When the brain remembers, proteins in two locations deep within the organ—the amygdala and hippocampus—encode the memory until it is stored, or “consolidated” in the vernacular. Neuroscientists once thought that a memory, when put in its place, became permanent and stable.
That’s a problem for patients with post-traumatic stress disorder (PTSD), plagued by crippling, debilitating memories that they cannot shake. “We wish that we could somehow target unpleasant or pathological memories and reduce their emotional strength,” says Bryan A. Strange, founder of the Laboratory of Clinical Science at the Universidad Politécnica de Madrid.
During the past two decades or so, it has become clear that these memories are not fixed and unshakable. They can be manipulated in ways that might ultimately ease the suffering of patients, not just ones with a PTSD diagnosis but also those afflicted by phobias, depression and other stress-related conditions.
Strange is among the researchers looking for leads to tamp down toxic memories. He and his colleagues reported in a Science Advances paper on March 20 that the anesthetic propofol can be used to alter such recollections, if administered in the right circumstances.
Their study turned in part on findings that have shown that consolidated memories could be reactivated by asking people to recall them or go where a frightening incident occurred. Such memories can become sensitive to modification for about 24 hours before becoming reconsolidated—locked down again.
This line of research has focused on weakening memories during that 24-hour window, with the goal of easing the suffering of patients with stress-related disorders. To do their study, Strange and his colleagues needed to administer propofol to human subjects to note its effects on memory. But that’s far too risky to do solely for research purposes. Then they realized that the hospital was full of potential subjects—patients undergoing endoscopy (the insertion of a tube down the digestive tract) or colonoscopy, all of whom were routinely treated with propofol.
The researchers enlisted 50 subjects, who, one week before their procedure, were shown an emotionally charged slide show—a boy struck and killed by a car or a woman abducted and molested by an ex-convict. All of the subjects saw emotionally neutral slide shows, too. Just before their procedure, the subjects were asked to recall the emotional stories, reactivating the memories. Then they received the dose of propofol required for their planned procedure.
Researchers tested the memories of some of the patients immediately afterward and then, knowing that reconsolidation takes a day, they repeated the assessment some 24 hours later. They found that the anesthetic made no immediate change in memory, but after 24 hours it impaired the memory of the emotionally charged slide show. By the 24-hour mark, reconsolidation had taken place—and the memory of the charged stories was impaired—not gone, but less likely to make the patient suffer.
The anesthetic functioned exactly as a PTSD drug should—impairing the disturbing memories and leaving the others alone. Some PTSD patients are now treated with so-called exposure therapies, which reactivate the memory while the patient is in a safe space, and these help some patients, Strange says. If propofol is shown in future studies to be effective it could be used for the more difficult cases, he says.
Jacek Debiec, a psychiatrist at the University of Michigan, says the Strange study suggests that propofol could become yet another tool for the treatment of PTSD. “We have a growing number of studies focused on demonstrating that reconsolidation is possible, that it occurs. And you can interfere with the memory,” he says. But researchers need to know more about how the drug works and what doses are appropriate before propofol becomes widely used, he adds.
Researchers have also explored the drug propranolol, which belongs to the class of beta blockers used to treat heart disease, which can also impair reconsolidation of memories.
Alain Brunet of McGill University in Montreal has done extensive research on propranolol and says it has now been proven in a randomized clinical trial he published last year that propranolol is more effective than a placebo.
He administers treatment over a six-week period. He asks patients “to recall their traumatic events by having them write an account of it—which includes the hot spot, the most difficult part of the event,” he said. “Then they read it to me under propranolol once a week for six weeks.”
Strange notes that emotionally charged memories have mixed effects, not all of them negative. Somebody who was threatened or hurt by a dog, for example, might need treatment to cope with fear of dogs. On the other hand, he says, that patient might want to remember not to approach a dog that looks like a threat. But gaining control over the caustic emotions attached to a lingering memory may create a new role for an anesthetic known for its effectiveness in the operating room in blotting out consciousness.