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.

Public Health Relevance

This proposal examines neurobehavioral mechanisms associated with newly developed behavioral techniques that improve the control of conditioned fear in healthy adults, using combined neuroimaging, psychophysiology, and virtual reality. This research will be carried forward to clinical populations to determine whether innovative strategies to improve the control of fear extend to individuals characterized by the inability to regulate fear and anxiety. The goal of these projects is to advance knowledge on behavioral techniques to improve the control of fear, identify biobehavioral risk/resilience factors in the control of fear, and ultimately contribute to innovative therapeutic interventions developed within a biologically-valid framework.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Career Transition Award (K99)
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Special Emphasis Panel (ZMH1-ERB-S (01))
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Desmond, Nancy L
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New York University
Schools of Arts and Sciences
New York
United States
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Dunsmoor, Joseph E; Niv, Yael; Daw, Nathaniel et al. (2015) Rethinking Extinction. Neuron 88:47-63
Coelho, Cesar A O; Dunsmoor, Joseph E; Phelps, Elizabeth A (2015) Compound stimulus extinction reduces spontaneous recovery in humans. Learn Mem 22:589-93