The Mind and the Brain (23 page)

The result was greeted with outright hostility. Most of the neuroscience community regarded the finding as somewhere between unlikely and impossible. “Whenever I talked about the extended implications of this, people were very antagonistic,” Merzenich recalls. “Hubel and Wiesel’s work had shown just the opposite: that after a critical period early in life the brain does not change as a result of changes in sensory input.” At scientific meetings, critics heaped scorn on the idea. The peer reviewers of the 1983 paper seemed astonished and doubted its validity. The prevailing view, that the adult brain is fixed and immutable, was so strong that Kaas and Merzenich’s work didn’t come close to toppling it. “No one had really thought about activity-dependent reorganization in adult animals until Merzenich and Kaas’s work,” says Terry Allard, who would later spend four years in Merzenich’s lab. “Even after this work, it seemed like no one really wanted to.”

Kaas found that out the hard way. In another study, he cut some of the retinal nerves in lab animals. After a while, the surviving nerves filled in the area in the visual cortex that the damaged nerves had once delivered inputs to (“so that there were no holes in the vision field,” as Kaas puts it). He submitted a paper describing that result to the journal
Science.
An anonymous reviewer dis
missed it out of hand, because “everyone knew” that the visual system was not plastic in the adult. Hubel and Wiesel had shown that. Kaas was incredulous. How can you say that, he asked, when the experiment had never been done until now?

Slicing up monkeys’ nerves was a pretty drastic way of inducing neuroplasticity, of course. Might the brain manage the feat more, well, naturally? In 1987 Merzenich and Kaas found out. They conducted, in adult owl and squirrel monkeys, experiments resembling Graham Brown and Sherrington’s of three-quarters of a century before: comparing cortical maps of the hand in monkeys of about the same size and age. The representation of the hand in the primary somatosensory cortex, they found, varied in size by more than a factor of 2. Representations of individual fingers or segments of digits varied upward of threefold; representation of the back of the hand sometimes occupied half the hand-zone area and sometimes just a small percentage of it. Differences between individuals often swamped differences between species averages—not that averages were looking very meaningful at this point. The different maps, Merzenich suspected, likely reflected the unique life history of each animal. The way the monkey ordinarily used its hands and fingers left an imprint on its brain. As they said, “We propose that the differences in the details of cortical map structure are the consequence of individual differences in lifelong use of the hands.”

In another tip of the hat to classic experiments, Merzenich and Kaas mapped the hand representations in the somatosensory cortices of monkeys two to four times. Between mappings, the monkeys lived their normal laboratory life. “Each time we did it the map was unequivocally different,” says Merzenich.

The brain’s response to messages from its environment is shaped by its experiences—experiences not only during gestation and infancy, as most neuroscientists were prepared to accept, but by our experiences throughout life. The life we live, in other words, shapes the brain we develop. To Merzenich, the real significance of the findings was what they said about the origins of behavior and mental impairments. “This machine we call the brain is being modified throughout life,” he mused almost twenty years later. “The potential for using this for good had been there for years. But it required a different mindset, one that did not view the brain as a machine with fixed parts and defined capacities, but instead as an organ with the capacity to change throughout life. I tried so hard to explain how this would relate to both normal and abnormal behavior. But there were very few takers. Few people grasped the implications.” For a while, it appeared that the monkeys’ brains were a lot more adaptable than the research community’s.

In an effort to break through, Merzenich decided to pose what he calls “a greater challenge to the brain.” Until now, he had typically altered sensory input by transecting a nerve; cutting the nerve to the palm, for example, resulted in an expansion of cortical areas dedicated to the hand’s hairy surfaces. But critics suggested that the hairy surfaces might have been connected to the palm area of the cortex all along. According to this line of argument, there was no true cortical remapping, in which neurons carrying signals from the back of the hand invaded the palm’s representation zone after its own input was cut off. Instead, maybe back-of-hand neurons had always been present, though silent, in the palm-side representation and were merely being “unmasked” once input from the
palm vanished. To (he hoped) overcome such objections, Merzenich and his UCSF team decided to go beyond nerve transection. They amputated a single finger in owl monkeys, removing all possibility of sensory input from the digit, by any route.

Two to eight months after the surgeries, the researchers anesthetized each animal and carefully recorded electrical activity in the somatosensory cortex. They found that the cortical representation of the hand had reorganized. Skin of the palm and of the still-intact fingers adjacent to the amputated finger had taken over the cortical representation of the missing finger, invading the “amputation zone.” Put another way, in the monkey version of the somatosensory homunculus, the little guy had lost his middle finger but grown a larger second finger. When the researchers stimulated the monkeys’ second digit, the region of the somatosensory cortex that registered sensation in that digit fired, as expected. But so did the representation of what had been the area for the amputated digit, they reported in 1984. When his second finger was touched, the monkey responded as if the scientists were touching his missing finger.

“The amputation work was regarded as the breakthrough experiment,” says Ed Taub, now more than a decade past his Silver Spring monkey trials. “Until the mid-1980s, it was an axiom of science that there was little or no plasticity in the adult nervous system. For that reason Merzenich’s data aroused a great deal of interest.”

Interest, however, is one thing; acceptance is another. The existing paradigm, denying the possibility of such cortical reorganization, would not die easily. The cortical reorganization that Merzenich and his colleagues reported was taking place over only two millimeters of cortical space—the distance, in the owl monkey’s brain, that neurons from the second digit had spread in the cortex after amputation of the third digit. Even when Merzenich performed two-digit amputations, to see whether the cortex could remodel over even greater distances, reorganization was confined
to a region no larger than a few millimeters. To those reluctant to accept the implications, this degree of rewiring seemed insignificant, perhaps even an error of measurement.

In 1984 Terry Allard, with a fresh Ph.D. from the Massachusetts Institute of Technology, arrived as a postdoc in Merzenich’s lab, where he teamed up with Sharon Clark, a talented microsurgeon. Their assignment was an experiment in artificial syndactyly. (
Syndactyly
is a birth defect in which the fingers are joined together, as if in a fist; in artificial syndactyly, two adjacent fingers are sewn together.) What inspired the experiment was a simple enough question: what creates separate representations, in the somatosensory cortex, of the five digits? Merzenich’s team hypothesized that the distinct representations reflect differences in the timing of their sensory input: because fingers receive noncoincident sensory stimulation, they develop discontinuous representations. If so, then surgically fusing the digits should eliminate separate representations. “I had basically no background in this,” says Allard, “but Mike was very convincing. If the somatosensory map is truly activity-dependent, he convinced me, then artificial syndactyly should be reflected in a new cortical map.”

To test their guess, the scientists first had to determine the lay of the land in the brains of adult owl monkeys before their fingers were fused. After anesthetizing each monkey, Bill Jenkins exposed its cortex and then carefully moved the animal to a large camera stand so he could take a four- by five-inch Polaroid of the surface of its brain. He marked several hundred spots on the photo—the places where he would check for activity by positioning electrodes there. Then he gently brushed a spot on the animal’s hand or fingers. Through the electrodes inserted into the marked spots, he determined which spot responded to the stimulus. “It was hugely time-consuming,” Jenkins recalled. “Constructing a hand map would take, typically, eight hours. It would usually be me and a
couple other people, me looking through the microscope and positioning the electrodes, and someone else defining the receptive fields based on the electrodes’ response.”

Once they had their baseline map, Sharon Clark split the skin of the ring finger and the middle finger of the owl monkeys and then sewed together the dorsal and ventral surfaces. Recalls Allard, “After that, the monkeys just lived their life in the cage. We didn’t do anything additional to drive stimulation. But after two or three months, we found that the cortex had been remapped. The very first monkey we did, there was no question the brain had reorganized.” Whereas before the surgery the monkeys’ fingers transmitted nonsimultaneous signals to the cortex, with the result that the cortex devoted separate little islands to receive input from each separate finger, once the fingers began sending only joint messages (since whenever one finger touched an object, so did the other, as if they were a single digit), the brain reassessed the situation. It seemed to figure that it needed only a single receiver rather than two. What had been separate representations of the fingers became a single, continuous, overlapping representation, they reported in 1988. “We felt we had found the language of the somatosensory cortex, the input that determines how it is organized,” says Allard. “We had a sense that we were part of something important, discovering an aspect of the brain that hadn’t been recognized before—this whole dynamic aspect of the brain.” Years later, researchers in New York would find that the same principle applied to people. Surgeons operated on two patients to separate their congenitally fused fingers. Before the surgery, the cortical map of their digits was shrunken and disorganized. But when the fused digits were separated, the brain quickly created separate receptive fields for the two digits.

Back at Vanderbilt, Kaas knew that no matter how many such breakthroughs were reported, mainstream neuroscience was not about to abandon Hubel and Wiesel’s antiplasticity paradigm—at
least not until someone challenged their findings head-on. So Kaas and his team turned their attention to the visual cortex of cats, the very animals and the very system that the earlier scientists’ Nobel-winning work had characterized as plastic only in infancy. “The organization of the visual cortex has been considered to be highly stable in adult mammals,” Kaas’s group declared, with some understatement. But when the researchers created small lesions in the cats’ retinas, the representation of the retina in the visual cortex shifted. Cortical neurons that formerly received input from the now-lesioned regions did the equivalent of changing pen pals after the original correspondent stops writing. With no input arriving from the lesioned areas of the retina, the cortex began processing inputs from parts of the retina surrounding the lesions. The adult visual cortex seemed just as capable of reorganizing itself as other areas of the brain were.

There was entrenched opposition even to considering whether the cortical reorganization that Merzenich, Kaas, and their colleagues had found in owl monkeys might be applicable to cortical injuries in people—in particular, injuries from stroke. “The reason people were interested but not excited was that the results did not seem to have the potential for recovery of function, because the region involved was too small,” recalls Taub. “Even if you extrapolated this to human beings, you were still talking about only 3 to 4 millimeters.” Although Merzenich and Kaas were by now convinced that the brain is dynamic and adaptive, creating its maps of the body on the basis of the inputs it receives, and changing those maps as the input changes, critics still dismissed the extent of reorganization they were finding as simply too small to have any significance.

But then Pons and Mishkin got permission to experiment on four of the Silver Spring monkeys. Their 1991 discovery that the deafferentation zone—the part of the somatosensory cortex that originally processed signals from the entire upper limb—was not
silent at all, but was instead receiving input from the macaques’ faces, changed everything. Merzenich’s amputation experiments had documented reorganization of the somatosensory cortex in adult owl monkeys of a millimeter or so; in the Silver Spring monkeys, cortical reorganization spanned a distance an order of magnitude greater, between one and two centimeters. And the reorganization was very complete: every single neuron from 124 recording sites tested in the deafferentation zone had a new connection. “This generated a great deal of excitement,” says Taub. “It had the odor of being involved in recovery of function. With this result, it began to look like you could get cortical reorganization on a massive scale, and that might mean something.”

At this point, however, there had never been a demonstration of cortical reorganization in people. That was about to change. As soon as the neurologist V. S. Ramachandran read the Silver Spring monkeys study, it “propelled me into a whole new direction of research,” he recalled. “My God! Might this be an explanation for phantom limbs?” If touching the faces of the Silver Spring monkeys could excite the somatosensory cortex representation of what was once their arm, Ramachandran wondered, might his amputees’ homunculi have been rearranged, too, in a way that would explain the phenomenon of phantom limbs? After all, in the human homunculus, the hand and arm are also near the face.