2010 — 2012 |
Dunsmoor, Joseph Edward |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Brain Mechanisms Supporting the Generalization of Learned Fear
DESCRIPTION (provided by applicant): A primary goal in conditioned learning research is to understand the principles underlying how organisms acquire and express learned behaviors. Pavlovian fear conditioning, for instance, has served as a model system for the study of how humans learn to fear otherwise innocuous stimuli through the process of contingency learning between a neutral cue and a biologically aversive stimulus. Significant progress has been made in unraveling the neurobiological basis of fear learning, and recent advances in cognitive neuroscience have informed behavioral treatments for clinical anxiety disorders ranging from specific phobias to posttraumatic stress disorder. The Specific Aims within this proposal are designed to extend knowledge of the behavioral and brain mechanisms involved in human fear learning by directly investigating processes supporting the generalization of learned fears. These investigations will explore how humans generalize to neutral objects that approximate a feared stimulus using psychophysiology and functional magnetic resonance imaging (fMRI) methods. We will uncover the biobehavioral and brain mechanisms involved in generalizing fear in the attempt to better characterize clinical disorders marked by exaggerated fear responses to neutral cues. In these studies, participants will learn that a particular object is fear relevant using Pavlovian fear conditioning methods. Subsequently, participants will be exposed to a range of objects that deviate from the fear conditioned object along a dimension of perceptual similarity (Aim 1) or semantic relatedness (Aim 2 and Aim 3). Individual differences in fear generalization will be assessed by constraining our interpretations of brain activity with behavioral psychophysiology measures. Furthermore, a primary goal in all three Aims is to investigate not only how humans generalize fear, but also learn to control fear responses to objects that are perceptually or conceptually related to a feared stimulus. PUBLIC HEALTH RELEVANCE: The proposed research contributes to a greater understanding of mental health disorders marked by heightened expression of fear. These neuroimaging investigations attempt to uncover the brain mechanisms supporting the generalization of fear from a known fear-relevant stimulus to emotionally neutral stimuli that approximate the feared stimulus, either perceptually or semantically. A greater recognition of how generalization modulates the cognitive processes involved in fear expression will strengthen understanding of certain mental health disorders (e.g. specific phobias and posttraumatic stress disorder) and may lead to model systems important for the treatment and prevention of these disorders.
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1 |
2015 — 2019 |
Dunsmoor, Joseph Edward |
K99Activity Code Description: To support the initial phase of a Career/Research Transition award program that provides 1-2 years of mentored support for highly motivated, advanced postdoctoral research scientists. R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Improving the Control of Fear: Healthy Adults to Pathological Anxiety
? DESCRIPTION (provided by applicant): The objective of this Pathway to Independence Award is to support new mentored training in the control of fear and clinical research, as the candidate transitions from a postdoc position to an independent research career specializing in translation of new experimental techniques to improve the control of fear from healthy adults to anxiety pathologies. Anxiety pathologies are the most common mental illness, with a 12-month prevalence estimate of about 40 million American adults. Theoretical and technical aspects of fear conditioning continue to provide a valuable model to characterize and understand the etiology, maintenance, and treatment for pathologies of fear and anxiety. An example in the treatment domain is exposure therapy, which is based on the principles of extinction. However, prominent learning theory models have long recognized the shortcomings of extinction as a therapeutic tool; extinction is a fragile form of learning that fails to generalize, and fear behavors tend to return over time. Clinical research in the past two decades has revealed serious deficits in the ability to control fear expression following extinction across anxiety disorder categories, including posttraumatic stress disorder, panic disorder, and phobias. Laboratory research on the limits to extinction can describe why many severe fears and anxieties relapse following clinical treatment. Accordingly, there is strong motivation to develop innovative behavioral techniques to improve the control of fear so that maladaptive fears and anxieties are more responsive to treatment and less prone to relapse. Yet, systematic neurobehavioral research on novel techniques to improve the control of fear in humans has received limited attention. During the mentored phase of this proposal, the candidate will incorporate new training on theoretical, technical, and empirical aspects of fear extinction to test new behavioral techniques to improve the control of fear in healthy adults using combination functional magnetic resonance imaging and psychophysiology methods. Aim 1 looks to override maladaptive threat associations by introducing surprising, novel, non-threat associations to the participant. Aim 2 looks to promote the generalizability of extinction learning by conducting extinction under multiple different virtul reality contexts. The R00 project will carry forward this knowledge to investigate these two new experimental tasks in clinical anxiety populations characterized by the inability to control fear expression following standard extinction procedures. Research in clinical populations will be fostered by new supervised training in clinical research developed during the mentored phase. The research proposed here has the potential to advance biological models of psychopathology, establish neurobehavioral risk/resilience factors for disorders of fear and anxiety, and ultimately contribute to innovative and more effective therapeutic interventions for pathological anxiety. This Pathway to Independence Award lays the groundwork for the candidate to achieve these research and training goals, and to develop interdisciplinary collaborations with clinical research experts at an early stage of his career.
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0.97 |
2018 |
Dunsmoor, Joseph Edward |
R00Activity Code Description: To support the second phase of a Career/Research Transition award program that provides 1 -3 years of independent research support (R00) contingent on securing an independent research position. Award recipients will be expected to compete successfully for independent R01 support from the NIH during the R00 research transition award period. |
Supplement to: Improving the Control of Fear: Healthy Adults to Pathological Anxiety @ University of Texas, Austin
Abstract attachment not required for PA-16-288.
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0.97 |
2021 |
Dunsmoor, Joseph Edward |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Localizing and Modulating Competing Memories of Fear and Safety in the Human Brain @ University of Texas, Austin
PROJECT SUMMARY. Pathologies characterized by excessive fear and anxiety are the most common mental illness with a 12-month prevalence estimate of about 40 million American adults. The primary treatment for anxiety and stress-related disorders is exposure therapy, which is informed by theoretical and technical aspects of Pavlovian extinction. However, extinguished behaviors are prone to relapse under a variety of circumstances. Further, clinical research reveals serious deficits across a host of psychiatric conditions in the ability to form and retrieve extinction memories, which likely contributes to relapse following extinction-based therapies. Accordingly, there is strong motivation to better understand how extinction memories are encoded, stored, and expressed so as to bolster the strength and generalization of clinical treatment. Pioneering research in rodents reveals that fear conditioning and extinction generate separate and measurable memory traces within and across discrete brain regions. Whether such an organization exists in the human brain is unknown. More precise knowledge on how threat and safety memories are represented and interact in the human brain will advance innovative treatments for pathological anxiety that are built on the neuroscience of learning and memory. The goal of this research is to better understand how competing memories of fear and safety are formed, stored, and retrieved in the human brain. To build directly on mechanistic insights from animal models, we utilize Pavlovian fear conditioning and extinction in adult humans during functional magnetic resonance imaging (fMRI). The research leverages advances in multivariate pattern analysis techniques, and integrates theoretical and technical advancements of fear extinction research from animal models with computational approaches developed to study human memory. Each study includes healthy adults and individuals with posttraumatic stress disorder (PTSD), as linking advances in fear extinction research to the pathophysiology of PTSD can have direct benefit to exposure therapy?the gold-standard treatment based on the principles of extinction. We also evaluate extinction memory at 24-hours and again at 1 month. Assessing long-term extinction retrieval in humans is extremely rare, but consistent with diagnostic criteria for assessing PTSD, and thus furthers the bridge to translational relevance. Aim 1 attempts to identify separate and stable memory traces of fear and extinction in by identifying the correspondence (overlap) between neural activity related to the formation and retrieval of fear and extinction over time. Aim 2 decodes a multivariate neural signature selective to the contextual encoding of extinction memories. Aim 3 uses a non-pharmacological behavioral strategy to modulate the strength of extinction to determine how enhanced fear extinction affects multivariate neural signature of extinction memory retrieval over time. These findings have the potential to establish new risk and resilience factors for anxiety and stress-related pathologies, and may ultimately contribute to innovative neuroscience-based treatments for psychiatric conditions marked by excessive fear and the inability to regulate unwanted emotional responses.
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0.97 |