The impact of extinction timing on pre-extinction arousal and subsequent return of fear.

Exposure-based therapy is effective in treating anxiety, but a return of fear in the form of relapse is common. Exposure is based on the extinction of Pavlovian fear conditioning. Both animal and human studies point to increased arousal during immediate compared to delayed extinction (>+24 h), which presumably impairs extinction learning and increases the subsequent return of fear. Impaired extinction learning under arousal might interfere with psychotherapeutic interventions. The aim of the present study was to investigate whether arousal before extinction differs between extinction groups and whether arousal before extinction predicts the return of fear in a later (retention) test. As a highlight, both the time between fear acquisition and extinction (immediate vs. delayed) and the time between extinction and test (early vs. late test) were systematically varied. We performed follow-up analyses on data from 103 young, healthy participants to test the above hypotheses. Subjective arousal ratings and physiological arousal measures of sympathetic and hypothalamic pituitary adrenal axis activation (tonic skin conductance and salivary cortisol) were collected. Increased pre-extinction arousal in the immediate extinction group was only confirmed for subjective arousal. In linear regression analyses, none of the arousal measures predicted a significant return of fear in the different experimental groups. Only when we aggregated across the two test groups, tonic skin conductance at the onset of extinction predicted the return of fear in skin conductance responses. The overall results provide little evidence that pre-extinction arousal affects subsequent extinction learning and memory. In terms of clinical relevance, there is no clear evidence that exposure could be improved by reducing subjective or physiological arousal.

Nicotine-related interpretation biases in cigarette smoking individuals.

Addictive behaviors are characterized by information processing biases, including substance-related interpretation biases. In the field of cigarette smoking, such biases have not been investigated yet. The present study thus adopted an open-ended scenario approach to measure smoking-related interpretation biases. Individuals who smoke, those who ceased smoking, and those without a smoking history (total sample N = 177) were instructed to generate spontaneous continuations for ambiguous, open-ended scenarios that described either a smoking-related or neutral context. Overall, people who smoke generated more smoking-related continuations in response to smoking-relevant situations than non-smoking individuals or people who had stopped smoking, providing evidence for a smoking-related interpretation bias. When differentiating for situation type within smoking-relevant scenarios, smoking individuals produced more smoking-related continuations for positive/social and habit/addictive situations compared to negative/affective ones. Additionally, the tendency to interpret habit/addictive situations in a smoking-related manner was positively associated with cigarette consumption and levels of nicotine dependence. Exploratory analyses indicated that other substance-related continuations were correlated with their respective behavioral counterparts (e.g., the level of self-reported alcohol or caffeine consumption). The present study is the first to demonstrate smoking-related interpretation biases in relation to current cigarette smoking. Future studies should investigate the causal role of such biases in the initiation and/or maintainance of nicotine addiction and the merit of Interpretation-Bias-Modification training to support smoking cessation.

The impact of past childhood adversity and recent life events on neural responses during fear conditioning.

BACKGROUND AND PURPOSE: Many studies have shown that exposure to life events can have a negative impact on mental health. Life events like the death of a spouse or the birth of a child pose a challenge and require temporal or permanent adjustments. Meta-analyses on brain stress responses found bilateral anterior insula activation in response to acute stress. Fear conditioning is assumed a crucial mechanism for the development of anxiety disorders associated with increased activation in the bilateral amygdala. Empirical evidence is lacking regarding the relationship of exposure to recent life events and past childhood adversity with neural processing during fear conditioning. METHODS: In the present study, we analyzed data from 103 young, healthy participants. Multiple linear regressions were performed on functional magnetic resonance imaging activation during fear conditioning with the Life Events Scale for Students and the Childhood Trauma questionnaire included as covariates in two separate models. RESULTS: We found a positive relationship between the number of life events in the last year and left amygdala activation to the conditioned stimulus. A second finding was a positive relationship between childhood adversity and right anterior insula response to the unconditioned stimulus. CONCLUSIONS: Many studies have shown increased amygdala activity after stressful life events. In addition, the anterior insula is activated during acute stress. The present study points to stressor-induced increased salience processing during fear conditioning. We suggest that this could be a potential mechanism for resilience versus mental illness.

Inhibitory control and its modification in spider phobia - Study protocol for an antisaccade training trial.

OBJECTIVES: Inhibitory control deficits are considered a key pathogenic factor in anxiety disorders. To assess inhibitory control, the antisaccade task is a well-established measure that assesses antisaccade performance via latencies and error rates. The present study follows three aims: (1) to investigate inhibitory control via antisaccade latencies and errors in an antisaccade task, and their associations with multiple measures of fear in patients with spider phobia (SP) versus healthy controls (HC), (2) to investigate the modifiability of antisaccade performance via a fear-specific antisaccade training in patients with SP and HC, and (3) to explore associations between putative training-induced changes in antisaccade performance in SPs and changes in diverse measures of fear. METHODS: Towards aim 1, we assess antisaccade latencies (primary outcome) and error rates (secondary outcome) in an emotional antisaccade task. Further, the baseline assessment includes assessments of psychophysiological, behavioral, and psychometric indices of fear in patients with SP and HCs. To address aim 2, we compare effects of a fear-specific antisaccade training with effects of a prosaccade training as a control condition. The primary and secondary outcomes are reassessed at a post-1-assessment in both SPs and HCs. Aim 3 employs a cross-over design and is piloted in patients with SP, only. Towards this aim, primary and secondary outcomes, as well as psychophysiological, behavioral, and psychometric measures of fear are reassessed at a post-2-assessment after the second training block. CONCLUSION: This study aims to better understand inhibitory control processes and their modifiability in spider phobia. If successful, antisaccade training may assist in the treatment of specific phobia by directly targeting the putative underlying inhibitory control deficits. This study has been preregistered with ISRCTN (ID: ISRCTN12918583) on 28th February 2022.

Repressive and vigilant coping styles in stress and relaxation: evidence for physiological and subjective differences at baseline, but not for differential stress or relaxation responses.

Introduction: Previous research suggested differential stress reactivity depending on individuals' coping style, e.g., as classified by the model of coping modes. Specifically, stronger physiological reactivity and weaker subjective stress ratings were found for repressors than for sensitizers. However, it remains to be investigated (i) whether these findings, which are largely based on social stress induction protocols, also generalize to other stressors, (ii) whether repressors vs. sensitizers also exhibit differential stress recovery following the application of a relaxation method, and (iii) which stress reactivity and recovery patterns are seen for the two remaining coping styles, i.e., fluctuating, and non-defensive copers. The current study thus examines stress reactivity in physiology and subjective ratings to a non-social stressor and the subsequent ability to relax for the four coping groups of repressors, sensitizers, fluctuating, and non-defensive copers. Methods: A total of 96 healthy participants took part in a stress induction (Mannheim Multicomponent Stress Test) and a subsequent relaxation intervention. Subjective ratings of stress and relaxation, heart rate (HR), heart rate variability (HRV), and blood pressure were assessed during the experiment. HR and blood pressure are markers of the sympathetic stress response that can be regulated by relaxation, while HRV should increase with relaxation. To investigate long-term relaxation effects, subjective ratings were also assessed on the evening of testing. Results: Despite successful stress induction, no differential responses (baseline to stress, stress to relaxation) were observed between the different coping groups on any of the measures. In contrast, a strong baseline effect was observed that persisted throughout the experiment: In general, fluctuating copers showed lower HR and higher HRV than non-defensive copers, whereas repressors reported lower subjective stress levels and higher levels of relaxation during all study phases. No differences in subjective ratings were observed in the evening of testing. Conclusion: Contrary to previous research, no differential stress reactivity pattern was observed between coping groups, which could be due to the non-social type of stressor employed in this study. The novel finding of physiological baseline differences between fluctuating and non-defensive individuals is of interest and should be further investigated in other stressor types in future research.

Close(d) to you? Avoidant attachment is associated with attenuated pupil responsivity to social stimuli.

Insecure attachment is thought to impair romantic relationships, presumably also contributing to mental health problems. Previous research has suggested a link to biased automatic processing of social information, potentially reflected in pupil dilation responses. To address this hypothesis, 37 adults were presented with attachment-related, emotional pictures of erotic couples, everyday couples, or interpersonal violence after assessment with the Experiences in Close Relationships Scale. Considerable variation in self-reported attachment behaviors regarding both attachment anxiety and avoidance was observed in our sample. Overall, pupil dilation was most pronounced during viewing of erotica and violence-related pictures. Relative to nature pictures as control, attachment avoidance was associated with attenuated pupillary responses to social content. However, this was not significant with erotica. For pictures of violence, this avoidant bias was also evident in reduced subjective arousal. In contrast, attachment anxiety was unrelated to differential pupil dilation. Our findings, although preliminary, suggest that previous attachment-related experiences may bias the processing of social stimuli, which in turn may be reflected in altered patterns of pupillary responses.

Neural correlates of immediate versus delayed extinction when simultaneously varying the time of the test in humans.

Anxiety disorders are effectively treated with exposure therapy based on the extinction of Pavlovian fear conditioning. Animal research indicates that both the timing of extinction and test are important factors to reduce the return of fear. However, empirical evidence in humans is incomplete and inconsistent. In this neuroimaging study, we, therefore, tested 103 young, healthy participants in a 2-factorial between-subjects design with the factors extinction group (immediate, delayed) and test group (+1 day and +7 days). Immediate extinction led to greater retention of fear memory at the beginning of extinction training indicated by increased skin conductance responses. A return of fear was observed in both extinction groups, with a trend toward a greater return of fear in immediate extinction. The return of fear was generally higher in groups with an early test. Neuroimaging results show successful cross-group fear acquisition and retention, as well as activation of the left nucleus accumbens during extinction training. Importantly, the delayed extinction group showed a larger bilateral nucleus accumbens activation during test. This nucleus accumbens finding is discussed in terms of salience, contingency, relief, and prediction error processing. It may imply that the delayed extinction group benefits more from the test as a new learning opportunity.

Associations between hair cortisol and subjective stress measures in a large occupational sample.

BACKGROUND: Hair cortisol concentrations (HCC) are commonly used to capture long-term cumulative cortisol secretion in stress research. However, data on associations between HCC and subjective stress measures have been inconsistent. This may partly be due to bias introduced by smaller-sized academic samples. Here, we investigate associations between HCC and (work-) stress-related measures in a large occupational, predominantly male, sample. METHODS: Demographic, anthropometric, and self-reported data were collected as part of an occupational health assessment for employees of an airplane manufacturing company (N = 1258). Hair samples (3 cm) were obtained and glucocorticoid concentrations (HCC and hair cortisone, HairE) were analyzed using liquid chromatography-tandem mass spectrometry. RESULTS: HCC and HairE were unrelated to self-report measures of perceived stress, work-related stress (effort-reward imbalance, overcommitment), and other stress-related constructs. Group-based analyses concerning associations with job strain revealed a small effect of individuals with high job strain (n = 281) exhibiting higher HCC than the remaining sample (n = 811). CONCLUSIONS: Our data replicate previous findings of no consistent associations between hair glucocorticoids and subjective stress-related questionnaire data, besides evidence for elevated HCC in a high job strain group. Further research addressing open methodological questions regarding HCC by means of advanced stress assessment methods is needed.

Pupil dilation tracks divergent learning processes in aware versus unaware Pavlovian conditioning.

Evidence regarding unaware differential fear conditioning in humans is mixed and even less is known about the effects of contingency awareness on appetitive conditioning. Phasic pupil dilation responses (PDR) might be more sensitive for capturing implicit learning than other measures, such as skin conductance responses (SCR). Here, we report data from two delay conditioning experiments utilizing PDR (alongside SCR and subjective assessments) to investigate the role of contingency awareness in aversive and appetitive conditioning. In both experiments, valence of unconditioned stimuli (UCS) was varied within participants by administering aversive (mild electric shocks) and appetitive UCSs (monetary rewards). Preceding visual stimuli (CSs) predicted either the reward, the shock (65% reinforcement), or neither UCS. In Exp. 1, participants were fully instructed about CS-UCS contingencies, whereas in Exp. 2, no such information was given. PDR and SCR demonstrated successful differential conditioning in Exp. 1 and in (learned) aware participants in Exp. 2. In non-instructed participants who remained fully unaware of contingencies (Exp. 2), differential modulation of early PDR (immediately after CS onset) by appetitive cues emerged. Associations with model-derived learning parameters further suggest that early PDR in unaware participants mainly reflect implicit learning of expected outcome value, whereas early PDR in aware (instructed/learned-aware) participants presumably index attentional processes (related to uncertainty/prediction error processing). Similar, but less clear results emerged for later PDR (preceding UCS onset). Our data argue in favor of a dual-process account of associative learning, suggesting that value-related processing can take place irrespective of mechanisms involved in conscious memory formation.

Increased pupil and heart-rate responses to sexual stimuli in men after physical exertion.

Physical stress has been found to enhance arousability by visual sexual stimuli on a short-term basis, as reflected in higher phasic pupil dilation responses, probably mediated by sympathetic nervous system (SNS)-related processes. However, previous research has not addressed the specificity of this effect in terms of emotional valence, that is, whether it reflects an instance of general excitation transfer or a more specific mechanism. Thus, to further investigate changes in sexual processing after acute stress exposure, 40 male participants underwent either a predominantly sympathetic stressor (3 min sustained handgrip) or similar control procedure. After stress induction, pictures varying in valence as well as sexual versus non-sexual arousal were presented (for 5000 ms each). Using principal component analysis, pupillary responses during picture viewing were dissociated into fast and slow components (early vs. late response phases). In addition, startle eyeblink responses were elicited by bursts of white noise (50 ms, 105 dB) in half of the trials and recorded at the orbicularis oculi via electromyography. Skin conductance and heart rate were co-registered, as well. While affective startle modulation and skin conductance responses to emotional stimuli were unaffected by previous stress exposure, both evoked heart-rate deceleration (but not acceleration) and pupil responses were specifically enhanced with sexually arousing stimuli in stressed participants, and this effect was mediated by blood pressure reactivity as an index of preceding SNS activation. Taken together, our findings provide strong evidence for enhancement of sexual processing by acute stress exposure in men and suggest differential involvement of parasympathetic versus sympathetic mechanisms.

Same same, but different: A psychometric examination of three frequently used experimental tasks for cognitive bias assessment in a sample of healthy young adults.

Cognitive bias research draws upon the notion that altered information processing is key for understanding psychological functioning and well-being. However, little attention has been paid to the question of whether the frequently used experimental paradigms hold adequate psychometric properties. The present study examined the psychometric properties of three widely used cognitive bias tasks: the Approach-Avoidance Task (AAT), the visual dot-probe-task, and the Implicit Association Test (IAT). Approach, attentional, and association biases towards valenced stimuli were repeatedly measured at five different time points in a sample of 79 healthy young adults. Two different devices were used for assessment: a personal computer (PC) and a touchscreen-based tablet. Reliability estimates included internal consistency and temporal stability. Validity was inferred from convergence across different behavioral tasks and correlations between bias scores and self-reported psychological traits. Reliability ranged widely amongst tasks, assessment devices, and measurement time points. While the dot-probe-task appeared to be completely unreliable, bias scores obtained from the PC-based version of the AAT and both (PC and touchscreen) versions of the IAT showed moderate reliability. Almost no associations were found across information processing tasks or between implicit and explicit measures. Cognitive bias research should adopt a standard practice to routinely estimate and report psychometric properties of experimental paradigms, investigate feasible ways to develop more reliable tools, and use tasks that are suitable to answer the precise research question asked.

Developmental aspects of fear generalization - A MEG study on neurocognitive correlates in adolescents versus adults.

BACKGROUND: Fear generalization is pivotal for the survival-promoting avoidance of potential danger, but, if too pronounced, it promotes pathological anxiety. Similar to adult patients with anxiety disorders, healthy children tend to show overgeneralized fear responses. OBJECTIVE: This study aims to investigate neuro-developmental aspects of fear generalization in adolescence - a critical age for the development of anxiety disorders. METHODS: We compared healthy adolescents (14-17 years) with healthy adults (19-34 years) regarding their fear responses towards tilted Gabor gratings (conditioned stimuli, CS; and slightly differently titled generalization stimuli, GS). In the conditioning phase, CS were paired (CS+) or remained unpaired (CS-) with an aversive stimulus (unconditioned stimuli, US). In the test phase, behavioral, peripheral and neural responses to CS and GS were captured by fear- and UCS expectancy ratings, a perceptual discrimination task, pupil dilation and source estimations of event-related magnetic fields. RESULTS: Closely resembling adults, adolescents showed robust generalization gradients of fear ratings, pupil dilation, and estimated neural source activity. However, in the UCS expectancy ratings, adolescents revealed shallower generalization gradients indicating overgeneralization. Moreover, adolescents showed stronger visual cortical activity after as compared to before conditioning to all stimuli. CONCLUSION: Various aspects of fear learning and generalization appear to be mature in healthy adolescents. Yet, cognitive aspects might show a slower course of development.

Evaluation and update of the expert consensus guidelines for the assessment of the cortisol awakening response (CAR).

The cortisol awakening response (CAR) is frequently assessed in psychobiological (stress) research. Obtaining reliable CAR data, however, requires careful attention to methodological detail. To promote best practice, expert consensus guidelines on the assessment of the CAR were published (Stalder et al., 2016, PNEC). However, it is unclear whether these highly cited guidelines have resulted in actual methodological improvements. To explore this, the PNEC editorial board invited the present authors to conduct a critical evaluation and update of current CAR methodology, which is reported here. (i) A quantitative evaluation of methodological quality of CAR research published in PNEC before and after the guidelines (2013-2015 vs. 2018-2020) was conducted. Disappointingly, results reveal little improvement in the implementation of central recommendations (especially objective time verification) in recent research. (ii) To enable an update of guidelines, evidence on recent developments in CAR assessment is reviewed, which mostly confirms the accuracy of the majority of the original guidelines. Moreover, recent technological advances, particularly regarding methods for the verification of awakening and sampling times, have emerged and may help to reduce costs in future research. (iii) To aid researchers and increase accessibility, an updated and streamlined version of the CAR consensus guidelines is presented. (iv) Finally, the response of the PNEC editorial board to the present results is described: potential authors of future CAR research to be published in PNEC will be required to submit a methodological checklist (based on the current guidelines) alongside their article. This will increase transparency and enable reviewers to readily assess the quality of the respective CAR data. Combined, it is hoped that these steps will assist researchers and reviewers in assuring higher quality CAR assessments in future research, thus yielding more reliable and reproducible results and helping to further advance this field of study.

Cross-paradigm integration shows a common neural basis for aversive and appetitive conditioning.

Sharing imaging data and comparing them across different psychological tasks is becoming increasingly possible as the open science movement advances. Such cross-paradigm integration has the potential to identify commonalities in findings that neighboring areas of study thought to be paradigm-specific. However, even the integration of research from closely related paradigms, such as aversive and appetitive classical conditioning is rare - even though qualitative comparisons already hint at how similar the 'fear network' and 'reward network' may be. We aimed to validate these theories by taking a multivariate approach to assess commonalities across paradigms empirically. Specifically, we quantified the similarity of an aversive conditioning pattern derived from meta-analysis to appetitive conditioning fMRI data. We tested pattern expression in three independent appetitive conditioning studies with 29, 76 and 38 participants each. During fMRI scanning, participants in each cohorts performed an appetitive conditioning task in which a CS+ was repeatedly rewarded with money and a CS- was never rewarded. The aversive pattern was highly similar to appetitive CS+ > CS- contrast maps across samples and variations of the appetitive conditioning paradigms. Moreover, the pattern distinguished the CS+ from the CS- with above-chance accuracy in every sample. These findings provide robust empirical evidence for an underlying neural system common to appetitive and aversive learning. We believe that this approach provides a way to empirically integrate the steadily growing body of fMRI findings across paradigms.

Self-guided virtual reality therapy for social anxiety disorder: a study protocol for a randomized controlled trial.

BACKGROUND: Social anxiety disorder (SAD) is a highly prevalent mental disorder associated with enormous stress and suffering. Cognitive behavior therapy (CBT) is the first-line treatment for SAD, yet its accessibility is often constrained with long waiting times. Digital therapeutic applications, including psychoeducation and self-guided behavioral experiments in virtual reality (VR), could facilitate access and reduce waiting times. The study aims to investigate if ultra-short-time therapy involving self-guided digital therapeutic applications with VR components can reduce the severity of SAD. METHODS: Forty SAD patients will participate in this randomized controlled trial. Half will get access to a self-guided, digital therapeutic application with exposure-based behavioral experiments in VR, while the other half will receive a control treatment. Both treatments include four therapeutic appointments. Changes in the severity of SAD will be measured after each appointment and on a 6-week follow-up assessment and will be compared between groups, with the change in SAD measured at baseline- and post-assessment as primary outcome. DISCUSSION: Self-guided digital therapeutic applications including ultra-short-time therapy combined with VR could help reduce the waiting time for patients and relieve the health system. The results of this study may inform psychotherapists regarding the potential of self-guided digital therapeutic applications including exposure-based behavioral experiments in VR for SAD and will provide important insight for future research on VR therapy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN18013983 . Registered on 1 February 2022.

Facilitating relaxation and stress reduction in healthy participants through a virtual reality intervention: study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Repeated or chronic stress is considered a major source of disease, in terms of both somatic and mental illnesses. The prevention of stress-related disease by interventions for relaxation has thus increased societal relevance. In this randomized controlled non-inferiority trial, we will compare a newly developed virtual reality (VR) environment for relaxation to an active control group applying a freely chosen relaxation method. To test if our VR environment supports relaxation in a situation of acute stress, a standardized stress induction protocol will precede the relaxation phase. METHODS: One hundred healthy participants will be recruited from the University of Siegen and randomly assigned to the VR or the active control group that will be free to choose their own relaxation strategy. The multi-sensory VR includes visual, acoustic, and haptic features to induce a strong feeling of presence. The laboratory testing will comprise a baseline measurement, a stress induction, a relaxation intervention, and a recovery measurement. The primary outcomes are self-reported stress and relaxation measured with a visual analog scale (VAS) at pre- and post-baseline, at the start, middle, and end of the stress induction, at pre- and post-relaxation, at pre- and post-recovery, and in the evening of testing. Secondary outcomes are the physiological parameters, namely heart rate and heart rate variability, tonic skin conductance level as well as the number of non-specific skin conductance responses, systolic and diastolic blood pressure and respiratory rate recorded during the four experimental phases as well as state mood, and state rumination assessed at four time points (pre- and post-stress, post-relaxation, and in the evening of testing). Finally, post-event processing will be assessed after relaxation and in the evening of testing. Repeated measures ANOVAs will be performed to test for statistical effects of group, time, and group × time interaction. DISCUSSION: The newly developed, multi-sensory VR offers an intervention for relaxation without prior training. Its immersive character might increase efficacy compared to other relaxation methods, especially in situations of acute stress. Future directions could be the development of a mobile version of the VR to enhance accessibility for users. To achieve a transfer of training effects to real life, VR components should successively be eliminated until relaxation is practiced without guidance by the VR. TRIAL REGISTRATION: ISRCTN Registry ISRCTN11162338 . Retrospectively registered on January 22, 2021.

Self-guided digital treatment with virtual reality for panic disorder and agoraphobia: a study protocol for a randomized controlled trial.

BACKGROUND: Cognitive behavioral therapy is the first-line treatment for patients with panic disorder (PD) and agoraphobia (AG). Yet, many patients remain untreated due to limited treatment resources. Digital self-guided short-term treatment applications may help to overcome this issue. While some therapeutic applications are already supported by health insurance companies, data on their efficacy is limited. The current study investigates the effect of self-guided digital treatment comprising psychoeducation and virtual reality exposure therapy (VRET). METHODS: Thirty patients diagnosed with PD, AG, or panic disorder with agoraphobia (PDA) will be randomly assigned to either the experimental group (EG) or the control group (CG). Participants of both groups will undergo baseline diagnostics in the first two sessions. The subsequent treatment for the EG consists of a self-guided 6-week phase of application-based psychoeducation, one therapy session preparing for the VRET, and 4 weeks of application-based self-guided VRET. To control for the potential effects of the therapy session with the therapist, the CG will receive relaxation and stress-reduction training instead. All patients will then undergo a closing session which terminates with the post-assessment (~ 10 weeks after baseline assessment) and a follow-up assessment 6 weeks following the closing session. Symptom severity (primary outcome) will be assessed at baseline, interim, post-treatment, and follow-up. Additionally, remission status (secondary outcome) will be obtained at follow-up. Both measures will be compared between the groups. DISCUSSION: The current study aims at providing insights into the efficacy of short-term treatment applications including psychoeducation and self-guided VRET. If successful, this approach might be a feasible and promising way to ease the burden of PD, AG, and PDA on the public health system and contribute to a faster access to treatment. TRIAL REGISTRATION: ISRCTN ISRCTN10661970 . Prospectively registered on 17 January 2022.

Neural correlates of fear conditioning are associated with treatment-outcomes to behavioral exposure in spider phobia - Evidence from magnetoencephalography.

BACKGROUND: Models of anxiety disorders and the rationale of exposure therapy (ET) are grounded on classical fear conditioning. Yet, it is unclear whether lower fear ratings of conditioned safety versus threat cues and corresponding neural markers of safety-learning and/or fear inhibition assessed before treatment would predict better outcomes of behavioral exposure. METHODS: Sixty-six patients with spider phobia completed pre-treatment clinical and experimental fear conditioning assessments, one session of virtual reality ET, a post-treatment clinical assessment, and a 6-month follow-up assessment. Tilted Gabor gratings served as conditioned stimuli (CS) that were either paired (CS+) or remained unpaired (CS-) with an aversive phobia-related and phobia-unrelated unconditioned stimulus (UCS). CS+/CS- differences in fear ratings and magnetoencephalographic event-related fields (ERFs) were related to percentual symptom reductions from pre- to post-treatment, as assessed via spider phobia questionnaire (SPQ), behavioral avoidance test (BAT), and remission status at 6-month follow-up. RESULTS: We observed no associations between pre-treatment CS+/CS- differences in fear ratings and any treatment outcome. CS+/CS- differences in source estimations of ERFs revealed that higher CS- activity in bilateral dorsolateral prefrontal cortex (dlPFC) was related with SPQ- and BAT-reductions. Associations between CS+/CS- differences and treatment outcomes were also observed in left ventromedial prefrontal cortex (vmPFC) regions, which additionally revealed associations with the follow-up remission status. CONCLUSIONS: Results provide initial evidence that neural pre-treatment CS+/CS- differences may hold predictive information regarding outcomes of behavioral exposure. Our findings highlight a key role of neural responses to safety cues with potentially inhibitory effects on affect-generating structures during fear conditioning.

Stressed in afterthought: Neuroendocrine effects of social self-threat during physical effort are counteracted by performance feedback after stress exposure.

Social self-threat during physical stress, such as exposure to the cold pressor test and isometric handgrip test, has been shown to induce activation of the HPA axis, in addition to autonomic responses. However, previous research has suggested that dysfunctional post-event processing may play a major role in neuroendocrine reactivity at initial as well as subsequent social stress exposure. In the present study, we investigated how the interplay of context (i.e. performance feedback) with state (i.e., self-esteem) as well as trait-like factors (i.e., ruminative tendencies) affects stress responses to repeated, short bouts of physical activity. On two sessions, 1 week apart, 53 participants (27 women) performed an isometric handgrip task for 3 min, during which they were exposed to social-evaluative threat. In addition, participants received fake feedback on their performance immediately after the task, labeling it as either 'above' (positive) or 'below average' (negative). In addition to neuroendocrine (cortisol), cardiovascular (heart rate, blood pressure) and subjective stress reactivity, performance-related and social dimensions of state self-esteem were assessed before and after stress induction. Substantial increases in cardiovascular parameters were found on both days, regardless of feedback condition. However, positive feedback led to significantly diminished neuroendocrine responses on day 1, whereas baseline cortisol on session 2 was significantly higher in the negative feedback group. Conversely, social self-esteem decreased after stress induction on both days only for participants who had received negative feedback. Changes in self-esteem reported on day 1 were associated with increased baseline cortisol at the second session, while interindividual differences in self-reported (trait) rumination were associated with cortisol reactivity at session 1. Taken together, the results suggest that effects of social evaluation during short periods of physical stress rely on post-event processing and might be counteracted by positive appraisal directly after stress exposure. Post-hoc framing (in terms of success vs. failure) may predict subsequent stress-related hormonal effects better than task demands per se, which should be considered as a potential moderator in future acute stress research, but might also be relevant to many practical applications in fields ranging from sports/performance to health psychology.

"Push it!" or "Hold it!"? A comparison of nicotine-avoidance training and nicotine-inhibition training in smokers motivated to quit.

RATIONALE: Recently, experimental paradigms have been developed to strengthen automatic avoidance or inhibitory responses for smoking cues. However, these procedures have not yet been directly compared regarding their effectiveness and mechanisms of action. OBJECTIVE: This study compared the effects of avoidance vs. inhibitory training as an add-on to a brief smoking cessation intervention. The standard Approach-Avoidance-Task (AAT) was adapted for both training types and control conditions. METHODS: One hundred twenty-four smokers attended behavioral counseling for smoking cessation and were thereafter randomized to one of four training conditions: avoidance-AAT, sham-avoidance-AAT, inhibition-AAT, sham-inhibition-AAT. During a 2-week training period including five training sessions, smokers in the avoidance-AAT trained to implicitly avoid all smoking-related cues, while smokers in the inhibition-AAT trained to implicitly inhibit behavioral response to smoking cues. During sham training, no such contingencies appeared. Self-report and behavioral data were assessed before and after training. Cigarette smoking and nicotine dependence were also assessed at 4- and 12-week follow-ups. RESULTS: At posttest, avoidance training was more effective in reducing daily smoking than inhibition training. However, this difference was no longer evident in follow-up assessments. All training conditions improved other smoking- and health-related outcomes. Neither training changed smoking-related approach biases or associations, but approach biases for smoking-unrelated pictures increased and Stroop interference decreased in all conditions. Smoking devaluation was also comparable in all groups. CONCLUSIONS: Avoidance training might be slightly more effective in reducing smoking than inhibitory training. Overall, however, all four training types yielded equivalent therapy and training effects. Hence, a clear preference for one type of training remains premature.