To sleep, perchance to forget one’s fears

For those who struggle with post-traumatic stress disorder, phobias, anxieties and other fearful memories, the bedroom may be the next big battleground. Researchers are finding that sleep may allow us not just to escape our cares temporarily, but to defang some of the fearful memories that hobble those with such anxiety disorders.

Two studies published in the past week break new ground in the effort to take the fright out of frightening memories, both of them exploring the opportunity afforded by sleep to do so. They proceed from two relatively recent neuroscientific insights about memories: that they change a little every time they are taken out, revisited and returned to storage; and that sleep is a time when old memories and new experiences alike are processed, prepared and filed into the brain’s long-term storage vault.

Just as many of us hoped while trying to cram for tests, research has shown it is possible to enhance the power of sleep-time to consolidate memories -- both those we’ve created and those we’ve revisited in the course of our waking day. Studies have found that the introduction of certain cues during sleep can help us consolidate memories that are spatial or episodic in nature (say, the directions to a new store we’ve just traveled to, or the range of merchandise the store carries).

But could sleep-time be used to revise and store old memories that are highly emotional in character? In mice and people alike, the studies find, the answer appears to be yes.

A study published Sept. 22 in the journal Nature Neuroscience put 15 healthy subjects through a fear-conditioning experiment with a fragrant twist: They looked at images of two different faces and, while seeing them, received a brief but painful shock. While being shocked and looking at each face, they were also quietly exposed to one of several distinctive smells, including mint, new-sneaker smell, lemon or clove.

The result was that all came to associate the faces and the specific smell that accompanied the related shock with pain and fear. And even after the shocks stopped, their fearful expectation of a shock was evident, both by increased perspiration and on a brain-imaging MRI, whenever they saw one of the faces or smelled the odor associated with that face.

The researchers, a team from Northwestern University’s Feinberg School of Medicine, then sought to partially “decondition” half of their subjects during their sleep cycle’s slow-wave interval -- a period of sleep closely associated with memory consolidation. There would be no more shocks. But they wouldn’t show the sleeping subject a face while not giving her a shock (that would be difficult to see through closed eyes). Instead, the researchers repeatedly pumped into the nap room the fragrance that those subjects had come to associate with being shocked and seeing one of the faces.

When they woke, all were wired up again and shown the images of the faces they had come to associate with getting a shock. For the half that were given repeated sleep-time exposure to the shock-related smell, researchers observed far more muted fear responses to seeing the face associated with the shock and that smell.

Essentially, the subjects were experiencing the effects of “exposure therapy” they had had while sleeping.

In a second study, published Tuesday in the journal Molecular Psychiatry, Stanford University researchers tried a related experiment on mice, only using sleep to strengthen emotional fear memories.

First, the researchers conditioned mice to respond fearfully to a certain odor by introducing it whenever the animal got a painful foot shock.

For half of the mice, things got even worse: Researchers pumped that shock-related odor into their cages during their non-rapid eye movement sleep intervals. Upon awakening, those mice were far more likely than those who did not get the sleep-time aromatherapy to freeze when they smelled the odor they associated with getting a shock.

Then, the study authors tried to weaken memories associated with a painful stimulus. Just before the mice slept, they injected protein synthesis inhibitor into the fear center -- the amygdala -- of the mice’s brains. This agent typically makes memories more slippery: They’re apt to change or weaken when they’re revisited and stored again.

After an unperturbed sleep, the mice treated with the protein synthesis inhibitor did, indeed, show less fear response when puffs of the shock-associated odor were pumped into their cage.

But when the mice got the protein synthesis inhibitor and also the reinforcing puffs of odor during sleep, the fear association between shock and its associated odor was so strong, it overpowered the expected effects of protein synthesis inhibitor.

“We see these findings as proof of the concept that memories can be manipulated during sleep, and that such manipulation offers diverse therapeutic potential,” the authors wrote.

For those plagued by post-traumatic stress or phobias, exposure therapy -- a revisiting of the fearful memory or circumstance under safe circumstances -- is very effective. But for some, it’s so difficult that progress can be fitful, or blocked. These two studies suggest that if mental health professionals could use a patient’s sleep-time to weaken fearful memories -- or to strengthen associated memories that are sources of comfort or strength -- patients might make better progress in overcoming the fears that haunt them.