The Mind and the Brain (21 page)

NIH, of course, was not stupid enough to call for the monkeys’ deaths in order to let scientists saw open their skulls and examine their brains. Instead, the institutes decided that when the animals became so ill that they had to be put down, then scientists could—with the animals under deep anesthesia—examine their brains, just before the animals were sacrificed. On July 1, 1988, William Raub wrote that the monkeys “are likely to require euthanasia eventually and that some almost surely would reach that stage this year.” NIH had therefore prepared a plan, he wrote: the deafferented animals would undergo a procedure, while still alive but before being anesthetized, in which scientists would remove part of their skull and probe their brain for signs of cortical reorganization. Only after this would a monkey be euthanized.

Alex Pacheco and PETA were livid. Even Representative Rose wrote, in a scathing letter to NIH, that experimenting on the animals would be “a very serious violation of a commitment to me, to the Congress and to the public.” The (first) Bush administration received thousands of letters protesting the decision; the first lady alone got 46,000, apparently from people who thought this kindly looking white-haired grandmother would intervene on behalf of the crippled monkeys. In 1988, animal rights groups successfully sought a restraining order prohibiting euthanasia if the brain sur
gery were to accompany it. By this point, Pacheco so mistrusted NIH that he suspected they would find any excuse to kill the animals in order to carry out the brain experiments.

Just when it seemed that matters could not get any worse, in the winter of 1989 Paul began to die. He started chewing apart the arm that had been deafferented; there was, of course, no feeling to signal him to stop. (Experience had shown that animals quickly maul any protective covering.) He actually cracked the bones in his hand. After the Tulane vets amputated half the arm and put him back in his cage, Paul stopped eating. Although the caretakers tried to soothe him, rubbing his back and offering him treats like peanut butter and sliced bananas, he refused all food. He began ripping apart his stump; gangrene streaked what remained of the limb. On the Fourth of July, vets amputated the rest of the arm at the shoulder. Even with force-feeding, Paul wasted away, finally dying on August 26, 1989, on the floor of his cage, with his head tucked beside the only arm that scientists had left him. He weighed seven pounds, compared to his original twenty. Throughout the ordeal, PETA had refused to acquiesce to euthanasia, convinced that Tulane’s description of Paul’s condition was an exaggeration, if not an outright lie.

Then it was Billy’s turn. Although he had two deafferented arms, he managed to scoot around his cage with grim determination. But his odd locomotion caused pressure wounds on the backs of his hands and made his spine curl. After developing a bone infection that failed to respond to antibiotics, he was reduced to huddling in a corner. Tulane asked PETA for permission to put Billy down, to spare him the tortured and drawn-out death that Paul had suffered. Although PETA’s own vet agreed that Billy should be euthanized, Pacheco rejected the advice. He didn’t believe Billy was suffering, or about to die, especially since Tulane refused to allow him or anyone else from PETA to see for himself. By this time Billy’s spine was fused in a curve and he was immobilized. “We had a crisis at Christmastime,” said Peter Gerone, who directed the pri
mate lab at the time. “He stopped eating.” Although the International Primate Protection League, citing a state animal-protection statute, asked for and received a temporary restraining order from the U.S. District Court for the Eastern District of Louisiana that held up experiments on the seven surviving monkeys, on January 10, 1990, Tulane won an order from the U.S. District Court of Appeals allowing scientists to carry out the brain experiment before euthanizing Billy.

On January 14, 1990, Billy became the first of the Silver Spring monkeys to undergo neurosurgery before being put to death. After anesthetizing him with ketamine hydrochloride, neuroscientists led by Pons and Mishkin administered a mixture of isoflurane gas and oxygen, a deep anesthetic. Placing his head in a frame to hold it steady, the scientists drilled through the skull covering the cortex opposite the deafferented limb. Then, using tungsten microelectrodes, they recorded from brain areas approximately 0.75 millimeter apart across the region of the somatosensory cortex, to measure the activity that occurred in Billy’s brain when they gently stroked different parts of his body with a camel’s-hair brush or cotton swab. The goal was to determine where, in the somatosensory cortex, the brain processed each sensory input. In particular, the researchers hoped to determine whether the region of the somatosensory cortex that had originally received sensory input from Billy’s arms, but that had been deprived of this normal input for more than twelve years as a result of the deafferentation, had changed. In macaques, earlier studies had established, the arm representation in the somatosensory cortex lies between the representation of the trunk and the representation of the face. The representation of the chin and lower jaw abuts the representation of the hand. In Billy, the zone representing the fingers, palm, lower and upper arm of the deafferented limb, remember, was not receiving any sensory input. It would not be far off to call this “deafferentation zone” the zone of silence: it was a radio dish tuned to a station that was no longer broadcasting.

Or so everyone thought. But when Pons took electrical recordings from the deafferentation zone, he found that the entire region “responded to stimulation of the face.” Touching or brushing Billy’s face, or even gently moving his facial hair, produced vigorous neuronal responses in the supposedly silent zone. Apparently, having waited so long for signals to arrive from the arm and hand, this region of cortex had done the neural equivalent of moving its antenna slightly to pick up signals from a different transmitter altogether. The cluster of neurons in the somatosensory cortex that responded to stimulation of the face had pushed so far into the once-silent zone—which originally received inputs from the deafferented arm—that it abutted the somatosensory representation of the monkey’s trunk. Indeed, all 124 recording sites in the “silent zone” now responded to light stimulation of the face. After the experiment, Billy was given an overdose of pentobarbital and put to sleep.

That month, an editorial in the journal
Stroke
argued against the relevance of such animal work to humans: “Each time one of these potential treatments is observed to be effective based upon animal research,” it said, “it propagates numerous further animal and human studies consuming enormous amounts of time and effort to prove that the observation has little or no relevance to human disease.” But Louis Sullivan, then secretary of HHS, glimpsed in the experiment a ray of hope for brain-injured people: “The investigators entered uncharted territory when they studied the brain of the first of the [Silver Spring] primates to be euthanized for humane reasons,” he declared. On July 6, 1990, Augustus, Domitian, and Big Boy were also experimented on and then euthanized. An appeal by PETA to the Supreme Court, asking the justices to block the euthanasia of Titus and Allen, was denied on April 12, 1991. Titus was put to sleep at 2:00
P.M.
that day. Allen was put under deep surgical anesthesia as part of a four-hour experiment; he never awoke.

The researchers reported their findings from four monkeys in
the journal
Science
in June 1991. (Taub’s name was also on the paper, but only because he had overseen the original deafferentation experiments more than twelve years before.) They found, they said, that the deafferented region, which included primary somatosensory maps of the fingers, palm, arm, and neck, was not the nonfunctional desert they expected; rather, the entire zone had responded when the researchers brushed the animal’s face. “Deafferentation zone,” then, was a misnomer: although part of the monkeys’ somatosensory cortex had been deprived of its original afferent input, from the arm, over the course of the previous dozen years it had been innervated by neurons from the face—specifically, the part of the face from the chin to the lower jaw. The part of the cortex that usually received sensory input from the monkey’s arm did not simply go out of business. Instead, neuronal axons from adjoining cortical regions had grown into it. The result was a rezoning of the monkey’s somatosensory cortex. Virtually the entire hand region, measuring 10 to 14 millimeters across, had been invaded by neurons of the face area. Like an abandoned industrial neighborhood that has been rezoned for residential use, the monkeys’ somatosensory cortex had been rezoned so that the arm region now received input from the face. The scientists had discovered, they wrote, “massive cortical reorganization” that was “an order of magnitude greater than those previously described.” Pons made it clear why they were able to discover what they did. “It was, in part, because of the long litigation brought about by animal-rights activists that [made] the circumstances extremely advantageous to study the Silver Spring monkeys,” he told the
Washington Post
.

All these years later Taub, who had been hired by the psychology department of the University of Alabama at Birmingham (UAB) in 1986, makes an admission. “Nothing was lost to science” as a result of the raid on his lab, he concedes. “Just a few years later Mike Merzenich [at the University of California, San Fran
cisco] made the discoveries that we were headed toward.” He pauses. “Though I must say, I wouldn’t have minded making those discoveries myself.” Instead, Taub was unable to conduct research for six years. Journals that once published his work wanted no part of him; agencies that once funded him turned down his grant proposals.

Taub’s experiments on deafferentation in monkeys generated two complementary lines of research. One was called
constraint-induced movement therapy
. It grew out of Taub’s discovery that animals with bilateral forelimb deafferentation eventually use their limbs extensively, whereas those with unilateral deafferentation—a lesion only half as extensive—have a virtually useless arm. The lack of purposeful movement, Taub concluded, reflected learned nonuse. For more than twenty years, until the 1981 raid on his lab, Taub had sought ways to overcome learned nonuse, motivating his monkeys through hunger or the desperate desire to avoid electric shock to use an arm they were otherwise content to leave hanging uselessly at their side. At UAB he would finally take up the idea he had broached so long ago, in that chapter he had written in 1980, on whether learned nonuse might explain a stroke patient’s inability to use a limb, and whether behavioral therapy might overcome it. Taub would not starve, let alone shock, his patients at UAB. He would simply put their good arm in a sling, and their good hand in an oven mitt, so that if they wanted to hold something, or feed themselves, or get dressed, or do the laborious rehabilitation exercises he put them through, they would have to use their “useless” arm. He called it constraint-induced movement therapy, or CI therapy for short. It was the work with the deafferented monkeys that had demonstrated to him that behavioral intervention might help patients overcome the learned nonuse of a limb affected, for instance, by stroke. In November 1992, a year after the experiments on the Silver Spring monkeys demonstrated massive cortical remapping, UAB granted Taub $25,000 to study whether stroke
patients could be taught to overcome learned nonuse of a limb. This is the subject of Chapter 5.

The other avenue of research was more purely scientific. Pons and Mishkin had shown that deafferentation results in cortical reorganization or remapping. The plasticity of the adult brain overturned an entrenched paradigm, opening the door to a greater understanding of the brain’s capacities. Cortical remapping became the first example of neural plasticity in the adult brain. As these things tend to do, the two lines of research would meet up again, eventually, when Taub discovered that the brains of rehab patients had changed as a result of constraint-induced movement therapy.

For almost twenty years the Silver Spring monkeys were famous not for what they had done, but for what had been done to them. But, looking back, it is clear that they left a double legacy. Their case prompted revision of the Animal Welfare Act in 1985, requiring that researchers reduce unnecessary suffering among lab animals. It made PETA a force in animal rights: the group went from “five people in a basement,” as Ingrid Newkirk puts it, to a national movement. It put biomedical researchers on notice that the rules had changed, that complying with the lenient animal use standards would not be enough to insulate them from the fury of animal rights advocates. “Until the Silver Spring monkeys,” says Newkirk, “people thought, yes, animals are used in labs, but there is nothing I can do about that. But then they saw the animals’ faces, and their suffering, and realized that there are things ordinary people can do. The animals came out of the lab for the first time, and people saw their suffering. After the Silver Spring monkeys, nothing was ever the same.” At Poolesville, which houses more than 1,000 monkeys, animals are now kept in large social groups rather than solitary cages, “since they are social creatures by nature,” says J. Dee Higley, who joined the facility in 1989 and studies violence associated with alcoholism. “When I first got here, hundreds of ani
mals were kept in single cages. Now we know that if you keep a primate in a single cage, you are very likely to have an abnormal animal.”

But the Silver Spring monkeys also changed forever the dogma that the adult primate brain has lost the plasticity of childhood. Instead, a new paradigm was beginning to emerge.

Looking back on it, there had been hints for decades. At the end of the nineteenth century, long before Allen and Domitian and Big Boy had their cortices mapped, long before the brains of OCD patients changed in response to therapy, scholars generally agreed that the adult brain is not immutable. To the contrary: most believed that learning physically alters the brain. As neuronal pathways are repeatedly engaged, the psychologist William James argued in the nineteenth century, those pathways become deeper, wider, stronger, like ruts in a well-traveled country road. In the chapter on habit in his magisterial 1890 work
Principles of Psychology
, James had this to say:

It was an idea that reflected the spirit of its age. With the scientific revolution of the eighteenth and nineteenth centuries, notions that had once existed solely as abstract hypotheses—electrons, atoms, species—were being shown to have a physical reality, a reality that could be quantified, measured, and probed. Now it was the mind’s turn. Farewell to the airy notion that our habits, to take James’s example, were patterns whose basis floated above the physical realm. Now theorists proposed that the experiences of our lives leave footprints in the sands of our brain like Friday’s on Robinson Crusoe’s island: physically real but impermanent, subject to vanishing with the next tide or to being overwritten by the next walk along the shore. Our habits, skills, and knowledge are expressions of something physical, James and others argued. And because that physical foundation can change, so, too, we can acquire new habits, new skills, new knowledge.

Experimentalists soon vindicated that theory. In the early twentieth century neuroanatomists began discovering something odd. They were investigating so-called movement maps of the brain, which show which spot in the motor cortex corresponds to moving which part of the body. The maps, more often than not, turned out to vary among individual animals: electrical stimulation of a particular spot in the motor cortex of one monkey moved the creature’s index finger, but stimulation of the same spot in another monkey moved the hand. You couldn’t even think of drawing a tidy movement map for, say, the “typical” squirrel monkey. Sure, you could draw a map for this monkey. But it would be different from the map for that monkey.

In 1912 T. Graham Brown and Charles Sherrington, the British neurophysiologist we met in the last chapter, decided to see whether this variability in movement maps reflected mere experimental sloppiness or something real. In landmark but long-forgotten experiments, the duo methodically applied surface electrical stimulation to lab animals’ motor cortices and observed which muscles responded. It was true: movement maps were as individual as fingerprints. Stimulating one animal’s motor cortex here produced a twitch of a cheek muscle; stimulating another animal in the exact same spot twitched a different muscle. What was the basis for this variability? Unlike fingerprints, the scientists concluded, the cortical representations of movements are not inborn. Instead, they reflect the history of use of the motor system—the footprints in the sand. Enduring changes in the complex neural circuits of our cerebral cortex, they proposed, must be induced by our behaviors. To take a fictitious example, a monkey in the habit of holding its fruit with its thumb and pinky would have a movement map in which the spots of the cortex moving those two fingers lie close together. If the monkey switched to habitually using its thumb and forefinger, then the brain would eventually shift too, rezoning the motor cortex so that neurons moving the thumb lay beside those moving the forefinger, with the pinky representation shunted aside. Sherrington’s and Brown’s work provided the earliest empirical evidence that, as James had guessed, habits are behavioral expressions of plastic changes in the physical substrate of our minds.

And it launched what would be a blossoming of research into neuroplasticity. Three years after the work on monkeys’ movement maps, a neurologist named S. Ivory Franz compared movement maps in the primary motor cortices of macaques. He, too, found high variability and concluded that the differences probably reflect the motor experiences and skills of the different monkeys. In 1917, Sherrington himself described “the excitable cortex of the chimpanzee, orang-utan and gorilla,” documenting great variation in the movement areas of the cortex. The brain, he concluded, is “an
enchanted loom, where millions of flashing shuttles weave a dissolving pattern, always a meaningful pattern, though never an abiding one.”

In 1923 Karl Lashley, a former colleague of Franz, added his voice. His work was a departure from that of his predecessors, who compared one animal to another. Logically, the differences they discovered between movement maps need not have been the result of the animals’ different life experiences; the idiosyncrasies might have been inborn. To rule out that explanation, Lashley derived four movement maps over the course of a month from the same adult rhesus monkey. If differences in the maps reflect only inborn differences, then the map of that monkey’s cortex today should be the same as its map last week. But it was not. Each time Lashley worked out the monkey’s movement map, he found that it differed in detail from the previous one, and even more from maps derived earlier. There must be, he surmised, a general “plasticity of neural function” that allows the movement map in the motor cortex to change throughout life, remodeling itself continually to reflect its owner’s motor experiences. Crucially, Lashley concluded that muscles that move more receive a greater cortical representation than muscles that move less. That bears repeating: the more a creature makes a movement, the larger the cortical area given over to that movement. Each time Friday walks his favorite route in the wet sands at the water’s edge, he leaves new imprints, fresh and sharp. If he walks the same route, his footprints become ever deeper, while those on the route less traveled fade away, until they barely dimple the sands.

By the middle of the twentieth century, there was a compelling body of evidence that the cerebral cortex is dynamic, remodeled continually by experience. Thus when Donald Hebb postulated coincident-based synaptic plasticity in 1949 (“Neurons that fire together, wire together,” as discussed in Chapter 3), he didn’t regard his proposal as particularly revolutionary: the notion that coincident inputs strengthen synapses was, he thought, generally
acknowledged. But there had always been voices of dissent over the notion of a plastic brain. In 1913 the great Spanish neuroanatomist Ramón y Cajal had argued that the pathways of the adult brain are “fixed, ended, immutable.” Although he also posited that “absolutely new relations between previously nonconnected neurons are elicited by learning,” by the 1950s the “immutable” paradigm had become the conventional wisdom in neuroscience. The theories and experimental findings of Sherrington, Franz, and Lashley were swept aside and largely forgotten. According to the prevailing camp at midcentury, the brain establishes virtually all of its connections in such primary systems as the visual cortex, auditory cortex, and somatosensory cortex in the first weeks of life. The groundbreaking work on the visual system by Hubel and Wiesel in the 1960s, as discussed in Chapter 3, seemed to establish once and for all the principle that, after a critical period early in life, experience can no longer change the brain much. The mature cortex is fixed and immutable. This became a tenet of neuroscience.

The few experiments that continued to mine the vein that Sherrington and his successors had opened therefore made all the impact of a whisper at a rock concert. Take the rats, for instance. Researchers reported in 1976 that the amount of auditory cortex given over to neurons that process a tone used in Pavlovian conditioning increases: the more the rat uses those neurons, the more space they occupy in the auditory cortex. Lashley would have been pleased. Or take the cats. In 1979, the neuroscientists John Kalaska and Bruce Pomeranz reported that denervation of the paws of kittens and adult cats causes the “paw cortex” in the brain to respond to stimulation of the felines’ forearm instead, suggesting that the forearm representation creeps into the paw representation once paw neurons no longer send signals to the cortex. (As you’ll recall from Chapter 4,
representation
is the space in the cortex devoted to processing particular sensory inputs or movement outputs.) This was precisely what Tim Pons and his team had found in the Silver Spring monkeys: if an animal stops receiving sensory input from
one part of its body, the area of somatosensory cortex that used to process that input remaps itself. Instead of wasting valuable processing space on the sounds of silence, the area starts listening to a part of the body that is still transmitting signals to headquarters. And don’t forget the raccoons (though neuroscientists did). In 1982, after amputating a raccoon’s fifth digit (pinky), Douglas Rasmusson found that its somatosensory cortex reorganized, reassigning the cortical region that used to handle incoming signals from the pinky to a part of the body (the fourth digit) that was still transmitting. Andrew Kelahan and Gernot Doetsch also found somatosensory reorganization in the cortices of raccoons after amputation of a digit.

But it is a rare neuroscientist who pays much attention to raccoon experiments. No one exactly rewrote the textbooks on the basis of these rats, cats, or raccoons. Their brains were assumed to be too simple to serve as models for the human brain. As a result, neuroscientists largely ignored experiments that, in the late 1970s and early 1980s, began raising questions about the permanence of the brain’s zoning maps, suggesting instead that the cortex is highly plastic and driven by experience. A loud silence greeted Patrick Wall’s prescient suggestion of the physical basis for such rearrangements and expansions. In a 1977 paper in
Philosophical Transactions of the Royal Society of London (Biological Sciences)
, Wall wrote, “There are substantial numbers of nerve terminals which are normally ineffective…. If the normally functioning afferent nerve fibres are blocked or cut…large numbers of cells begin to respond to new inputs. The presence of ineffective synapses in the adult offers…a possible mechanism to explain plasticity of connections in adult brains.” Little wonder scientists failed to pick up on Wall’s suggestion of a mechanism for neural plasticity. After all, the phenomenon wasn’t even supposed to exist.

What everyone “knew” to be true can still be seen in any lavishly illustrated brain book. There, in full-color diagrams, the structures of the brain are clearly mapped and labeled: areas that control lan
guage and areas that receive visual input, areas that process auditory input and areas that sense tactile stimulation of the left big toe or the right elbow. The thing resembles nothing so much as a zoning map produced by the most rigid of land-use boards. Every bit of real estate is assigned a function; and territory given the job of, say, processing sensations from the lower leg seem no more able to start recording feelings from the cheek than a plot of land zoned residential could suddenly become the site of a tractor factory. This view of the brain dates back to 1857, when the French neurosurgeon Paul Broca discovered that particular regions are specialized for particular functions. Throughout the nineteenth century neuroscientists had a field day demonstrating that different clusters of neurons located in well-defined places assumed specific functions. The neuroanatomist who determined the function of a region first was often awarded (or claimed) pride of nomenclature: thus we now have Broca’s region (speech), for instance, and Wernicke’s region (language comprehension).

The discovery of links between structure and function gave rise to a view that became axiomatic: namely, that different parts of the brain are hard-wired for certain functions. Nowhere was this clearer than in every medical illustrator’s favorite brain structure, the somatosensory cortex. A band that runs from about halfway along the top of the brain to just above each ear, the somatosensory cortex processes feelings picked up by peripheral nerves. Every surface of the body has a corresponding spot on this strip of cortical tissue, called a representation zone, as the Canadian neurosurgeon Wilder Penfield found in his experiments in the 1940s and 1950s, reviewed in Chapter 1. While patients were under local anesthesia for brain surgery, Penfield, who studied under Sherrington, stimulated spots on the surface of the exposed brain with a tiny electrode. Then he asked his conscious subjects what they felt. They didn’t hesitate: depending on which spot Penfield’s electrode tickled on the somatosensory strip, the patient would report feeling a sensation in the fingers, lips, feet, or other part of the body.