Background: Mental images of threat are common in panic disorder and may contribute to its onset and maintenance, making them potential relevant targets for treatment. They can be related to distressing memories or catastrophic future simulations (i.e., “ flashforwards ”). This study explored the similarities and differences between these two types of threat representations in terms of the credibility of encapsulated beliefs, emotional intensity, distress, controllability, aversiveness, sensory complexity, and episodic and semantic details. Methods: Forty-six patients diagnosed with panic disorder were asked about distressing memories and flashforwards related to their disorder using structured audio-recorded interviews and questionnaires before the treatment. The narratives were coded for episodic and semantic details. Results Results showed that both distressing memories and flashforwards were common and highly similar in image characteristics, but overall memories were self-rated as being more sensory-complex. Flashforwards were rated as more aversive, but threat representations did not differ in terms of credibility of encapsulated beliefs, emotional intensity, distress, and controllability. Compared to flashforwards, memories contained more episodic details, but threat representations did not differ in the number of semantic details or in relative scores. Conclusions Distressing memories and flashforwards in panic disorder are highly similar but differ in complexity and perceived aversiveness. The theoretical and clinical implications of distinguishing between these two types of threat representation are discussed.

Extinction learning is regarded as a core mechanism underlying exposure therapy. Under this assumption, studies have looked at the predictive value of the extinction learning paradigm for exposure therapy outcomes. However, predicting factors of long-term exposure therapy success have not been established. Participants with a specific phobia (SP) for spiders were included in a double-blind randomized controlled trial. Participants were randomly assigned to receive exposure therapy (n = 25, 24 females) or an active control intervention, progressive muscle relaxation (PMR; n = 18, 15 females). Symptom levels were measured with the Fear of Spiders questionnaire (FSQ) at baseline (T0), after the intervention (T1), and at six- (T2) and twelve (T3) months follow-up. At baseline, participants completed a three-day fMRI fear conditioning, extinction learning, and extinction recall paradigm. Indices of extinction were defined as self-reported threat expectancy and fear, and neural activation during stimulus presentations and threat omission in the ventromedial prefrontal cortex and nucleus accumbens, based on prior data. Mixed model analysis revealed that the exposure therapy group had an overall stronger decrease in phobic symptoms over time than the PMR group (β = 10.95, p < .001). However, none of the indices of extinction learning were predictive for FSQ scores after exposure therapy at the longest follow-up measurement (T3). In sum, the current results show the long-term effectiveness of a single session of exposure therapy for reducing a specific fear of spiders but no baseline characteristics were identified that predicted individual differences in exposure therapy success after one year.

During Eye Movement Desensitisation and Reprocessing (EMDR) therapy, patients recall traumatic memories while performing dual attention tasks to tax the limited capacity of the working memory (WM). Increasing WM load during recall has shown to improve memory-degrading effects. This research aims to explore how technological tools can be used to more effectively increase WM load. Two experiments involving healthy participants utilised Random Interval Repetition (RIR) tasks to investigate the WM-taxing effects of specific digital dual-attention tasks and task manipulations. In experiment 1 (N = 41), conducted in a lab-based virtual reality setting, participants performed auditory RIR tasks while varying the speed and direction of eye movements (EM), with or without an additional visual RIR task. Experiment 2 (N = 49), conducted online via a smartphone application, compared solo and combined auditory and visual RIR tasks presented either simultaneously or serially under varying EM speeds. Results showed that combining RIR tasks increased auditory RTs, while a simultaneous combination and higher EM speeds selectively increased visual RTs only. These findings suggest that task addition and manipulation effectively increase WM load, though the involvement of WM sub-modalities and high-demand tasks influences their effects. These insights could refine face-to-face and online EMDR practices and optimise therapeutic effectiveness.

Background and Objectives: During a standard dual-task intervention, an individual recalls a memory while performing a dual-task. It is yet unclear to which extent a memory needs to be activated during a dual-task intervention to be most effective for memory desensitization. We investigated whether boosting memory activation by adding a visual retrieval cue during a dual-task intervention could enhance the desensitization of aversive memories.Methods: An aversive memory was induced using a trauma film. Then, participants (N = 136) were randomly assigned to either (1) Recall + Working Memory (WM) Task + Screenshot, (2) Recall + WM Task, (3) Recall Only, or (4) WM Task Only condition. Memory vividness and distress were assessed prior and after the intervention, and at 1-week follow-up.Results: Overall, the evidence suggested that adding a visual retrieval cue of an aversive memory to a standard dual-task intervention did not lead to greater reductions in memory vividness and distress compared to a standard dual-task intervention without a cue. Exploratory analyses revealed that there was strong evidence for an alternative hypothesis: All conditions involving WM taxation were equally effective in reducing memory distress and vividness, irrespective of recall instructions or reactivation cues, and outperformed the Recall Only condition.Limitations: Participants did not think more of the trauma film when provided with a visual retrieval cue during the standard dual-task intervention compared to not seeing such a cue. Hence, it is possible that the visual retrieval cue was not processed sufficiently to boost memory activation.Conclusions: Adding a visual retrieval cue to a dual-task intervention did not enhance memory desensitization in this study with non-clinical participants. Instead, based on the exploratory analyses, the data more likely suggest that (continuous) reactivation of aversive memories during a dual-task intervention may not be necessary for effective memory desensitization.

•DBS impacts the life of OCD patients beyond changes in their core symptoms.•Qualitative methods allow gathering in-depth knowledge of DBS-related experiences.•Positive and negative psychological and physical experiences are reported.•Attention should be given to each individual treatment trajectory.•Proper assessment tools should be developed for continuous monitoring and support.

Exposure-based therapy is the treatment of choice for anxiety disorders, but many patients do not benefit sufficiently from it. Distressing images of threat related to the future or past may maintain the anxiety symptomatology or impede exposure therapy. An intervention that targets threat-related imagery is eye movement desensitization and reprocessing (EMDR) therapy. The main goal of this multicenter randomized controlled trial is to investigate whether EMDR therapy plus exposure therapy, relative to supportive counseling plus exposure therapy, improves treatment efficacy, tolerability, and adherence in patients with panic disorder. In addition, we will examine potential predictors of optimal treatment allocation, mechanisms of change as well as the long term effects of treatment. Finally, we will assess cost-effectiveness. A multicenter randomized controlled trial mixed design will be conducted. Participants will be 50 patients, aged ≥ 18, diagnosed with a panic disorder. They will be randomly assigned to one of two conditions: EMDR therapy (i.e., flashforward strategy) or supportive counseling (each consisting of four weekly sessions of 90 min each) prior to exposure therapy (consisting of eight weekly sessions of 90 min each). Assessments will be made pre-treatment (T1), between-treatments (T2), post-treatment (T3), one month post-treatment (FU1) and six months post-treatment (FU2) by an assessor blind to treatment condition. The primary outcome measure is severity of panic-related symptoms. Secondary outcome measures are: tolerability of exposure therapy (initial avoidance, willingness to start exposure therapy, considered drop-out; no-show and drop-out), related symptomatology (generalized anxiety, depression), and functional impairment. The primary goals of this research are to compare the efficacy, tolerability, and adherence of EMDR therapy plus exposure therapy and supportive counseling plus exposure therapy and to identify predictors, moderators, and mediators for treatment success. This multi-center research aims to make a significant contribution to our understanding as to how treatment for patients with anxiety disorders can be optimized, and elucidate who can benefit most from this novel approach. ISRCTN—ISRCTN29668369: Improving anxiety treatment by modifying emotional memories before real-life exposure. Registered 27 June 2022—retrospectively registered. ISRCTN—ISRCTN29668369.

Panic disorder is characterized by the paroxysmal occurrence and fear of bodily symptoms. In recent years it has been proposed that patients “learn” to fear cardiorespiratory sensations through interoceptive conditioning. This study sought to model the initial stage of this process in healthy volunteers (N=44) using mild cardiac sensations. An additional aim was to explore whether anxiety sensitivity – a known risk factor for panic disorder – modulates such interoceptive learning. Infusions of pentagastrin and saline were used to manipulate the presence versus absence of cardiac sensations, respectively, and served as conditioned stimuli in a differential interoceptive conditioning paradigm. Inhalation of 35% CO2-enriched air served as the panicogenic, unconditioned stimulus (UCS). In half of the participants (“prepared” condition), cardiac sensations caused by pentagastrin were followed by inhalation of CO2-enriched air (penta CS+), whereas the absence of such sensations (saline) was followed by room air (saline CS−). The reversed combination (“unprepared” condition) was used in the other half of the participants. Conditioning effects showed up for self-reported UCS-expectancy, but not for skin conductance and anxiety ratings. Only participants from the prepared group learned to expect the UCS, and differential learning was impaired with higher scores on anxiety sensitivity. Expectancy learning was more easily established towards the presence compared to the absence of cardiac sensations, whereas the reverse effect was observed for safety learning. Modeling impaired discriminatory learning and the moderating effect of anxiety sensitivity provides new insight in the development of panic disorder.

Panic attacks (PAs), the core feature of panic disorder, represent a common phenomenon in the general adult population and are associated with a considerable decrease in quality of life and high health care costs. To date, the underlying pathophysiology of PAs is not well understood. A unique feature of PAs is that they represent a rare example of a psychopathological phenomenon that can be reliably modeled in the laboratory in panic disorder patients and healthy volunteers. The most effective techniques to experimentally trigger PAs are those that acutely disturb the acid-base homeostasis in the brain: inhalation of carbon dioxide (CO2), hyperventilation, and lactate infusion. This review particularly focuses on the use of CO2 inhalation in humans and rodents as an experimental model of panic. Besides highlighting the different methodological approaches, the cardio-respiratory and the endocrine responses to CO2 inhalation are summarized. In addition, the relationships between CO2 level, changes in brain pH, the serotonergic system, and adaptive physiological and behavioral responses to CO2 exposure are presented. We aim to present an integrated psychological and neurobiological perspective. Remaining gaps in the literature and future perspectives are discussed. (C) 2015 Elsevier Ltd. All rights reserved.

Inhaling carbon dioxide (CO2)-enriched air induces fear and panic symptoms resembling real-life panic attacks, the hallmark of panic disorder. The present study aimed to describe the emotional and cardiovascular effects evoked by inhaling CO2, taking shortcomings of previous studies into account. Healthy volunteers underwent a double inhalation of 0, 9, 17.5, and 35% CO2, according to a randomized, cross-over design. In addition to fear, discomfort, and panic symptom ratings, blood pressure and heart rate were continuously monitored. Results showed a dose-dependent increase in all self-reports. Systolic and diastolic blood pressure rose with increasing CO2 concentration, whereas heart rate results were less consistent. Diastolic blood pressure and heart rate variation correlated with fear and discomfort. Based on this relationship and the observation that the diastolic blood pressure most accurately mimicked the degree of self-reported emotions, it might serve as a putative biomarker to assess the CO2-reactivity in the future.

In cognitive theory it is hypothesized that panic attacks are provoked by catastrophic misinterpretations of bodily sensations. The aim of the present study was to investigate the ability of associated word pairs referring to catastrophic thinking (e.g. palpitations-heart attack) in producing panic attacks. Patients with PD (n = 20), patients with mixed anxiety disorders (n = 20), and a healthy control group (n = 30) participated in the present study. To enhance ecological validity we first conducted a stimulus validation experiment. Subsequently, nine suitable panic and neutral word pairs were presented in block to the participants. Anxiety levels were assessed before and after the presentation. PD patients were more anxious when reading these word pairs, compared to neutral word pairs. However, none of the participants experienced a panic attack upon reading the word pairs. From the present results it seems that catastrophic thinking is rather related to the anticipatory anxiety for panic attacks, but not necessarily with the occurrence of the panic attacks themselves.

More than 20% of the general population experience a panic attack at least once in their lives; however, only a minority goes on to develop panic disorder (PD). Conditioning mechanisms have been proposed to explain this evolution in persons who are susceptible to developing panic disorder upon a "traumatic" panic attack. According to preparedness theory, some cues are more likely to condition than others, namely, those referring to internal, bodily signals of danger. The aim of the present study was to test this theory in a differential conditioning paradigm, making use of scripts referring to different internal, bodily sensations as conditioned stimulus (CS) and inhalation of 35% CO(2) as unconditioned stimulus (UCS). Thirty-three healthy volunteers were assigned to three scripts conditions: "suffocation," "neutral," or "urgency." During acquisition, one of two versions of a particular script was always followed by an inhalation of 35% CO(2) (CS+) and the other by room air (CS-). Acquisition was followed by a test phase, where only inhalations of room air were administered. In line with our hypothesis, only participants in the suffocation condition exhibited a selective conditioning effect. They were more fearful and showed a significantly higher increase in tidal volume than participants in the two control conditions. Results are discussed with relation to interoceptive conditioning, preparedness, and the possible role of tidal volume in PD.

Cognitive models assume that panic disorder is characterised by a tendency to misinterpret benign bodily symptoms (e.g. breathlessness) in a catastrophic fashion (e.g. suffocation). This is a central part of the cognitive model which presents a core focus for treatment. Several studies have supported this hypothesis. These studies have, however, almost always relied on self-report. In addition to susceptibility to biases (e.g. distortions of memory), a limitation of research based on verbal report is its inability to capture the spontaneous/automatic nature that is attributed to these catastrophic interpretations. The present paper reports on two experiments in which a priming procedure was used to test the hypothesis that panic disorder is characterised by spontaneous catastrophic interpretations and whether this effect is 'specific' to panic disorder. In line with predictions from the cognitive model, it was observed in the first experiment that the panic group demonstrated facilitated responses to trials consisting of a 'symptom' prime and a 'catastrophic outcome' target (e.g. breathlessness - suffocate). Similar effects were not observed for an anxious control group and a nonclinical control group, supporting the specificity of this effect. Interestingly, however, significant priming effects were observed for a group of mental health professionals (part of the healthy control group) who had no history of panic disorder. Subsequently, this unexpected observation was explicitly addressed in a second experiment, which confirmed the findings of Experiment 1. Together, these results suggest that associations between mental representations of benign bodily symptoms and catastrophic outcomes might develop as part of professional knowledge and experience, and should not necessarily be viewed as pathogenic. Theoretical and clinical implications are discussed.

According to cognitive theories, panic patients are assumed to have an attentional bias toward bodily sensations. To date, there is only some indirect evidence of such a bias measured by an emotional Stroop task. Moreover, the content and disorder specificity of this bias is rather unclear. The aim of this study was to investigate the specificity of attentional bias in patients with panic disorder (PD). Patients with PD (n=32), patients with mixed anxiety disorders (n=25), and a healthy control group (n=26) performed an emotional Stroop task with three word types: panic threat, general threat, and neutral. There were no differences on reaction times between the different groups, or on the different word types. Despite the generally accepted existence of attentional biases in anxiety disorders, we found no evidence of a specific attentional bias in patients with PD.