Researchers at New York University have developed a non-invasive technique to block the return of fear memories in humans. The technique, reported in the latest issue of the journal Nature, may change how we view the storage processes of memory and could lead to new ways to treat anxiety disorders.
Researchers have long sought to understand fear memories. These are expressed as the body's emotional reaction to objects or events previously linked to potential danger. It is known that, over time, such emotional responses could dissipate in a process called extinction in which the same event is experienced in a safe environment. After extinction, the fear memory is merely suppressed, not erased, and therefore these memories could resurface under certain conditions, such as unrelated stress. In some cases, the re-emergence of the emotional memory is maladaptive, leading to anxiety disorders. Because of this, researchers have sought to find ways to prevent the return of fear.
While researchers have traditionally seen long-term memory as fixed and resistant, it is now becoming clear that memory is, in fact, dynamic and flexible. As a result, the act of remembering makes the memory vulnerable until it is stored again -- a process called reconsolidation. During this instability period, new information could be incorporated into the old memory. This was the phase during which the NYU researchers sought to employ a technique to block the return of fear memories.
The NYU researchers showed that reactivating fear memories in humans allows them to be updated with non-fearful information, a finding that was previously demonstrated in rodents. As a result, fear responses no longer return.
To achieve this, the researchers created a fear memory in the laboratory by showing participants a visual object and pairing it with mild electric shocks -- a process known as classical fear conditioning. Fear conditioning is successful when subjects show a fear response to the object when it is subsequently presented on its own. In order to measure the fear memory, they examined the skin conductance response to the object, an indication of arousal.
Once this fear memory was formed, participants were reminded of the object a day later. This reactivation of the memory was intended to initiate the reconsolidation process. During this process, information that the same object was now "safe" was provided through extinction training. Presenting this new "safe" information during reconsolidation was designed to incorporate it into the initial fear memory. A day later, the participants were tested again to see whether they continued to demonstrate a fear response when presented with the object.
Extinction training on its own led to the reduction of fear, but fear returned when tested at a later time or when following stress. However, the NYU researchers found that if extinction training was conducted during the reconsolidation window, when the memory was temporarily unstable, fear responses did not return. They also showed that rewriting of the fear memory as safe was specific to the object that was reactivated prior to extinction. Fear memories for other objects returned following extinction, suggesting that the technique is selective rather than having a general effect on memories.
The experiment was conducted over three days: the memory was formed in the first day, rewritten on the second day, and tested for fear on the third day. However, to examine how enduring this effect is, a portion of the participants was tested again about a year later. Even after this period of time, the fear memory did not return in those subjects who had extinction during the reconsolidation window. These results suggest that the old fear memory was changed from its original form and that this change persists over time.
The study was conducted by researchers from NYU's Department of Psychology and Center for Neural Science in the laboratory of NYU Psychology Professor Elizabeth Phelps. The study's lead author was post-doctoral fellow Daniela Schiller. Co-authors include Joseph LeDoux and Marie Monfils (now at the University of Texas at Austin), who previously published a similar finding in rodents, as well as David Johnson, a former NYU undergraduate, and Candace Raio, an NYU doctoral candidate.
"Our research suggests that during the lifetime of a memory there are windows of opportunity where it becomes susceptible to be permanently changed," said Schiller. "By understanding the dynamics of memory we might, in the long run, open new avenues of treatment for disorders that involve abnormal emotional memories."
Phelps added, "Previous attempts to disrupt fear memories have relied on pharmacological interventions. Our results suggest such invasive techniques may not be necessary. Using a more natural intervention that captures the adaptive purpose of reconsolidation allows a safe way to prevent the return of fear."
The research was funded by the James S. McDonnell Foundation and the National Institutes of Health.
- Schiller D, Monfils MH, Raio CM, Johnson DC, LeDoux JE, Phelps EA. Preventing the return of fear in humans using reconsolidation update mechanisms. Nature, 2009; DOI: 10.1038/nature08637
- Monfils MH, Cowansage KK, Klann E, LeDoux JE. Extinction-Reconsolidation Boundaries: Key to Persistent Attenuation of Fear Memories. Science, 2009; 324 (5929): 951 DOI: 10.1126/science.1167975
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