@phdthesis{Gromer2021, author = {Gromer, Daniel}, title = {Mechanisms Underlying Virtual Reality Exposure Therapy for Specific Phobias}, doi = {10.25972/OPUS-20733}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-207334}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2021}, abstract = {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.}, subject = {Virtuelle Realit{\"a}t}, language = {en} } @article{SchieleZieglerKollertetal.2018, author = {Schiele, Miriam A. and Ziegler, Christiane and Kollert, Leonie and Katzorke, Andrea and Schartner, Christoph and Busch, Yasmin and Gromer, Daniel and Reif, Andreas and Pauli, Paul and Deckert, J{\"u}rgen and Herrmann, Martin J. and Domschke, Katharina}, title = {Plasticity of Functional MAOA Gene Methylation in Acrophobia}, series = {International Journal of Neuropsychopharmacology}, volume = {21}, journal = {International Journal of Neuropsychopharmacology}, number = {9}, doi = {10.1093/ijnp/pyy050}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228571}, pages = {822-827}, year = {2018}, abstract = {Epigenetic mechanisms have been proposed to mediate fear extinction in animal models. Here, MAOA methylation was analyzed via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells before and after a 2-week exposure therapy in a sample of n = 28 female patients with acrophobia as well as in n = 28 matched healthy female controls. Clinical response was measured using the Acrophobia Questionnaire and the Attitude Towards Heights Questionnaire. The functional relevance of altered MAOA methylation was investigated by luciferase-based reporter gene assays. MAOA methylation was found to be significantly decreased in patients with acrophobia compared with healthy controls. Furthermore, MAOA methylation levels were shown to significantly increase after treatment and correlate with treatment response as reflected by decreasing Acrophobia Questionnaire/Attitude Towards Heights Questionnaire scores. Functional analyses revealed decreased reporter gene activity in presence of methylated compared with unmethylated pCpGfree_MAOA reporter gene vector constructs. The present proof-of-concept psychotherapy-epigenetic study for the first time suggests functional MAOA methylation changes as a potential epigenetic correlate of treatment response in acrophobia and fosters further investigation into the notion of epigenetic mechanisms underlying fear extinction.}, language = {en} } @article{GromerMadeiraGastetal.2018, author = {Gromer, Daniel and Madeira, Oct{\´a}via and Gast, Philipp and Nehfischer, Markus and Jost, Michael and M{\"u}ller, Mathias and M{\"u}hlberger, Andreas and Pauli, Paul}, title = {Height Simulation in a Virtual Reality CAVE System: Validity of Fear Responses and Effects of an Immersion Manipulation}, series = {Frontiers in Human Neuroscience}, volume = {12}, journal = {Frontiers in Human Neuroscience}, number = {372}, issn = {1662-5161}, doi = {10.3389/fnhum.2018.00372}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196113}, year = {2018}, abstract = {Acrophobia is characterized by intense fear in height situations. Virtual reality (VR) can be used to trigger such phobic fear, and VR exposure therapy (VRET) has proven effective for treatment of phobias, although it remains important to further elucidate factors that modulate and mediate the fear responses triggered in VR. The present study assessed verbal and behavioral fear responses triggered by a height simulation in a 5-sided cave automatic virtual environment (CAVE) with visual and acoustic simulation and further investigated how fear responses are modulated by immersion, i.e., an additional wind simulation, and presence, i.e., the feeling to be present in the VE. Results revealed a high validity for the CAVE and VE in provoking height related self-reported fear and avoidance behavior in accordance with a trait measure of acrophobic fear. Increasing immersion significantly increased fear responses in high height anxious (HHA) participants, but did not affect presence. Nevertheless, presence was found to be an important predictor of fear responses. We conclude that a CAVE system can be used to elicit valid fear responses, which might be further enhanced by immersion manipulations independent from presence. These results may help to improve VRET efficacy and its transfer to real situations.}, language = {en} } @article{KiserGromerPaulietal.2022, author = {Kiser, Dominik P. and Gromer, Daniel and Pauli, Paul and Hilger, Kirsten}, title = {A virtual reality social conditioned place preference paradigm for humans: Does trait social anxiety affect approach and avoidance of virtual agents?}, series = {Frontiers in Virtual Reality}, volume = {3}, journal = {Frontiers in Virtual Reality}, issn = {2673-4192}, doi = {10.3389/frvir.2022.916575}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293564}, year = {2022}, abstract = {Approach and avoidance of positive and negative social cues are fundamental to prevent isolation and ensure survival. High trait social anxiety is characterized by an avoidance of social situations and extensive avoidance is a risk factor for the development of social anxiety disorder (SAD). Therefore, experimental methods to assess social avoidance behavior in humans are essential. The social conditioned place preference (SCPP) paradigm is a well-established experimental paradigm in animal research that is used to objectively investigate social approach-avoidance mechanisms. We retranslated this paradigm for human research using virtual reality. To this end, 58 healthy adults were exposed to either a happy- or angry-looking virtual agent in a specific room, and the effects of this encounter on dwell time as well as evaluation of this room in a later test without an agent were examined. We did not observe a general SCPP effect on dwell time or ratings but discovered a moderation by trait social anxiety, in which participants with higher trait social anxiety spent less time in the room in which the angry agent was present before, suggesting that higher levels of trait social anxiety foster conditioned social avoidance. However, further studies are needed to verify this observation and substantiate an association with social anxiety disorder. We discussed the strengths, limitations, and technical implications of our paradigm for future investigations to more comprehensively understand the mechanisms involved in social anxiety and facilitate the development of new personalized treatment approaches by using virtual reality.}, language = {en} } @article{MadeiraGromerLatoschiketal.2021, author = {Madeira, Octavia and Gromer, Daniel and Latoschik, Marc Erich and Pauli, Paul}, title = {Effects of Acrophobic Fear and Trait Anxiety on Human Behavior in a Virtual Elevated Plus-Maze}, series = {Frontiers in Virtual Reality}, volume = {2}, journal = {Frontiers in Virtual Reality}, doi = {10.3389/frvir.2021.635048}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258709}, year = {2021}, abstract = {The Elevated Plus-Maze (EPM) is a well-established apparatus to measure anxiety in rodents, i.e., animals exhibiting an increased relative time spent in the closed vs. the open arms are considered anxious. To examine whether such anxiety-modulated behaviors are conserved in humans, we re-translated this paradigm to a human setting using virtual reality in a Cave Automatic Virtual Environment (CAVE) system. In two studies, we examined whether the EPM exploration behavior of humans is modulated by their trait anxiety and also assessed the individuals' levels of acrophobia (fear of height), claustrophobia (fear of confined spaces), sensation seeking, and the reported anxiety when on the maze. First, we constructed an exact virtual copy of the animal EPM adjusted to human proportions. In analogy to animal EPM studies, participants (N = 30) freely explored the EPM for 5 min. In the second study (N = 61), we redesigned the EPM to make it more human-adapted and to differentiate influences of trait anxiety and acrophobia by introducing various floor textures and lower walls of closed arms to the height of standard handrails. In the first experiment, hierarchical regression analyses of exploration behavior revealed the expected association between open arm avoidance and Trait Anxiety, an even stronger association with acrophobic fear. In the second study, results revealed that acrophobia was associated with avoidance of open arms with mesh-floor texture, whereas for trait anxiety, claustrophobia, and sensation seeking, no effect was detected. Also, subjects' fear rating was moderated by all psychometrics but trait anxiety. In sum, both studies consistently indicate that humans show no general open arm avoidance analogous to rodents and that human EPM behavior is modulated strongest by acrophobic fear, whereas trait anxiety plays a subordinate role. Thus, we conclude that the criteria for cross-species validity are met insufficiently in this case. Despite the exploratory nature, our studies provide in-depth insights into human exploration behavior on the virtual EPM.}, language = {en} } @article{GromerKiserPauli2021, author = {Gromer, Daniel and Kiser, Dominik P. and Pauli, Paul}, title = {Thigmotaxis in a virtual human open field test}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, doi = {10.1038/s41598-021-85678-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259850}, pages = {6670}, year = {2021}, abstract = {Animal models are used to study neurobiological mechanisms in mental disorders. Although there has been significant progress in the understanding of neurobiological underpinnings of threat-related behaviors and anxiety, little progress was made with regard to new or improved treatments for mental disorders. A possible reason for this lack of success is the unknown predictive and cross-species translational validity of animal models used in preclinical studies. Re-translational approaches, therefore, seek to establish cross-species translational validity by identifying behavioral operations shared across species. To this end, we implemented a human open field test in virtual reality and measured behavioral indices derived from animal studies in three experiments (N=31, N=30, and N=80). In addition, we investigated the associations between anxious traits and such behaviors. Results indicated a strong similarity in behavior across species, i.e., participants in our study-like rodents in animal studies-preferred to stay in the outer region of the open field, as indexed by multiple behavioral parameters. However, correlational analyses did not clearly indicate that these behaviors were a function of anxious traits of participants. We conclude that the realized virtual open field test is able to elicit thigmotaxis and thus demonstrates cross-species validity of this aspect of the test. Modulatory effects of anxiety on human open field behavior should be examined further by incorporating possible threats in the virtual scenario and/or by examining participants with higher anxiety levels or anxiety disorder patients.}, language = {en} } @article{GromerReinkeChristneretal.2019, author = {Gromer, Daniel and Reinke, Max and Christner, Isabel and Pauli, Paul}, title = {Causal interactive links between presence and fear in virtual reality height exposure}, series = {Frontiers in Psychology}, volume = {10}, journal = {Frontiers in Psychology}, number = {141}, doi = {10.3389/fpsyg.2019.00141}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-201855}, year = {2019}, abstract = {Virtual reality plays an increasingly important role in research and therapy of pathological fear. However, the mechanisms how virtual environments elicit and modify fear responses are not yet fully understood. Presence, a psychological construct referring to the 'sense of being there' in a virtual environment, is widely assumed to crucially influence the strength of the elicited fear responses, however, causality is still under debate. The present study is the first that experimentally manipulated both variables to unravel the causal link between presence and fear responses. Height-fearful participants (N = 49) were immersed into a virtual height situation and a neutral control situation (fear manipulation) with either high versus low sensory realism (presence manipulation). Ratings of presence and verbal and physiological (skin conductance, heart rate) fear responses were recorded. Results revealed an effect of the fear manipulation on presence, i.e., higher presence ratings in the height situation compared to the neutral control situation, but no effect of the presence manipulation on fear responses. However, the presence ratings during the first exposure to the high quality neutral environment were predictive of later fear responses in the height situation. Our findings support the hypothesis that experiencing emotional responses in a virtual environment leads to a stronger feeling of being there, i.e., increase presence. In contrast, the effects of presence on fear seem to be more complex: on the one hand, increased presence due to the quality of the virtual environment did not influence fear; on the other hand, presence variability that likely stemmed from differences in user characteristics did predict later fear responses. These findings underscore the importance of user characteristics in the emergence of presence.}, language = {en} }