The prevalence of anxiety disorders is estimated to be up to 18% of the US adult population. A primary treatment for anxiety disorders is exposure therapy, which is based on the principles of fear extinction. Although extinction based therapies can be effective, their efficacy is limited, in part due to the nature of extinction learning itsel. There is abundant evidence that extinction learning does not result in a significant alteration of the original fear memory, but rather results in new learning that the previously feared event is now safe. One consequence is that the original fear memory and the extinction memory may compete for expression. A range of circumstances, such as the passage of time (spontaneous recovery), alterations in context (renewal), and stress (reinstatement), can result in the fear returning. This potential for fear memory recovery even after extensive extinction training highlights the need to discover more persistent and robust techniques to diminish fear. Using simple classical fear conditioning paradigms, research in non-human animals has identified two potential mechanisms to prevent the return of fear. The first is by manipulating the reconsolidation or re-storage of the original fear memory. The second is by allowing the animal experience with control over the stressor, which has been shown to have lasting effects on reducing the likelihood of fear recovery. The goal of the proposed research is to assess in humans the efficacy, specificity, and underlying neural mechanisms of techniques that have been shown to prevent the return of fear in non- human animals. Studies under Aim 1 examine techniques to disrupt or alter the reconsolidation of conditioned fear in humans. Specifically, the pharmacological disruption of reconsolidation is explored and the specificity and the psychological and neural consequences of behavioral interference techniques used to alter the reconsolidation of conditioned fear are examined.
Aim 2 examines whether experience with control over a stressor can diminish the likelihood that a fear memory returns. Finally, the studies under Aim 3 examine the success of these techniques in patients who suffer from PTSD to determine if the neural consequences of this anxiety disorder alters the effectiveness of these procedures. The overarching goal of all the proposed studies is to discover how and when we might be able to prevent the return of fear in humans, which has the potential to lead to novel and more effective treatments for anxiety disorders.

Public Health Relevance

The prevalence of anxiety disorders is estimated to be up to 18% of the US adult population and a primary treatment for these disorders is exposure therapy, which is based on the principles of fear extinction. One limitation of fear extinction is that the original memory is not altered and in some circumstances the fear can return. The proposed studies aim to discover how and when we might be able to improve on extinction-based therapies and prevent the return of fear in humans, potentially leading to novel and more effective treatments for anxiety disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH097085-03
Application #
8661034
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Vicentic, Aleksandra
Project Start
2012-06-11
Project End
2017-04-30
Budget Start
2014-05-08
Budget End
2015-04-30
Support Year
3
Fiscal Year
2014
Total Cost
$378,740
Indirect Cost
$128,740
Name
New York University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
041968306
City
New York
State
NY
Country
United States
Zip Code
10012
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Apergis-Schoute, Annemieke M; Schiller, Daniela; LeDoux, Joseph E et al. (2014) Extinction resistant changes in the human auditory association cortex following threat learning. Neurobiol Learn Mem 113:109-14
Steinfurth, Elisa C K; Kanen, Jonathan W; Raio, Candace M et al. (2014) Young and old Pavlovian fear memories can be modified with extinction training during reconsolidation in humans. Learn Mem 21:338-41
Hartley, Catherine A; Gorun, Alyson; Reddan, Marianne C et al. (2014) Stressor controllability modulates fear extinction in humans. Neurobiol Learn Mem 113:149-56
Raio, Candace M; Orederu, Temidayo A; Palazzolo, Laura et al. (2013) Cognitive emotion regulation fails the stress test. Proc Natl Acad Sci U S A 110:15139-44