Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders.

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.

Improving Exposure Therapy: Rationale and Design of an International Consortium.

The Exposure Therapy Consortium (ETC) was established to advance the science and practice of exposure therapy. To encourage participation from researchers and clinicians, this article describes the organizational structure and activities of the ETC. Initial research working group experiences and a proof-of-principle study underscore the potential of team science and larger-scale collaborative research in this area. Clinical working groups have begun to identify opportunities to enhance access to helpful resources for implementing exposure therapy effectively. This article discusses directions for expanding the consortium's activities and its impact on a global scale.

Sudden gains in routine clinical care: application of a permutation test for trauma-focused cognitive behavioural therapy.

Background: Sudden gains, defined as large and stable improvements of psychopathological symptoms, are a ubiquitous phenomenon in psychotherapy. They have been shown to occur across several clinical contexts and to be associated with better short-term and long-term treatment outcome. However, the approach of sudden gains has been criticized for its tautological character: sudden gains are included in the computation of treatment outcomes, ultimately resulting in a circular conclusion. Furthermore, some authors criticize sudden gains as merely being random fluctuations.Objective: Use of efficient methods to evaluate whether the amount of sudden gains in a given sample lies above chance level.Method: We used permutation tests in a sample of 85 patients with posttraumatic stress disorder (PTSD) treated with trauma-focused cognitive behaviour therapy in routine clinical care. Scores of self-reported PTSD symptom severity were permuted 10.000 times within sessions and between participants to receive a random distribution.Results: Altogether, 18 participants showed a total of 24 sudden gains within the first 20 sessions. The permutation test yielded that the frequency of sudden gains was not beyond chance level. No significant predictors of sudden gains were identified and sudden gains in general were not predictive of treatment outcome. However, subjects with early sudden gains had a significantly lower symptom severity after treatment.Conclusions: Our data suggest that a significant proportion of sudden gains are due to chance. Further research is needed on the differential effects of early and late sudden gains.

Treatment-related sudden gains exhibit clinical significance when their manifestation is above chance level.We used permutation tests to examine their occurrence in trauma-focused cognitive behaviour therapy as applied in a naturalistic treatment setting.The occurrence of sudden gains in general was not significantly higher than chance, yet early sudden gains were associated with improved treatment outcome.

Temporal dynamics of costly avoidance in naturalistic fears: Evidence for sequential-sampling of fear and reward information.

Excessive avoidance is characteristic for anxiety disorders, even when approach would lead to positive outcomes. The process of how such approach-avoidance conflicts are resolved is not sufficiently understood. We examined the temporal dynamics of approach-avoidance in intense fear of spiders. Highly fearful and non-fearful participants chose repeatedly between a fixed no spider/low reward and a spider/high reward option with varying fear (probability of spider presentation) and reward information (reward magnitude). By sequentially presenting fear and reward information, we distinguished whether decisions are dynamically driven by both information (sequential-sampling) or whether the impact of fear information is inhibited (cognitive control). Mouse movements were recorded to assess temporal decision dynamics (i.e., how strongly which information impacts decision preference at which timepoint). Highly fearful participants showed stronger avoidance despite lower gains (i.e., costly avoidance). Time-continuous multiple regression of their mouse movements yielded a stronger impact of fear compared to reward information. Importantly, presenting either information first (fear or reward) enhanced its impact during the early decision process. These findings support sequential sampling of fear and reward information, but not inhibitory control. Hence, pathological avoidance may be characterized by biased evidence accumulation rather than altered cognitive control.

Exposure traced in daily life: improvements in ecologically assessed social and physical activity following exposure-based psychotherapy for anxiety disorders.

BACKGROUND: Although exposure-based cognitive-behavioral therapy for anxiety disorders has frequently been proven effective, only few studies examined whether it improves everyday behavioral outcomes such as social and physical activity. METHODS: 126 participants (85 patients with panic disorder, agoraphobia, social anxiety disorder, or specific phobias, and 41 controls without mental disorders) completed smartphone-based ambulatory ratings (activities, social interactions, mood, physical symptoms) and motion sensor-based indices of physical activity (steps, time spent moving, metabolic activity) at baseline, during, and after exposure-based treatment. RESULTS: Prior to treatment, patients showed reduced mood and physical activity relative to healthy controls. Over the course of therapy, mood ratings, interactions with strangers and indices of physical activity improved, while reported physical symptoms decreased. Overall results did not differ between patients with primary panic disorder/agoraphobia and social anxiety disorder. Higher depression scores at baseline were associated with larger changes in reported symptoms and mood ratings, but smaller changes in physical activity CONCLUSIONS: Exposure-based treatment initiates increased physical activity, more frequent interaction with strangers, and improvements in everyday mood. The current approach provides objective and fine-graded process and outcome measures that may help to further improve treatments and possibly reduce relapse.

A network perspective on real-life threat, anxiety, and avoidance.

BACKGROUND: Anxiety, approach, and avoidance motivation crucially influence mental and physical health, especially when environments are stressful. The interplay between anxiety and behavioral motivation is modulated by multiple individual factors. This proof-of-concept study applies graph-theoretical network analysis to explore complex associations between self-reported trait anxiety, approach and avoidance motivation, situational anxiety, stress symptoms, perceived threat, perceived positive consequences of approach, and self-reported avoidance behavior in real-life threat situations. METHODS: A total of 436 participants who were matched on age and gender (218 psychotherapy patients, 218 online-recruited nonpatients) completed an online survey assessing these factors in response to the COVID-19 pandemic. RESULTS AND DISCUSSION: The resulting cross-sectional psychological network revealed a complex pattern with multiple positive (e.g., between trait anxiety, avoidance motivation, and avoidance behavior) and negative associations (e.g., between approach and avoidance motivation). The patient and online subsample networks did not differ significantly, however, descriptive differences may inform future research.

Enhancing the effectiveness of CBT for patients with unipolar depression by integrating digital interventions into treatment: A pilot randomized controlled trial.

OBJECTIVE: Blended cognitive behavioral therapy (bCBT) combines face-to-face therapy with digital elements, such as digital health apps. This pilot study aimed to explore the effectiveness and safety of a novel bCBT application for treating unipolar depression in adults combined with cognitive behavioral therapy (CBT) compared to CBT alone in routine care. METHODS: Patients (N = 82) were randomly assigned to bCBT (n = 42) or CBT (n = 40) over 12 weeks. bCBT consisted of weekly CBT sessions accompanied by the elona therapy depression module (a bCBT application for unipolar depression) for use between sessions. Standard CBT consisted of weekly CBT sessions. Outcomes (6,12 weeks) were analyzed with linear mixed models. RESULTS: Improvements in depressive symptoms (BDI-II, PHQ-9) were descriptively larger for the bCBT group. Yet, this difference did not reach statistical significance. bCBT was superior to standard CBT in secondary outcome measures of psychological health (d = .50) and generalized anxiety symptoms (d = -.45). In other secondary outcomes (BAI, PSWQ, GSE, WHOQOL-BREF), improvements were descriptively larger for bCBT compared to CBT. CONCLUSION: This pilot study provided preliminary evidence that bCBT might be advantageous in comparison to CBT alone in the treatment of depression, but larger RCTs of the bCBT application are needed.

The degree of safety behaviors to a safety stimulus predicts development of threat beliefs.

Safety behaviors are behavioral responses that aim to prevent or minimize an imminent threat when confronting a feared stimulus. Despite its adaptive purpose, preliminary evidence suggests that unnecessary safety behaviors to a safety stimulus induce threat beliefs to it. By allowing participants to engage in safety behaviors dimensionally, this study tested whether the degree of safety behaviors to a safety stimulus predicts the subsequent level of threat expectancies to it. To this end, participants first acquired safety behaviors to a threat-related stimulus (A). Safety behaviors then became available only for one safety stimulus (C), but not to another safety stimulus (B). After engaging in safety behaviors to C, participants exhibited greater threat expectancies to C compared to B, albeit with a small effect size. Importantly, the degree of safety behaviors predicted an increase in threat expectancies. The current findings suggest that safety behaviors to safety stimuli are linked to the development of threat beliefs.

Persistence of extensively trained avoidance is not elevated in anxiety disorders in an outcome devaluation paradigm.

BACKGROUND: A habitual avoidance component may enforce the persistence of maladaptive avoidance behavior in anxiety disorders. Whether habitual avoidance is acquired more strongly in anxiety disorders is unclear. METHODS: Individuals with current social anxiety disorder, panic disorder and/or agoraphobia (n = 62) and healthy individuals (n = 62) completed a devaluation paradigm with extensive avoidance training, followed by the devaluation of the aversive outcome. In the subsequent test phase, habitual response tendencies were inferred from compatibility effects. Neutral control trials were added to assess general approach learning in the absence of previous extensive avoidance training. RESULTS: The compatibility effects indicating habitual control did not differ between patients with anxiety disorders and healthy controls. Patients showed lower overall approach accuracy, but this effect was unrelated to the compatibility effects. CONCLUSIONS: In this study, anxiety disorders were characterized by reduced approach but not stronger habitual avoidance. These results do not indicate a direct association between anxiety disorders and the acquisition of pervasive habitual avoidance in this devaluation paradigm.

Efficacy of a Brief Blended Cognitive Behavioral Therapy Program for the Treatment of Depression and Anxiety in University Students: Uncontrolled Intervention Study.

BACKGROUND: Blended cognitive behavioral therapy (bCBT)-the combination of cognitive behavioral therapy and digital mental health applications-has been increasingly used to treat depression and anxiety disorders. As a resource-efficient treatment approach, bCBT appears promising for addressing the growing need for mental health care services, for example, as an early intervention before the chronification of symptoms. However, further research on the efficacy and feasibility of integrated bCBT interventions is needed. OBJECTIVE: This study aimed to evaluate the efficacy of a novel bCBT program comprising short (25 min), weekly face-to-face therapy sessions combined with a smartphone-based digital health app for treating mild to moderate symptoms of depression or anxiety. METHODS: This prospective uncontrolled trial comprised 2 measurement points (before and after treatment) and 2 intervention groups. We recruited university students with mild to moderate symptoms of depression or anxiety. On the basis of the primary symptoms, participants were assigned to either a depression intervention group (n=67 completers) or an anxiety intervention group (n=33 completers). Participants in each group received 6 weekly individual psychotherapy sessions via videoconference and completed modules tailored to their respective symptoms in the smartphone-based digital health app. RESULTS: The depression group displayed medium to large improvements in the symptoms of depression (Cohen d=-0.70 to -0.90; P<.001). The anxiety group experienced significant improvements in the symptoms of generalized anxiety assessed with the Generalized Anxiety Disorder-7 scale with a large effect size (Cohen d=-0.80; P<.001) but not in symptoms of anxiety assessed with the Beck Anxiety Inventory (Cohen d=-0.35; P=.06). In addition, both groups experienced significant improvements in their perceived self-efficacy (Cohen d=0.50; P<.001 in the depression group and Cohen d=0.71; P<.001 in the anxiety group) and quality of life related to psychological health (Cohen d=0.87; P<.001 in the depression group and Cohen d=0.40; P=.03 in the anxiety group). Work and social adjustment of patients improved significantly in the depression group (Cohen d=-0.49; P<.001) but not in the anxiety group (Cohen d=-0.06; P=.72). Patients' mental health literacy improved in the anxiety group (Cohen d=0.45; P=.02) but not in the depression group (Cohen d=0.21; P=.10). Patient satisfaction with the bCBT program and ratings of the usability of the digital app were high in both treatment groups. CONCLUSIONS: This study provides preliminary evidence for the feasibility and efficacy of a novel brief bCBT intervention. The intervention effects were generalized across a broad spectrum of patient-reported outcomes. Hence, the newly developed bCBT intervention appears promising for treating mild to moderate depression and anxiety in young adults.

The associations of Positive and Negative Valence Systems, Cognitive Systems and Social Processes on disease severity in anxiety and depressive disorders.

Background: Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders. Methods: Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP). Results: The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: ß = -0.35; NVS: ß = 0.39; CS: ß = -0.12; SP: ß = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association. Limitations: The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for. Conclusion: Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.

Do changes in dysfunctional posttraumatic cognitions differentially predict PTSD symptom clusters?

OBJECTIVE: In recent years, it has been suggested that the modification of dysfunctional posttraumatic cognitions plays a central role as a mechanism of change in cognitive behavioral therapy (CBT) for posttraumatic stress disorder (PTSD). Indeed, several studies have shown that changes in dysfunctional posttraumatic cognitions precede and predict symptom change. However, these studies have investigated the influence on overall symptom severity-despite the well-known multidimensionality of PTSD. The present study therefore aimed to explore differential associations between change in dysfunctional conditions and change in PTSD symptom clusters. METHOD: As part of a naturalistic effectiveness study evaluating trauma-focused cognitive behavioral therapy for PTSD in routine clinical care, 61 patients with PTSD filled out measures of dysfunctional posttraumatic cognitions and PTSD symptom severity every five sessions during the course of treatment. Lagged associations between dysfunctional cognitions and symptom severity at the following timepoint were examined using linear mixed models. RESULTS: Over the course of therapy, both dysfunctional cognitions and PTSD symptoms decreased. Posttraumatic cognitions predicted subsequent total PTSD symptom severity, although this effect was at least partly explained by the time factor. Moreover, dysfunctional cognitions predicted three out of four symptom clusters as expected. However, these effects were no longer statistically significant when the general effect for time was controlled for. CONCLUSION: The present study provides preliminary evidence that dysfunctional posttraumatic cognitions predict PTSD symptom clusters differentially. However, different findings when employing a traditional versus a more rigorous statistical approach make interpretation of findings difficult. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effective-and Tolerable: Acceptance and Side Effects of Intensified Exposure for Anxiety Disorders.

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 (ß = 0.25) and stronger side effects (ß = 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.

Reduction of costly safety behaviors after extinction with a generalization stimulus is determined by individual differences in generalization rules.

Exposure-based treatment involves repeated presentation of feared stimuli or situations in the absence of perceived threat (i.e., extinction learning). However, the stimulus or situation of fear acquisition (CS+) is highly unlikely to be replicated and presented during treatment. Thereby, stimuli that resemble the CS+ (generalization stimuli; GSs) are typically presented. Preliminary evidence suggests that depending on how one generalizes fear (i.e., different generalization rules), presenting the same GS in extinction leads to differential effectiveness of extinction learning. The current study aimed to extend this finding to safety behaviors. After differential fear and avoidance conditioning, participants exhibited discrete generalization gradients that were consistent with their reported generalization rules (Similarity vs Linear). The Linear group showed stronger safety behaviors to a selected GS compared to the Similarity group, presumably due to higher threat expectancy. After extinction learning to this GS, the Linear group exhibited stronger reduction in safety behaviors generalization compared to the Similarity group. The results show that identifying distinct generalization rules allows one to predict expectancy violation to the extinction stimulus, in addition to corroborating the idea that strongly violating threat expectancy leads to better extinction learning and its generalization. With regard to clinical implications, identifying one's generalization rule (e.g., threat beliefs) help designing exposure sessions that evoke strong expectancy violation, enhancing the reduction in the generalization of maladaptive safety behaviors.

Mapping Research Domain Criteria using a transdiagnostic mini-RDoC assessment in mental disorders: a confirmatory factor analysis.

This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.

Sometimes I feel the fear of uncertainty: How intolerance of uncertainty and trait anxiety impact fear acquisition, extinction and the return of fear.

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.

Threat belief determines the degree of costly safety behavior: Assessing rule-based generalization of safety behavior with a dimensional measure of avoidance.

Excessive generalization of safety behavior to innocuous stimuli that resemble a feared stimulus is oftentimes pathological especially with inflicted impairments. Safety behavior is conventionally assessed dichotomously, requiring multiple presentations of each test stimulus for assessing the proportion of safety behavior executed. Thus, the generalization gradient confounds with ongoing extinction learning during non-reinforced test trials. The present study employed a recently developed dimensional measure of avoidance to examine the extent of safety behavior generalization. We found that a dimensional measure of avoidance was able to assess the generalization gradients of safety behavior even when each test stimulus was presented once, thus minimizing the effect of ongoing extinction learning. Of equal importance is whether higher-order cognitive processes shape generalization of safety behavior. We found a range of distinct generalization gradients in safety behavior, which were highly consistent with participants' verbally reported relational rules. This rule-based generalization parallels to how clinically anxious individuals develop different threat beliefs after trauma exposure, and models how these distinct threat beliefs determine the extent of safety behavior engagement.

Costly avoidance of Pavlovian fear stimuli and the temporal dynamics of its decision process.

Conflicts between avoiding feared stimuli versus approaching them for competing rewards are essential for functional behavior and anxious psychopathology. Yet, little is known about the underlying decision process. We examined approach-avoidance decisions and their temporal dynamics when avoiding Pavlovian fear stimuli conflicted with gaining rewards. First, a formerly neutral stimulus (CS+) was repeatedly paired with an aversive stimulus (US) to establish Pavlovian fear. Another stimulus (CS-) was never paired with the US. A control group received neutral tones instead of aversive USs. Next, in each of 324 trials, participants chose between a CS-/low reward and a CS+/high reward option. For the latter, probability of CS+ presentation (Pavlovian fear information) and reward magnitude (reward information) varied. Computer mouse movements were tracked to capture the decision dynamics. Although no more USs occurred, pronounced and persistent costly avoidance of the Pavlovian fear CS+ was found. Time-continuous multiple regression of movement trajectories revealed a stronger and faster impact of Pavlovian fear compared to reward information during decision-making. The impact of fear information, but not reward information, modestly decreased across trials. These findings suggest a persistently stronger weighting of fear compared to reward information during approach-avoidance decisions, which may facilitate the development of pathological avoidance.

Avoidance of learnt fear: Models, potential mechanisms, and future directions.

Avoiding stimuli that were previously associated with threat is essential for adaptive functioning, but excessive avoidance that persists in the absence of threat can turn dysfunctional and results in severe impairments. Fear and avoidance conditioning models have substantially contributed to the understanding of safety behaviors towards learnt fear stimuli. Safety behaviors are executed in the presence of a feared stimulus to prevent the upcoming threat and are well-established in laboratory models. Avoidance of learnt fear, i.e., avoidance of the feared stimulus itself, is typically initiated before the onset of a feared stimulus: individuals oftentimes avoid fear stimuli to prevent negative emotions evoked by them or ultimately the associated threat. Avoidance of learnt fear is surprisingly understudied despite its prevalence in pathological anxiety. The current overview proposes potential behavioral mechanisms and neural circuits of avoidance of learnt fear in humans, and discusses findings and paradigms suitable for examining it. Specifically, higher-order conditioning, decision making paradigms, and context-cue conditioning investigate distinct forms of avoidance of learnt fear. We also discuss the clinical prospects and future directions of research in avoidance of learnt fear.

Avoiding a feared stimulus: Modelling costly avoidance of learnt fear in a sensory preconditioning paradigm.

Avoidance of learnt fear prevents the onset of a feared stimulus and the threat that follows. In anxiety-related disorders, it turns pathological given its cost and persistence in the absence of realistic threat. The current study examined the acquisition of costly avoidance of learnt fear in healthy individuals (n = 45), via a sensory preconditioning paradigm. Two neutral preconditioning stimuli (PSs) were paired with two neutral conditioned stimuli (CSs). One CS then came to predict an aversive outcome whereas the other CS came to predict safety. In test, participants engaged in stronger avoidance to the PS associated with the fear-related CS than the PS associated with the safety-related CS. Of note, executing behavioral avoidance led to missing out a competing reward, thus rendering avoidance costly. The results also provide preliminary evidence that threat anticipation and a negative change in valence play a role in driving costly avoidance of learnt fear. Future studies should examine how avoidance of learnt fear maintains pathological anxiety.