The application of virtual reality exposure versus relaxation training in music performance anxiety: a randomized controlled study.

BACKGROUND: Performance anxiety is the most frequently reported anxiety disorder among professional musicians. Typical symptoms are - on a physical level - the consequences of an increase in sympathetic tone with cardiac stress, such as acceleration of heartbeat, increase in blood pressure, increased respiratory rate and tremor up to nausea or flush reactions. These symptoms can cause emotional distress, a reduced musical and artistical performance up to an impaired functioning. While anxiety disorders are preferably treated using cognitive-behavioral therapy with exposure, this approach is rather difficult for treating music performance anxiety since the presence of a public or professional jury is required and not easily available. The use of virtual reality (VR) could therefore display an alternative. So far, no therapy studies on music performance anxiety applying virtual reality exposure therapy have investigated the therapy outcome including cardiovascular changes as outcome parameters. METHODS: This mono-center, prospective, randomized and controlled clinical trial has a pre-post design with a follow-up period of 6 months. 46 professional and semi-professional musicians will be recruited and allocated randomly to an VR exposure group or a control group receiving progressive muscle relaxation training. Both groups will be treated over 4 single sessions. Music performance anxiety will be diagnosed based on a clinical interview using ICD-10 and DSM-5 criteria for specific phobia or social anxiety. A behavioral assessment test is conducted three times (pre, post, follow-up) in VR through an audition in a concert hall. Primary outcomes are the changes in music performance anxiety measured by the German Bühnenangstfragebogen and the cardiovascular reactivity reflected by heart rate variability (HRV). Secondary outcomes are changes in blood pressure, stress parameters such as cortisol in the blood and saliva, neuropeptides, and DNA-methylation. DISCUSSION: The trial investigates the effect of VR exposure in musicians with performance anxiety compared to a relaxation technique on anxiety symptoms and corresponding cardiovascular parameters. We expect a reduction of anxiety but also a consecutive improvement of HRV with cardiovascular protective effects. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov. (ClinicalTrials.gov Number: NCT05735860).

Relevance of Religiosity for Coping Strategies and Disability in Patients with Fibromyalgia Syndrome.

Coping strategies are essential for the outcome of chronic pain. This study evaluated religiosity in a cohort of patients with fibromyalgia syndrome (FMS), its effect on pain and other symptoms, on coping and FMS-related disability. A total of 102 FMS patients were recruited who filled in questionnaires, a subgroup of 42 patients participated in a face-to-face interview, and data were evaluated by correlation and regression analyses. Few patients were traditionally religious, but the majority believed in a higher existence and described their spirituality as "transcendence conviction". The coping strategy "praying-hoping" and the ASP dimension "religious orientation" (r = 0.5, P < 0.05) showed a significant relationship independent of the grade of religiosity (P < 0.05). A high grade of belief in a higher existence was negatively associated with the choice of ignoring as coping strategy (r = - 0.4, P < 0.05). Mood and affect-related variables had the highest impact on disability (b = 0.5, P < 0.05). In this cohort, the grade of religiosity played a role in the choice of coping strategies, but had no effects on health and mood outcome.

Mindfulness-based relapse prevention combined with virtual reality cue exposure for methamphetamine use disorder: Study protocol for a randomized controlled trial.

BACKGROUND: Mindfulness-based relapse prevention (MBRP) is a method that combines cognitive behavioral relapse prevention with mindfulness practice. Research suggests that MBRP can effectively reduce withdrawal/craving in people with substance use disorder (SUD). An important part of MBRP is to practice mindfulness meditation to cope with high-risk situations for relapse, such as stimuli and situations associated with drug taking. Virtual reality cue exposure (VRCE) may be a complementary approach to MBRP as it allows for controlled and graded presentations of various high-risk situations with distal and proximal drug cues. The aim of the study is to investigate the effects of MBRP combined with VRCE, in comparison to MBRP alone or treatment as usual, on craving and emotional responses in people with methamphetamine use disorders. METHOD/DESIGN: The study is a parallel randomized controlled study including 180 participants with methamphetamine use disorder. Three parallel groups will receive 8 weeks of MBRP combined with VRCE, MBRP alone, or treatment as usual, respectively. Craving, virtual cue reactivity, anxiety, depression, emotion regulation, mindfulness and drug-related attention bias will be assessed at pre-treatment, post-treatment, and 3 and 6 months of follow-up. DISCUSSION: This innovative study aims at investigating the effects of MBRP combined with VRCE in people with SUD. The combined intervention may have important clinical implications for relapse prevention due to its ease of application and high cost-effectiveness. This study may also stimulate research on the neuronal and psychological mechanisms of MBRP in substance use disorder. TRIAL REGISTRATION NUMBER: ChiCTR-INR-17013041.

Reinstatement of contextual conditioned anxiety in virtual reality and the effects of transcutaneous vagus nerve stimulation in humans.

Since exposure therapy for anxiety disorders incorporates extinction of contextual anxiety, relapses may be due to reinstatement processes. Animal research demonstrated more stable extinction memory and less anxiety relapse due to vagus nerve stimulation (VNS). We report a valid human three-day context conditioning, extinction and return of anxiety protocol, which we used to examine effects of transcutaneous VNS (tVNS). Seventy-five healthy participants received electric stimuli (unconditioned stimuli, US) during acquisition (Day1) when guided through one virtual office (anxiety context, CTX+) but never in another (safety context, CTX-). During extinction (Day2), participants received tVNS, sham, or no stimulation and revisited both contexts without US delivery. On Day3, participants received three USs for reinstatement followed by a test phase. Successful acquisition, i.e. startle potentiation, lower valence, higher arousal, anxiety and contingency ratings in CTX+ versus CTX-, the disappearance of these effects during extinction, and successful reinstatement indicate validity of this paradigm. Interestingly, we found generalized reinstatement in startle responses and differential reinstatement in valence ratings. Altogether, our protocol serves as valid conditioning paradigm. Reinstatement effects indicate different anxiety networks underlying physiological versus verbal responses. However, tVNS did neither affect extinction nor reinstatement, which asks for validation and improvement of the stimulation protocol.

Diaphragmatic breathing during virtual reality exposure therapy for aviophobia: functional coping strategy or avoidance behavior? a pilot study.

BACKGROUND: Although there is solid evidence for the efficacy of in vivo and virtual reality (VR) exposure therapy for a specific phobia, there is a significant debate over whether techniques promoting distraction or relaxation have impairing or enhancing effects on treatment outcome. In the present pilot study, we investigated the effect of diaphragmatic breathing (DB) as a relaxation technique during VR exposure treatment. METHOD: Twenty-nine patients with aviophobia were randomly assigned to VR exposure treatment either with or without diaphragmatic breathing (six cycles per minute). Subjective fear ratings, heart rate and skin conductance were assessed as indicators of fear during both the exposure and the test session one week later. RESULTS: The group that experienced VR exposure combined with diaphragmatic breathing showed a higher tendency to effectively overcome the fear of flying. Psychophysiological measures of fear decreased and self-efficacy increased in both groups with no significant difference between the groups. CONCLUSIONS: Our findings indicate that diaphragmatic breathing during VR exposure does not interfere with the treatment outcome and may even enhance treatment effects of VR exposure therapy for aviophobic patients. TRIAL REGISTRATION: Retrospectively registered. ClinicalTrials.gov NCT02990208 . Registered 07 December 2016.

Effects of context preexposure and delay until anxiety retrieval on generalization of contextual anxiety.

Animal studies suggest that time delay between acquisition and retrieval of contextual anxiety increases generalization. Moreover, such generalization is prevented by preexposure to the context (CTX), presumably due to an improved representation of such context. We investigated whether preexposure and time-passing modulate generalization of contextual anxiety, in humans. On Day 1, 42 participants (preexposure group) explored two virtual offices, while 41 participants (no-preexposure group) explored a virtual stadium. On Day 2 (24 h later), all participants learned to associate one office (CTX+) with unpredictable unconditioned stimuli (USs), and another office (CTX-) with safety. On Day 3, either 24 h (recent test) or 2 wk (remote test) later, participants revisited CTX- and CTX+ without USs, as well as a generalization context (G-CTX). Results revealed successfully conditioned anxiety and anxiety generalization for ratings (G-CTX was as aversive as CTX+ was), while safety generalization was found for startle responses (G-CTX elicited startle attenuation as CTX- did). Time between learning and testing enhanced generalization as reflected by comparable startle responses to all three offices in the remote test. Contextual preexposure facilitated extinction of explicit conditioned anxiety assessed with ratings. These results suggest that memory trace of a context degrades with passage of time in humans like in animals and, consequently, anxiety generalization enhances. After context preexposure, high cognitive processes seem to be crucially involved in facilitating extinction (or safety) learning.

Emotional processing and rTMS: does inhibitory theta burst stimulation affect the human startle reflex?

Repetitive transcranial magnetic stimulation (rTMS) enables the local and non-invasive modulation of cortical activity and has proved to achieve antidepressant effects. To a lesser extent, rTMS is investigated as a treatment option for anxiety disorders. As the prefrontal cortex and the amygdala represent key components of human emotion regulation, we investigated how prefrontally applied rTMS affects the responsiveness of the subcortical amygdala during a fear-relevant study paradigm to examine potential cortico-limbic effects. Sham-controlled, randomised inhibitory rTMS (continuous theta burst stimulation, TBS) was applied to 102 healthy subjects (female = 54) over the right dorsolateral prefrontal cortex. Subsequently, the emotion-potentiated (unpleasant, neutral, and pleasant International Affective Picture System pictures) acoustic startle response was investigated. Subjective anxiety ratings (anxiety sensitivity, trait and state anxiety) were considered. Picture category affected the startle magnitude as expected for both TBS intervention groups (highest startle response for unpleasant, lowest for pleasant pictures). However, no modulatory effects of TBS on startle potentiation were discerned. No significant interaction effects of TBS intervention, subjective anxiety ratings, and gender were identified. Interestingly, startle habituation was influenced by TBS intervention on a trend-level, with verum TBS leading to an accelerated habituation. We found no evidence for the hypothesis that prefrontal inhibitory TBS affects the responsiveness of the amygdala during the presentation of emotionally relevant stimuli in healthy subjects. Instead, we found accelerated habituation under verum TBS on a statistical trend-level. Hence, some preliminary hints for modulatory effects of inhibitory TBS on basic learning mechanisms could be found.

Reinstatement of contextual anxiety in humans: Effects of state anxiety.

After successful extinction of conditioned fear, the presentation of an unsignaled unconditioned stimulus (US) leads to return of fear, thus, the previously extinguished conditioned stimulus (CS) triggers fear responses again. Human studies on such reinstatement processes are still inconclusive. Some revealed a general increase of fear reactions, both to the fear (CS+) and the safety stimulus (CS-), whereas other studies discovered a differential return of fear with enhanced fear responses to the CS+ only. Moreover, we know little about reinstatement of contextual anxiety, a state of general anxious apprehension and chronic worry. Therefore, the present study investigated reinstatement of contextual anxiety with an ecological valid virtual reality (VR) design. Additionally, we examined whether the current state anxiety might modulate the reinstatement of contextual anxiety. To this end, two groups underwent context conditioning on Day 1, i.e., one context (CXT+) became paired with unpredictable USs, but not the other context (CXT-), and an extinction training on Day 2. On Day 3 a reinstatement test was conducted, i.e., one group (reinstatement group, n=21) received one unsignaled US before testing, whereas the control group (n=21) did not. Only the reinstatement group showed a differential return of contextual anxiety as measured by fear-potentiated startle and anxiety ratings. Interestingly, the reinstatement of fear-potentiated startle was additionally influenced by state anxiety. Conclusively, an anxious state before an unsignaled aversive event might favor a return of contextual anxiety.

Sustained attention in context conditioning: Evidence from steady-state VEPs.

In classical fear conditioning an aversive event is paired repeatedly with a predictive stimulus, which later elicits fear. Repeated presentation of an aversive event in the absence of a predictive cue however may induce anxiety, and the context may gain a threatening value. As such conditioned anxiety can be considered a sustained reaction compared to phasic fear, it would be interesting to track continuous cortical responses during context conditioning. The present study realized a differential context conditioning paradigm and assessed sustained cortical activations to the threatening and the safe context and how neutral cues are processed within both contexts. Two pictures of different office rooms presented for 20s served as contexts. One room became associated with an unpleasant noise that was presented unpredictably (CTX+) while the other office (CTX-) was never associated with this unpleasant noise. After acquisition, a social agent or an object was presented as a distractor in both contexts. Cortical activations in response to contexts and distractors were assessed separately by steady-state visually evoked potentials (ssVEPs) using frequency tagging. Results revealed enhanced ssVEP-amplitudes for CTX+ compared to CTX- in a lateral occipital cluster during acquisition. Similarly, CTX+ elicited higher ssVEP-amplitudes during the test phase, and these context conditioning effects were not reduced by the simultaneous presentation of novel distractors. These results indicate that context conditioning was successfully implemented and that the anxiety context received facilitated cortical processing across the whole viewing time. We conclude that threatening contexts capture attention over a longer period of time, and are immune to distraction by new objects.

Illusory correlations between neutral and aversive stimuli can be induced by outcome aversiveness.

Anxiety is often characterised by an overestimation of the contingency between concern-relevant and aversive stimuli, and an amplified aversiveness of such aversive stimuli. Here we tested whether outcome aversiveness causally enhances contingency estimates. Twenty-four participants were exposed to neutral visual cues which were followed by startle sounds. The loudness and hence the aversiveness of the cue was determined by the cue colour while the likelihood of the startle sound always remained constant (50%). Results indicated an illusory correlation specifically for the cue followed by the most aversive startle sound as reflected in enhanced on-line and a posteriori covariation estimates. This bias was positively correlated with state and trait anxiety. Physiological arousal measured by pupil diameter was enhanced in response to the most aversive startle sound confirming its distinct processing. In conclusion, these results suggest that aversive outcomes may induce illusory correlations, most likely in anxious persons, and explain previous findings of illusory correlations in anxiety disorders.

After-training emotional interference may modulate sequence awareness in a serial reaction time task.

The purpose of the present experiment was to investigate the effects of emotional interference on consolidation of sequential learning. In different sessions, 6 groups of subjects were initially trained on a serial reaction time task (SRTT). To modulate consolidation of the newly learned skill, subjects were exposed, after the training, to 1 of 3 (positive, negative or neutral) different classes of emotional stimuli which consisted of a set of emotional pictures combined with congruent emotional musical pieces or neutral sound. Emotional intervention for each subject group was done in 2 different time intervals (either directly after the training session or 6 h later). After a 72 h post-training interval, each group was retested on the SRTT. Re-test performance was evaluated in terms of response times and accuracy during execution of a target sequence. Emotional intervention did not influence either response times or accuracy of re-testing SRTT target task performance, both variables sensitive to implicit knowledge acquired during SRTT training. However, explicit awareness of sequence knowledge after 72 h was enhanced when negative stimuli had been applied at 0 h after training. These findings suggest that consolidation of explicit aspects of procedural learning may be more responsive toward emotional interference than implicit aspects.

Methylphenidate normalizes emotional processing in adult patients with attention-deficit/hyperactivity disorder: preliminary findings.

Emotional-motivational dysfunctions may significantly contribute to symptoms of attention-deficit/hyperactivity disorder (ADHD). Hyperactive-impulsive symptoms and sensation seeking could be the result of a search for reinforcers, and cognitive dysfunctions might be due to a low motivational drive. Emotional-motivational dysfunctions could also explain social dysfunctions in ADHD patients because they may lead to misinterpretations of emotional and social clues. Since methylphenidate (MPH) is the first choice as a pharmacological treatment in ADHD, we examined its influence on dysfunctional emotional processes. 13 adult ADHD patients were examined twice, without and after intake of MPH according to their personal medication regimen. The affect-modulated startle paradigm was used to assess physiological (affect-modulated startle response) and subjective (valence and arousal ratings) responses to pleasant, neutral and unpleasant visual stimuli. Healthy controls displayed affective startle modulation as expected, with startle attenuation and potentiation while watching pleasant and unpleasant pictures, respectively. In contrast, unmedicated ADHD patients displayed deficient responses to pleasant stimuli; no startle attenuation during the exposure to pleasant pictures was observed. However, MPH reinstated a normal affective startle modulation, as indicated by attenuation and potentiation associated with pleasant and unpleasant pictures, respectively. Valence and arousal ratings of patients were not affected by MPH. The data suggest that MPH as first choice treatment in ADHD has a positive impact on emotional processes in adult ADHD patients and points to the clinical relevance of emotional-dysfunctions in ADHD.

Pain modulation during drives through cold and hot virtual environments.

Evidence exists that virtual worlds reduce pain perception by providing distraction. However, there is no experimental study to show that the type of world used in virtual reality (VR) distraction influences pain perception. Therefore, we investigated whether pain triggered by heat or cold stimuli is modulated by "warm "or "cold " virtual environments and whether virtual worlds reduce pain perception more than does static picture presentation. We expected that cold worlds would reduce pain perception from heat stimuli, while warm environments would reduce pain perception from cold stimuli. Additionally, both virtual worlds should reduce pain perception in general. Heat and cold pain stimuli thresholds were assessed outside VR in 48 volunteers in a balanced crossover design. Participants completed three 4-minute assessment periods: virtual "walks " through (1) a winter and (2) an autumn landscape and static exposure to (3) a neutral landscape. During each period, five heat stimuli or three cold stimuli were delivered via a thermode on the participant's arm, and affective and sensory pain perceptions were rated. Then the thermode was changed to the other arm, and the procedure was repeated with the opposite pain stimuli (heat or cold). We found that both warm and cold virtual environments reduced pain intensity and unpleasantness for heat and cold pain stimuli when compared to the control condition. Since participants wore a head-mounted display (HMD) in both the control condition and VR, we concluded that the distracting value of virtual environments is not explained solely by excluding perception of the real world. Although VR reduced pain unpleasantness, we found no difference in efficacy between the types of virtual world used for each pain stimulus.

Covariation bias and its physiological correlates in panic disorder patients.

A covariation bias, i.e., the overestimation of random contingencies between fear-relevant stimuli and aversive consequences, seems to characterize anxiety disorders. Panic patients (n=30) and healthy controls (n=25) were exposed to panic-relevant, neutral, and phobia-relevant but panic-irrelevant picture stimuli, followed randomly be aversive consequences (acoustic startle stimuli). While covariation estimates reflected objective contingencies in both groups, only panic patients revealed a more negative Contingent Negative Variation (CNV) to panic-relevant than to phobia-relevant and neutral pictures. For startle reflex, only main effects of picture category were found, indicating that valence effects of picture stimuli were not specifically distorted in panic patients. CNV presumably reflects a biased processing of disorder-relevant stimuli by panic patients, perhaps with the expectation that aversive consequences will follow these stimuli.