Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Although much progress has been made in uncovering the neural basis of fear learning through studies of Pavlovian conditioning, little is known about how to reduce or eliminate traumatic memories in pathological cases, which is of great clinical concern. We have recently devised a novel behavioral paradigm that attenuates and prevents the return of fear memories. Our results indicate that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. In parallel, a new computational model developed in our collaborator's lab (Dr. Yael Niv, at Princeton University) provides a principled explanation for our results, and will help generate testable predictions to refine our protocol, and better understand the mechanisms that underlie the persistent updating of fear memories. In the proposed studies, we will first refine our protocol using computationally-derived predictions. Next, we will test the limits of this optimized protocol, and examine whether it may be used to target stronger, older, and more complex fear memories, with the hopes that it may eventually be employed to attenuate traumatic memories in clinical populations.

Public Health Relevance

Exaggerated or persistent fear is a common occurrence in psychiatric disorders. Two paradigms (blockade of reconsolidation and extinction) have been used in the laboratory setting to reduce acquired fear;however, the clinical efficacy of these techniques has been limited. We have recently presented a novel behavioral paradigm that attenuates and prevents the return of fear memories by combining reconsolidation and extinction principles (Ret+Ext). Our findings suggest that subtle modifications to a commonly employed clinical treatment (exposure therapy) could greatly improve outcome, and reduce the potential for relapse in individuals suffering from post-traumatic stress disorder or specific phobias. Here, we propose to extend these findings to isolate the neural mechanisms that underlie our fear-reducing treatment, and to closely examine the strengths, weaknesses, and possible consequences of using this Ret+Ext paradigm.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH091147-02
Application #
8204555
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Vicentic, Aleksandra
Project Start
2010-12-06
Project End
2015-11-30
Budget Start
2011-12-01
Budget End
2012-11-30
Support Year
2
Fiscal Year
2012
Total Cost
$380,105
Indirect Cost
$130,105
Name
University of Texas Austin
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Cofresí, Roberto U; Lee, Hongjoo J; Monfils, Marie-H et al. (2018) Characterizing conditioned reactivity to sequential alcohol-predictive cues in well-trained rats. Alcohol 69:41-49
Auchter, Allison; Cormack, Lawrence K; Niv, Yael et al. (2017) Reconsolidation-Extinction Interactions in Fear Memory Attenuation: The Role of Inter-Trial Interval Variability. Front Behav Neurosci 11:2
Cofresí, Roberto U; Lewis, Suzanne M; Chaudhri, Nadia et al. (2017) Postretrieval Extinction Attenuates Alcohol Cue Reactivity in Rats. Alcohol Clin Exp Res 41:608-617
Meyza, K Z; Bartal, I Ben-Ami; Monfils, M H et al. (2017) The roots of empathy: Through the lens of rodent models. Neurosci Biobehav Rev 76:216-234
Gershman, Samuel J; Monfils, Marie-H; Norman, Kenneth A et al. (2017) The computational nature of memory modification. Elife 6:
Jones, Carolyn E; Monfils, Marie-H (2016) Post-retrieval extinction in adolescence prevents return of juvenile fear. Learn Mem 23:567-75
Jones, Carolyn E; Monfils, Marie-H (2016) Dominance status predicts social fear transmission in laboratory rats. Anim Cogn 19:1051-1069
Jones, Carolyn E; Monfils, Marie-H (2016) Fight, Flight, or Freeze? The Answer May Depend on Your Sex. Trends Neurosci 39:51-53
Lee, Hongjoo J; Haberman, Rebecca P; Roquet, Rheall F et al. (2015) Extinction and Retrieval + Extinction of Conditioned Fear Differentially Activate Medial Prefrontal Cortex and Amygdala in Rats. Front Behav Neurosci 9:369
Powers, Mark B; Medina, Johnna L; Burns, Stephanie et al. (2015) Exercise Augmentation of Exposure Therapy for PTSD: Rationale and Pilot Efficacy Data. Cogn Behav Ther 44:314-27

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