LeDoux Lab 2008 SfN Abstracts |
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Program#/Poster#: | 591.16/UU3 |
Title: | Behavioral blockade of the return of fear in humans |
Location: | Washington Convention Center: Hall A-C |
Presentation Time: | Tuesday, Nov 18, 2008, 11:00 AM -12:00 PM |
Authors: | *D. SCHILLER1,2,
M.-H. MONFILS1, D. C. JOHNSON2, C. M. RAIO2,
J. E. LEDOUX1, E. A. PHELPS1,2; 1Ctr. for Neural Sci., 2Psychology, New York Univ., New York, NY |
Abstract: | A common way to modify fear learning
is through extinction. In this process, learned fear responses are no longer
expressed after repeated exposure to conditioned stimuli (CSs) that are
de-coupled from aversive consequences. Nearly all forms of behavioral therapy
rely, at least partially, on extinction learning through exposure to fear
arousing stimuli in a safe context. Although extinction provides a relief
from fear, this relief might be temporary, as extinguished fear responses
often reemerge with the passage of time or with re-exposure to the unconditioned
stimulus in the original context. The aim of the present study was to investigate
new possible way to prevent the return of fear following extinction. The fact that extinguished fear can be recovered under certain conditions has been taken to suggest that the fear memory is not erased but rather suppressed. In recent years, there has been abundant research attempting to erase old memories by targeting a particular phase in which memories are labile again, namely, reconsolidation. Specifically, it has been suggested that once an old, fully consolidated, memory is retrieved, this reactivation is followed by an additional phase of consolidation, which is susceptible to interference. There is considerable evidence from animal studies that pharmacological and molecular manipulations at this stage result in inability to retrieve such memories, suggesting they might have been erased. However, there has yet to be convincing evidence that reconsolidation can be impaired in humans. This is in part due to obvious limitations in the use of invasive manipulations, such as drugs, and the risk of side effects. Thus, there is a critical need to develop drug-free behavioral manipulations to achieve blockade of fear recovery. New evidence reported at the present conference shows that that a single isolated retrieval trial prior to extinction prevents the return of fear in rats (Monfils and colleagues). This suggests that extinction learning interfered with the reconsolidation of the retrieved memory and may have led to its erasure. To test this hypothesis in humans, we used a fear conditioning paradigm where two CSs were paired with a shock. A day later, subjects received a single presentation of one of the CSs, after which both CSs were extinguished. We tested the recovery of fear following reinstatement and found that only fear to the non-reactivated CS returned. This suggests that retrieval, and hence reconsolidation, helps strengthen extinction. This finding has important implications for the treatment of anxiety disorders, suggesting that the use of drugs might not be required for preventing fear memories from resurfacing. |
Support: | NIH grants R01 MH46516, R37 MH38774, K05 MH067048, and P50 MH58911 to JEL; A James S. McDonnell Foundation grant, and NIH grants R21 MH072279 and R21 MH081088 to EAP |