TY - JOUR A1 - Hilger, Kirsten A1 - Häge, Anne-Sophie A1 - Zedler, Christina A1 - Jost, Michael A1 - Pauli, Paul T1 - Virtual reality to understand pain-associated approach behaviour: a proof-of-concept study JF - Scientific Reports N2 - Pain-associated approach and avoidance behaviours are critically involved in the development and maintenance of chronic pain. Empirical research suggests a key role of operant learning mechanisms, and first experimental paradigms were developed for their investigation within a controlled laboratory setting. We introduce a new Virtual Reality paradigm to the study of pain-related behaviour and investigate pain experiences on multiple dimensions. The paradigm evaluates the effects of three-tiered heat-pain stimuli applied contingent versus non-contingent with three types of arm movements in naturalistic virtual sceneries. Behaviour, self-reported pain-related fear, pain expectancy and electrodermal activity were assessed in 42 healthy participants during an acquisition phase (contingent movement-pain association) and a modification phase (no contingent movement-pain association). Pain-associated approach behaviour, as measured by arm movements followed by a severe heat stimulus, quickly decreased in-line with the arm movement-pain contingency. Slower effects were observed in fear of movement-related pain and pain expectancy ratings. During the subsequent modification phase, the removal of the pain contingencies modified all three indices. In both phases, skin conductance responses resemble the pattern observed for approach behaviour, while skin conductance levels equal the pattern observed for the self-ratings. Our findings highlight a fast reduction in approach behaviour in the face of acute pain and inform about accompanying psychological and physiological processes. We discuss strength and limitations of our paradigm for future investigations with the ultimate goal of gaining a comprehensive understanding of the mechanisms involved in chronic pain development, maintenance, and its therapy. KW - anxiety KW - human behaviour Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357817 VL - 13 ER - TY - JOUR A1 - Stegmann, Yannik A1 - Andreatta, Marta A1 - Pauli, Paul A1 - Keil, Andreas A1 - Wieser, Matthias J. T1 - Investigating sustained attention in contextual threat using steady‐state VEPs evoked by flickering video stimuli JF - Psychophysiology N2 - Anxiety is characterized by anxious anticipation and heightened vigilance to uncertain threat. However, if threat is not reliably indicated by a specific cue, the context in which threat was previously experienced becomes its best predictor, leading to anxiety. A suitable means to induce anxiety experimentally is context conditioning: In one context (CTX+), an unpredictable aversive stimulus (US) is repeatedly presented, in contrast to a second context (CTX−), in which no US is ever presented. In this EEG study, we investigated attentional mechanisms during acquisition and extinction learning in 38 participants, who underwent a context conditioning protocol. Flickering video stimuli (32 s clips depicting virtual offices representing CTX+/−) were used to evoke steady‐state visual evoked potentials (ssVEPs) as an index of visuocortical engagement with the contexts. Analyses of the electrocortical responses suggest a successful induction of the ssVEP signal by video presentation in flicker mode. Furthermore, we found clear indices of context conditioning and extinction learning on a subjective level, while cortical processing of the CTX+ was unexpectedly reduced during video presentation. The differences between CTX+ and CTX− diminished during extinction learning. Together, these results indicate that the dynamic sensory input of the video presentation leads to disruptions in the ssVEP signal, which is greater for motivationally significant, threatening contexts. KW - anxiety KW - EEG KW - oscillation KW - threat KW - time frequency analyses KW - visual processes Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-312430 VL - 60 IS - 5 ER - TY - JOUR A1 - Schiele, Miriam A. A1 - Ziegler, Christiane A1 - Kollert, Leonie A1 - Katzorke, Andrea A1 - Schartner, Christoph A1 - Busch, Yasmin A1 - Gromer, Daniel A1 - Reif, Andreas A1 - Pauli, Paul A1 - Deckert, Jürgen A1 - Herrmann, Martin J. A1 - Domschke, Katharina T1 - Plasticity of Functional MAOA Gene Methylation in Acrophobia JF - International Journal of Neuropsychopharmacology N2 - 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. KW - monoamine oxidase A KW - anxiety KW - extinction KW - epigenetics KW - DNA methylation Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228571 VL - 21 IS - 9 ER - TY - JOUR A1 - Wiemer, Julian A1 - Rauner, Milena M. A1 - Stegmann, Yannik A1 - Pauli, Paul T1 - Reappraising fear: is up-regulation more efficient than down-regulation? JF - Motivation and Emotion N2 - Catastrophizing thoughts may contribute to the development of anxiety, but functional emotion regulation may help to improve treatment. No study so far directly compared up- and down-regulation of fear by cognitive reappraisal. Here, healthy individuals took part in a cued fear experiment, in which multiple pictures of faces were paired twice with an unpleasant scream or presented as safety stimuli. Participants (N = 47) were asked (within-subjects) to down-regulate, to up-regulate and to maintain their natural emotional response. Valence and arousal ratings indicated successful up- and down-regulation of the emotional experience, while heart rate and pupil dilation increased during up-regulation, but showed no reduction in down-regulation. State and trait anxiety correlated with evaluations of safety but not threat stimuli, which supports the role of deficient safety learning in anxiety. Reappraisal did not modulate this effect. In conclusion, this study reveals evidence for up-regulation effects in fear, which might be even more efficient than down-regulation on a physiological level and highlights the importance of catastrophizing thoughts for the maintenance of fear and anxiety. KW - anxiety KW - fear conditioning KW - cognitive reappraisal KW - pupil diameter KW - heart rate Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-269187 SN - 1573-6644 VL - 45 IS - 2 ER - TY - JOUR A1 - Gromer, Daniel A1 - Kiser, Dominik P. A1 - Pauli, Paul T1 - Thigmotaxis in a virtual human open field test JF - Scientific Reports N2 - 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. KW - anxiety KW - human behavior KW - anciety-like behavior KW - approach-avoidance conflict KW - elevated plus-maze KW - spatial navigation KW - mental disorders KW - fear KW - threat KW - circuits KW - reality KW - metaanalysis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259850 VL - 11 ER - TY - JOUR A1 - Madeira, Octavia A1 - Gromer, Daniel A1 - Latoschik, Marc Erich A1 - Pauli, Paul T1 - Effects of Acrophobic Fear and Trait Anxiety on Human Behavior in a Virtual Elevated Plus-Maze JF - Frontiers in Virtual Reality N2 - 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. KW - elevated plus-maze KW - EPM KW - anxiety KW - virtual reality KW - translational neuroscience KW - acrophobia KW - trait anxiety Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258709 VL - 2 ER - TY - JOUR A1 - Gromer, Daniel A1 - Madeira, Octávia A1 - Gast, Philipp A1 - Nehfischer, Markus A1 - Jost, Michael A1 - Müller, Mathias A1 - Mühlberger, Andreas A1 - Pauli, Paul T1 - Height Simulation in a Virtual Reality CAVE System: Validity of Fear Responses and Effects of an Immersion Manipulation JF - Frontiers in Human Neuroscience N2 - 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. KW - anxiety KW - fear behavior KW - virtual reality KW - presence KW - immersion KW - acrophobia Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196113 SN - 1662-5161 VL - 12 IS - 372 ER - TY - JOUR A1 - Platte, Petra A1 - Herbert, Cornelia A1 - Pauli, Paul A1 - Breslin, Paul A. S. T1 - Oral Perceptions of Fat and Taste Stimuli Are Modulated by Affect and Mood Induction JF - PLoS ONE N2 - This study examined the impact of three clinical psychological variables (non-pathological levels of depression and anxiety, as well as experimentally manipulated mood) on fat and taste perception in healthy subjects. After a baseline orosensory evaluation, ‘sad’, ‘happy’ and ‘neutral’ video clips were presented to induce corresponding moods in eighty participants. Following mood manipulation, subjects rated five different oral stimuli, appearing sweet, umami, sour, bitter, fatty, which were delivered at five different concentrations each. Depression levels were assessed with Beck’s Depression Inventory (BDI) and anxiety levels were assessed via the Spielberger’s STAI-trait and state questionnaire. Overall, subjects were able to track the concentrations of the stimuli correctly, yet depression level affected taste ratings. First, depression scores were positively correlated with sucrose ratings. Second, subjects with depression scores above the sample median rated sucrose and quinine as more intense after mood induction (positive, negative and neutral). Third and most important, the group with enhanced depression scores did not rate low and high fat stimuli differently after positive or negative mood induction, whereas, during baseline or during the non-emotional neutral condition they rated the fat intensity as increasing with concentration. Consistent with others’ prior observations we also found that sweet and bitter stimuli at baseline were rated as more intense by participants with higher anxiety scores and that after positive and negative mood induction, citric acid was rated as stronger tasting compared to baseline. The observation that subjects with mild subclinical depression rated low and high fat stimuli similarly when in positive or negative mood is novel and likely has potential implications for unhealthy eating patterns. This deficit may foster unconscious eating of fatty foods in sub-clinical mildly depressed populations. KW - analysis of variance KW - anxiety KW - citric acid KW - depression KW - glutamate KW - quinine KW - sensory perception KW - sucrose Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96421 ER -