Motivated by the recent replicability crisis we tested replicability of functional magnetic resonance imaging (fMRI) group activations in two independent samples. An identical behavioral and fMRI test battery for the longitudinal investigation of stress resilience mechanisms was developed for the Mainz Resilience Project (MARP) and conducted in a discovery (N = 54) and a replication sample (N = 103). The test battery consisted of a stress reactivity task, a reward sensitivity task, a fear conditioning and extinction paradigm, two volitional reappraisal tasks and an emotional interference inhibition task. Replicability of group activations was tested with the Jaccard index and the Intra Class Correlation (ICC). Overall, we observed good to excellent replicability of activations at the whole brain level. Only a minority of contrasts showed unsatisfactory replicability. Replicability at the level of individual regions of interest (ROIs) was generally lower. Tasks with stronger activation in the discovery sample showed better replicability.

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

Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. Such good longer-term mental health outcomes despite adversity presumably result from complex and dynamic processes of adaptation to stressor exposure (‘resilience processes’), which in many cases include changes in individual properties. Measuring resilience and identifying resilience processes in observational studies requires longitudinal designs involving repeated and frequent monitoring of mental health, stressor exposure, and potential adaptations. We here present a generic design solution that is currently employed in two cohort studies, the Mainz Resilience Project (MARP) and the Longitudinal Resilience Assessment (LORA). Both projects focus on resilience to everyday life stressors (i.e., microstressors), but we argue that the design scheme is also suitable for studying resilience to macrostressors, or trauma, and can solve some of the pertinent problems of trauma resilience research. We quantify resilience by indexing the reactivity of individuals’ mental health to stressors during a time interval of several months in a ‘stressor reactivity’ (SR) score, derived using a previously introduced residualization approach. SR scores are regularly re-calculated in sliding time windows, to thus build SR time courses that reflect intra-individual temporal variability in resilience. By linking these time courses to repeated measures of (temporally varying) individual properties, resilience processes can be identified. We finish by a discussion of limitations of our approach and potential future developments.

Resilience is the maintenance or rapid recovery of mental health during and after stressor exposure. It is becoming increasingly clear that resilience results from a complex and dynamic process of adaptation to stressors involving the biological, psychological and social levels. Positive appraisal style theory of resilience (PASTOR) claims that the common final pathway to maintained mental health lies in the non-negative (non-catastrophizing, non-pessimistic) appraisal of potential stressors, permitting the organism to fine-tune stress responses to optimal levels, thus avoiding unnecessary stress, inefficient deployment of resources and concomitant deleterious allostatic load effects. Successful adaptation consists in developing or strengthening a positive appraisal style. Another key element of PASTOR is that a positive appraisal style is strongly determined by the efficacy and efficiency of the neural and cognitive processes that underlie positive stressor appraisal. We here present a combined behavioral and functional magnetic resonance imaging (fMRI) battery designed to assess such processes repeatedly in longitudinal settings. The battery includes tests of stress reactivity and recovery, reward sensitivity, safety learning and memory in the context of fear conditioning and extinction, volitional situation-focused reappraisal, volitional self-focused reappraisal, and emotional interference inhibition, along with structural MRI and resting-state MRI scans. A detailed description of the battery methods is provided. The feasibility of the battery was successfully tested in N=55 healthy subjects; group results of the individual tasks largely replicate existing literature.

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.

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.