Editing Out the ‘Fear’ in Fearful Memories

May 1, 2009

Much of the “trauma” in traumatic memories might be erasable relatively easily, Dutch researchers suggest. By giving people the blood-pressure drug propranolol and then reactivating a fearful memory, they say, they were able to reduce the emotional response to the memory almost completely while leaving the rest of the memory intact.

The study is largely consistent with previous research in rodents and follows early clinical experiments with propranolol in patients with post-traumatic stress disorder (PTSD). McGill University researcher Karim Nader, who has done prominent work in the field, says that the Dutch study is valuable because it suggests a way to use ordinary human subjects—not just mice—to study the fear-memory process in detail and develop better erasure techniques: “It fills a gap that needed to be filled.”

In the study, Merel Kindt and colleagues at the University of Amsterdam took 40 test subjects and conditioned them to associate images of spiders with a mild electric shock to the wrist. A day later, the researchers gave half of the subjects a single dose of propranolol and the other half a placebo, and then reactivated the spider-shock memory with a single presentation of both stimuli together. The following day, they ran an “extinction trial” in which the subjects were exposed to the images of spiders without the shocks.

Normally for such an extinction trial, subjects, over multiple exposures to the images without the shocks, would first show an elevated fear-response and then a gradual loss of that response—in this case measured with an electrical probe over the muscles that control eye-blink reflexes. However, only the placebo group showed this tailing off of the fear response. The probe data indicated that the propranolol group had no fear response to lose, evidently having already lost it after the previous day’s reactivation trials.

Meanwhile the conscious, “declarative” aspect of the propranolol subjects’ memory stayed intact. Their subjective expectations of how much fear they would experience when they saw the spider images started off high in the extinction trials and tailed off normally, just like the placebo subjects’ expectations.

Previous work in this area had shown that after the extinction of a fear memory, it can be reinstated quickly by exposing subjects to the original fearful stimulus (in this case the shock). But when Kindt and her colleagues tried this reinstatement procedure in their subjects, the propranolol group had responses that were no greater than those they had shown when first encountering the noise and image two days before—suggesting that the combination of propranolol with memory reactivation on day two had wiped all functional traces of the fear response to the spider image. None of these fear-erasure effects occurred in a third group of 20 propranolol subjects for whom the memory reactivation procedure on day two was skipped.

The report by Kindt and her colleagues, published Feb. 15 in Nature Neuroscience, is consistent with previous work in rodents, which suggested that reactivation triggers a memory-reconsolidation process in the amygdala, where the fear element of fearful memories is stored. Blocking the molecular signaling required for this reconsolidation process appears to disrupt the fear memory or its links to physiological responses without disturbing the declarative part of the memory, which is believed to be gathered in different regions in and around the hippocampus. Propranolol is considered a good candidate for a fear-memory eraser because it blocks beta-adrenergic receptors on neurons, which in the amygdala appear to be crucial for memory reconsolidation.

Propranolol is already FDA-approved as a blood pressure drug, and its availability has led some doctors to prescribe it experimentally to reduce the fear response to memories in people who have recently been traumatized and even in those who have suffered from PTSD for decades. So far in these studies it does appear to reduce the emotional force of traumatic memories, but not completely and not by every measure. Nader notes that the experimental setup reported by Kindt and colleagues and using ordinary human subjects seems useful for doing the basic research still needed in this area. “It could take decades if we had only PTSD patients to work with,” he says.

Underscoring the fact that work in this area remains at an early stage, Elizabeth Phelps, a psychologist at New York University, notes that she and her colleagues recently performed a study with seemingly minor differences from the Kindt study, “but we didn’t get the same results.”

Phelps and her colleagues will now try to replicate her study using Kindt’s protocol, but she thinks that in general “there’s still a lot of research still to be done to figure out when and how and what you need to do” to optimize the management of fear memories.