The Mind and the Brain (25 page)

That fell short of winning over the establishment, however. Throughout 1992 and 1993, Taub recalls, he was rejected for funding by NIH “right and left” because his proposed stroke therapy was so beyond the pale. But as he and his colleagues ran more and more patients, and as other labs replicated their work, it became clear that his hunch, and his hope, were correct.

The Department of Veterans Affairs (Veterans Administration), which has a large population of elderly stroke survivors, finally awarded Taub a grant to extend his research beyond the top-functioning stroke patients to lower-functioning ones. In 1997 he found that patients in the top three quartiles exhibited significant improvement on standard tests of motor ability. The constraint-induced movement therapy worked for them, too, though not as
well: the more-affected patients improved by a score of 1.7 on a scale of motor ability, compared to a change of 2.2 for higher-functioning patients. Patients who were functioning best before therapy retained most of their gains even two years afterward; second- and third-quartile patients lost a small fraction of their gains after two years, suggesting the need for what Taub calls “brush-up” training. But the point had been made. The therapy has restored function to patients who had their stroke as much as forty-five years before. “CI therapy appears to be applicable to at least 75 percent of the stroke population,” concluded Taub.

The VA also supported an extension of Taub’s work to stroke patients who had lost the use of a leg. In this case, constraining the unaffected limb isn’t part of the therapy. Patients walk on a treadmill, wearing a body harness for support if necessary, to give them the confidence that they will not collapse as they try to use a leg that they had dismissed as hopelessly impaired. They walk up and down the hall of the Birmingham VA hospital. They rise from a sitting position, climb steps, and do balance exercises. They work for seven hours a day for three weeks. In Taub’s first group of sixteen stroke patients with lower-limb impairment, four had not been able to walk at all without support. Two of them learned to walk independently, if awkwardly. Two learned to walk again with only minimal assistance. Of the twelve less-impaired patients, all improved substantially.

What might be the basis for the improvement? In 1998 and 1999 two important studies on patients who underwent the arduous regimen of constraint-induced movement therapy began to provide the answers. In the first, Joachim Liepert and Cornelius Weiller of Friedrich-Schiller University in Jena, Germany, led an investigation of brain changes in six chronic stroke patients. They evaluated the patients before and after they were treated with fourteen days of CI therapy. All six showed significant improvement of motor function. Moreover, all six also showed “an increase of excitability of the neuronal networks in the damaged hemisphere,” they found.
“Following CI therapy, the formerly shrunken cortical representation of the affected limb was reversed…. [O]nly two weeks of CI therapy induced motor cortex changes up to seventeen years after the stroke.” Taub’s method of stroke rehabilitation had resulted in a clinically meaningful “recruitment of motor areas adjacent to the original location” involved in control of the limb.

In 1999, Taub and his German collaborators reported on four patients whose strokes had left the right arm extremely weak. The patients again underwent two weeks of CI therapy. All improved significantly. Then, three months later, the scientists recorded changes in the brain’s electrical activity. In the most striking finding, when the patients moved their affected arm, the motor cortex on the same side crackled with activity. Ordinarily, the left motor cortex controls the right side of the body, and vice versa. But in these patients, the motor cortex on the same side as the affected arm “had been recruited to generate movements of [that] arm,” Taub says. This suggests that the healthy side of the brain had been drafted into service by the patient’s continued use of the affected arm. Normally, activity in one hemisphere suppresses the activity of the mirror-image region on the other side, apparently through the bundle of connecting nerves called the corpus callosum. But when activity in the original region is silenced, as by a stroke, that suppression is lifted. Something more than the absence of suppression was needed, however. The increase in the use of the affected arm had, through sustained and repeated movements, “induced expansion of the contralateral cortical area controlling movement of the…arm and recruitment of new ipsilateral area.” Taub, adopting Mike Merzenich’s term, called it
use-dependent cortical reorganization
. He suspected that it served as the neural basis for the permanent improvement in function of what had been thought a useless limb.

One of the patients Taub is proudest of is James Faust, who lives in Calera, Alabama. After a stroke damaged the left side of his cortex, Faust’s right arm was so completely paralyzed that he even
thought about asking a surgeon to cut off the useless appendage. But hearing about Taub’s CI movement therapy, Faust enrolled. After only a few weeks the change was astounding. One evening, when Faust and his wife were having dinner at a restaurant, she looked across the table at him. Her jaw dropped. James was holding a steak knife in his right hand and slicing away as if the stroke had never happened. That was all the encouragement he needed. From that evening on, he began using his right hand as much as he did before the stroke, even more so than he did with the at-home exercises Taub had prescribed: Faust had overcome the “learned nonuse” that Taub had first seen in his monkeys. Success bred success. The more Faust used his right arm and hand, the greater the cortical area the brain presumably devoted to their movement; the greater the cortical area devoted to their movement, the better they moved. Faust is now able to tie his shoes, shave, brush his teeth, and drive.

These two studies were the first to demonstrate a systematic change in brain function in stroke patients as a result of CI therapy. They documented that treatment produces a marked enhancement in the cortical areas that become active during movement of a muscle of an affected limb. Through CI therapy, the brain had recruited healthy motor cortex tissue in the cause of restoring movement to the stroke-affected hand. “Repetitive use of the affected limb induces an extremely large use-dependent cortical reorganization,” says Taub. “The area that is responsible for producing movements of the affected arm almost doubles in size, and parts of the brain that are not normally involved, areas adjacent to the infarct, are recruited. You also get recruitment of parts of the brain that are not usually involved in generating movement in the affected arm—that is, areas on the other side of the brain.”

The results Taub was obtaining with his stroke patients, corroborated in labs adopting his constraint-induced movement approach, made people more willing to accept such explanations of how and why that therapy worked at a neurological level. In 1999
his UAB team and Emory University received funding from the National Institutes of Health for a national clinical trial of constraint-induced movement therapy at six sites. It would be the first national clinical trial for stroke ever funded by NIH. Sadly, no previous therapy had achieved results sufficient to warrant one. The record of smaller clinical trials for ischemic stroke, as the UCLA neurologist Chelsea Kidwell put it in 2001, was “remarkably dismal.”

In the spring of 2000, Taub and his colleagues reported on thirteen more stroke patients in what would be the definitive paper on the power of CI therapy. The thirteen had been living with their disabilities for between six months and seventeen years. They underwent twelve days of CI therapy. When it was over, the amount of motor cortex firing to move the disabled hand had almost doubled. Rehab, it seemed, had recruited new enlistees as effectively as anything the army has ever tried: huge numbers of previously uninvolved neurons were now devoted to moving the stroke-affected hand. Constraint-induced movement therapy had produced cortical remapping. And the improvements in function that accompanied these brain changes remained when the scientists tested the patients after four weeks, and again after six months. “This is the first time we have seen, in effect, the re-wiring of the brain as a result of physical therapy after a stroke,” said Dr. David Goode of Wake Forest University.

It was the result that Taub had been working toward from his days with the Silver Spring monkeys and thus, for him, a personal vindication. It was, more than any other, the breakthrough that brought him in from the cold, and almost made up for his period in the wilderness, for the trial, for the fact that his name would forever be associated with the most notorious animal cruelty trial in the history of American research. Few people outside the animal rights community even remembered the Silver Spring monkeys. Those who did hardly cared. In November 2000, at the annual meeting of the Society for Neuroscience, Taub could mention before a roomful
of reporters “some monkeys that lived for more than twelve years after deafferentation” without eliciting a single curious inquiry.

Cortical regions supporting sensory and motor functions are better understood, with their little homunculi, than are areas underlying memory and language, two functions whose loss after a stroke can be most devastating. It might seem almost natural, if the region of the motor cortex that once controlled the hand were damaged, for hand control to be taken up by the region that once controlled the shoulder. It’s all motor cortex, after all, and therefore not so different from, say, one clothing boutique’s blowing through a wall to annex the adjoining haberdashery. But can the same approach apply to higher-level functions? Taub was sure it could, probably through cortical reorganization like that in motor cortex. “If a stroke knocks out your Broca’s region, I am suggesting, you can in effect grow a new Broca’s region,” he says. “That’s the whole point. Functions are assigned in the brain in a very general way based on genetics, but they can be co-opted by new patterns of use. If you increase the use you create a competition for available cortical space, which is won by the function that is being most used. That’s what we demonstrated in the motor cortex in stroke. So why shouldn’t it be applicable in speech? It’s just brain.” Taub made good on this prediction in 2001, when a similar therapy was used successfully to treat patients who had been left aphasic—unable to speak—by a stroke.

Neurologists had debated for more than a century what lay behind spontaneous (that is, not in response to therapy) language recovery after stroke. One school held that unaffected language regions in the (otherwise damaged) left hemisphere begin playing a greater role. Another, more proplasticity school suspected that regions in the right hemisphere, which in most people are not specialized for language, suddenly undergo a midlife career change. In 1995 researchers led by Cornelius Weiller addressed this question. They studied six men whose devastating left-hemisphere stroke
had largely destroyed their Wernicke’s area. This region, lying near the junction of the left temporal and parietal lobes, is critical to understanding speech. The men had serious impairments in their ability to use and comprehend spoken words. Over time and with intensive therapy, however, all six largely regained their ability to speak and communicate. What happened? To find out, the researchers scanned the patients’ brains with positron emission tomography (PET) while they carried out two word exercises. The PET scans showed that regions in the right hemisphere, corresponding in position to the left cortex’s Wernicke’s area and other language centers, became active. Recovery, it seemed, had been accompanied by cortical reorganization. Right brain areas analogous to the left brain’s damaged language zones had taken over their function.

The next year, Randy Buckner and colleagues in Saint Louis reported a similar finding. They studied a patient who had suffered a lesion to a small area in the left frontal lobe that plays a role in tasks like completing words from three-letter fragments. In normal subjects, turning letter strings such as
cou
- into words like
courage
activates this region. Although the patient was initially unable to master many language functions, within six months of his stroke and with no specific therapy he was performing at almost normal levels on this test. Brain scan results showed that, although the left frontal lobe region normally used to carry out this verbal task was quiet and dark (having been knocked out by the stroke), the mirror-image spot in the right frontal lobe was working away. As the investigators described it, “a pathway similar to that of normal subjects was activated except that, instead of left prefrontal cortex, [our patient] activated right prefrontal cortex.” How could this be? Just as in the Weiller study, damage to the original language region in the left hemisphere apparently lifted the suppression of the corresponding region on the right, allowing it to step in and assume the functions of its impaired counterpart.

More support for the “It’s all just brain” school of thinking
emerged in 1996 from Mark Hallett’s lab at NIH. They studied people who had been blind from an early age. In such patients, the primary visual cortex does not receive input from the expected sources, namely, the retina via the optic nerve. But it doesn’t take this silence as a license to retire. Instead, Hallett found, reading Braille and performing other fine tactile discrimination tasks activate the visual cortex. But “reading” Braille, of course, means running fingers over raised dots, a task usually handled by the somatosensory cortex. From an early age, it seems, the visual cortex recognizes that it is not receiving signals from the eye. So it switches jobs, taking up tactile processing. The result is that a brain area usually dedicated to vision starts working on the sense of touch, a process that may explain the superior tactile sense of the congenitally blind. This is called
cross-modal functional plasticity
: brain areas that were thought to be genetically “hard-wired” for one function take on totally different functions.