we can draw from laboratory research.},
  subject      = {Aufmerksamkeit},
  language  = {en}
}