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A context can be conceptualized as a stable arrangement of elements or as the sum of single elements. Both configural and elemental representations play a role in associative processes. This study aimed to explore the respective contributions of these two representations of a context in the acquisition of conditioned anxiety in humans. Virtual reality (VR) can be an ecologically valid tool to investigate context-related mechanisms, yet the influence of the sense of presence within the virtual environment remains unclear. Forty-eight healthy individuals participated in a VR-based context conditioning wherein electric shocks (unconditioned stimulus, US) were unpredictably delivered in one virtual office (CTX+), but not in the other (CTX-). During the test phase, nine elements from each context were presented singularly. We found a cluster of participants, who exhibited heightened anticipation of the US for anxiety-related elements as compared to the other group. In contrast to their clear elemental representation, these individuals showed diminished discriminative responses between the two context's configurations. Discriminative responses to the contexts were boosted in those individuals, who had a weaker elemental representation. Importantly, the individual sense of presence significantly influenced the conditioned responses. These findings align with the dual-representation view of context and provide insights into the role of presence in eliciting (conditioned) anxiety responses.
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Ansiedade , Condicionamento Clássico , Realidade Virtual , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Condicionamento Clássico/fisiologia , EletrochoqueRESUMO
OBJECTIVE: Cognitive Behavior Therapy (CBT) is an effective treatment for anxiety and depression disorders. Nonetheless, nearly 50% of all patients do not respond. Besides other factors, nonresponse may be linked to traumatic life events. This study aims to assess the relationship between trauma history, applied therapy interventions, and therapy outcomes. METHODS: We analyzed data from 340 CBT outpatients diagnosed with a depression or anxiety disorder and possibly a trauma history treated under naturalistic conditions. Based on their therapy files, we collected information on trauma history, diagnoses, applied interventions, and severity of depression and anxiety symptoms at the start and end of therapy. The relationship between trauma, diagnoses, and intervention use and the development of depression and anxiety symptoms was analyzed using Linear Mixed Models. RESULTS: Patients with a trauma history reported higher pre- and posttreatment symptom severity than those without trauma. No differences in applied interventions or decrease in symptom severity were found between patients with and without a trauma history. Specialized interventions were seldom applied. CONCLUSION: Although no differences between patients with and without a trauma history were found in therapy response, patients with a trauma history maintained higher levels of symptom severity. These results indicate a need for more personalized interventions and evidence-based guidelines to personalize CBT for patients with a trauma history and high symptom severity.
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Transtornos de Ansiedade , Terapia Cognitivo-Comportamental , Humanos , Terapia Cognitivo-Comportamental/métodos , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , Transtornos de Ansiedade/terapia , Transtorno Depressivo/terapia , Pacientes Ambulatoriais , Trauma Psicológico/terapia , Adulto JovemRESUMO
Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.
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Transtornos de Ansiedade , Terapia Cognitivo-Comportamental , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Transtornos de Ansiedade/terapia , Transtornos de Ansiedade/diagnóstico por imagem , Transtornos de Ansiedade/fisiopatologia , Adulto , Terapia Cognitivo-Comportamental/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Adulto Jovem , Terapia Implosiva/métodosRESUMO
In order to memorize and discriminate threatening and safe stimuli, the processing of the actual absence of threat seems crucial. Here, we measured brain activity with fMRI in response to both threat conditioned stimuli and their outcomes by combining threat learning with a subsequent memory paradigm. Participants (N = 38) repeatedly saw a variety of faces, half of which (CS+) were associated with an aversive unconditioned stimulus (US) and half of which were not (CS-). When an association was later remembered, the hippocampus had been more active (than when forgotten). However, the ventromedial prefrontal cortex predicted subsequent memory specifically during safe associations (CS- and US omission responses) and the left dorsolateral prefrontal cortex during outcomes in general (US and US omissions). In exploratory analyses of the theoretically important US omission, we found extended involvement of the medial prefrontal cortex and an enhanced functional connectivity to visual and somatosensory cortices, suggesting a possible function in sustaining sensory information for an integration with semantic memory. Activity in visual and somatosensory cortices together with the inferior frontal gyrus also predicted memory performance one week after learning. The findings imply the importance of a close interplay between prefrontal and sensory areas during the processing of safe outcomes-or 'nothing'-to establish declarative safety memory.
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Medo , Córtex Pré-Frontal , Humanos , Medo/fisiologia , Córtex Pré-Frontal/fisiologia , Memória/fisiologia , Aprendizagem/fisiologia , Condicionamento Clássico/fisiologia , Imageamento por Ressonância Magnética , Mapeamento EncefálicoRESUMO
The COVID-19 pandemic and associated countermeasures had an immensely disruptive impact on people's lives. Due to the lack of systematic pre-pandemic data, however, it is still unclear how individuals' psychological health has been affected across this incisive event. In this study, we analyze longitudinal data from two healthy samples (N = 307) to provide quasi-longitudinal insight into the full trajectory of psychological burden before (baseline), during the first peak, and at a relative downturn of the COVID-19 pandemic. Our data indicated a medium rise in psychological strain from baseline to the first peak of the pandemic (d = 0.40). Surprisingly, this was overcompensated by a large decrease of perceived burden until downturn (d = - 0.93), resulting in a positive overall effect of the COVID-19 pandemic on mental health (d = 0.44). Accounting for this paradoxical positive effect, our results reveal that the post-pandemic increase in mental health is driven by individuals that were already facing psychological challenges before the pandemic. These findings suggest that coping with acute challenges such as the COVID-19 pandemic can stabilize previously impaired mental health through reframing processes.
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COVID-19 , Angústia Psicológica , Humanos , Saúde Mental , COVID-19/epidemiologia , Pandemias , Nível de SaúdeRESUMO
The experience of threat was found to result-mostly-in increased pain, however it is still unclear whether the exact opposite, namely the feeling of safety may lead to a reduction of pain. To test this hypothesis, we conducted two between-subject experiments (N = 94; N = 87), investigating whether learned safety relative to a neutral control condition can reduce pain, while threat should lead to increased pain compared to a neutral condition. Therefore, participants first underwent either threat or safety conditioning, before entering an identical test phase, where the previously conditioned threat or safety cue and a newly introduced visual cue were presented simultaneously with heat pain stimuli. Methodological changes were performed in experiment 2 to prevent safety extinction and to facilitate conditioning in the first place: We included additional verbal instructions, increased the maximum length of the ISI and raised CS-US contingency in the threat group from 50% to 75%. In addition to pain ratings and ratings of the visual cues (threat, safety, arousal, valence, and contingency), in both experiments, we collected heart rate and skin conductance. Analysis of the cue ratings during acquisition indicate successful threat and safety induction, however results of the test phase, when also heat pain was administered, demonstrate rapid safety extinction in both experiments. Results suggest rather small modulation of subjective and physiological pain responses following threat or safety cues relative to the neutral condition. However, exploratory analysis revealed reduced pain ratings in later trials of the experiment in the safety group compared to the threat group in both studies, suggesting different temporal dynamics for threat and safety learning and extinction, respectively. Perspective: The present results demonstrate the challenge to maintain safety in the presence of acute pain and suggest more research on the interaction of affective learning mechanism and pain processing.
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Dor Aguda , Medo , Humanos , Medo/psicologia , Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Percepção da Dor , Resposta Galvânica da PeleRESUMO
Photorealistic avatars show great potential in social VR and VR collaboration. However, identity and privacy issues are threatening avatars' authenticity in social VR. In addition to the necessary authentication and protection, effective solutions are needed to convey avatars' authenticity status to users and thereby enhance the overall trustworthiness. We designed several visual indicators (VIs) using static or dynamic visual effects on photorealistic avatars and evaluated their effectiveness in visualizing avatars' authenticity status. In this study we explored suitable attributes and designs for conveying the authenticity of photorealistic avatars and influencing their perceived trustworthiness. Furthermore, we investigated how different interactivity levels influence their effectiveness (the avatar was either presented in a static image, an animated video clip, or an immersive virtual environment). Our findings showed that using a full name can increase trust, while most other VIs could decrease users' trust. We also found that interactivity levels significantly impacted users' trust and the effectiveness of VIs. Based on our results, we developed design guidelines for visual indicators as effective tools to convey authenticity, as a first step towards the improvement of trustworthiness in social VR with identity management.
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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.
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Dor Aguda , Dor Crônica , Humanos , Comportamento de Escolha , Estudo de Prova de ConceitoRESUMO
It is widely accepted that impaired safety learning to a safe stimulus is a pathological feature of anxiety disorders. Safety learning refers to learning that a stimulus is associated with the absence of threat. Cognitive mechanisms that underlie successful threat and safety learning are, however, poorly understood. This study aimed to identify various physiological markers, including neural oscillations and event-related potentials (ERPs) that predict successful threat and safety learning. Therefore, to detect potential differences in these markers, we measured EEG in a fear learning framework combined with a subsequent memory paradigm. Thirty-seven participants were asked to memorize a series of associations between faces and an aversive unconditioned stimulus (US) or its omission. We found a decrease of power in the alpha band in occipital brain regions during learning for both threatening (conditioned stimuli, CS+) and safe faces (control stimuli, CS-) that were subsequently remembered to be associated with a US or not. No effects in theta band were found. In regard to ERPs, a late positive potential (LPP) and a P300 component were larger for remembered than for forgotten CS-US associations. The P300 was also enhanced to remembered US and US omissions, thus replicating previous findings. These results point to the importance of cognitive resource allocation as an underlying mechanism of fear learning and electrophysiological measurements as potential biomarkers for successful threat and safety learning.
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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).
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Música , Ansiedade de Desempenho , Terapia de Exposição à Realidade Virtual , Realidade Virtual , Humanos , Terapia de Relaxamento , Estudos Prospectivos , Ansiedade/terapia , Terapia de Exposição à Realidade Virtual/métodosRESUMO
Virtual humans, including virtual agents and avatars, play an increasingly important role as VR technology advances. For example, virtual humans are used as digital bodies of users in social VR or as interfaces for AI assistants in online financing. Interpersonal trust is an essential prerequisite in real-life interactions, as well as in the virtual world. However, to date, there are no established interpersonal trust measurement tools specifically for virtual humans in virtual reality. This study fills the gap, by contributing a novel validated behavioural tool to measure interpersonal trust towards a specific virtual social interaction partner in social VR. This validated paradigm is inspired by a previously proposed virtual maze task that measures trust towards virtual characters. In the current study, a variant of this paradigm was implemented. The task of the users (the trustors) is to navigate through a maze in virtual reality, where they can interact with a virtual human (the trustee). They can choose to 1) ask for advice and 2) follow the advice from the virtual human if they want to. These measures served as behavioural measures of trust. We conducted a validation study with 70 participants in a between-subject design. The two conditions did not differ in the content of the advice but in the appearance, tone of voice and engagement of the trustees (alleged as avatars controlled by other participants). Results indicate that the experimental manipulation was successful, as participants rated the virtual human as more trustworthy in the trustworthy condition than in the untrustworthy condition. Importantly, this manipulation affected the trust behaviour of our participants, who, in the trustworthy condition, asked for advice more often and followed advice more often, indicating that the paradigm is sensitive to assessing interpersonal trust towards virtual humans. Thus, our paradigm can be used to measure differences in interpersonal trust towards virtual humans and may serve as a valuable research tool to study trust in virtual reality.
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Despite striking empirical support, exposure-based treatments for anxiety disorders are underutilized. This is partially due to clinicians' concerns that patients may reject exposure or experience severe side effects, particularly in intensive forms of exposure. We examined acceptance and side effects of two randomly assigned variants of prediction error-based exposure treatment differing in temporal density (1 vs. 3 sessions/week) in 681 patients with panic disorder, agoraphobia, social anxiety disorder, and multiple specific phobias. Treatment acceptance included treatment satisfaction and credibility, engagement (i.e., homework completion), and tolerability (i.e., side effects, dropout, and perceived treatment burden). Side effects were measured with the Inventory for the Balanced Assessment of Negative Effects of Psychotherapy (INEP). We found treatment satisfaction, credibility, and engagement to be equally high in both variants of exposure-based treatment, despite higher treatment burden (ßâ¯=â¯0.25) and stronger side effects (ßâ¯=â¯0.15) in intensified treatment. 94.1% of patients reported positive effects in the INEP. 42.2% reported side effects, with treatment stigma (16.6%), low mood (14.8%) and the experience to depend on the therapist (10.9%) being the most frequently reported. The mean intensity of side effects was low. We conclude that prediction error-based exposure treatment is well accepted by patients with different anxiety disorders and that patients also tolerate temporally intensified treatment, despite higher perceived treatment burden and stronger side effects. Clinicians should be aware of the most frequent side effects to take appropriate countermeasures. In sum, temporal intensification appears to be an acceptable strategy to achieve faster symptom reduction, given patients' well-informed consent.
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Transtorno de Pânico , Transtornos Fóbicos , Humanos , Agorafobia/terapia , Transtornos de Ansiedade/terapia , Transtorno de Pânico/terapia , Transtornos Fóbicos/terapia , PsicoterapiaRESUMO
Emotions are frequently considered as the driving force of behavior, and psychopathology is often characterized by aberrant emotional responding. Emotional states are reflected on a cognitive-verbal, physiological-humoral, and motor-behavioral level but to date, human research lacks an experimental protocol for a comprehensive and ecologically valid characterization of such emotional states. Virtual reality (VR) might help to overcome this situation by allowing researchers to study mental processes and behavior in highly controlled but reality-like laboratory settings. In this chapter, we first elucidate the role of presence and immersion as requirements for eliciting emotional states in a virtual environment and discuss different VR methods for emotion induction. We then consider the organization of emotional states on a valence continuum (i.e., from negative to positive) and on this basis discuss the use of VR to study threat processing and avoidance as well as reward processing and approach behavior. Although the potential of VR has not been fully realized in laboratory and clinical settings yet, this technological tool can open up new avenues to better understand the neurobiological mechanisms of emotional responding in healthy and pathological conditions.
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Neurociências , Realidade Virtual , Humanos , Emoções/fisiologia , Cognição , NeurobiologiaRESUMO
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.
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Ansiedade , Potenciais Evocados Visuais , Humanos , Atenção/fisiologia , Aprendizagem , Transtornos de AnsiedadeRESUMO
OBJECTIVES: Previous research on stress-induced pain modulation suggests that moderate psychological stress usually leads to hyperalgesia while more severe threat results in hypoalgesia. However, existing studies often lack suitable control conditions imperative to identify mere stress effects. Similarly, research mainly focused on pure anticipation of a social threat, not taking into consideration actual experiences of social evaluation. Therefore, we set out to investigate actual social up- and downgrading combined with a standardized stress paradigm to evaluate short-term and prolonged changes in pain perception and their potential association with neuroendocrine and subjective stress parameters. METHODS: We allocated 177 healthy women to four experimental conditions, either the standard version of the Trier Social Stress Test (TSST) followed by positive, negative or no performance feedback, or a well-matched but less demanding placebo version of the TSST. Stress responses were assessed with ratings, salivary alpha-amylase, and salivary cortisol. To capture putative effects of stress on pain, heat pain threshold, ratings of phasic heat pain stimuli, and conditioned pain modulation were measured. RESULTS: Despite a largely successful stress induction, results do not support a reliable influence of experimentally induced social stress-with or without subsequent performance feedback-on pain in women. Further, we found no clear association of pain modulation and changes in neuroendocrine or subjective stress responses. CONCLUSIONS: Our results contrast previous studies, which repeatedly demonstrated stress-induced hypo- or hyperalgesia. This might be due to methodological reasons as former research was often characterized by high heterogeneity regarding the applied stressors, low sample sizes, and lacking or inconclusive control conditions. Thus, our results raise the question whether pain modulation in women by experimental psychosocial stress might have been overestimated in the past. Future research is necessary, which should employ parametric stress induction methods including well-matched control tasks, taking into consideration the participants' gender/sex and the time course of the stress response relative to pain assessment. The study is registered as DRKS00026946 at 'Deutsches Register Klinischer Studien' (DRKS) and can be also found at the World Health Organization's search portal.
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Hiperalgesia , Saliva , Feminino , Humanos , Retroalimentação , Limiar da Dor , Estresse Psicológico/psicologiaRESUMO
It is hypothesized that the ability to discriminate between threat and safety is impaired in individuals with high dispositional negativity, resulting in maladaptive behavior. A large body of research investigated differential learning during fear conditioning and extinction protocols depending on individual differences in intolerance of uncertainty (IU) and trait anxiety (TA), two closely-related dimensions of dispositional negativity, with heterogenous results. These might be due to varying degrees of induced threat/safety uncertainty. Here, we compared two groups with high vs. low IU/TA during periods of low (instructed fear acquisition) and high levels of uncertainty (delayed non-instructed extinction training and reinstatement). Dependent variables comprised subjective (US expectancy, valence, arousal), psychophysiological (skin conductance response, SCR, and startle blink), and neural (fMRI BOLD) measures of threat responding. During fear acquisition, we found strong threat/safety discrimination for both groups. During early extinction (high uncertainty), the low IU/TA group showed an increased physiological response to the safety signal, resulting in a lack of CS discrimination. In contrast, the high IU/TA group showed strong initial threat/safety discrimination in physiology, lacking discriminative learning on startle, and reduced neural activation in regions linked to threat/safety processing throughout extinction training indicating sustained but non-adaptive and rigid responding. Similar neural patterns were found after the reinstatement test. Taken together, we provide evidence that high dispositional negativity, as indicated here by IU and TA, is associated with greater responding to threat cues during the beginning of delayed extinction, and, thus, demonstrates altered learning patterns under changing environments.
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Extinção Psicológica , Resposta Galvânica da Pele , Ansiedade , Extinção Psicológica/fisiologia , Medo/fisiologia , Humanos , IncertezaRESUMO
Background: Craving associated with drug-related memory is one of the key factors that induce the relapse of methamphetamine (MA). Disruption or modulation of the reconsolidation of drug-related memory may serve as an option for clinical treatment of MA addiction. This protocol proposes to use virtual reality (VR) to retrieve drug-associated memory and then use transcranial magnetic stimulation (TMS) at the neural circuit that encodes the reward value of drug cues to provide a non-invasive intervention during reconsolidation. We aim to evaluate the effectiveness of TMS treatment after VR retrieval on the reduction of cue reactivity and craving of MA. Methods: This is a randomized, double-blind, sham-controlled, parallel group trial, targeting participants with MA use disorder aged from 18 to 45 years old. Forty-five eligible volunteers in Shanxi Drug Rehabilitation Center will be recruited and be randomly allocated into three parallel groups, receiving either 1) MA-related cues retrieval in VR combined with active TMS (MA VR scene + TBS) or 2) sham TMS (MA VR scene + sham TBS), or 3) neutral cues retrieval in VR combined with active TMS (neutral VR scene + TBS). Two sessions of post-VR-retrieval TBS will be scheduled on two separate days within 1 week. The primary outcome will detect the memory-related activity by the electroencephalography (EEG) reactivity to drug cues in VR scenes. Secondary outcomes are the self-reported MA craving in VR scene, the physiological parameter (cue-induced heart rate) and the scores of psychological questionnaires including anxiety, depression, and mood. All primary and secondary outcomes will be assessed at baseline, 1-week, and 1-month post-intervention. Assessments will be compared between the groups of 1) MA VR scene + TBS, 2) MA VR scene + sham TBS and 3) neutral VR scene + TBS. Discussion: This will be the first study to examine whether the TMS modulation after VR retrieval can reduce self-reported craving and drug-related cue reactivity. It will promote the understanding of the neural circuit mechanism of the reconsolidation-based intervention and provide an effective treatment for MA use disorder patients. Clinical Trial Registration: [Chinese Clinical Trial Registry], identifier [ChiCTR1900026902]. Registered on 26 October 2019.
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Adequate defensive responding is crucial for mental health but scientifically not well understood. Specifically, it seems difficult to dissociate defense and approach states based on autonomic response patterns. We thus explored the robustness and threat-specificity of recently described oculomotor dynamics upon threat in anticipation of either threatening or rewarding stimuli in humans. While visually exploring naturalistic images, participants (50 per experiment) expected an inevitable, no, or avoidable shock (Experiment 1) or a guaranteed, no, or achievable reward (Experiment 2) that could be averted or gained by a quick behavioural response. We observed reduced heart rate (bradycardia), increased skin conductance, pupil dilation and globally centralized gaze when shocks were inevitable but, more pronouncedly, when they were avoidable. Reward trials were not associated with globally narrowed visual exploration, but autonomic responses resembled characteristics of the threat condition. While bradycardia and concomitant sympathetic activation reflect not only threat-related but also action-preparatory states independent of valence, global centralization of gaze seems a robust phenomenon during the anticipation of avoidable threat. Thus, instead of relying on single readouts, translational research in animals and humans should consider the multi-dimensionality of states in aversive and rewarding contexts, especially when investigating ambivalent, conflicting situations.
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Bradicardia , Medo , Medo/fisiologia , Medo/psicologia , Humanos , RecompensaRESUMO
Adaptive approach and avoidance in responses to reward and threat are fundamental to prevent harm and to ensure well-being. In contrast, maladaptive approach or avoidance behavior likely contributes to anxiety or substance abuse disorders, respectively. Therefore, there is a need to assess such behavior in humans objectively. Conditioned place preference (CPP) is a well-established animal paradigm investigating approach-avoidance mechanisms, i.e., context-associated appetitive/aversive effects of unconditioned stimuli. Recently, the retranslation of this paradigm for human research started. This meta-analysis provides the first systematic overview of this developing field. A total of 17 studies published before June 2020 fulfil our inclusion criteria: (1) Usage of a rewarding agent, (2) implementation of either virtual or real environments, (3) human subjects, and (4) report of standardized outcome measures. These studies were evaluated and analyzed following the DIAD model and the PRISMA guidelines, respectively, and specific subanalyses were preformed to identify modulating factors of CPP effects (e.g., Virtual Reality applications, biased/unbiased). Overall, a significant medium effect size for the behavioral measure of dwell time (g =.62, p < .001, 95%-CI =.43-.81) and a significant small effect size for verbal self-ratings (g =.33, p < .001, 95%-CI =.04-.63) were observed, although across-study results were characterized by substantial heterogeneity (l2 > 65%). These results indicate great potential for CPP to study approach-avoidance behavior in humans, directly in analogy to animal studies. We provide guidelines for future CPP research to improve comparability of studies and to facilitate new insights into anxiety disorders and drug abuse.
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Condicionamento Clássico , Transtornos Relacionados ao Uso de Substâncias , Animais , Transtornos de Ansiedade , Condicionamento Operante , Humanos , RecompensaRESUMO
OBJECTIVES: The patient-physician relationship is essential for treatment success. Previous studies demonstrated that physicians who behave empathic in their interaction with patients have a positive effect on health outcomes. In this study, we investigated if the mere perception of physicians as empathic/not empathic modulates pain despite an emotionally neutral interaction with the patients. METHODS: N = 60 women took part in an experimental study that simulated a clinical interaction. In the paradigm, each participant watched two immersive 360° videos via a head-mounted display from a patient's perspective. The physicians in the videos behaved either empathic or not empathic towards a third person. Importantly, these physicians remained emotionally neutral in the subsequent virtual interaction with the participants. Finally, participants received a controlled, painful pressure stimulus within the narratives of the videos. RESULTS: The physicians in the high compared with the low empathy videos were rated as more empathic and more likable, indicating successful experimental manipulation. In spite of later neutral behaviour of physicians, this short observation of physicians' behaviour towards a third person was sufficient to modulate pain tolerance of the participants. CONCLUSIONS: The finding of this study that the mere observation of physicians' behaviour towards a third person modulates pain, despite a neutral direct interaction with the participants, has important clinical implications. Further, the proposed paradigm enables investigating aspects of patient-physician communication that are difficult to examine in a clinical setting.