BioEd Online

Fearful memories can be wiped out for at least a year using a drug-free technique, according to a study done in the United States.

The technique exploits the way that human brains store and recall memories. When a long-term memory is recalled, it goes through a brief period of vulnerability, after which it must be stored anew to be remembered again. While the memory is in its fragile state, it can be modified or disrupted.

Studies in animals¹ have used drugs to interfere with this reconsolidation process, stirring hope for therapies to blunt the haunting memories associated with conditions such as post-traumatic stress disorder. But although these experiments have helped to understand reconsolidation, most of the drugs used are toxic to humans. A study done earlier this year in humans used a drug that's used to treat high blood pressure, called propranolol, but the treatment does not work for everyone².

Now, psychologist Elizabeth Phelps and her colleagues at New York University have developed a way to interfere with fear memories in humans using a behavioural technique, and the results last for at least a year. The results are published in Nature³.

"We took advantage of a long history of research in animal models that tells us about this process," says Phelps. "Now we can do interventions in humans in a way that's more sophisticated, and possibly take it to the clinic."

Timing is everything

Humans struggling with horrific memories are often treated with a psychotherapeutic technique called extinction therapy, in which the patient is repeatedly exposed to whatever conjures up the memory — such as snakes or a gunshot — and gradually learns that the stimulus is safe. But while getting back on the horse has some success, the old memories are still stored in the brain and often strike again.

The authors tweaked the timing of extinction therapy so they could take advantage of the fragile reconsolidation period — a window of malleability that opens about three minutes after the memory is reactivated, but closes a few hours later.

The authors showed people coloured squares and gave them mild electric shocks to the wrist after a certain colour appeared (see video). After training, the coloured squares that had been paired with the shock incited fear in the volunteers, which experimenters measured as changes in skin conductance — an indication of sweat-gland activity.

The next day the authors began the modified extinction training. First they called up the fear memory by showing the coloured square. Ten minutes later, while the memory was in its vulnerable state, they repeatedly showed the coloured square again without shocking the volunteers. A day later the fear response to the coloured square was gone, suggesting that the reconsolidation process had been blocked. The fear showed no sign of returning even a year later.

Meanwhile, people who got the extinction training 6 hours — instead of 10 minutes — after the reminder, or who got no reminder at all, still showed a significant fear response the next day and the next year.

From bench to battlefield?

How well these lab-based findings would translate to the clinic remains unclear, as a mild shock to the wrist is a far cry from the battlefields of Iraq.

Co-author Joseph LeDoux acknowledges that "there is a huge gap between fear in the lab and post-traumatic stress disorder" but that "the stuff we study is relevant because the [brain] circuits are proven to overlap".

Cognitive scientist Lynn Nadel at the University of Arizona in Tucson is cautious for a different reason. "We know that [fear] extinction tends to be context specific," he says. "If you're using extinction on someone with post-traumatic stress disorder from the war, they might feel safe if they have a flashback in the laboratory but not in the real world."

Merel Kindt, the lead author of the study that used propranolol to block fear memories and a psychologist at the University of Amsterdam, was surprised that the authors used skin conductance as the only measure of fear, she says, as it is not specific to fear — it also indicates arousal, for instance.

Phelps agrees that the technique is not ready for prime time. "It's really intriguing, but it's going to take a lot more understanding of exactly when, how and where this works to create something that's really going to be clinically useful," she said. "We just barely understand this."