A New Tool To Reverse Traumatic Memories
Posted by Richard Conniff on April 23, 2014
My latest for Smithsonian magazine.
The best way to forget an alarming memory, oddly, is to remember it first. That’s why soldiers returning from war with post-traumatic stress disorder (or PTSD) often find themselves being asked by therapists to read scripts or view scenes recalling the incident that taught them the crippling fear in the first place.
Stirring up a memory makes it a little unstable, and for a window of perhaps three hours, it’s possible to modify it before it settles down again, or “reconsolidates,” in the brain. Getting patients to relive their traumatic memories over and over in safe conditions can thus help them unlearn the automatic feeling of alarm. It’s what researchers call “fear extinction” therapy—a way, almost, of reversing the past.
The trouble is that this therapy works with recent memories, but not so well with deeply entrenched long-term horrors. But a new study in mice, from the laboratory of neuroscientist Li-Huei Tsai at MIT, now promises to change that.
The scientists, who published their study in the journal Cell, taught lab mice fear by the standard technique of applying a mild electric shock, accompanied by a loud beep. Mice show fear by freezing in place, and they quickly learned to freeze simply on being put in the test box or hearing the beep. It was a “conditioned response,” like Ivan Pavlov ringing a bell to make dog’s salivate, in his pioneering experiments on learning and memory.
For the mice, fear extinction ear extinction therapy meant going back in the test box for a while, but without the shock. That was enough to unlearn the conditioned response if it was a new memory, just one day old. But if the mice had been trained 30 days earlier, the therapy didn’t work on what had by then become a long-term memory.
To change that, Tsai and lead author Johannes Gräff combined extinction therapy with a type of drug that has recently shown promise as a way to improve thinking and memory in patients with Alzheimer’s disease and other cognitive disorders. HDAC inhibitors (that is, histone deacetylase inhibitors) are compounds that alter the expression of genes. Injecting HDAC inhibitors seems temporarily to increase the ability of neurons, the basic working cells of the central nervous system, to form new connections. And those new connections are the basis of learning.
The HDAC inhibitors alone had no effect. But drugs and fear extinction therapy together seemed to allow the therapy to open up and reconnect the neurons where long-term traumatic memory had until then been permanently locked away. The new learning was highly specific: Depending on how they tailored the therapy, the researchers could train the mice to ignore the entire conditioned response, or just a part—ignoring the beep, for instance, but still freezing on being put in the test box.
Getting from mice to humans is of course always a great leap, requiring extensive testing, for instance, to understand how HDAC inhibitors work: Do they modify the old memory? Or do they merely lay down a new memory trace on top of the old one, meaning the old one might spontaneously return? But the U.S. Food and Drug Administration has already approved investigative use of some HDAC inhibitors in treatment of certain cancers and inflammatory disorders. That could make it easier, Gräff speculates, to get to clinical testing in human psychiatric therapy in as little as five years.
Marie Monfils, who studies fear memory at the University of Texas at Austin, calls the new study “beautifully done,” with potential to “open up really interesting avenues for research and treatment.” That could be big news for a society alarmed by the surge in military suicides and other PTSD-related problems from more than a decade of war. For the desperate patients themselves, science now holds out hope that it will soon be possible, in effect, to rewind memory to a time before trauma stole their peace of mind.