While Mischel closely follows the steady acc.u.mulation of data from the laptops and the brain scans, he"s most excited by what comes next. "I"m not interested in looking at the brain just so we can use a fancy machine," he says. "The real question is what can we do with this fMRI data that we couldn"t do before?" Mischel is applying for an NIH grant to investigate various mental illnesses, like obsessive-compulsive disorder and attention-deficit disorder, in terms of the ability to control and direct attention. Mischel and his team hope to identify crucial neural circuits that cut across a wide variety of ailments. If there is such a circuit, then the same cognitive tricks that increase delay time in a four-year-old might help adults deal with their symptoms. Mischel is particularly excited by the example of the substantial subset of people who failed the marshmallow task as four-year-olds but ended up becoming high-delaying adults. "This is the group I"m most interested in," he says. "They have substantially improved their lives."
Mischel is also preparing a large-scale study involving hundreds of schoolchildren in Philadelphia, Seattle, and New York City to see if self-control skills can be taught. Although he previously showed that children did much better on the marshmallow task after being taught a few simple "mental transformations," such as pretending the marshmallow was a cloud, it remains unclear if these new skills persist over the long term. In other words, do the tricks work only during the experiment or do the children learn to apply them at home, when deciding between homework and television?
Angela Lee Duckworth, an a.s.sistant professor of psychology at the University of Pennsylvania, is leading the program. She first grew interested in the subject after working as a high school math teacher. "For the most part, it was an incredibly frustrating experi ence," she says. "I gradually became convinced that trying to teach a teenager algebra when they don"t have self-control is a pretty futile exercise." And so, at the age of thirty-two, Duckworth decided to become a psychologist. One of her main research projects looked at the relationship between self-control and grade point average. She found that the ability to delay gratificationa"eighth-graders were given a choice between a dollar right away or two dollars the following weeka"was a far better predictor of academic performance than IQ. She said that her study shows that "intelligence is really important, but it"s still not as important as self-control."
Last year, Duckworth and Mischel were approached by David Levin, the cofounder of KIPP, an organization of sixty-six public charter schools across the country. KIPP schools are known for their long workdaya"students are in cla.s.s from 7:25 A.M. to 5 P.M. a"and for dramatic improvement of inner-city students" test scores. (More than 80 percent of eighth-graders at the KIPP academy in the South Bronx scored at or above grade level in reading and math, which was nearly twice the New York City average.) "The core feature of the KIPP approach is that character matters for success," Levin says. "Educators like to talk about character skills when kids are in kindergartena"we send young kids home with a report card about "working well with others" or "not talking out of turn." But then, just when these skills start to matter, we stop trying to improve them. We just throw up our hands and complain."
Self-control is one of the fundamental "character strengths" emphasized by KIPPa"the KIPP academy in Philadelphia, for instance, gives its students a shirt emblazoned with the slogan "Don"t Eat the Marshmallow." Levin, however, remained unsure about how well the program was workinga""We know how to teach math skills, but it"s harder to measure character strengths," he saysa"so he contacted Duckworth and Mischel, promising them unfettered access to KIPP students. Levin also helped bring together additional schools willing to take part in the experiment, including Riverdale Country School, a private school in the Bronx; the Evergreen School for gifted children, in Sh.o.r.eline, Washington; and the Mastery Charter Schools, in Philadelphia.
For the past few months, the researchers have been conducting pilot studies in the cla.s.sroom as they try to figure out the most effective way to introduce complex psychological concepts to young children. Because the study will focus on students between the ages of four and eight, the cla.s.sroom lessons will rely heavily on peer modeling, such as showing kindergartners a video of a child successfully distracting herself during the marshmallow task. The scientists have some encouraging preliminary resultsa"after just a few sessions, students show significant improvements in the ability to deal with hot emotional statesa"but they are cautious about predicting the outcome of the long-term study. "When you do these large-scale educational studies, there are ninety-nine uninteresting reasons the study could fail," Duckworth says. "Maybe a teacher doesn"t show the video, or maybe there"s a field trip on the day of the testing. This is what keeps me up at night."
Mischel"s main worry is that even if his lesson plan proves to be effective, it might still be overwhelmed by variables the scientists can"t control, such as the home environment. He knows that it"s not enough just to teach kids mental tricksa"the real challenge is turning those tricks into habits, and that requires years of diligent practice. "This is where your parents are important," Mischel says. "Have they established rituals that force you to delay on a daily basis? Do they encourage you to wait? And do they make waiting worthwhile?" According to Mischel, even the most mundane routines of childhooda"such as not snacking before dinner, or saving up your allowance, or holding out until Christmas morninga"are really sly exercises in cognitive training: we"re teaching ourselves how to think so that we can outsmart our desires. But Mischel isn"t satisfied with such an informal approach. "We should give marshmallows to every kindergartner," he says. "We should say, "You see this marshmallow? You don"t have to eat it. You can wait. Here"s how.""
KATHLEEN MCGOWAN Out of the Past.
FROM Discover.
RITA MAGIL WAS DRIVING down a Montreal boulevard one sunny morning in 2002 when a car came blasting through a red light straight toward her. "I slammed the brakes, but I knew it was too late," she says. "I thought I was going to die." The oncoming car smashed into hers, pushing her off the road and into a building with large cement pillars in front. A pillar tore through the car, stopping only about a foot from her face. She was trapped in the crumpled vehicle, but to her shock, she was still alive.
The accident left Magil with two broken ribs and a broken collarbone. It also left her with posttraumatic stress disorder (PTSD) and a desperate wish to forget. Long after her bones healed, Magil was plagued by the memory of the cement barriers looming toward her. "I would be doing regular thingsa"cooking something, shopping, whatevera"and the image would just come into my mind from nowhere," she says. Her heart would pound; she would start to sweat and feel jumpy all over. It felt visceral and real, like something that was happening at that very moment.
Most people who survive accidents or attacks never develop PTSD. But for some, the event forges a memory that is pathologically potent, erupting into consciousness again and again. "PTSD really can be characterized as a disorder of memory," says the McGill University psychologist Alain Brunet, who studies and treats psychological trauma. "It"s about what you wish to forget and what you cannot forget." This kind of memory is not misty and watercolored. It is relentless.
More than a year after her accident, Magil saw Brunet"s ad for an experimental treatment for PTSD, and she volunteered. She took a low dose of a common blood-pressure drug, propranolol, that reduces activity in the amygdala, a part of the brain that processes emotions. Then she listened to a taped re-creation of her car accident. She had relived that day in her mind a thousand times. The difference this time was that the drug broke the link between her factual memory and her emotional memory. Propranolol blocks the action of adrenaline, so it prevented her from tensing up and getting anxious. By having Magil think about the accident while the drug was in her body, Brunet hoped to permanently change how she remembered the crash. It worked. She did not forget the accident but was actively able to reshape her memory of the event, stripping away the terror while leaving the facts behind.
Brunet"s experiment emerges from one of the most exciting and controversial recent findings in neuroscience: that we alter our memories just by remembering them. Karim Nader of McGilla"the scientist who made this discoverya"hopes it means that people with PTSD can cure themselves by editing their memories. Altering remembered thoughts might also liberate people imprisoned by anxiety, obsessive-compulsive disorder, even addiction. "There is no such thing as a pharmacological cure in psychiatry," Brunet says. "But we may be on the verge of changing that."
These recent insights into memory are part of a larger about-face in neuroscience research. Until recently, long-term memories were thought to be physically etched into our brain, permanent and unchanging. Now it is becoming clear that memories are surprisingly vulnerable and highly dynamic. In the lab they can be flicked on or dimmed with a simple dose of drugs. "For a hundred years, people thought memory was wired into the brain," Nader says. "Instead, we find it can be rewireda"you can add false information to it, make it stronger, make it weaker, and possibly even make it disappear." Nader and Brunet are not the only ones to make this observation. Other scientists probing different parts of the brain"s memory machinery are similarly finding that memory is inherently flexi ble.
Someday this new science of memory could cure PTSD and other mental traumas. Already it corrodes our trust in what we know and how we know it. It pokes holes in eyewitness testimony, in memoirs, in our most intimate records of truth. Every time we remember, it seems, we add new details, shade the facts, prune and tweak. Without realizing it, we continually rewrite the stories of our lives. Memory, it turns out, has a surprising amount in common with imagination, conjuring worlds that never existed until they were forged by our minds.
On the Trail of the Memory Meme.
Neuroscientists have long viewed memory as a kind of neural architecture, a literal physical reshaping of the microstructure of the brain. In the nineteenth century, the pioneering neuroanatomist Santiago Ramn y Cajal theorized that information was processed in our heads each time an electrical impulse traveled across a synapse, the gap between one nerve cell and the next. Memories were made or altered, he proposed, when structures near the synapse changed.
More than a century later, the textbook description of episodic memory (conscious knowledge of an event) is a more sophisticated version of that same basic idea. Memory formation requires an elaborate chemical ch.o.r.eography of more than a hundred proteins, but the upshot is that sensory information, coded as electrical pulses, zips through neural networks of the brain. The impulses cause glutamate (one of the brain"s main neurotransmitters) to pop out of one nerve cell and travel across the synapse to activate the next by binding to its receptors, chemically active signaling stations on the cell surface. Ultimately the electrical and chemical signals reach the centers of memory, the almond-size amygdala and the banana-shaped hippocampus, adjacent structures buried on either side of the brain.
Neuroscientists believe that memory forms when neurons in these key brain structures are simultaneously activated by glutamate and an electrical pulse, a result of everyday sensory experience. The experience triggers a biochemical riot, causing a specialized glutamate receptor, called NMDA, to spring open and allow calcium ions to flood the cells. The ions stimulate dozens of enzymes that reshape the cells by opening up additional receptors and by prompting the formation of more synapses and new protrusions that contain still more receptors and synapses. In aggregate, these changes make neurons more sensitive to each other and put the anatomical scaffold of a memory in place.
Enacting all these changes takes time, and for up to a few hours the memory is like wet concretea"solidifying but not quite set, still open to interference. Once the process is over, though, the memory is said to be "consolidated." In the textbook description, neuroscientists talk of memory the way geoscientists describe mountainsa"built through a dynamic process, but once established almost impossible to reshape quickly except by extraordinary means. By the late 1990s, this explanation of memory was so widely accepted by neuroscientists that its major author, the Columbia University neuroscientist Eric Kandel, was awarded the n.o.bel Prize. It seemed that the most important questions about memory had been answered.
No wonder, then, that Nadera"at the time a young postdoc studying the neurobiology of fear at New York Universitya"was electrified when he attended one of Kandel"s lectures. "It was so beautiful and so convincing," Nader says. But he began to wonder: What actually happens when we recall the past? Does the very act of remembering undo what happened? Does a memory have to go through the consolidation process again? Nader asked his adviser, the noted fear researcher Joseph LeDoux, if he could study these questions. LeDoux says his initial response was "Don"t waste our time and money," but Nader talked him into it, little suspecting just how far this line of research would go.
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 s.e.xual 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, the 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 five. 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 eight. Apparently, even the most basic facts about a past event (such as who experienced it) could be lost.
Even harrowing memoriesa"the so-called flashbulb memories that feel as if they have been permanently seared into the braina"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 sc.r.a.ps 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 cellsa"a literal engraving of informationa"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 rankeda"a lowly postdoc, only thirty-three 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 a.s.sociate a tone with an elec tric 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 fourteen 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 c.r.a.p,"" 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 receptora"which solidifies memorya"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., forty-three 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 twelve doses of propranolol have shown better results. Collaborating with the Harvard psychiatrist Roger Pitman, who was the first to try propranolol for posttraumatic stress, the McGill group has treated about forty-five 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 inex tricably linked to a feeling of extreme danger. No matter how the phobic person tries, his emotional memory refuses to update itself to incorporate rea.s.suring information. A treatment that restores his emotional memory to a flexible state could help him cope.
Addiction is another kind of pathological remembering, but in this case the memory is pleasurable. Just as adrenaline sears emotional memories into the brain with the help of the amygdala, drugs of abuse enlist the amygdala and the brain"s reward centers to forge unforgettable memories of pleasure. Anything connected to the bliss reawakens the memory, in the form of craving. "When you see someone with a beer and a smoke and you get a craving, you are suffering from reminiscence, from an emotional memory," Brunet says. Adapting experimental methods of forgetting to addiction might make it easier to quit.
The Reconsolidated Life.
While neuroscientists were skeptical of Nader"s findings, cognitive scientists were immediately fascinated that memory might be constantly revamped. It certainly seemed to explain their observations: The home run you hit in Little League? Your first kiss? As you replay these memories, you reawaken and reconsolidate them hundreds of times. Each time, you replace the original with a slightly modified version. Eventually you are not really remembering what happened; you are remembering your story about it. "Reconsolidation suggests that when you use a memory, the one you had originally is no longer valid or maybe no longer accessible," LeDoux says. "If you take it to the extreme, your memory is only as good as your last memory. The fewer times you use it, the more pristine it is. The more you use it, the more you change it." We"ve all had the experience of repeating a dramatic story so many times that the events seem dead, as if they came from a novel rather than real life. This might be reconsolidation at work.
Reconsolidation research has helped foster a growing sense that the flexibility of memory might be functionala"an advantage rather than a bug in the brain. Reconsolidation might be how we update our store of knowledge, by making old memories malleable in response to new information. "When you encounter a familiar experience, you are remembering the original memory at the same time, and the new experience somehow gets blended in," says Jonathan Lee of the University of Birmingham in England, who recently found evidence for this effect in animals. "That is essentially what reconsolidation is." The evident purpose of episodic memory, after all, is to store facts in the hope of antic.i.p.ating what might happen next. From the perspective of survival, constructive memory is an a.s.set. It allows you to pull together sc.r.a.ps of information to simulate the future on the fly.
"The brain knows there is a future," says the neuroscientist Yadin Dudai, head of the department of neurobiology at the Weizmann Inst.i.tute of Science in Israel, who collaborates with Nader and LeDoux. Facing something new, we want to link the novel information with memories to better interpret the situation. If the side effect is a few mistakes, that is probably a small price to pay. "Having a memory that is too accurate is not always good," he says.
Put another way, memory and imagination are two sides of the same coin. Like memory, imagination allows you to put yourself in a time and place other than the one you actually occupy. This isn"t just a clever a.n.a.logy: in recent neuroimaging studies, the Harvard psychologist Daniel Schacter has shown that remembering and imagining mobilize many of the same brain circuits. "When people are instructed to imagine events that might happen in their personal future and then to remember actual events in the past, we find extensive and very striking overlap in areas of brain activation," he says. Other researchers have found that people with severe amnesia lose their ability to imagine. Without memory, they can barely picture the future at all.
The Spotless Mind.
Reconsolidation modifies old memories, but other new research points the way toward erasing them wholesale. One technique for blanking out the past, developed by Joe Tsien at the Medical College of Georgia, flows from his studies of memory formation. When calcium floods a neuron as a memory is formed, it turns on an enzyme called CaMkII (calcium/calmodulin-dependent protein kinase). Among many other things, the enzyme responds to signals from NMDA receptors, leading to more receptor activity and stronger signaling throughout the network of cells.
You would think, therefore, that the more CaMkII, the more robust a memory would be. But in experiments with mice, Tsien has found there is a limit. If he drives CaMkII above the normal limit while the animal is actively remembering an experience, the memory simply vaporizes, as the connections between the cells suddenly weaken. The effect happens within minutes, and it is permanent and selective, affecting the recalled memory while leaving the others unchanged. Indeed, when Tsien trained a mouse to fear both an unfamiliar cage and a particular tone, then pumped up CaMkII while the mouse was in the cage, it forgot the cage-fear memory but not the tone-fear memory. "At the time the memory was retrieved, it disappeared," he says. "It erases the memory being recalled. It is feasible that by manipulating specific molecules, we can selectively alter memories in the brain."
Todd Sacktor, a professor of physiology, pharmacology, and neurology at the State University of New York Downstate Medical Center in Brooklyn, has found a blunter but more powerful technique that can eradicate whole categories of memory. He studies protein kinase M-zeta (PKM-zeta), which is involved in memory maintenance. As calcium rushes into a memory neuron, PKM-zeta is synthesized, linking up with spare glutamate receptors and dragging them to the synapse, where memory construction occurs. With more receptors at the synapse, signals are boosted and amplified and the memory persists.
When Sacktor deactivated PKM-zeta with a compound called zeta-inhibitory peptide (ZIP), he got a spectacular response: total amnesia for one type of memory. Rats that had learned a day or a month before to avoid part of a platform that was rigged with electric shock forgot everything they knew about the location generating the jolt. "You inhibit the PKM-zeta and those glutamate receptors float away very, very fast," he says. "As a result, the memory is losta"very, very fast."
Certain types of memory are encoded in different brain areas, and depending on where Sacktor injects the inhibitor in his animals, he can zap away different categories of memory. In the hippocampus, he erases memory for spatial locations like the platform; in the amygdala, fear memories; in the insular cortex, memories of nauseating taste. Very rarely, Sacktor says, neurosurgeons remove nerve cl.u.s.ters to help disturbed psychiatric patients who do not respond to any other treatment. His research may eventually provide a way to erase memory without causing damage.
The implications are staggering. If stored memories were inscribed in the brain, it is hard to imagine how flipping one chemical switch could erase them so quickly. "It really is a paradigm shift in how people think about long-term memories," Sacktor says. In the old view, erasure should cause permanent brain damage as the synapses are ripped apart. Instead, Sacktor"s rats" brains remain intact. Once the ZIP treatment wears off, the animals behave and even learn normally again. "It"s like wiping a hard disk," he says.
ZIP is nowhere near ready for human use. First, the compound would have to be made activity-dependent in order to target specific memories. You would also have to find a way to get it to the right spot in the brain without using a needle. People are clamoring to be test subjects anyway. When Sacktor"s study first came out in 2006, people, especially rape survivors, tracked him down, imploring him to eradicate their painful memories. "They were suffering," he says. "They couldn"t work or have relationships. Some of them wanted everything erased." They didn"t care that it would also vaporize all they had ever known.
Benevolent Forgetting.
If you feel that you"ve heard this story before, there"s a reason. Moviemakers love the idea of erasing memory, and they work a consistent theme: if you try to undo the past, you pay the price. Nader"s research supposedly inspired the 2004 movie Eternal Sunshine of the Spotless Mind, in which Jim Carrey and Kate Winslet both pay to have memories of their painful love affair obliterated. Needless to say, it makes them both miserable. But not as miserable as Arnold Schwarzenegger"s character in Total Recall, from 1990, in which he learns that his real memories have been erased, that his life is a fake, and that his faux wife, played by Sharon Stone, is trying to kill him.
You don"t have to be a rape survivor or a soldier to have memories you would rather forget. For most people, though, unpleasant memories also serve as a guide. Indeed, some fear the consequences of undermining appropriately bad memoriesa"say, allow ing a murderer to forget what he did. Members of the President"s Council on Bioethics warn that altering the memory of a violent crime could unleash moral havoc by lifting the repercussions of malice. "Perhaps no one has a greater interest in blocking the painful memory of evil than the evildoer," their report cautions.
Beyond all this, memory is the essence of who we are. Eternal Sunshine of the Spotless Mind is difficult to watch as Carrey"s character flails around in confusion and loss. His fear and desperation may be a realistic portrayal of what it would be like to erase your memory: basically, a waking nightmare. Memory is how you know who you are, how you point yourself toward a destination. We already know that people with Alzheimer"s disease do not feel liberated. They feel utterly lost.
Thankfully, Nader and Brunet"s studies suggest much more benevolent possibilities. If he had received reconsolidation therapy, Carrey"s character would not have forgotten Winslet"s. He simply wouldn"t care that much about her anymore. He would be able to look at his failed relationship as if through the wrong end of a telescope. What is on the other side is still visible, but it is tiny and far away.
That is basically what all these scientists hope to do. Nader, Brunet, and Pitman are now expanding their PTSD study with a new, $6.7 million grant from the U.S. Army, looking for drugs that go beyond propranolol. They are increasingly convinced that reconsolidation will prove to be a powerful and practical way to ease traumatic memories. Sacktor also believes that some version of the techniques they apply in the lab will eventually be used to help people. Most recently, LeDoux"s lab has figured out a way to trigger reconsolidation without drugs to weaken memory, simply by carefully timing the sessions of remembering. "The protocol is ridiculously simple," LeDoux says.
None of these researchers are looking to create brain-zapped, amoral zombiesa"or even amnesiacs. They are just trying to take control of the messy, fragile biological process of remembering and rewriting and give it a nudge in the right direction. Brunet"s patients remember everything that happened, but they feel a little less tortured by their own pathological powers of recollection. "We"re turning traumatic memories into regular bad memories," Brunet says. "That"s all we want to do."
JOHN COLAPINTO Brain Games.
FROM The New Yorker.
ONE MORNING IN JANUARY, a tall, gray-haired man whom I will call Arthur Jamieson arrived at the Mandler Hall psychology building at the University of California, San Diego, in La Jolla. Jamieson is seventy years old and lives in the Midwest. He is a physician and an amateur cellist and has been married for forty-seven years. He also suffers from a rare and bewildering condition called apotemnophilia, the compulsion to have a perfectly healthy limb amputateda"in his case, the right leg, at midthigh. He had come to La Jolla not to be cured of his desire (like most people with the syndrome, he believed that relief would come only with the removal of the limb) but to gain insight into its cause. To that end, he had scheduled a meeting with Dr. Vilayanur"S. Ramachandran, an Indian-born behavioral neurologist who is the director of the Center for Brain and Cognition at UCSD and who has a reputation among his peers for being able to solve some of the most mystifying riddles of neuroscience.
Ramachandran, who is fifty-seven, has held prestigious fellowships at All Souls College in Oxford and at the Royal Inst.i.tution in London. His 1998 book, Phantoms in the Brain, about rare neurological disorders, was adapted as a miniseries on BBC television, and the Indian government recently accorded him the t.i.tle Padma Bhushan, the country"s third-highest civilian honor. But it is the awe that he inspires in his scientific colleagues that best illuminates his position in neuroscience, where the originality of his thinking and the simple elegance of his experiments give him a unique status. "Ramachandran is a latter-day Marco Polo, journeying the silk road of science to strange and exotic Cathays of the mind," Richard Dawkins once wrote. Eric Kandel, the Columbia University neuroscientist whose work on the physiological basis of learning and memory earned him a n.o.bel Prize in 2000, invoked two pioneering brain scientists to describe Ramachandran"s contribution to the field: "He is a continuation of a tradition in neurology that goes back to the nineteenth century, to giants like Broca and Wernicke, who gave us, from studying clinical material, enormous insights into the functioning of the human mind."
Ramachandran, who has dark skin, curly black hair, and a mustache, cultivates a slightly rebellious image, often wearing dark polo shirts and a black leather jacket. However, when he meets with patients he tends to dress more conservatively. The day that he met with Jamieson, he was wearing a wool blazer and a tie. He greeted Jamieson in his office, whose dcor reflects Ramachandran"s many interests outside neurology: Darwinian evolution, plate tectonics, Indian art, Victorian medicine, paleontology, optical illusions. A four-foot stone sculpture of the G.o.d Shiva stood behind his desk. On one wall, there was a 300-million-year-old fossil of a mesosaur, a freshwater reptile found only in South America and Africa (and which, as Ramachandran likes to explain, is a central piece of evidence in the theory of continental drift). On a side table was an array of antique scientific items: a bra.s.s Gilbert telescope, a hand-cranked electrical machine for curing "nervous diseases," a box of gla.s.s tubes containing Victorian homeopathic medicines. Another table held what appeared to be a smoothly sanded wooden sculpture of a woman"s pelvis. Ramachandran often tells visitors that the object is a Henry Moore before revealing, with a booming laugh, that it is actually a specimen of the world"s largest seed, from the coco-de-mer palm.
Ramachandran listened closely as Jamieson talked about his condition. In a specialty that today relies chiefly on the power of multi-million-dollar imaging machines to peer deep inside the brain, Ramachandran is known for his low-tech method, which often involves little more than interviews with patients and a few hands-on testsa"an approach that he traces to his medical education in India, in the 1970s, when expensive diagnostic machines were scarce. "The lack of technology actually forces you to be ingenious," he told me. "You have to rely on your clinical ac.u.men. You have to use your Sherlock Holmes-like deductive abilities to figure things out."
Ramachandran suspected that apotemnophilia was a neurological disorder and not, as Freudians have theorized, a psychological syndrome a.s.sociated with repressed s.e.xual desires. After interviewing several apotemnophiliacsa"Jamieson is the fifth person with the disorder whom he has studieda"Ramachandran was struck by the fact that all of them said they became aware of the compulsion in early childhood, that it centered on a particular limb (or limbs), that they could draw a line at the exact spot where they wanted the amputation to occur, and that they attached little or no erotic significance to the condition. Furthermore, none rejected the limb as "not belonging" to them, as some stroke victims do in the case of a paralyzed arm or leg, and as Ramachandran had predicted they might. Instead, they said that the limb over-belonged to them: it felt intrusive. "If you talk to independent apotemnophiliacs, they say the same b.l.o.o.d.y things," Ramachandran told me. ""The line for cutting is here." "It started in early childhood." "It"s over-present." They"re not crazy."
Jamieson, who was born and raised in New York City, first remembers having an unusual relationship with his right leg when, at around the age of seven, he was waiting for a bus. He found himself thinking that if he stuck out his leg it would be crushed and severed by the bus. "What came to me was not "No, I don"t want to do that" but "How would I ever explain this?"" he told Ramachandran. In recounting his childhood memories, he said, "One of the things that"s astonishing to me is how clear these recollections are."
"These things are very salient," Ramachandran said in a resonant baritone, which carries a British-inflected Indian accent. "It"s interesting to contrast these very clear-cut descriptions with these vague, Freudian notions about this whole phenomenona"that it"s primarily connected with s.e.xual stuff."
"Yeah," Jamieson said with disgust. "I"ve got no desire to cozy up to anyone with a stump. It"s psychobabble."
Asked where he would make the cut line for the amputation, Jamieson unhesitatingly drew an index finger across the middle of his right thigh. As to whether he felt that his leg didn"t "belong" to him, Jamieson was emphatic. "Somehow, for me, that just doesn"t compute, that kind of language," he said. "I have always been fascinated by amputation and wished that I had one. Why? Who the h.e.l.l knows?"
Ramachandran is one of a dozen or so scientists and doctors who, in the past thirty years, have revolutionized the field of neurology by overturning a paradigm that dates back more than a hundred years: that of the brain as an organ with discrete modules (for vision, touch, pain, language, memory, and so on) that are fixed early in life and immutable. Neurological syndromes, such as paralysis from stroke, forms of mental illness, and the perception of pain in an amputated limb (a phenomenon known as phantom-limb pain), were considered largely untreatable. But Ramachandran and other researchers have shown that the brain is what scientists call "plastic"a"it can reorganize itself. Not only are different regions of the brain engaged in ongoing communication with one another, with the body, and with the surrounding world; these relationships can be manipulated in ways that can reverse damage or dysfunction previously believed to be permanent. Ramachandran"s work with patients at UCSD has led to one of the most effective treatments for chronic phantom-limb pain and to a new therapy for paralysis resulting from a stroke. (In both instances, his treatment involves only a five-dollar household mirror.) It has also provided suggestive insights into the physiological cause of such mystifying syndromes as autism.
Until the mid-1990s, Ramachandran"s specialty was visual perception, but he had been interested in brain science since his days as a medical student in India. He made the switch to neurology in midcareer. "A scientist with that kind of creativitya"it"s rare," says Michael Merzenich, a neuroscientist at the University of California, San Francisco, whose experiments with monkeys in the 1980s provided much of the groundwork for understanding brain plasticity. "It"s usually not allowed, in some sense. You"re not supposed to be a b.u.t.terfly like that."
Little about Ramachandran"s scientific career has been conventional. He was born in Tamil Nadu, in southern India, to a Hindu family of the Brahman caste. His grandfather, Alladi Krishnaswamy Iyer, was the attorney general of Madras and a framer of India"s const.i.tution. Ramachandran"s father was a diplomat in the United Nations. However, science ran in the family. His mother had a master"s degree in mathematics; one uncle was a professor of optics at the University of Sydney; another was an expert in theoretical physics and relativity.
At around the age of nine, Ramachandran began collecting fossils and seash.e.l.ls and became fascinated by taxonomy and evolution. He wrote to a conchologist at the American Museum of Natural History. "Here"s this little kid from India sending him sketches of sh.e.l.ls and asking, "Are these new species?"" Ramachandran said. "And he is writing back saying, "A, B, C, and D are well-known species; E is very rare and has not been reported from your locality and is very interesting." So for a while I was the only conchologist in India!" Ramachandran continues to collect fossils and has gone on digs in South Dakota, where he has found specimens of trilobites and a 30-million-year-old oreodon, a sheeplike creature. His most notable find, however, was not in the field but at the annual Tucson Gem and Mineral Show, in 2004, when he noticed on a table, amid heaps of bones and rocks, a skull that he thought could be a new species of ankylosaur, a herbivorous dinosaur from the Jura.s.sic and Cretaceous periods. Ramachandran"s friend Cliff Miles, a paleontologist, was with him and suggested that Ramachandran buy the fossil so that it could be studied and described. In January of this year, Miles and his brother Clark, also a paleontologist, announced the discovery of a new species of ankylosaur from the Upper Cretaceous period: Minotaurasaurus ramachandrani.
In his early teens, Ramachandran began conducting experiments in chemistry and biology in a makeshift laboratory under the staircase in the family"s house in Bangkok, where his father was stationed. He also read books on the history of science and was struck by the role of intuition and play in many important discoveries: Galileo adapting a child"s spygla.s.s and discovering the moons of Jupiter, which led him to challenge the geocentric model of the universe; Faraday tinkering with a magnet and coil and discovering electromagnetism. Ramachandran often recounts these anecdotes to his students. "These stories are inspirational and fun," he told me. "But they"re also telling you about how to do science."
Ramachandran"s father discouraged him from pursuing a career as a researcher. "My father was intensely pragmatic," Ramachandran said. "He told me, "Forget about chemistry and biology and all that. I know it"s fun, but you"re not going to make a living out of this."" He urged his son to become a doctor, and Ramachandran duly enrolled at Stanley Medical College, in Madras. But he continued to read British and American science journals, and in his sec ond year, he devised an experiment that was inspired in part by conversations he had had as a child with his uncle the optics professor. The experiment addressed a question debated by experts since the time of Hermann von Helmholtz, in the late nineteenth century, about how the brain harmonizes the two slightly different images seen by each eye. For years, scientists believed that when the eyes are given conflicting informationa"for instance, a green image in front of one eye and a red one in front of the othera"the brain accepts input from one retina at a time. Ramachandran, using an old-fashioned stereoscope and volunteers from his medical-school cla.s.s, found that, when presented with a pattern that was colored differently for each eye, his test subjects continued to see in three dimensions. He concluded that a neural channel was still active in the "shut-down" eyea"even though his subjects were consciously seeing only one eye"s color at a time. "This suggests that concepts of retinal rivalry need drastic revision," Ramachandran wrote in a report of the experiment.
He sent the report to Nature in December 1971, a few months after his twentieth birthday. "To my astonishment, it was published without revision," Ramachandran told me. Soon he published a more ambitious paper, "The Role of Contours in Stereopsis," which explored ideas about visual processing that became influential decades later. Ramachandran also wrote to one of the foremost vision scientists at the time, Dr. William Rushton, a professor of physiology at Trinity College, Cambridge, describing several original experiments that he was eager to try. The letter was pa.s.sed to Oliver Bradd.i.c.k, a psychology lecturer who worked on vision. "The letter was obviously the product of a very fertile young mind," Bradd.i.c.k, who is now a professor of experimental psychology at Oxford, told me. "Perhaps a little kind of spinning off in all directions. But he had all these great ideas."
Bradd.i.c.k and another researcher, Fergus Campbell, invited Ramachandran to visit Cambridge for a month, at the university"s expense, to conduct experiments. The results of one experiment, on which Bradd.i.c.k collaborated, were published as "Orientation-Specific Learning in Stereopsis," in the journal Perception. "Maybe fifteen years later, various people started publishing in this area of how specific developments of perceptual skills could be highly related," Bradd.i.c.k told me.
Ramachandran returned to Madras to complete his medical degree, and in the fall of 1974 he enrolled at Trinity College to begin a Ph.D. in visual perception. "I thought they"d all be like Faraday and the great Renaissance scientists," he said of the researchers he met in England. "Ninety percent of them are like Indian scientists, or scientists here, for that matter, or anywherea"it"s a nine-to-five job. They"re not moved by the great romantic spirit of science, and they"re not great Renaissance people. So I was a bit disillusioned. Then I ran into Richard Gregory soon after I arrived, and I said, "Well, at least there"s some of them here!""