The Mind and the Brain (28 page)

Wang trained monkeys in a task that would finally shed light on what had gone wrong in the brains of people like Laura Silverman and other victims of focal hand dystonia. The monkeys placed one hand on a form-fitting handgrip containing two little metal bars. One bar, perpendicular to the fingertips, stimulated the tips of the second, third, and fourth fingers simultaneously. A second bar stimulated the same three fingers just above the knuckles. To make sure the monkeys were paying attention to the alternating stimuli (as we have seen, attention is a prerequisite for use-dependent brain
changes), the scientists rewarded the animals for responding whenever two consecutive stimuli were applied by either bar. The monkeys underwent the behavioral training for some 500 trials day in and day out, for six and sometimes seven days a week. “I was supposed to go to my Hopkins graduation that May [of 1991], but I skipped it because I was training the monkeys,” Wang recalls. “I didn’t have the heart to leave in the middle.”

After four to six weeks of training the monkeys, Wang mapped their brains. To produce a map with the necessary high resolution, he recorded with microelectrodes from 300 locations, each just a few micrometers apart in the somatosensory cortex. The goal was to see which clutches of neurons fired in response to a light touch on a finger. Since both monkey and human fingers usually feel stimuli nonsimultaneously (we tend not to move our fingers as one, unless we are waving bye-bye to a toddler), the intense synchronous input across the monkeys’ digits was expected to produce changes in the brain. And it did. “Individual fingers were no longer differentiated,” says Wang. The normal segregation of fingers in primary somatosensory cortex “was completely broken down.” In control animals whose fingers had been stimulated asynchronously, the brain represented each finger discretely. But when digits were stimulated synchronously, their representation in the brain fused, much as had happened to Laura Silverman: a single region of somatosensory cortex responded to the touch of two or even three fingers. Simultaneous stimulation, whether by bars in a lab or by too many andante movements, fools the brain’s primary somatosensory cortex into thinking that different fingertips are part of a single unit. This discovery strongly reinforced Merzenich’s findings nearly a decade earlier that fusing fingers to create syndactyly breaks down the discrete representations of fingers, and that separating long-fused digits reseparates the fused representation in the somatosensory cortex. It all flows from the basic Hebbian principle: Cells that fire together wire together. In this way our brain, it seems, contains the spatial-memory traces of the timing of the signals it receives
and uses temporal coincidence to create and maintain its representations of the body.

The motor cortex, you’ll recall, is arranged like a little homunculus. But it is hardly a static layout. From day to day and even moment to moment, the motor cortex map changes, reflecting the kinds of movements it controls. Complex movements result in outputs from the motor cortex that strengthen some synapses and weaken others, producing enduring changes in synaptic strength that result in those things we call motor skills. Learning to ride a bicycle is possible, in all likelihood, not merely because of something called muscle memory but also because of motor-cortex memory.

In 1995, Alvaro Pascual-Leone, following up on his Braille study, conducted an experiment that, to me, has not received nearly the attention it deserves. This one modest study serves as the bridge between the experiments on humans and monkeys showing that changes in sensory input change the brain, on the one hand, and my discovery that OCD patients can, by changing the way they think about their thoughts, also change their brain. What Pascual-Leone did was have one group of volunteers practice a five-finger piano exercise, and a comparable group merely think about practicing it. They focused on each finger movement in turn, essentially playing the simple piece in their heads, one note at a time. Actual physical practice produced changes in each volunteer’s motor cortex, as expected. But so did mere mental rehearsal, and to the same degree as that brought about by physical practice. Motor circuits become active during pure mental imagery. Like actual, physical movements, imagined movements trigger synaptic change at the cortical level. Merely
thinking about
moving produced brain changes comparable to those triggered by actually moving.

These were the opening shots in what would be a revolution in our understanding of the origins of human disabilities as diverse as focal hand dystonia, dyslexia, and cerebral palsy. Merzenich firmly
believed that the focus of the previous two decades—attributing neurological illness (especially developmental abnormalities) primarily to molecular, genetic, or physical defects—had missed the boat. Instead, he suspected, it is the brain’s essential capacity for change—neuroplasticity—that leaves the brain vulnerable to such disabilities. But if that is true, Merzenich persisted, surely the reverse would hold as well: if neuroplasticity opens the door to disabilities, then maybe it can be harnessed to reverse them, too—just as it reversed the “errors” caused by the ministroke in the food-pellet-retrieving monkeys. Just as a few thousand practice trials at retrieving pellets resulted in a new brain that supported a new skill in the monkeys, so, too, might several thousand “trials” consisting of hearing spoken language imperfectly, or playing the same piano notes over and over, result in a new brain—and possibly a new impairment—in people. The brain changes causing these impairments could become so severe that Merzenich coined a term to capture their magnitude:
learning-based representational catastrophe
, as he characterized it to a scientific meeting in the late fall of 2000.

If an increased cortical representation of the fingering hand of string players, and a strengthening of motor circuits in the brains of people (and lab animals) learning a motor skill, is the positive side of use-dependent cortical reorganization, then focal hand dystonia is the dark side. In fact, Laura’s doctors were not far off when they said that her condition was all in her head. “The musician loses control over one or more of the digits of one hand, and that usually terminates his or her professional career,” says Taub. A pianist, or a typist, loses the ability to make rapidly successive movements with two (usually adjacent) fingers: when the index finger rises, for instance, the middle finger follows uncontrollably. “There is a fusion of the representation of the fingers in the dystonic hand,” says Taub. “We think it has something to do with simultaneous excitation of the fingers, typically from playing rapid passages forcefully.”

In 1990 Merzenich’s group was already suggesting, on the basis
of their monkey findings, that focal hand dystonia reflects brain plasticity. In the early 1990s Merzenich hooked up with Nancy Byl, director of the graduate program in physical therapy at UCSF, for a study in which they simulated writer’s cramp in two adult owl monkeys by training them to grasp a handgrip that repeatedly opened and closed, moving their fingers about a quarter-inch each time, up to 3,000 times during a one- or two-hour daily training session. To keep the monkeys focused on the task, Byl rewarded them with food pellets for holding onto the hand grip. After three months of this for one monkey and six months for the other, the animals could no longer move their fingers individually. In the brain, the receptive field of fingers’ sensory neurons had grown ten- or twentyfold, often extending over multiple fingers. “Rapid, repetitive, highly stereotypic movements applied in a learning context can actively degrade cortical representations of sensory information guiding fine motor hand movements,” Byl told the 1999 meeting of the Society for Neuroscience. “Near-simultaneous, coincident, repetitive inputs to the skin, muscles, joints and tendons of the hand may cause the primary sensory cortex in the brain to lose its ability to differentiate between stimuli received from various parts of the hand.” A patient with focal hand dystonia may feel a touch of her fingertip as a touch of another finger. She may have trouble identifying objects by feel. Fishing keys out from the bottom of a bag becomes hopeless.

If focal hand dystonia arises from highly attended, repetitive, simultaneous sensory input to several fingers, then the logical treatment is obvious. Correcting the problem, Merzenich believed, “requires a re-differentiation…of these cortical representations,” through highly attended, repetitive, nonsimultaneous movements. In early 1999 Byl and colleagues therefore launched small-scale studies based on this premise, with the goal that patients with focal hand dystonia would remap their own somatosensory cortex. They had the patients carry out tasks that demand acute sensory discrimination, such as reading Braille or playing dominoes blind
folded, all the while focusing their attention like a laser beam on the task. Byl encouraged them to use mental imagery and mentally to practice using the disabled hand and fingers; just as Pascual-Leone found that mentally practicing a piano exercise produces brain changes comparable to those produced by actually hitting the ivories, so patients with focal hand dystonia, she suspected, might break apart the merged representation of their fingers by imagining moving each finger individually. It would be wrong to minimize the challenge of this therapy, however. Merzenich’s findings suggest that lab animals need something like 10,000 to 100,000 repetitions to degrade the initial representation of a body part; Byl therefore suspects that people require a comparable number of repetitions of a therapeutic exercise to restore normal representation. Her early findings look encouraging. In 2000, she reported an 85 to 98 percent improvement in fine motor skills in three musicians with focal hand dystonia after they took part in her “sensorimotor retraining program.” Two of three returned to performing. The implication? In at least some patients with focal hand dystonia, the degraded cortical representation can be repaired.

In 1998, after confirming that in focal hand dystonia the somatosensory representations of the affected digits are fused, Taub and Elbert’s team in Germany also developed a therapy based on the finding. To come up with an appropriate therapy, a grad student, Victor Candia, applied Taub’s constraint-induced approach to restrain the movement of one or more less-dystonic fingers. The researchers recruited professional musicians with focal hand dystonia: five pianists (all soloists except one chamber music player) and two guitarists. Despite their disability, five of the musicians were still concertizing, masking their dystonia in some cases through atypical fingerings that avoided the dystonic finger. Taub and his colleagues thought they could do better. The scientists therefore restrained one or more of the healthy, less-dystonic fingers. The subject then used his dystonic finger to perform instrumental exercises, under a therapist’s supervision, for one and a half
to two and a half hours each day for eight straight days, followed by home exercises of one hour or more a day. The exercises consisted of sequential movements of two or three digits, including the dystonic one, followed by a brief rest and then another sequence. If the subject’s ring finger was dystonic, for instance, and the pinky had been compensating for its neighbor’s impairment, then the researchers restrained the pinky and had the patient run through the exercise index-middle-ring-middle-index. In simple terms, this separate stimulation teaches the brain that the ring finger is a separate entity, distinct from its digital neighbors. All five pianists were successfully treated, though one who did not keep up his exercises regressed. Two resumed concertizing without resorting to the fingering tricks they had used before. Four of the original seven played as well as they had before the dystonia struck. “Our suspicion was that we were breaking apart the fusion of the brain’s representation of three and sometimes four fingers,” says Taub.

The plasticity of the motor cortex might even underlie something so common, unremarkable, and seemingly inevitable as the tentative gait that many elderly people adopt. With age, walking becomes more fraught with the risk of a spill, so many people begin to walk in an ever-more constrained way. Old people become erect and stiff, or stooped, using shorter steps and a slower pace. As a result, they get less “practice” at confident striding—bad idea. Because they no longer walk normally and instead “overpractice” a rigid and shuffling gait, the motor-cortex representation of fluid movement degrades, just as in monkeys that stop practicing retrieving little pellets from wells. The result: we burn a trace of the old-folks’ walk into our brain, eventually losing the ability to walk as we once did. It is the sadder facet of the neural traces burned into our brain at the beginning of life. There is, though, a bright side: there is every reason to believe that practicing normal movements with careful guided exercise may help prevent, or even reverse, the maladaptive changes.

Tinnitus
, or ringing in the ears, is characterized by the percep
tion of auditory signals in the absence of any internal or external source of sound. It strikes an estimated 35 percent of the population at some point in life. In about 1 percent, the condition is severe enough, and maddening enough, to interfere with daily life. The source of the problem had remained a mystery for centuries: half of the investigators interested in tinnitus thought the central nervous system was involved, and half didn’t. Taub and Thomas Elbert were squarely in the first camp, suspecting that tinnitus reflects cortical reorganization that is the a result of sensory input increase. Taub and Elbert again teamed up, this time with Werner Mühlnickel, a grad student. They compared ten subjects with tinnitus (in the range of 2,000 to 8,000 hertz) to fifteen without it. To the healthy subjects, they played four sets of pure tones, of 1,000, 2,000, 4,000, and 8,000 hertz. The tinnitus subjects heard the tone that matched their tinnitus frequency (determined by having subjects move a cursor on a computer screen that varied the tone of the sound output, until they reached the one that they always heard), and then the three standard tones (usually 1,000, 2,000, and 8,000 hertz). Usually, sound frequencies are represented in the auditory cortex according to a logarithmic scale: the lowest frequencies are near the surface of the brain, and higher frequencies are toward the interior. But in tinnitus sufferers, the scientists reported in 1998, the tinnitus tone had invaded neighboring regions. “The tonotopic map was normal except at this frequency, where there was a huge distortion, with more area given over to the tinnitus tone,” says Taub. “Not only do you get cortical reorganization, but the strength of tinnitus is related to the amount of cortical reorganization.” Increased sensory input to the auditory cortex at a particular frequency had apparently produced use-dependent cortical reorganization. And that suggests a therapy for what had been an untreatable syndrome: if patients attend to and discriminate acoustic stimuli that are near the frequency of the tinnitus tone, that might drive cortical reorganization of the nontinnitus frequencies into the cortical representation of the tinnitus tone. That should reduce the tinnitus
representation, diminishing the sense that this tone is always sounding.