The Best American Science and Nature Writing 2010 Page 12

  During his four years at Cambridge, Ramachandran commuted regularly to Bristol to design experiments with Gregory. They have since written a number of scientific papers together, including groundbreaking work on the blind spot, the region at the back of the eyeball where the retina's photoreceptors are interrupted by the optic nerve. This region creates a gap in our vision the size of a palm held at arm's length, but, owing to several strategies of the brain, we never perceive it. Using optical illusions to trick the eyes and the brain, Ramachandran and Gregory determined how the brain "fills in" the gap, and published influential articles on stroke victims suffering from scotoma—a particularly large blind spot sometimes caused by a focal lesion in the visual cortex.

  In the mid-nineties, Gregory visited Ramachandran at UCSD to undertake further experiments on scotoma, but they were unable to find a patient with a focal lesion. Instead, they spent Gregory's weeklong visit investigating a phenomenon that had long fascinated Ramachandran: the reported ability of flounder to cam ouflage itself against patterned backgrounds. Leading ichthyologists disagreed about whether the fish changed its appearance or whether the camouflage effect was an illusion. Ramachandran's local pet store had no cold-water flounder, so he bought five peacock flounder, a related species that lives in tropical coral reefs. The men placed the fish on the bottom of four small tanks against various backgrounds: widely spaced polka dots, a neutral gray, and two checkerboard patterns. The fish, whose natural tendency is to lie flat on the sea bottom, precisely matched on their bodies the patterns at the bottom of the tanks—and they did so within two to eight seconds, far faster than the hours and, in some cases, days reported by researchers using cold-water flounder. Ramachandran and Gregory surmised that the rapid change was an adaptive mechanism, since the species lived among bright colors and patterns. The experiment, which they meticulously documented in photographs and on videotape, effectively ended the debate on flounder camouflage—and, incidentally, throws an instructive sidelight on visual processing in human beings. Even though the fish sees the background close up and in a distorted, slanted perspective, it re-creates the pattern on its body with perfect fidelity, as viewed from directly above. Human beings, Ramachandran points out, visually process the world in the same way. "Your eyeball distorts the image—it's curved," he says. "Your lens inverts it—it's upside down. And your two eyes double it. The brain interprets the image."

  When they wrote up the results of the experiment, Ramachandran and Gregory laced their paper with puns. In a caption for a photograph showing one fish on a polka-dot background, they wrote, "Spot the flounder," and they said that they had conducted the experiments "just for the halibut."

  "So we sent this off to Nature," Ramachandran told me, "and back come the referees' comments: 'Brilliant paper, publish it right away, but remove all the puns.'" He laughed. The paper, "Rapid Adaptive Camouflage in Tropical Flounders," was published in a 1996 issue of Nature. "Since then," Ramachandran said, "I get papers on octopuses and squids and fish—because they all think I'm an expert on ichthyology!"

  In 1983 Ramachandran joined the psychology department at UCSD as an assistant professor working on visual perception. In 1991 he became interested in the work of Tim Pons, a neuroscientist at the National Institute of Mental Health, who had been investigating the ability of neurons in the sensory cortex to adapt to change.

  The sensory cortex is in the deeply ridged tissue that makes up the outermost layer of the brain. Until recently, much of what was known about it was the result of the work of Wilder Penfield, a neurosurgeon in Montreal who, beginning in the 1930s, had conducted a series of extraordinary experiments while performing open-skull operations on cancer and epilepsy patients. Seeking to distinguish healthy tissue from diseased tissue, Penfield touched the surface of his patients' brains with an electric probe, and, because the brain lacks pain receptors, the patients were fully conscious and able to talk to him about what they felt. As he stimulated different areas of the brain, his patients reported feeling touch sensations in specific parts of their bodies. In this way, over several decades and hundreds of operations, Penfield mapped areas of the brain according to their corresponding body parts. The "Penfield homunculus," as it came to be called, is oriented upside down: the areas corresponding to the feet and the legs are at the top of the brain, the arms and the hands are in the middle, and the face is near the bottom. Body parts with the greatest sensitivity—lips, fingertips—take up a far larger area of the cortical surface than less sensitive areas.

  The regions representing separate body parts on the Penfield homunculus, like the brain centers, were believed to be unchangeable. This view came under challenge as the technology for mapping the brain improved. Whereas Penfield had used a large electrode that affected thousands of neurons at a time, brain researchers in the fifties began to use tiny microelectrodes, which could be inserted into the brains of animals to record the firing of single neurons and, thus, communication among them. In the seventies, Michael Merzenich became expert at using microelectrodes to map the sensory cortex of monkeys. In one experiment, he mapped a monkey's hand area in the brain, then amputated its middle finger. Some months later, he remapped the monkey's hand and discovered that the brain map for the missing finger had vanished and been replaced by maps for the two adjacent fingers, which had spread to fill the gap. The results, published in the Jour nal of Comparative Neurology in 1984, were decisive proof that the brain can reorganize itself—at least across very short distances of one to two millimeters.

  Pons, at NIMH, was curious to know whether the brain could accomplish more dramatic reorganizations, across greater distances. He wondered what happened in the brains of monkeys that had lost brain input from an entire hand and arm, and he thought that he could procure some animals to test. In 1981 a member of PETA had infiltrated a Maryland lab where a researcher studying stroke paralysis had severed the sensory nerves in a group of macaque monkeys that connected the animals' arms to their spinal cords—a procedure known as deafferentation. PETA released photographs of the monkeys, and the animals were seized and placed in the custody of the National Institutes of Health. By 1990 the monkeys had grown old and were about to be euthanized. Pons successfully appealed to the NIH to allow him to conduct a final experiment on four of them.

  Pons anesthetized the first animal, opened its skull, and inserted electrodes into the brain-map area for the deafferented arm. He stroked the corresponding limb. As expected, the brain electrodes recorded no activity, since no messages were being sent to the brain from the arm. But when Pons stroked the monkey's face, the neurons in the map of the deafferented arm began to fire. The experiment showed that the neurons in the face map had invaded the area of the hand-and-arm map, which had been inactive for twelve years. Fourteen millimeters of the monkey's arm map had been reorganized to process sensory input from the face. Pons repeated the experiment on three more monkeys and published the results in Science in 1991, as a paper titled "Massive Cortical Reorganization After Sensory Deafferentation in Adult Macaques."

  Ramachandran read Pons's paper and wondered whether it could help solve the long-standing medical puzzle of phantom limbs. Many amputees continue to experience sensations—often painful—from a missing limb, and the phenomenon has baffled scientists since it was first reported, in the sixteenth century, by the French surgeon Ambroise Paré. Ramachandran says that his interest in phantom limbs was a natural extension of his work in visual processing. "I was interested in the 'filling in' of the blind spot and other holes in the visual field; how the brain deals with undersam pled regions—gaps," he said. "This resulted in my asking, 'How do you "fill in" a missing limb?'" Pons's monkeys seemed to offer a clue.

  "Often, the best experiments begin as jokes," Ramachandran told me. "I joked with my students. I said, 'Hey, this means that if I touch the monkey's face the monkey should feel it in the hand.' And they all laughed, and I said, 'Hey, why not?' Then they said, 'Well, how do you train a monkey to tell you what i
t's feeling?' And I said, 'Why do you need a monkey? Let's try it on a person.'"

  Ramachandran arranged to examine a seventeen-year-old boy whom he calls Tom, who had recently lost his left arm, just above the elbow, in a car crash. In a basement lab at Mandler Hall, Ramachandran lightly stroked Tom's cheek with a Q-Tip. Tom said that he felt the touch in his cheek but also in his phantom thumb. A touch on the lip he felt on his phantom index finger, a touch on the lower jaw in his phantom pinkie. Ramachandran realized that every time Tom moved his face and his lips—smiling, talking, frowning—the nerve impulses from his face activated the "hand" area in his cortex. "Stimulated by all these spurious signals," he later wrote, "Tom's brain literally hallucinates his arm."

  Ramachandran immediately telephoned his wife, Diane Rogers-Ramachandran, and told her, "Come in right now. You've got to see this guy."

  Rogers-Ramachandran is also a scientist, specializing in vision and experimental psychology. She and Ramachandran met in the late 1970s at a vision conference in Florida. She was then a graduate student at the University of North Carolina, Chapel Hill. They married in 1987. (They have two boys: Chandramani, who is nineteen, and Jaya, fourteen.) Rogers-Ramachandran rushed from their home in nearby Del Mar to watch the experiment. In the course of a few hours, she and her husband mapped Tom's phantom hand on his face. In a later experiment, they applied warm water to Tom's cheek. He felt heat in his phantom hand. When the water trickled down his cheek, he felt it running down his phantom arm. Ramachandran and his wife published their findings in 1992 in Science.

  Rogers-Ramachandran, a vivacious woman with bright blue eyes, continues to collaborate with her husband on papers, and they write a regular science column for Scientific American Mind. She says that it has sometimes been a challenge to be married to a man of Ramachandran's mental energy and intellectual curiosity. "Like, when we got married," she said one evening, over dinner at a restaurant with her husband and Jaya, "we went to England for our honeymoon and spent the whole time going to bookstores and collecting prints, books, scientific instruments. Never went to a play! None of those things! The collecting! He went from scientific instruments to fossils, to learning about his Indian heritage, to art. You say, 'Well, can't we just go walk on the beach?'"

  She mentioned Ramachandran's abstracted air—it's as if he were constantly mulling over an abstruse neurological conundrum. I knew something about this. On the first day of my visit to UCSD, Ramachandran was unable to remember where in the parking lot he had left his car and finally had to activate the alarm on the remote control to locate it. His embarrassment suggested that this was the first time such a thing had happened. Yet during the six days that I spent with him, it happened every time. When I told this story to Diane at dinner, she snorted.

  "When we leave a place, he'll go into the parking lot, and a lot of time he'll just start walking," she said. "He has no idea where he's going. He just walks. One time I picked him up from a trip—"

  "Oh, don't tell him that," Ramachandran said.

  But Diane went on. "He reached in his pocket and he said, 'Oh, my God, I had a rental car in that city! I completely forgot! I have the keys and I didn't turn the car in!' Another time," she continued, "I got a call from Sears and a woman said, 'There's a man here who says he's your husband and he's trying to purchase something on this credit card.' I said, 'Ye-e-e-s.' And she said, 'We're kind of concerned if it's really your husband, because he doesn't know your birth date.' I said, 'Oh, that's my husband!'"

  "Ha-ha-ha-ha-ha!" Ramachandran boomed. "That is a good story."

  I could not resist asking whether Ramachandran had since learned Diane's birthday. They have been married for twenty-two years.

  "I know she's a Leo," he said slowly, eying her from across the table.

  "I'm not a Leo," Diane said. "You're a Leo."

  "No," he corrected himself. "Virgo! Virgo!"

  "Yup," she said.

  "August eighteenth," he said with confi dence.

  "No," Diane said. Then she turned to me. "See, he gets the month, because it's the same as his."

  "It's not the eighteenth?" Ramachandran asked.

  "No."

  "Twenty-second?" he offered.

  "No."

  At this point, Jaya asked, "Do you know my birthday?"

  Ramachandran looked helplessly at his son and shrank into his seat. "It doesn't mean I don't love you," he said.

  In 1994 Ramachandran published a paper in Nature that is now considered a landmark in the field of neuroplasticity. He described experiments that he had conducted with UCSD's multimillion-dollar magnetoencephalography machine, which records the changing magnetic fields caused by brain activity. (Though he calls himself a "technophobe," Ramachandran occasionally uses high-tech gadgetry, chiefly as a means to support his hunches.) The high-resolution MEG scans clearly showed that in the brains of arm amputees the area associated with the face had invaded the area associated with the missing arm—"the first direct demonstration of massive reorganization of sensory maps in the adult human brain," Ramachandran wrote.

  His most startling revelation about the brain's capacity for reorganizing itself was yet to come. It emerged from his efforts to address phantom-limb pain, which afflicts up to 90 percent of amputees. Some report feeling that they are clenching their phantom fist so hard that their phantom fingernails are digging into their phantom palm. Phantom-limb pain can be so agonizing that some sufferers commit suicide.

  For more than a century, doctors theorized that the pain was psychological or originated in the stump—in swollen nerve endings called neuromas. Some resorted to repeated amputations, making the stump shorter and shorter. When this didn't work, they tried severing the nerves at the spinal cord and even disabling parts of the thalamus, an organ at the base of the brain that processes pain. All to no avail. "They can chase the phantom farther and farther into the brain, but of course they'll never find it," Ramachandran once wrote. The phantoms, as he had shown, are produced in the sensory cortex, where neurons for the face have invaded territory once reserved for the arm.

  Ramachandran posited that the phantom sensations are also created by higher brain centers, produced by a complex interplay among the sensory cortex, the motor cortex in the frontal lobes, and a "body image" map in the right superior parietal lobule, a section of the cerebral cortex just above the right ear. One of the main tasks of the right superior parietal lobule is to assemble a coherent body image from touch signals ("I feel my fingers touch the cup"), visual signals ("I see my hand reaching for the cup"), and nerve signals from the muscles, joints, and tendons ("I feel my arm extending toward the cup"). Even though amputees no longer received these signals from the nonexistent limb, Ramachandran believed that memories of these inputs remained in the nervous system and the brain.

  Reviewing the histories of amputees, Ramachandran noticed that many who suffered from cramping or clenching spasms had experienced, before their amputations, a period during which the limb was immobilized, sometimes for months, in a sling or a cast. He theorized that a kind of "learned paralysis" was burned into the brain's circuitry, as repeated commands from the patients' brains to move the limb were met with touch, visual, and nerve evidence that the limb could not move. When the limb was later amputated, the patient was stuck with a revised body-image map, which included a paralyzed phantom whose neural pathways retained a memory of pain signals that could not be shut off. Ramachandran wondered what would happen if such a patient was presented with evidence that the phantom could move ("I see my hand reaching for the cup"). If the brain could be tricked into thinking that the phantom was moving, would the cramping sensations cease?

  His first test subject was a young man who a decade earlier had crashed his motorcycle and torn from his spinal column the nerves supplying his left arm. After keeping the useless arm in a sling for a year, the man had the arm amputated above the elbow. Ever since, he had felt unremitting cramping in the phantom limb, as though it were immobilized in an awk
ward position.

  In his office in Mandler Hall, Ramachandran positioned a twenty-inch-by-twenty-inch drugstore mirror upright and perpen dicular to the man's body and told him to place his intact right arm on one side of the mirror and his stump on the other. He told the man to arrange the mirror so that the reflection created the illusion that his intact arm was the continuation of the amputated one. Then Ramachandran asked the man to move his right and left arms simultaneously, in synchronous motions—like a conductor—while keeping his eyes on the reflection of his intact arm. "Oh, my God!" the man began to shout. "Oh, my God, Doctor, this is unbelievable." For the first time in ten years, the patient could feel his phantom limb "moving," and the cramping pain was instantly relieved. After the man had used the mirror therapy ten minutes a day for a month, his phantom limb shrank—"the first example in medical history," Ramachandran later wrote, "of a successful 'amputation' of a phantom limb."

  Ramachandran conducted the experiment on eight other amputees and published the results in Nature in 1995. In all but one patient, phantom hands that had been balled into painful fists opened, and phantom arms that had stiffened into agonizing contortions straightened. "People always ask, 'How did you think of the mirror?'" Ramachandran told me. "And I say, 'I don't know!' There was a mirror in the lab, so that must have been in my mind, and I said, 'Let's try it.' It's not any more mysterious than if you say something 'popped into' your mind."

  Dr. Jack Tsao, a neurologist for the U.S. Navy, was doing graduate work in physiology at Oxford University when he read Ramachandran's Nature paper on mirror therapy for phantom-limb pain. "I said, 'Why the heck should this work? It doesn't make sense,'" Tsao told me. Several years later, in 2004, Tsao began working at Walter Reed Military Hospital, where he saw hundreds of soldiers with amputations returning from Iraq and Afghanistan. Ninety percent of them had phantom-limb pain, and Tsao, noting that the painkillers routinely prescribed for the condition were ineffective, suggested mirror therapy. "We had a lot of skepticism from the people at the hospital, my colleagues as well as the amputee subjects themselves," Tsao said. But in a clinical trial of eighteen service members with lower-limb amputations, in which six were given mirror therapy and the twelve others were evenly divided between two control therapies (a covered mirror and mental visualization), the six who used the mirror reported that their pain decreased (and, in some cases, disappeared altogether). In the two control groups, only three patients reported pain relief, and others found that their pain increased. Tsao published his results in the New England, Journal of Medicine in 2007. "The people who really got completely pain-free remain so, two years later," said Tsao, who is currently conducting a study involving mirror therapy on upper-limb amputees at Walter Reed.