Meanwhile, doubts about the standard theory of memory were piling up in the world outside the neuroscience lab. In the early 1990s many people began reporting what seemed to be long-buried memories of childhood sexual abuse. These traumatic recollections frequently surfaced with the help of recovered-memory therapy techniques like hypnosis and guided imagery, in which patients are encouraged to visualize terrible experiences. Cognitive scientists suspected that some of these memories were bogus, the unwitting product of suggestion by the therapist. In support of this view, psychologist Elizabeth Loftus, then of the University of Washington, proved how easy it is to implant a false memory, especially one that is plausible. In a famous experiment, she gave volunteers a booklet narrating three true stories of events from their own childhood along with an invented tale that described their getting lost in the mall at age 5. When prompted later to write down all they could remember about the events, 25 percent were sure that all four events had actually happened to them.
Spurred on by the controversy over recovered memory, other cognitive scientists found that false memory is a normal phenomenon. David Rubin, who studies autobiographical memory at Duke University, observed that adult twins often disagree over who experienced something in childhood. Each might believe, for example, that he was the one to get pushed off his bike by a neighbor at age 8. Apparently, even the most basic facts about a past event (such as who experienced it) could be lost.
Even harrowing memories—the so-called flashbulb memories that feel as if they have been permanently seared into the brain—are not as accurate as we think. Less than a year after a cargo plane crashed into an Amsterdam apartment building in 1992, 55 percent of the Dutch population said they had watched the plane hit the building on TV. Many of them recalled specifics of the crash, such as the angle of descent, and could report whether or not the plane was on fire before it hit. But the event had not been caught on video. The “memory” shared by the majority was a hallucination, a convincing fiction pieced together out of descriptions and pictures of the event.
By the late 1990s, hundreds of psychology experiments suggested that the description of memory as a neurally encoded recapitulation of the past was so oversimplified as to completely miss the point. Instead of being a perfect movie of the past, psychologists found, memory is more like a shifting collage, a narrative spun out of scraps and constructed anew whenever recollection takes place. The science of memory was conflicted, with the neurobiological and psychological versions at odds. If a memory is wired into brain cells—a literal engraving of information—then why is it so easy to alter many years after the fact? It took an outsider to connect the dots.
Rewriting the Past
In the hierarchy of memory science, Karim Nader hardly ranked—a lowly postdoc, only 33 years old, and not even a memory researcher. But in 1999, inspired by Kandel’s talk, he set out to satisfy his big questions about how we recall and forget through a simple experiment. Nader tweaked a standard method used in fear research, in which rats are trained to associate a tone with an electric shock to the foot. The animals quickly learn that the sound is bad news. If they hear it weeks later, they freeze in fear. It is an easy way for the experimenter to know that they remember what took place.
Nader trained some rats, then played the tone again 14 days later, prompting them to remember. He also simultaneously injected them with a protein-synthesis inhibitor, which prevents new memory from forming by prohibiting alteration at the synapses. According to the standard model of memory, the chemical should have no effect since the memory of the tone has already consolidated. In reality, the treated rats’ memory disappeared. When Nader sounded the tone again later, the animals did not freeze. LeDoux was won over by this simple but powerful demonstration. In 2000 Nader’s paper on reconsolidation sparked a commotion in the world of memory research. He showed that reactivating a memory destabilizes it, putting it back into a flexible, vulnerable state.
Immediately reconsolidation became a fighting word. The gossip Nader heard terrified him; some of the biggest bigwigs of memory research thought he had made a ludicrous mistake. “I had no idea how much of a backlash there was going to be,” he says. Even so, Nader kept at his experiments, and in the fall of 2001, he was scheduled to present his research at a huge Society for Neuroscience meeting. It would be his moment of truth, his one chance to persuade the field to take his finding seriously. “I knew the old guard was saying, ‘This sucks; it’s all crap,’?” he says. “I knew if I didn’t hit a grand slam, this thing was dead.” The talk drew an overflow crowd of more than a thousand, including the legend himself, Eric Kandel. (“I really wanted to die,” Nader says.)
That day, by addressing the major criticisms of his research, Nader managed to convince his colleagues that memory reconsolidation was at least worth a serious look. Various labs took on the challenge, soon repeating his findings and discovering that many types of memory in many different species reconsolidate. Other groups began teasing out the reconsolidation process molecule by molecule. Nader’s group found that the NMDA glutamate receptor—which solidifies memory—also is involved in destabilizing it. A group led by Sue-Hyun Lee at Seoul National University demonstrated that proteins must be actively dismantled to destabilize a memory, more evidence that the old memory is actually changed as it is recalled.
Brain researchers are still grappling with the implications of this idea, trying to figure out exactly how malleable memory really is. “People are willing to say we have to go back to the drawing board,” says LeDoux, whose group has also continued to study reconsolidation. At the 2008 Society for Neuroscience meeting in Washington, D.C., 43 presentations focused on reconsolidation, and Nader was besieged by students and young researchers eager to talk.
With this new understanding of memory has come the even more startling possibility of new ways to control it: The era of memory treatment has arrived. For Rita Magil, who got just two doses of propranolol over the course of a single day, the results were encouraging. Her heart rate and muscle tension eased while the drug was in her body. She sensed the difference too. “I felt more detached from it,” she says. “I felt that I was relating a narrative rather than describing something right in front of me right now.” After the study was over, the flashbacks returned, though with less intensity. For her, the only real cure was time.
Six-session treatments with a total of 12 doses of propranolol have shown better results. Collaborating with Harvard psychiatrist Roger Pitman, who was the first to try propranolol for post-traumatic stress, the McGill group has treated about 45 PTSD patients, ranging from soldiers to rape victims. Most had been suffering for years. But after the longer treatment, their symptoms declined by half and stayed that way even six months afterward. They still remember what happened, but it is less disturbing. “They say: ‘I’m not thinking about it as much. It just doesn’t bother me as much anymore,’?” Brunet says. As a group, they are considered to be in remission.
The researchers must still prove that the improvement will last. If it does, it could offer rare hope to millions of people with PTSD, a disorder from which only a third completely recover.
Brunet hopes that similar treatments can address other psychiatric problems, too. Anxiety, acquired phobias, and addiction are increasingly described as disorders of emotional memory. An overly powerful fear memory, for example, can crystallize into a phobia, in which a relatively safe experience like flying in a plane is inextricably linked to a feeling of extreme danger. No matter how the phobic person tries, his emotional memory refuses to update itself to incorporate reassuring information. A treatment that restores his emotional memory to a flexible state could help him cope.