Exposure-based Therapy Research Articles

Evaluating Psychological Effects of Amputation Through Virtual Reality Embodiment: A Study on Anxiety and Body Appreciation

Background/Objectives: A high number of patients who suffer the amputation of a lower limb will present psychological problems such as anxiety, depression, and post-traumatic stress disorder after surgery. This study embodies participants in a self-avatar with a right lower-limb amputation in a virtual reality environment. The aim was to determine if this experience increases anxiety levels compared to embodiment in a normal avatar. The study also examines whether body appreciation is related to anxiety levels. Methods: Subjects completed the Body Appreciation Scale (BAS) questionnaire before being immersed in the virtual environment, the Visual Analogue Scale for Anxiety (VAS-A) after each condition, and the Embodiment Questionnaire at the end of the experiment. Results: Univariate analysis showed that participants reported significantly higher levels of anxiety when exposed to the virtual avatar with an amputation compared to the full virtual body avatar. These results indicate that lower levels of body appreciation were associated with higher levels of anxiety across conditions, suggesting that participants with lower body appreciation experienced greater psychological maladjustment (measured by anxiety) in response to the virtual scenarios. Conclusions: The results suggest that the virtual avatar with a lower-limb amputation elicited significantly greater anxiety, and that body appreciation plays a key role in moderating this psychological response. Future research could focus on developing virtual exposure-based therapy for amputees using virtual reality to help reduce the anxiety experienced by patients during this process.

Virtual reality exposure therapy for sexual aversion: a proof-of-concept study on acceptability, adequacy, and clinical effects.

Sexual dysfunctions impair theintimate relationships of up to one-third of the population. Virtual reality (VR) offers innovative treatment options for both mental and sexual disorders, such as female orgasmic disorder and erectile disorder. Sexual aversion disorder (SAD)-the anxiety, disgust, and avoidance of sexual contexts-is a chronic condition commonly treated with anxiety-reducing strategies, such as exposure-based therapy. Despite exposure's efficacy in reducing SAD symptoms, VR exposure therapy's (VRET) effectiveness remains unexplored for this condition. This proof-of-concept study examines the acceptability, adequacy, and clinical effects of a VRET's simulation protocol for SAD. In the laboratory, 15 adults suffering from SAD (Mage = 35.00; SD = 11.36) viewed 15 virtual sexual scenarios of increasing intensity (eg, flirting, nudity, genital stimulation) adjusted to their sexual preferences and gender identities. Levels of anxiety, disgust, and catastrophizing beliefs were measured throughout the scenarios using standard self-report measures. Participants also completed validated questionnaires on sexual presence and simulation realism, as well as open-ended questions on scenarios' representativeness and adequacy immediately after immersion. Six months after the laboratory visit, participants completed a negative effects questionnaire and were screened for SAD symptoms again. Repeated-measures ANOVAs and descriptive analyses were performed. Levels of anxiety and disgust significantly increased with the intensity of sexual scenarios. Catastrophizing levels were high and tended to augment with increasing exposure levels. A significant reduction in symptoms of SAD was found from pre-simulation to the 6-month follow-up assessment. Sexual presence and realism scores were moderate. Qualitative assessment revealed that all participants reported the sexual scenarios were representative of real-life situations that tend to elicit SAD symptoms for them. Reported negative effects were generally mild. This proof-of-concept study suggests that VRET may have the potential to elicit self-reported emotional and cognitive manifestations of SAD (sex-related anxiety, disgust, and catastrophizing), while also hinting at its acceptability, adequacy, and benefits in alleviating SAD symptoms. While this study marks the first exploration of the clinical relevance of gender-inclusive virtual sexual scenarios for SAD, its design and sample composition may impact observed effects and the generalizability of findings. This study invites future clinical trials to assess VRET efficacy for SAD.

Augmented Reality as an Aid to Behavior Therapy for Anxiety Disorders: A Narrative Review.

Anxiety disorders are among the most common mental disorders worldwide. These conditions are characterized by excessive anxiety that is difficult to control. In most anxiety disorders, symptoms are triggered by exposure to specific objects or situations. This leads sufferers to avoid such exposures, leading to impaired social and occupational functioning and reduced quality of life. Therapies based on behavioral principles, either alone or in combination with cognitive techniques, are the most effective psychological interventions for anxiety disorders. However, the effectiveness of these therapies may be limited due to a lack of generalization from clinic to real-world settings. Augmented reality (AR) is a technology that provides an interactive experience by superimposing computer-generated content, often in multiple sensory modalities, on the real world. Emerging evidence suggests that AR may be useful in treating a broad range of mental disorders, including anxiety disorders. This review examines the evidence for the use of AR-based techniques as an aid to behavioral or cognitive-behavioral therapies for anxiety disorders. The available evidence suggests that this method may offer significant advantages over conventional therapies, particularly in the case of specific phobias, but also in social anxiety disorder. AR can also be combined with other novel technologies to monitor psychophysiological markers of anxiety and its reduction over the course of treatment. The advantages of AR could be related to its combination of real and simulated content, allowing for better generalization of the benefits of conventional exposure-based therapy. Though the safety, efficacy, and cost-effectiveness of this method need to be confirmed in larger samples, it could lead to a paradigm shift in the way behavioral therapies for anxiety disorders are conceptualized and delivered.

Internet-Delivered Exposure-Based Cognitive Behavior Therapy for Irritable Bowel Syndrome: A Clinical Effectiveness Study.

Irritable bowel syndrome (IBS) is a common and debilitating disorder. When dietary and pharmacological interventions are not satisfactory, psychological treatment may produce good results. However, the access to such treatment is scarce, and therefore, it is of importance to make use of technical solutions. In this study, we wanted to investigate the real-world effectiveness of an Internet-delivered exposure-based cognitive behavior therapy (ECBT) for IBS and to replicate an earlier finding regarding the working mechanism of the treatment. A total of 309 consecutively recruited patients from the Internet Psychiatry Clinic in Stockholm received ECBT for 12 weeks. The patients' IBS symptoms, quality of life, avoidance behaviors, and gastrointestinal symptom-specific anxiety were monitored, and we used a bivariate cross-lagged panel model to investigate time-related change in symptoms and avoidance behaviors. IBS symptoms, measured with the Gastrointestinal Symptom Rating Scale for IBS, were reduced from 48.06 (SD = 11.26) before treatment to 33.06 (SD = 10.81) 6 months after treatment ( P < 0.001). The effect size (calculated by Cohen d ) was 1.30 (1.08-1.51). There was a significant ( P < 0.001) cross-lagged effect from reduction in avoidance behavior to reduction in symptoms but not in the reverse direction, indicating that the treatment effect is mediated by behavioral change. We conclude that ECBT is effective under real-world conditions, also when delivered through the Internet, and that an important treatment mechanism is the reduction of avoidance behaviors.

Advancing the treatment of anxiety disorders in transition-age youth: a review of the therapeutic effects of unconscious exposure.

The real-world effectiveness of exposure-based therapies for youth depends on the willingness and ability of young people to tolerate confronting their fears, which can be experienced as highly aversive and create problems with treatment engagement and acceptance. Recently, neuroscientific research on the nonconscious basis of fear has been translated into novel exposure interventions that bypass conscious processing of feared stimuli and that thus do not cause phobic youth to experience distress. We present a review of these unconscious exposure interventions. A PRISMA-based search yielded 20 controlled experiments based on three paradigms that tested if fear-related responses could be reduced without conscious awareness in highly phobic, transition-age youth: 14 randomized controlled trials (RCTs), 5 fMRI studies (1 was also an RCT), 4 psychophysiological studies (3 were also RCTs), and 1 ERP study. We conducted meta-analyses of outcomes where feasible. Unconscious exposure interventions significantly (1) reduced avoidance behavior (range of Cohen's d = 0.51-0.95) and self-reported fear (d = 0.45-1.25) during in vivo exposure to the feared situation; (2) reduced neurobiological indicators of fear (d = 0.54-0.62) and concomitant physiological arousal (d = 0.55-0.64); (3) activated neural systems supporting fear regulation more strongly than visible exposure to the same stimuli (d = 1.2-1.5); (4) activated regions supporting fear regulation that mediated the reduction of avoidance behavior (d = 0.70); (5) evoked ERPs suggesting encoding of extinction memories (d = 2.13); and (6) had these effects without inducing autonomic arousal or subjective fear. Unconscious exposure interventions significantly reduce a variety of symptomatic behaviors with mostly moderate effect sizes in transition-age youth with specific phobias. fMRI and physiological findings establish a neurophysiological basis for this efficacy, and suggest it occurs through extinction learning. Unconscious exposure was well tolerated, entirely unassociated with drop out, and is highly scalable for clinical practice. However, a number of limitations must be addressed to assess potential clinical impacts, including combining unconscious exposure with exposure therapy to boost treatment acceptance and efficacy.

A General Factor of Psychopathology Predicts Treatment and Long-Term Outcomes in Children and Adolescents With Obsessive-Compulsive Disorder

Children and adolescents with obsessive-compulsive disorder (OCD) are at risk of long-term adversity, but factors influencing long-term outcomes are unclear. A general factor of psychopathology, often referred to as the p factor, captures variance shared by all mental disorders and has predicted long-term outcomes in youth with anxiety and depressive disorders. The p factor has never been examined in relation to outcomes in pediatric OCD. Here, we examine whether the p factor predicts four important outcomes over both short and long durations in youth with OCD. We used data from the Nordic Long-term OCD Treatment Study (NordLOTS), where youth with OCD (N=248, Mage: 12.83 years [SD = 2.72], 52.0% girls) received exposure-based cognitive-behavioral therapy. The p factor was estimated using parent-reported Child Behavior Check List data at baseline and was examined in relation to clinician-rated OCD severity, clinician-rated psychosocial functioning, self-reported depressive symptoms, and self- and parent-reported quality of life directly after treatment and 1, 2, and 3 years after treatment. The p factor was associated with acute treatment outcomes for OCD severity and psychosocial functioning, but not for depressive symptoms and quality of life. For the long-term outcomes, the p factor was significantly associated with all outcomes except OCD severity. The p factor outperformed traditional psychiatric comorbidity as a predictor of long-term outcomes. Youth with OCD who experience symptoms across multiple psychiatric domains have poorer long-term outcomes. Compared to traditional classification of psychiatric diagnoses, assessing psychopathology using a dimensional p factor approach may be advantageous for informing prognosis in pediatric OCD.

The impact of the left inferior frontal gyrus on fear extinction: A transcranial direct current stimulation study

IntroductionFear extinction is a fundamental component of exposure-based therapies for anxiety-related disorders. The renewal of fear in a different context after extinction highlights the importance of contextual factors. In this study, we aimed to investigate the causal role of the left inferior frontal gyrus (LiFG) in the context-dependency of fear extinction learning via administration of transcranial direct current stimulation (tDCS) over this area. Methods180 healthy subjects were assigned to 9 groups: 3 tDCS conditions (anodal, cathodal, and sham) × 3 context combinations (AAA, ABA, and ABB). The fear conditioning/extinction task was conducted over three consecutive days: acquisition, extinction learning, and extinction recall. tDCS (2 mA, 10min) was administered during the extinction learning phase over the LiFG via a 4-electrode montage. Skin conductance response (SCR) data and self-report assessments were collected. ResultsDuring the extinction learning phase, groups with excitability-enhancing anodal tDCS showed a significantly higher fear response to the threat cues compared to cathodal and sham stimulation conditions, irrespective of contextual factors. This effect was stable until the extinction recall phase. Additionally, excitability-reducing cathodal tDCS caused a significant decrease of the response difference between the threat and safety cues during the extinction recall phase. The self-report assessments showed no significant differences between the conditions throughout the experiment. ConclusionIndependent of the context, excitability enhancement of the LiFG did impair fear extinction, and led to preservation of fear memory. In contrast, excitability reduction of this area enhanced fear extinction retention. These findings imply that the LiFG plays a role in the fear extinction network, which seems to be however context-independent.

Moving beyond symptom reduction: A meta-analysis on the effect of exposure therapy for PTSD on quality of life.

Quality of life (QOL) is a multidimensional construct including emotional well-being, life satisfaction, and physical health. Individuals with posttraumatic stress disorder (PTSD) consistently report low QOL, highlighting the importance of assessing the effectiveness of first-line PTSD treatments (e.g., exposure-based therapies) on QOL. This meta-analysis examined the efficacy of exposure therapy for PTSD on QOL compared to control conditions (e.g., waitlist, medication, treatment-as-usual) at posttreatment and follow-up (ranging from 1 month to 2 years). Building on a previous meta-analysis of exposure-based therapy for PTSD, we searched PsycINFO and Medline in December 2021, July 2022, and March 2023 to include randomized controlled trials of exposure-based treatments for adult PTSD assessing QOL. We screened 295 abstracts for initial eligibility; 20 articles met inclusion criteria and were included (N = 2729 participants). Risk of bias was evaluated using the Cochrane Risk of Bias tool 2.0. At posttreatment, exposure-based therapies showed a medium effect on QOL relative to control conditions (k = 25, g = 0.67). This effect was not observed at follow-up for the small subset of studies with follow-up data (k = 8, g = 0.16). At posttreatment, effect size varied significantly as a function of the control condition (p < .0001). There were no differences in QOL effects across exposure therapies at posttreatment or follow-up (p = .09). Exposure therapy was associated with greater improvement in QOL compared to control conditions at posttreatment. Exposure was not superior to control conditions at follow-up, and the longer-term impact of exposure on QOL is unclear. The implications of these findings are discussed, along with the need for more PTSD treatment studies to examine QOL outcomes at posttreatment and follow-up.

A novel independence intervention to treat child anxiety: A nonconcurrent multiple baseline evaluation

Rates of child and adolescent anxiety have increased markedly over the past decade (Haidt & Twenge, 2023). Exposure-based cognitive-behavioral therapy is the gold standard in the treatment of anxious children (Hofmann et al. (2012)). However, many clinicians refrain from using exposure due to concerns about its safety, effectiveness, and ethics (Deacon et al., 2013; Whiteside et al., 2016). We propose a novel treatment approach for child anxiety composed of independence activities (IAs), which are child-directed, fun, unstructured, developmentally challenging tasks performed without parents’ help. These tasks are purposely topographically unrelated to the stimuli that cause anxiety, in direct contrast to exposure therapy. Despite this dissimilarity, IAs target putative mechanisms involved in the development and maintenance of child anxiety (e.g., parental accommodation and overinvolvement, child avoidance, unhelpful thinking styles). Using a nonconcurrent multiple baseline design, this five-session treatment provided preliminary evidence of high treatment acceptability from children and parents. Medium to large improvements were reported in child anxiety and avoidance, parent and child (behavioral and cognitive) mechanisms involved in the maintenance of child anxiety, and untargeted secondary outcomes such as child happiness. Results may suggest a new treatment paradigm, which is desperately needed, given unabated increases in child and adolescent anxiety despite vast resources being directed toward the problem.

Photophobia and Visual Triggers in Vestibular Migraine.

Vestibular migraine (VM) is a prevalent vestibular disorder characterized by episodic vertigo. However, the relationship between photophobia and visual triggers in VM remains unexplored. We investigated the correlation of photophobia during the VM attack with interictal photosensitivity and visually triggering dizziness in patients with VM. We enrolled patients diagnosed with VM, with or without photophobia, across seven specialized vertigo and headache clinics in China. Healthy individuals were also included as a control group. Using a cross-sectional survey design, we collected data related to light intensity and dizziness frequency triggered by flicker, glare, and eyestrain using the Headache Triggers Sensitivity and Avoidance Questionnaire. A total of 366 patients were recruited. The photosensitivity and frequency of dizziness induced by flicker, glare, and eyestrain observed in patients with VM and photophobia were significantly elevated compared with those in patients without photophobia and control participants (P < 0.001). A significant positive correlation was observed between photosensitivity levels and dizziness frequency triggered by flicker, glare, and eyestrain in patients with VM and photophobia (P < 0.001). This study unequivocally established a positive association of ictal photophobia with interictal photosensitivity and visually triggering dizziness, strongly advocating the need for further research on exposure-based therapies for managing VM. ClinicalTrial.gov Identifier, NCT04939922, retrospectively registered, 14th June 2021.

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.

To SHARE or not to SHARE: Exploring incarcerated women's decisions about enrolling in exposure-based group therapy.

Exposure therapies effectively treat traumatic stress sequelae, including that which follows sexual violence victimization (SVV). Carceral facilities house women with significantly higher rates of SVV than community samples, yet they rarely implement this form of treatment. In this study, women with histories of SVV (n = 63) completed semistructured qualitative interviews about their decision to enroll or not enroll in an exposure-based group therapy called Survivors Healing from Abuse: Recovery through Exposure while incarcerated. All study participants were previously incarcerated in a prison, where they were offered the opportunity to enroll in Survivors Healing from Abuse: Recovery through Exposure. We used the theory of planned behavior to analyze factors that affected enrollment decisions. Results revealed that enrollment decisions among incarcerated women can be categorized within the theory of planned behavior framework. Interview responses indicated that recognizing current problems as related to experiences of SVV, holding positive attitudes about mental health treatment, observing peers engaging in help-seeking behaviors, and perceiving treatment as accessible were linked with enrollment. Negative perceptions of treatment, fear of judgment, and negative peer influence (e.g., distrust of peers) were linked to decisions not to enroll. While certain beliefs were influenced by contextual features of incarceration (e.g., peer interactions outside of group therapy), many overlapped with factors found to influence help-seeking among nonincarcerated populations. Findings have implications for how to engage members of underserved populations in resource-deprived contexts who have a great need for treatment of traumatic symptoms secondary to sexual violence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The influence of pretreatment respiratory sinus arrhythmia dimensions on trauma-focused cognitive behavioral therapy outcomes: Findings from a randomized controlled feasibility trial.

Child maltreatment is associated with respiratory sinus arrhythmia (RSA) dysregulation, a physiological indicator of emotion regulation that predicts elevated posttraumatic stress disorder (PTSD) symptoms and may be a mechanism of action for exposure-based therapies, such as trauma-focused cognitive behavioral therapy (TF-CBT). Animal-assisted therapy (AAT) has been proposed as an adjunct to TF-CBT for improving emotion regulation following maltreatment. The current study reports findings from a randomized controlled feasibility trial (N = 33; Mage = 11.79 years, SD = 3.08; 63.6% White; 66.7% female) that measured youths' resting RSA, RSA reactivity, and RSA recovery in response to a pretreatment laboratory challenge. We tested whether (a) lower pretreatment resting RSA was associated with blunted RSA during the challenge; (b) either of the pretreatment RSA dimensions predicted more severe pretreatment PTSD symptoms; and (c) either of the pretreatment RSA dimensions predicted less severe posttreatment PTSD symptoms and, as an exploratory aim, whether this was moderated by treatment group (i.e., TF-CBT vs. TF-CBT + AAT). Results from multiple linear regression indicated that, after controlling for pretreatment symptom severity, there was a large effect size for higher resting RSA predicting less severe caregiver-reported posttreatment PTSD symptoms, β = -.52, p =.058, and higher RSA during recovery predicting less severe child-reported posttreatment PTSD symptoms, β = -.70, p =.056, although these findings were not significant. These preliminary results offer important insights for future studies to investigate how the ability to regulate RSA informs which children need additional support to benefit from psychotherapeutic treatment.

The effect of social anxiety on threat acquisition and extinction: a systematic review and meta-analysis.

Although exposure-based therapy has been found to be effective at alleviating symptoms of social anxiety disorder, it often does not lead to full remission, and relapse after treatment is common. Exposure therapy is based on theoretical principles of extinction of conditioned fear responses. However, there are inconsistencies in findings across experiments that have investigated the effect of social anxiety on threat conditioning and extinction processes. This systematic review and meta-analysis aimed to examine whether elevated levels of social anxiety are associated with abnormalities in threat conditioning and extinction processes. A second aim was to examine the sensitivity of various study designs and characteristics to detect social anxiety-related differences in threat conditioning and extinction. A systematic search was conducted, which identified twenty-three experiments for inclusion in the review. The findings did not demonstrate compelling evidence that high levels of social anxiety are associated with atypical threat conditioning or extinction. Further, when systematically examining the data, there was no convincing support that the use of a particular psychophysiological measure, subjective rating, or experimental parameter yields more consistent associations between social anxiety and conditioning processes during threat acquisition or extinction. Meta-analyses demonstrated that during threat extinction, the use of anxiety ratings as a dependent variable, socially relevant unconditioned stimuli, and a higher reinforcement schedule produced more detectable effects of social anxiety on compromised extinction processes compared to any other dependent variable (subjective or physiological) or experimental parameter. Overall, the results of this study suggest that social anxiety is not reliably related to deficits in conditioning and extinction processes in the context of laboratory-based Pavlovian conditioning paradigms.

Virtual realities, real recoveries: exploring the efficacy of 3MDR therapy for treatment-resistant PTSD.

Exposure-based therapies have shown promise in treating post-traumatic stress disorder (PTSD), but challenges exist in maintaining patient engagement and finding appropriate stimuli for graded exposure. Virtual reality (VR) technology has been used to enhance exposure therapy, but current software lacks customization and some patients remain treatment-resistant. A novel approach called multimodular motion-assisted memory desensitization and reconsolidation (3MDR) has the potential to solve some of the current limitations of VR-assisted exposure therapy. This study examines the efficacy of 3MDR treatment for individuals with treatment-resistant PTSD through a systematic review of relevant literature and clinical studies. Preliminary findings indicate promise for 3MDR in reducing PTSD symptoms, including emotional regulation and moral injury. However, further research with larger samples and controlled studies is needed to understand underlying mechanisms and validate these results. Moreover, this study highlights the importance of health-economic evaluations to assess costs and resource utilization associated with implementing 3MDR treatment in clinical services.

Shared and distinct effect mediators in exposure-based and traditional cognitive behavior therapy for fibromyalgia: Secondary analysis of a randomized controlled trial

Fibromyalgia is a chronic pain condition associated with substantial suffering and societal costs. Traditional cognitive behavior therapy (T-CBT) is the most evaluated psychological treatment, but exposure therapy (Exp-CBT) has shown promise with a pronounced focus on the reduction of pain-related avoidance behaviors. In a recent randomized controlled trial (N = 274), we found that Exp-CBT was not superior to T-CBT (d = −0.10) in reducing overall fibromyalgia severity. This study investigated pain-related avoidance behaviors, pain catastrophizing, hypervigilance, pacing, overdoing and physical activity as potential mediators of the treatment effect. Mediation analyses were based on parallel process growth models fitted on 11 weekly measurement points, and week-by-week time-lagged effects were tested using random intercepts cross-lagged panel models. Results indicated that a reduction in avoidance behaviors, pain catastrophizing, and hypervigilance were significant mediators of change in both treatments. An increase in pacing and a reduction in overdoing were significant mediators in T-CBT only. Physical activity was not a mediator. In the time-lagged analyses, an unequivocal effect on subsequent fibromyalgia severity was seen of avoidance and catastrophizing in Exp-CBT, and of overdoing in T-CBT. Exposure-based and traditional CBT for fibromyalgia appear to share common treatment mediators, namely pain-related avoidance behavior, catastrophizing and hypervigilance.

Parietal-Frontal Pathway Controls Relapse of Fear Memory in a Novel Context

BackgroundFear responses significantly affect daily life and shape our approach to uncertainty. However, the potential resurgence of fear in unfamiliar situations poses a significant challenge to exposure-based therapies for maladaptive fear responses. Nonetheless, how novel contextual stimuli are associated with the relapse of extinguished fear remains unknown. MethodsUsing a context-dependent fear renewal model, the functional circuits and underlying mechanisms of the posterior parietal cortex (PPC) and anterior cingulate cortex (ACC) were investigated using optogenetic, histological, in vivo, and ex vivo electrophysiological and pharmacological techniques. ResultsWe demonstrated that the PPC-to-ACC pathway governs fear relapse in a novel context. We observed enhanced populational calcium activity in the ACC neurons that received projections from the PPC and increased synaptic activity in the basolateral amygdala–projecting PPC-to-ACC neurons upon renewal in a novel context, where excitatory postsynaptic currents amplitudes increased but inhibitory postsynaptic current amplitudes decreased. In addition, we found that parvalbumin–expressing interneurons controlled novel context-dependent fear renewal, which was blocked by the chronic administration of fluoxetine. ConclusionsOur findings highlight the PPC-to-ACC pathway in mediating the relapse of extinguished fear in novel contexts, thereby contributing significant insights into the intricate neural mechanisms that govern fear renewal.

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.

Transcranial focused ultrasound stimulation in the infralimbic cortex facilitates extinction of conditioned fear in rats

Transcranial focused ultrasound (tFUS) neuromodulation emerges as a promising non-invasive approach for improving neurological conditions. Extinction of conditioned fear has served as a prime model for exposure-based therapies for anxiety disorders. We investigated whether tFUS stimulation to a critical brain area, the infralimbic subdivision of the prefrontal cortex (IL), could facilitate fear extinction using rats. In a series of experiments, tFUS was delivered to the IL of a freely-moving rat and compared to sham stimulation (tFUS vs. SHAM). Initially, Fos expression in the IL was measured shortly after the stimulation. The results show that Fos expression was significantly increased in the IL but not in the neighboring regions compared to SHAM. Subsequently, two groups of rats were subjected to fear conditioning, extinction, and retention while receiving stimulation during the extinction. Rats in the tFUS group froze significantly less than SHAM during both extinction and retention tests. Importantly, the reduced freezing in the tFUS group was not attributable to non-specific effect such as auditory noise, as both groups demonstrated a similar level of locomotive activity in an open field regardless of the stimulation condition. Finally, we replicated the procedure with a shortened conditioning-to-extinction interval (15 min) to induce immediate extinction deficit. The tFUS group showed a facilitated reduction in freezing during the extinction, which persisted in the subsequent retention session compared to SHAM. In summary, the current findings suggest that tFUS stimulation in the IL facilitates fear extinction, offering a potential therapeutic regimen for fear-related psychiatric disorders.

Neural circuits for the adaptive regulation of fear and extinction memory.

The regulation of fear memories is critical for adaptive behaviors and dysregulation of these processes is implicated in trauma- and stress-related disorders. Treatments for these disorders include pharmacological interventions as well as exposure-based therapies, which rely upon extinction learning. Considerable attention has been directed toward elucidating the neural mechanisms underlying fear and extinction learning. In this review, we will discuss historic discoveries and emerging evidence on the neural mechanisms of the adaptive regulation of fear and extinction memories. We will focus on neural circuits regulating the acquisition and extinction of Pavlovian fear conditioning in rodent models, particularly the role of the medial prefrontal cortex and hippocampus in the contextual control of extinguished fear memories. We will also consider new work revealing an important role for the thalamic nucleus reuniens in the modulation of prefrontal-hippocampal interactions in extinction learning and memory. Finally, we will explore the effects of stress on this circuit and the clinical implications of these findings.