The Best American Science and Nature Writing 2010 Page 13

  Buoyed by these successes, in the mid-nineties Ramachandran abandoned his work in visual perception to devote himself to neurology. "Vision was getting overcrowded," he told me. Neurology seemed like virgin territory. Much of the specialty was concerned with describing strange syndromes rather than with explaining their cause or alleviating symptoms. "You've got a hundred papers saying, 'My God, they can move their phantom'—but it stayed at that level, a descriptive level," Ramachandran said. "We said, 'Look, we can do experiments. What if you do this to the patient?' And I took that same style to other syndromes. Then the sky was the limit. No one was studying these things."

  Gradually, Ramachandran began to specialize in rare conditions and disorders, including the Capgras delusion, in which an otherwise lucid victim of a head injury insists that close loved ones (spouses, parents, children) are impostors. Freudians had theorized that Capgras patients were suffering from unbearable Oedipal desires aroused by the blow to the head, but Ramachandran demonstrated that severed neural pathways between the facial-recognition areas of the visual cortex and the emotional centers of the brain were responsible for the disorder. He also investigated post-stroke syndromes, in which patients deny that a paralyzed limb has become immobile or, in a more severe version, insist that the paralyzed arm or leg belongs to someone else. Ramachandran traced the delusion to damage in the right superior parietal lobule, the body-map region, where the discrepancy between the absence of signals from the limb to the brain and the presence of the limb on the body results in a defensive rationalization that the arm or leg must be someone else's. A few years ago, Ramachandran began studying apotemnophilia, the compulsion to amputate a healthy limb. He is, he said, "ninety-five percent sure" that he has figured out the cause of the disorder. His consultation with Arthur Jamieson strengthened this conviction.

  After interviewing Jamieson in his office, Ramachandran led him to a lab for a galvanic skin response, or GSR, test, which would reveal how Jamieson's legs reacted to a mild pain stimulus. He escorted Jamieson into a small room that held only a table, a desktop computer, and two chairs. He asked Jamieson to sit with his back to the computer. Then David Brang, one of Ramachandran's graduate students, attached a sensor to the middle two fingers of Jamieson's right hand using a Velcro strap. The sensor would measure the reaction of Jamieson's sympathetic nervous system by monitoring the sweat on his fingers. With a sterilized pin, Brang pricked Jamieson's legs at random points, waiting a few seconds between each prick. A scrolling graph on the computer screen registered Jamieson's responses.

  The unaffected leg—the left one—and the right leg above where he wished to have it amputated showed a normal response: the graph at first shot upward with each prick, but with further pricks it ceased to rise, then began to flatten out, indicating that Jamieson's nervous system was getting used to the stimulus. But when Brang pricked Jamieson anywhere on the leg below the amputation line, his nervous system responded with increasing distress, the graph climbing higher and higher with each prick.

  The experiment seemed to support Ramachandran's theory about the disorder. He believed that people with apotemnophilia had a deficit in the right superior parietal lobule, where the body-image map is assembled. According to this notion, Jamieson was missing the neurons in the map that corresponded to his right leg from the midthigh down. He had normal sensation in the unwanted part of his leg—he felt the pin prick. But when the pain signal traveled to the right superior parietal lobule, there was nothing in the body-image map to receive it.

  "So there's a big discrepancy—a clash—and the brain doesn't like discrepancies," Ramachandran said. "When a discrepancy comes in, it says, 'Shit! What the hell is going on here?' and it kicks in and sends a message to the insular part of the brain, which is involved in emotional reactions—so you're getting this crazy GSR." In apotemnophilia sufferers, the discrepancy causes a feeling of distress that is no less agonizing for being below the level of conscious awareness.

  In the past two years, Ramachandran has tested four other apotemnophiliacs using MEG brain scans. "You touch them any where in the body and the right superior parietal lobule lights up, as you would expect," Ramachandran said. "But if you touch him here"—he gestured to a point on Jamieson's leg below the amputation line—"nothing happens." Ramachandran said that the experiment needed to be repeated by other researchers, but, he added, "This takes a spooky psychological phenomenon and, as Shakespeare said, gives it a 'habitation and a name.'" Furthermore, the findings suggested to Ramachandran a possible method for alleviating the oppressive sensations in the unwanted limb.

  Later, he asked Jamieson to stand in a corner of his office and placed a three-foot-high mirror in front of him in such a way that in place of his right leg Jamieson saw his left, which he held bent at the knee. Jamieson gazed into the mirror. "Astonishing," he said. For a moment, the leg looked "right."

  The mirror was a less risky kind of sham amputation than the method that Jamieson had recently adopted: injecting anesthetic to block the sciatic nerve of his right leg, shutting down the touch sensation. (As a physician, Jamieson had learned how to perform the nerve block.) The anesthetic provided up to five hours of relief, Jamieson said. Apotemnophiliacs, like transsexuals, anorexics, and others with body-image disorders, often do not seek a "cure" for their condition, and Ramachandran spoke gingerly when he suggested that using both the mirror and the drug could potentially yield powerful results. "It's conceivable—nobody knows—but if you do this repeatedly, and I'm not suggesting that you try this, because I know you don't want to be 'changed,' but if you do it repeatedly, both the injections and the visual amputation, it might actually eliminate this desire," he said.

  Ramachandran describes his approach to science as "opportunistic": "You come across something strange—what Thomas Kuhn, the famous historian and philosopher of science, called 'anomalies.' Something seems weird, doesn't fit the big picture of science—people just ignore it, doesn't make any sense. They say, 'The patient is crazy.' A lot of what I've done is to rescue these phenomena from oblivion." Ramachandran is conscious of the fact that this focus might lead some to think that he works on the margins of his field. "Now, you could say that about Oliver," he told me, referring to his friend and colleague Oliver Sacks, the neurologist and author of The Man Who Mistook His Wife for a Hat. "'Oh, he studies spooky things,'" Ramachandran went on. "That's bullshit. This man has deep insight into the human condition. He's a poet of neurology." Ramachandran says that his own interest in oddities is not for their own sake but for what they can tell us about the normal brain, including, he said, "very enigmatic aspects of the brain that few people have dared to approach, like what is a metaphor? How do you construct a body image? Things of that nature."

  In 1999 Ramachandran turned his attention to synesthesia, an intermingling of the senses that causes some people to see each letter of the alphabet in a particular color. Others identify musical notes with colors; still others mix touch sensations with strong emotions, so that sandpaper might evoke disgust; velvet, envy; wood grain, guilt. Vladimir Nabokov described his letter-color synesthesia in Speak, Memory: "I see q as browner than k, while s is not the light blue of c, but a curious mixture of azure and mother-of-pearl." As an artist, Nabokov was, according to Ramachandran's research, eight times more likely to have synesthesia than someone who is not an artist; the fact that Nabokov's mother also had the condition suggested a genetic component. (The phenomenon runs in families.)

  The most common synesthesia is number-color. Ramachandran believed it was not coincidental that the fusiform gyrus, where number shapes are processed in the brain, lies next to the area where colors are processed. He suspected that a cross-wiring in the brain, similar to that in phantom-limb patients, was responsible. Brain scans confirmed his hunch: in synesthetes, there are excess neural connections between the two brain centers. This suggested to Ramachandran that the syndrome arises from a defect in the gene responsible for pruning away the neural fibers that connec
t the various centers of the brain as it develops early in life. "What do artists, poets, and novelists have in common?" Ramachandran asked me. "The propensity to link seemingly unrelated things. It's called metaphor. So what I'm arguing is, if the same gene, instead of being expressed only in the fusiform gyrus, is expressed diffusely through the brain, you've got a greater propensity to link seemingly unrelated brain areas in concepts and ideas. So it's a very phrenological view of creativity."

  In the mid-nineties, Ramachandran read a paper by Italian researchers who had discovered that a set of neurons in the frontal lobes of monkeys fired not only when the monkeys reached for an object but also when they observed another monkey performing the same action. Ramachandran wondered if these so-called "mirror neurons" also exist in humans—a difficult thing to test, since the Italians had inserted electrodes into the brains of living monkeys, a technique that it is impossible to use on people. But Ramachandran knew of experiments from the 1950s in which noninvasive EEG scans were used. These had shown that deliberate movements in humans suppress a kind of brain activity in the motor cortex called mu waves. Ramachandran and a postdoctoral fellow, Eric Altschuler, ran EEGs on volunteers as they observed another person performing an action such as opening and closing a hand. The tests showed that merely witnessing an action in others caused mu-wave suppression in the watcher—evidence that mirror neurons exist in humans, too. Other researchers have since confirmed that people have several systems of mirror neurons, which perform different functions.

  "So let's take the broader theoretical implications of this," Ramachandran said one afternoon while we were visiting the San Diego Rehabilitation Institute at Alvarado Hospital, where he had examined a paralyzed stroke patient suffering from limb denial. He was sitting in the hospital cafeteria with the clinic's medical director, Lance Stone. "These mirror-neuron experiments are showing that, through and through, the brain is a dynamic system not only interacting with your skin receptors, up here"—he pointed at his own head—"but with Lance!" He pointed across the cafeteria table at Dr. Stone. "Your brain is hooked up to Lance's brain! The only thing separating you from Lance and me is your bloody skin, right? So much for Eastern philosophy." He laughed, but he wasn't kidding. Ramachandran has dubbed mirror neurons "Gandhi neurons"—"because," he said, "they're dissolving the barrier between you and me."

  Ramachandran wondered whether mirror neurons were implicated in autism, a condition whose primary characteristic is severe social impairment, including an inability to imitate and a lack of empathy. Ramachandran, Altschuler, and Jaime Pineda, a UCSD colleague, ran EEGs on autistic children. They got normal mu-wave suppression when the subjects moved their own hands. But when the children watched another person move his hand, their brains didn't respond. At a neuroscience conference in 2000, Ramachandran and his coauthors presented their findings and speculated that autism was caused by a deficit in the mirror-neuron system. The idea initially met with resistance from autism researchers, some of whom argue that the disorder is caused primarily by deficits in the cerebellum. Unlike his earlier foray into ichthyology, Ramachandran was entering a sphere of science fraught with politics. "The trouble is, it's a minefield," he told me. "The parents are involved. There's big money involved. Suppose you invested your life in saying that the cerebellum is what's going on, then someone comes along and spends one year on it and says, 'It's the mirror-neuron system'?"

  In the past nine years, however, mirror neurons have become a central topic in autism research. Almost at the same time as Ramachandran, a group in Scotland had also suggested the link. Among those who have provided further evidence are researchers at the Helsinki University of Technology, who used MEG scans to show mirror-neuron deficits in autistic teenagers and adults. Lindsay Oberman, a former graduate student of Ramachandran's, who now works as a postdoctoral fellow at Beth Israel Deaconess Medical Center in Boston, has begun using a technology called trans-cranial magnetic stimulation—a technique that triggers targeted areas of neurons in the brain—to influence brain plasticity in autistics. "So far, we have done some amazing things," Oberman has written. "We have found evidence that we can improve the functioning of the mirror-neuron system and some communication skills following repeated application of TMS."

  On the last day of my visit with Ramachandran, I attended the lab discussion that he holds each Monday with his postdoctoral and graduate students at the Center for Brain and Cognition Laboratory, on the second floor of Mandler Hall. The lab, a room of modest size, was dominated by a long central table heaped with the strange tools of Ramachandran's trade: a foam-rubber hand of the type you buy at a horror shop (for a demonstration that Ramachandran likes to do to show visitors how the brain projects touch sensations onto objects that are not part of the body); a mirror ball of the type that M. C. Escher liked to draw; a boxed set of the BBC miniseries of Sherlock Holmes (for inspiration); several plastic minimizing lenses (Ramachandran has found that viewing a painful arm or leg through a lens that makes the limb look smaller dramatically reduces pain); a reflective metal tube that could be twisted into various amoebic shapes (when I asked if this puzzle had "experimental significance," Ramachandran said, "No," then quickly corrected himself: "Well, it's fun"); a series of oddly shaped metal boxes outfitted with slanting mirrors (for inducing perceptual distortions in those who peer through the eyeholes); and a plaster cast of Minotaurasaurus ramachandrani, a creature that resembles a medieval gargoyle, with three nasal openings on either side of its ridged and crenellated head. Ramachandran has asked one of his postdocs, Paul McGeoch, to perform a CAT scan of the skull in order to learn about the creature's olfactory lobes, and, in this way, to test Ramachandran's theory that his ankylosaur's heightened sense of smell might allow the beast to sniff out mates or carrion from a great distance (although it was more likely a vegetarian).

  Seated around the table were members of Ramachandran's research group. Most were in their middle to late twenties, except for a man in his eighties with a British accent: John Smythies, whom Ramachandran introduced to me as the person who launched the drug revolution in the sixties. Smythies demurred, explaining that as a postdoc at Cambridge in the fifties, while performing psychopharmacology experiments involving mescaline, he had merely introduced Aldous Huxley to a colleague, who then administered to Huxley the hallucinogens that led him to write The Doors of Perception, which later became a bible of the Woodstock generation.

  Ramachandran, who was dressed in his usual black leather jacket and dark polo shirt, took a seat at the table and fielded questions from his students, helping them to refine their methodologies and using the brisk interchanges to hone ideas for research. At one point, Lisa Williams, a Ph.D. student who specializes in schizophrenia—a disorder that Ramachandran first began exploring about a decade ago—mentioned in passing the difficulty that schizophrenics have in differentiating between phenomena that are internally and externally generated.

  "Oh!" Ramachandran cut in. "Speaking of that, I have an idea—I'm sure it's been done—but you know that when people think to themselves you get unconscious movements of the vocal cords? Now, has anybody done that with schizophrenia to see if it's enhanced?"

  "I don't know," Williams said. "I'll look that up."

  If such enhanced subvocalization occurs when schizophrenics think, that would support Ramachandran's view of the brain as an organ in dynamic equilibrium—and of mental illnesses as resulting from a neurological disruption that destroys that equilibrium. In the case of schizophrenia, whose sufferers often complain of "hearing voices," Ramachandran suspected damage or deficit in a sensory mechanism in the vocal cords, which, when normal people think, sends a signal to the brain indicating "This is simply a thought; no one is actually saying this." If this mechanism was damaged, the subconscious movement of the vocal cords could be interpreted as an outside voice speaking in one's head.

  "By the way," Ramachandran continued, "I have a theory that if you take people with carcinoma of the larynx, and you remov
e the vocal cords, and they think to themselves, they may actually start hallucinating. A prediction."

  This remark prompted Laura Case, a first-year graduate student who has focused on autism, to speak. "That could be interesting in autism, too," Case said. "Because if they lack the robust mirror activation for actions, which they do—"

  Ramachandran interjected, "Then they confuse—so they may confuse their own vocalizations with somebody else's! And people have linked autism to schizophrenia. The old theory was that it was early-childhood schizophrenia! Was that a coincidence?"

  The discussion proceeded in this freewheeling manner for more than an hour, with Ramachandran seizing on notions that seemed to offer fruitful possibilities for further investigation and tactfully deflecting those which he thought were dead ends. When the discussion ended, at 6 P.M., and Ramachandran's students had departed, I asked him if he thought that his work was aimed at constructing a "grand unified theory" of the brain. He said that neuroscience was still too young a discipline for such an ambition. Nevertheless, in recent years he has increasingly focused on the biggest mystery of the brain: consciousness. Mirror neurons play a role, he thinks. "One of the theories we put forward," he said, as he packed up his bag, "is that the mirror-neuron system is used for modeling someone else's behavior, putting yourself in another per son's shoes, looking at the world from another person's point of view. This is called an allocentric view of the world, as opposed to the egocentric view. So I made the suggestion that at some point in evolution this system turned back and allowed you to create an allocentric view of yourself. This is, I claim, the dawn of self-awareness."