Fear Conditioning Interventions for PTSD
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen byMohammed Milad, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: The University of Texas Health Science Center, Houston
Must not be taking: Neuroleptics
Disqualifiers: Neurologic disease, Suicidal ideation, Seizure, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The purpose of this research study is to study how the brain learns to avoid certain stimuli or situations using an experimental paradigm. The big goal is to measure brain responses and subject's feelings and expectations when they are learning to actively avoid experimental stimuli, and how fear extinction learning and monetary cost can change how and when subjects are to avoid.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are using neuroleptics, you must not have taken them within one year prior to the study.
What data supports the effectiveness of the treatment Avoidance conditioning, Fear Conditioning, and related therapies for PTSD?
Research shows that fear conditioning and extinction-based therapies, like exposure therapy, can reduce fear symptoms in PTSD patients, although some may experience a return of fear. Combining these therapies with approach-avoidance training may further reduce fear and prevent its return.
12345Is fear conditioning therapy safe for humans?
The research does not provide specific safety data for fear conditioning therapy, but it is commonly used in exposure therapy for anxiety and PTSD, suggesting it is generally considered safe in clinical settings.
13678How does the fear conditioning treatment for PTSD differ from other treatments?
Fear conditioning treatment for PTSD is unique because it focuses on understanding and modifying the fear learning processes, such as fear extinction and inhibition, which are often impaired in PTSD. This approach uses experimental paradigms to study and potentially improve the way individuals with PTSD respond to fear-related cues, offering a novel method compared to traditional therapies that may not specifically target these underlying fear mechanisms.
19101112Eligibility Criteria
This trial is for adults aged 18-70 with current PTSD, diagnosed through specific assessments (CAPS and SCID). It's also open to trauma-exposed healthy controls without any history of psychiatric disorders or PTSD. Participants must be willing to undergo experiments involving avoidance of stimuli.Inclusion Criteria
I have been diagnosed with PTSD as my primary condition.
I am either female or male.
I am between 18 and 70 years old.
+3 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Baseline Assessment
Initial assessment visit to establish baseline measures before experimental visits
1 day
1 visit (in-person)
Experimental Visits
Participants undergo an emotional learning paradigm and fMRI scan over two consecutive days
2 days
2 visits (in-person)
Follow-up
Participants are monitored for any delayed responses or effects post-experiment
4 weeks
Participant Groups
The study tests how people with PTSD learn to avoid things that scare them. It involves measuring brain responses and feelings during tasks like paying to avoid shocks, learning about fear, avoiding conditioned stimuli, and overcoming learned fears.
1Treatment groups
Experimental Treatment
Group I: Emotional learning paradigmExperimental Treatment4 Interventions
After the initial screening / baseline assessment visit, participants will undergo two Experimental Visits, which include participation in an emotional learning paradigm and an fMRI scan over the course of two consecutive days. Participants will be asked to look at pictures on a computer screen to measure physiological response physiological response (skin conductance response) and brain responses using a functional Magnetic Resonance Imaging (fMRI) machine. These two visits will be scheduled within a month from the baseline assessment visit.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UTHealth HoustonHouston, TX
NYU Langone HealthNew York, NY
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Who Is Running the Clinical Trial?
The University of Texas Health Science Center, HoustonLead Sponsor
NYU Langone HealthLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
The clinical applications and practical relevance of human conditioning paradigms for posttraumatic stress disorder. [2019]The classical conditioning paradigm of fear learning has spawned a number of experimental variations for the explanation of posttraumatic stress disorder (PTSD) etiology. These paradigms include extinction learning and recall, fear inhibition, fear generalization, and conditioned avoidance. As such, each of these paradigms have significant applications for understanding the development, maintenance, treatment, and relapse of the fear-related features of PTSD. In the present review, we describe each of these conditioning-based paradigms with reference to the clinical applications, and supported by case examples from patients with severe PTSD symptoms. We also review the neurobiological models of conditioning and extinction in animals, psychiatrically healthy humans, and PTSD patients, and discuss the current balance of evidence suggesting a number of biological, behavioral, and cognitive mechanisms/moderators of the conditioning and extinction process in experimental and clinical contexts.
The associations between posttraumatic stress disorder and delay discounting, future orientation, and reward availability: A behavioral economic model. [2022]The theoretical framework of behavioral economics, a metatheory that integrates operant learning and economic theory, has only recently been applied to posttraumatic stress disorder (PTSD). A behavioral economic theory of PTSD reflects an expansion of prior behavioral conceptualization of PTSD, which described PTSD in terms of respondent and operant conditioning. In the behavioral economic framework of PTSD, negatively reinforced avoidance behavior is overvalued, in part due to deficits in environmental reward, and may be conceptualized as a form of reinforcer pathology (i.e., excessive preference for and valuation of an immediate reinforcer). We investigated cross-sectional relationships between PTSD severity and several constructs rooted in this behavioral economic framework, including future orientation, reward availability, and delay discounting in a sample of 110 military personnel/veterans (87.2% male) who had served combat deployments following September 11, 2001. Total PTSD severity was inversely related to environmental reward availability, β = -.49, ΔR2 = 0.24, p < .001; hedonic reward availability, β = -.32, ΔR2 = 0.10, p = .001; and future orientation, β = -.20, ΔR2 = 0.04, p = .032, but not delay discounting, r = -.05, p = .633. An examination of individual symptom clusters did not suggest that avoidance symptoms were uniquely associated with these behavioral economic constructs. The findings offer support for a behavioral economic model of PTSD in which there is a lack of positive reinforcement as well as a myopic focus on the present.
Effects of Approach-Avoidance Training on the Extinction and Return of Fear Responses. [2018]Exposure therapy for anxiety involves confronting a patient with fear-evoking stimuli, a procedure based partially on Pavlovian extinction. Exposure and other extinction-based therapies usually lead to (partial) reduction of fear symptoms, but a substantial number of patients experience a return of fear after treatment. Here we tested whether the combination of fear extinction with modification of approach-avoidance tendencies using an Approach-Avoidance Task (AAT) would result in the further reduction of conditioned fear and/or help prevent return of fear after extinction.
An Innovative Framework for Delivering Psychotherapy to Patients With Treatment-Resistant Posttraumatic Stress Disorder: Rationale for Interactive Motion-Assisted Therapy. [2020]Despite an array of evidence-based psychological treatments for patients with a posttraumatic stress disorder (PTSD), a majority of patients do not fully benefit from the potential of these therapies. In veterans with PTSD, up to two-thirds retain their diagnosis after psychotherapy and often their disorder is treatment-resistant, which calls for improvement of therapeutic approaches for this population. One of the factors hypothesized to underlie low response in PTSD treatment is high behavioral and cognitive avoidance to traumatic reminders. In the current paper we explore if a combination of personalized virtual reality, multi-sensory input, and walking during exposure can enhance treatment engagement, overcome avoidance, and thereby optimize treatment effectiveness. Virtual reality holds potential to increase presence and in-session attention and to facilitate memory retrieval. Multi-sensory input such as pictures and music can personalize this experience. Evidence for the positive effect of physical activity on fear extinction and associative thinking, as well as embodied cognition theories, provide a rationale for decreased avoidance by literally approaching cues of the traumatic memories. A dual-attention task further facilitates new learning and reconsolidation. These strategies have been combined in an innovative framework for trauma-focused psychotherapy, named Multi-modular Motion-assisted Memory Desensitization and Reconsolidation (3MDR). In this innovative treatment the therapeutic setting is changed from the face-to-face sedentary position to a side-by-side activating context in which patients walk toward trauma-related images in a virtual environment. The framework of 3MDR has been designed as a boost for patients with treatment-resistant PTSD, which is illustrated by three case examples. The intervention is discussed in context of other advancements in treatment for treatment-resistant PTSD. Novel elements of this approach are activation, personalization and empowerment. While developed for veterans with PTSD who do not optimally respond to standardized treatments, this innovative framework holds potential to also be used for other patient populations and earlier stages of treatment for patients with PTSD.
Weaker situations: Uncertainty reveals individual differences in learning: Implications for PTSD. [2023]Few individuals who experience trauma develop posttraumatic stress disorder (PTSD). Therefore, the identification of individual differences that signal increased risk for PTSD is important. Lissek et al. (2006) proposed using a weak rather than a strong situation to identify individual differences. A weak situation involves less-salient cues as well as some degree of uncertainty, which reveal individual differences. A strong situation involves salient cues with little uncertainty, which produce consistently strong responses. Results from fear conditioning studies that support this hypothesis are discussed briefly. This review focuses on recent findings from three learning tasks: classical eyeblink conditioning, avoidance learning, and a computer-based task. These tasks are interpreted as weaker learning situations in that they involve some degree of uncertainty. Individual differences in learning based on behavioral inhibition, which is a risk factor for PTSD, are explored. Specifically, behaviorally inhibited individuals and rodents (i.e., Wistar Kyoto rats), as well as individuals expressing PTSD symptoms, exhibit enhanced eyeblink conditioning. Behaviorally inhibited rodents also demonstrate enhanced avoidance responding (i.e., lever pressing). Both enhanced eyeblink conditioning and avoidance are most evident with schedules of partial reinforcement. Behaviorally inhibited individuals also performed better on reward and punishment trials than noninhibited controls in a probabilistic category learning task. Overall, the use of weaker situations with uncertain relationships may be more ecologically valid than learning tasks in which the aversive event occurs on every trial and may provide more sensitivity for identifying individual differences in learning for those at risk for, or expressing, PTSD symptoms.
Avoidance learning as predictor of posttraumatic stress in firefighters. [2021]Avoidance is a well-established maintenance factor in anxiety-related psychopathology. Individuals prone to anxiety show more maladaptive avoidance responses in conditioning paradigms aimed at avoidance learning, which indicates impairments in safety learning. To what extent avoidance learning is associated with posttraumatic stress disorder (PTSD) is still unclear, despite the logical relevance to the symptomatology. In this prospective study, we investigate avoidance learning responses in first responders, a population at high risk for traumatic exposure and thus PTSD development, and studied whether avoidance learning was associated with concurrent and future PTSD symptoms.
Avoidance learning, Pavlovian conditioning, and the development of phobias. [2019]This paper examines the role of Pavlovian conditioning in the acquisition, maintenance and elimination of human phobias. Because many conceptualizations of human fears and phobias are based on data from studies of avoidance learning in animals, we first review theories of avoidance. Our conclusion is that none of the extant theories provides an adequate account of avoidance learning, and we propose a model of avoidance that involves Pavlovian, but not instrumental learning. We then analyse critically arguments that Pavlovian conditioning plays only a small role in the aetiology of fears. Finally, the paper examines the implications of a conditioning model of avoidance for the study of human fears and phobias.
Using acceptance and commitment therapy techniques to enhance treatment engagement in veterans with posttraumatic stress disorder. [2021]Evidence-based treatments for posttraumatic stress disorder (PTSD) are available for veterans, but many do not benefit due to low treatment engagement. This may be partially due to avoidance behaviors characteristic of individuals with PTSD. Acceptance and Commitment Therapy (ACT) is a transdiagnostic treatment approach that aims to reduce avoidance. The authors propose the use of adjunctive ACT techniques to enhance engagement with treatment for PTSD. ACT techniques such as cognitive defusion and values clarification have been shown to promote engagement with other cognitive-behavioral treatments, but no studies to date have examined these techniques as adjuncts to treatment for PTSD. Because of its focus on reducing avoidance, ACT is uniquely suited for promoting treatment engagement with the "gold standard" treatments for PTSD. The authors review the existing research on ACT as an adjunctive intervention, discuss specific concepts and techniques from ACT that are relevant to PTSD, and provide recommendations for future research.
Conditioned fear associated phenotypes as robust, translational indices of trauma-, stressor-, and anxiety-related behaviors. [2021]Post-traumatic stress disorder (PTSD) is a heterogeneous disorder that affects individuals exposed to trauma (e.g., combat, interpersonal violence, and natural disasters). It is characterized by hyperarousal, intrusive reminders of the trauma, avoidance of trauma-related cues, and negative cognition and mood. This heterogeneity indicates the presence of multiple neurobiological mechanisms underlying the development and maintenance of PTSD. Fear conditioning is a robust, translational experimental paradigm that can be employed to elucidate these mechanisms by allowing for the study of fear-related dimensions of PTSD (e.g., fear extinction, fear inhibition, and generalization of fear) across multiple units of analysis. Fear conditioning experiments have identified varying trajectories of the dimensions described, highlighting exciting new avenues of targeted, focused study. Additionally, fear conditioning studies provide a translational platform to develop novel interventions. The current review highlights the versatility of fear conditioning paradigms, the implications for pharmacological and non-pharmacological treatments, the robustness of these paradigms to span an array of neuroscientific measures (e.g., genetic studies), and finally the need to understand the boundary conditions under which these paradigms are effective. Further understanding these paradigms will ultimately allow for optimization of fear conditioning paradigms, a necessary step towards the advancement of PTSD treatment methods.
Behavioral and neural mechanisms of latent inhibition. [2023]Fear is an adaptive emotion that serves to protect an organism against potential dangers. It is often studied using classical conditioning paradigms where a conditioned stimulus is paired with an aversive unconditioned stimulus to induce a threat response. Less commonly studied is a phenomenon that is related to this form of conditioning, known as latent inhibition. Latent inhibition (LI) is a paradigm in which a neutral cue is repeatedly presented in the absence of any aversive associations. Subsequent pairing of this pre-exposed cue with an aversive stimulus typically leads to reduced expression of a conditioned fear/threat response. In this article, we review some of the theoretical basis for LI and its behavioral and neural mechanisms. We compare and contrast LI and fear/threat extinction-a process in which a previously conditioned cue is repeatedly presented in the absence of aversive outcomes. We end with highlighting the potential clinical utility of LI. Particularly, we focus on how LI application could be useful for enhancing resilience, especially for individuals who are more prone to continuous exposure to trauma and stressful environments, such as healthcare workers and first responders. The knowledge to be gained from advancing our understanding of neural mechanisms in latent inhibition could be applicable across psychiatric disorders characterized by exaggerated fear responses and impaired emotion regulation.
Value estimation and latent-state update-related neural activity during fear conditioning predict posttraumatic stress disorder symptom severity. [2023]Learning theories of posttraumatic stress disorder (PTSD) purport that fear-learning processes, such as those that support fear acquisition and extinction, are impaired. Computational models designed to capture specific processes involved in fear learning have primarily assessed model-free, or trial-and-error, reinforcement learning (RL). Although previous studies indicated that aspects of model-free RL are disrupted among individuals with PTSD, research has yet to identify whether model-based RL, which is inferential and contextually driven, is impaired. Given empirical evidence of aberrant contextual modulation of fear in PTSD, the present study sought to identify whether model-based RL processes are altered during fear conditioning among women with interpersonal violence (IPV)-related PTSD (n = 85) using computational modeling. Model-free, hybrid, and model-based RL models were applied to skin conductance responses (SCR) collected during fear acquisition and extinction, and the model-based RL model was found to provide the best fit to the SCR data. Parameters from the model-based RL model were carried forward to neuroimaging analyses (voxel-wise and independent component analysis). Results revealed that reduced activity within visual processing regions during model-based updating uniquely predicted higher PTSD symptoms. Additionally, after controlling for model-based updating, greater value estimation encoding within the left frontoparietal network during fear acquisition and reduced value estimation encoding within the dorsomedial prefrontal cortex during fear extinction predicted greater PTSD symptoms. Results provide evidence of disrupted RL processes in women with assault-related PTSD, which may contribute to impaired fear and safety learning, and, furthermore, may relate to treatment response (e.g., poorer response to exposure therapy).
Extinction learning before trauma and subsequent posttraumatic stress. [2022]Fear conditioning theories propose that persistent stress reactions may occur as a result of impaired extinction learning, and a poor capacity for extinction learning may predispose some individuals to posttraumatic stress disorder development. This study indexed the extent to which deficits in extinction learning before trauma exposure are a risk factor for persistent posttraumatic stress after trauma exposure.