Through behavioral manipulation, scientists have been able to selectively block a conditioned fear memory in humans for the first time. Led by Elizabeth Phelps, Ph.D., of New York University, a grantee of the National Institutes of Health's National Institute of Mental Health (NIMH), the research team found evidence that reactivating an emotional memory opened a six-hour window during which the memory can be altered using a specific training procedure. After the procedure, study participants reported being free of the fear memory for at least one year.
"Our results suggest a non-pharmacological, naturalistic approach to more effectively manage emotional memories," said Phelps
The NIMH is hopeful that these study findings may lead to enhanced therapies for the treatment of anxiety disorders, namely post-traumatic stress disorder (PTSD). Each time a memory is reactivated, it is reconsolidated, opening a short period of time when it can be modified.
"This adaptive update mechanism appears to have evolved to allow new information available at the time of retrieval to be incorporated into the brain's original representation of the memory," explained Phelps.
Researchers explored their findings further by trying to erase a fear memory in rats. In this experiment:
• Researchers conditioned rats to fear a tone by combining it with intermittent shocks.
• One day later, the rats were exposed to the tone again, reactivating the fear memory.
• The rats then underwent extinction training to rewrite the fear, presenting the tone repeatedly without shocks.
Based on this experiment, the researchers discovered that the timing of the extinction training was critical. The fear memory disappeared only in rats trained within a six-hour window after re-exposure to the tone. After that window closed, fear responses returned.
While extinction training normally only suppresses the fear memory, researchers were able to permanently erase by first reactivating it – sounding the tone – just prior to extinction training.
In the human study:
• Researchers conditioned study participants to fear colored squares by intermittently combining them with mild wrist shocks.
• One day later, the memory was reactivated by exposing participants to the squares again.
Next, participants underwent extinction training, repeatedly beingexposed to the colored squares without shocks.As in the rats, there was a six-hour window during which the fear memory could be erased.
In a follow-up experiment one year later, 19 of the original participants received four shocks followed by presentations of the colored squares to reinstate the fear. The participants who had undergone extinction training within the six-hour window were spared significant effects, whereas those whose training occurred outside the six-hour window or who hadn't experienced fear memory reactivation prior to extinction training did re-experience the fear response. Interestingly, the fear memory was blocked only for the specific colored square shown prior to extinction training. In other words, the effect did not generalize to a differently colored square associated with the shocks.
"Timing may have a more important role in the control of fear than previously appreciated," Phelps suggested. "Our memory reflects our last retrieval of it rather than an exact account of the original event."
Like a number of experimental medications currently being studied, behavioral manipulation works on the amygdala in the brain, but with fewer risks or potential side effects.
"Using a more natural intervention that captures the adaptive purpose of reconsolidation allows a safe and easily implemented way to prevent the return of fear," noted the researchers.
