TADPOLE MUSIC STUDIO

New Scientist

The strain is in the brain

Too much typing can leave you in agony. But rather than damaged muscles or tendons being to blame for RSI, says Bob Holmes, things might be going wrong in the brain IN a small, darkened cage, a tiny owl monkey is working for its dinner. Like anyone who spends long hours on an assembly line or at a computer keyboard, the animal's livelihood depends on fast, accurate handwork. If the monkey manages to squeeze and release a pistol grip in less than about three-quarters of a second, he will earn a morsel of food.

"That's where they get their food pellets each day, so they're driven to do it just like you're driven to do your job because you need the money," says Nancy Byl, a physical therapist at the University of California at San Francisco, who has trained several monkeys to earn their keep in this way over the past few years.

Like hundreds of thousands of human wage slaves, these monkeys pay a price for their repetitive hand movements. Within a few months of hour-a-day training, the monkeys are reluctant to use their hands and show signs of pain and stiffness. Almost all become increasingly clumsy and eventually can no longer work the lever reliably in the required time. When this happens to people, we call it repetitive strain injury, or RSI. In its most severe forms, this workplace ailment can permanently limit what people do with their hands.

But Byl's interest is not so much in her monkeys' hands as in their brains. Her controversial idea is that their RSI-like hand injuries stem from pushing the brain past the limit of its ability to learn fast, delicate movements. When this happens, she thinks, the monkey's brain begins to lose track of which finger is which, leading to clumsiness and muscle spasms.

What Byl sees in the monkeys may happen to people, too. In the past few months several research teams have noticed the same kind of abnormality in the brains of people suffering from one especially severe form of RSI. If these findings prove to be real, the most intuitive way of treating the condition-resting or immobilising a painful hand or arm-might be completely wrong. Instead, Byl reasons, therapists might choose to treat movement disorders with exercises that sharpen the sense of touch and gradually retrain the brain to control delicate movements. Sure enough, her early attempts have helped several people regain normal use of their hands. No one knows yet whether this approach will apply to other, more common forms of RSI, but if so, the implications will be enormous.

"We've imagined RSI to be a physical problem that sits in the arm," says Byl's colleague Michael Merzenich, a neuroscientist at the University of California at San Francisco. "As a consequence, it's been treated in the arm since the beginning of time. There are thousands of arms that have been operated on, and that's probably a substantially wrong way to treat it if the real problem is a learning problem that sits in the brain."

Certainly, nothing in human evolution could have prepared our brains for eight hours at a computer keyboard, five hours of piano practice, or any of the other incredibly complex, sustained tasks that modern society expects of our hands on a daily basis. "The way the brain is used in the modern human has to be very different from ten thousand years ago, because we've developed all these hand-using devices," says Merzenich. "Even if ancient man was a flint-knapper, he didn't do it day and night. There's just no precedent for this."

So it's not surprising that RSI has become a big problem. It affects more than a million people each year in the US and Britain together, according to government estimates. And, a huge number of cases of RSI were reported in Australia in the 1980s. The number of new cases dropped after the government trimmed compensation for afflicted workers, leading some experts to label patients as malingerers.

RSI in its broadest sense is a catch-all term, covering everything from tendinitis, where the tendons become inflamed, to carpal tunnel syndrome and other injuries to nerves in the arm and hand. Many experts use RSI in a narrower sense, to refer to "overuse syndrome" a mysterious diffuse pain, where there are no tell-tale signs of any tissue damage.

One of the most disabling forms of RSI (in its broad sense) is focal hand dystonia-often dubbed writer's or musician's cramp. This dystonia is characterised by clumsy and uncontrollable hand movements and spasms of the fingers and wrist. Though less common than other forms of RSI, focal dystonia is so difficult to treat that patients often have no option but to change careers. "It's a sensation like having a magnet in the palm of the hand pulling the fingers in a very strong manner," says Victor Candia, a clinical neuroscientist at the University of Konstanz in Germany, who gave up his career as a classical guitarist when he developed focal dystonia and now studies the disease instead. "I remember trying to touch the guitar and my fingers and whole hand cramping. It was not possible to do anything."

For several years, researchers have suspected that there might be a problem in the brains of dystonia patients. Only recently, though, have they found what that defect might be. The problem seems to be with the "body maps" in the brain. Signals from touch sensors all over the skin feed into a sensory body map, lying like a headband over a strip of the cerebral cortex (see Diagram). There the inputs from different body parts are laid out in an orderly arrangement that segregates information from adjacent areas-hand and wrist, say-in adjacent parts of the cortex as well. A similar topography exists in the motor cortex, where adjacent brain areas control neighbouring muscle groups.

As neuroscientists refine their techniques, they have been able to read these maps ever more precisely, identifying zones that represent individual fingers and even tiny parts of a single fingertip. They have also found that the brain is constantly tinkering with these maps, rewiring connections to reflect its experiences. At a cellular level, this is just like other types of learning. The brain recognises experiences, in this case muscle movements, that happen together, and then links up the neurons that encode them.

Randy Nudo and his colleagues at the University of Kansas Medical Center in Kansas City showed how the maps can change as sequences of movements are learnt, by training three squirrel monkeys to pick food pellets from a narrow well.

Before and after the monkeys had mastered the movement, Nudo probed the hand and arm zones of the motor cortex with a microelectrode, stimulating nerve cells to see which neurons prompted which muscles to twitch. As the monkeys became more efficient at reaching the pellets, the movements became more rapid and more stereotyped. When this happened he found that the muscles the monkeys used responded to stimulation over a larger patch of the motor cortex. Moreover, whereas each spot on the cortex had controlled just one muscle before training, after training some spots now controlled two or more muscles that the monkey used simultaneously to extract the pellet. The cortex had learnt to treat the compound muscle movements as a single stereotyped action, with overlapping regions that controlled the muscles of the wrist and the fingers.

A similar sort of rewiring takes place in the sensory body map. Merzenich and his colleagues trained three owl monkeys to respond to a bar that tapped either the base or the tip of three fingers simultaneously. After training, when the researchers probed the animals' brains with microelectrodes, they found that the usually precise map in the sensory cortex had blurred so that a single neuron might respond no matter which finger they touched. Once again, the brain had rewired and lost resolution.

A fine mess

Merzenich and Byl wondered if the repetitive motion that led to dystonia might cause similar changes in the brain. It was this idea that prompted them to train owl monkeys to work for their food by squeezing a handgrip. Within a few months almost all the monkeys developed classic signs of focal hand dystonia.

When Merzenich and Byl looked at the brain maps in the injured monkeys, they turned out to be a real mess. "Our first response was to think we were making a mistake, that we were not very good at this mapping procedure," says Byl. But the messy layouts were real: the map of the hand on the sensory cortex had smeared so badly that some neurons responded to a touch not just on a small part of one finger, but anywhere on the front of the hand.

Since the brain uses tactile input to help plan movements, such a striking degeneration of the normal sensory map could lead to the clumsiness and loss of muscle control seen in focal dystonia, says Byl. Later this year, she hopes to have Nudo examine one of her monkeys to see if its repeated hand motions have blurred the map in its motor cortex as well.

The same thing may happen in the brains of humans who try to do too much, too quickly with their hands. Repeated, rapid movements-think of a pianist playing a trill or a typist's fingers dancing over the computer keyboard-force the brain to process a stream of sensations and muscle commands in quick succession. If this goes on long enough, Byl and Merzenich hypothesise, the brain may inappropriately learn to lump some of these consecutive experiences together and so try, for example, to raise and lower a single finger at the same time. "Now it's formed a trap," says Merzenich. "Now you're trying to make the right movement but you're generating the aberrant movement." That further reinforces the damage, he says.

No one can test this idea by doing Byl's before-and-after monkey experiment in humans, of course. However, in the past few months a flurry of studies have shown that the brain maps of people with dystonia differ from those without the disorder.

William Bara-Jimenez and his colleagues at the National Institute of Neurological Disorders and Stroke near Washington DC, fitted a network of 122 external scalp electrodes onto volunteers while gently stimulating either the thumb or little finger. By measuring how "loud" the resulting brainwave was at each electrode, they calculated where the thumb and little-finger zones were in the sensory cortex. In six people with no history of hand problems, the zones were about 12 millimetres apart. But in six dystonia patients, they occupied almost exactly the same bit of brain-just as you'd expect if the map had smeared as in Byl's monkeys.

At almost the same time, a team led by Thomas Elbert at the University of Konstanz reported similar findings using magnetic source imaging to map the sensory cortex of dystonic musicians. And an unpublished study led by Frederick Lenz, a neurosurgeon at Johns Hopkins University Hospital in Baltimore, found the same kind of smearing in the thalamus, a structure near the base of the brain that contains another map used to direct movements.

If inappropriate learning patterns cause these abnormalities to form in the brain maps and so lead to dystonia, then conventional therapies-rest, anti-inflammatory drugs, biomechanical coaching, and the injection of botulinum toxin to paralyse recalcitrant muscles-might be missing the point. "The only way to get out of it is by learning your way out of it. Anything else is not dealing with the cause," says Merzenich.

With this in mind, Byl is trying to treat focal dystonia patients using exercises that force them to make ever more delicate sensory discriminations with their fingers. This should, she believes, help them to relearn fine distinctions between neighbouring patches in the sensory cortex map. She blindfolds patients and asks them to identify numbers or letters traced on their fingertips or to play dominoes by feel.

So far, Byl has tried sensory retraining on 16 patients with severe hand dystonia who have not been helped by other therapies. After just 12 weeks of therapy, all but two had improved enough to go back to work, and five of the patients now feel they have recovered completely. And brain scans of one patient before and after therapy showed that the sensory map was moving back towards a more normal arrangement.

Therapy directed at retraining motor maps may be just as effective. A similar principle is already used for some stroke patients. A stroke can damage the motor control regions of the brain, but eventually other regions can learn to take over the job. Many patients recover the use of a weakened arm more quickly if the good arm is strapped down so they are forced to use the weaker one, according to studies by Edward Taub, a behavioural neuroscientist at the University of Alabama in Birmingham.

Working with Taub, Victor Candia and his colleagues in Germany tried a similar technique on dystonic musicians. They splinted one or more of the unaffected fingers on the dystonic hand to persuade the remaining fingers to relearn old patterns of movement. Within two weeks, all five patients-two guitarists and three pianists -reported big improvements in dexterity, even when the splint was taken off. The researchers are now analysing brain scans done before and after therapy to see if the maps have also changed for the better.

As promising as these results seem, however, they are not yet conclusive proof of Byl's idea. As well as sensory retraining, her patients continued to get standard therapies, and these may have finally begun to pay off. Moreover, Byl's presence alone might have a big effect. Patients will often improve regardless of the therapy if they get personal attention and encouragement from an enthusiastic therapist. "We haven't isolated Nancy out yet," says Frank Wilson, a neurologist at UCSF, who specialises in hand problems of musicians. Nor can Byl test her therapy in owl monkeys to see if it restores their brain maps-these monkeys are too ham-fisted to do the fine tasks the therapy requires, she says.

But it's difficult to imagine the placebo effect alone explaining the fact that Candia's sensorimotor-retraining therapy worked for dystonic pianists and guitarists, and not for oboists or flautists. Candia thinks wind players may need a more complex retraining process because they use their hands, and especially their thumbs, to hold the instrument as well as finger it.

But even if dystonic patients have "learned" their hand injuries, that can't be the whole story. "There are many people that play the piano for five hours a day for many years. Only a small percentage of them come down with dystonia. What is the difference?" says Mark Hallett, a neurologist at the National Institute of Neurological Disorders and Stroke. The unlucky few may have a genetic predisposition to this pathological type of learning, he speculates. "That sets up the cortex in these people so that normal processes of learning go awry."

Structural problems might predispose some people to develop hand injuries. "There are almost always some biomechanical or postural issues-something about the physical structure that has been set to a task that it's not particularly well suited for," says Wilson. For example, he finds that most dystonic musicians have an unusually poor ability to spread the middle fingers. This tightness would put the hand under abnormally high tension as the musician plays, which may make dystonia more likely.

If Byl has found even a partial explanation of dystonia and a treatment that works, she will have made a big difference to tens of thousands of patients. But if she's right in suggesting that similar brain changes could account for other, more common forms of RSI, her ideas would have a much wider impact.

Like most-though not all-experts in movement disorders, Hallett thinks the brain map changes in dystonia are unlikely to explain other forms of RSI, since dystonia can look very different from tendinitis or overuse syndrome. "I cannot put the two disorders together, since virtually every focal dystonia patient I see has very little pain, and the pain patients have very little incoordination," he says.

In response, Byl points out that most cases of chronic pain seem to involve some sort of brain changes. "For most people disabled by chronic pain, there is no local physiology to explain the pain. Something about the nervous system would appear to interpret things that were normal as now painful," she says. One likely candidate site would be the sensory map in the cortex, where scientists already know that repetitive use can activate sensory connections that are usually suppressed. If repetition also reduces suppression of pain signals, this could crank up the volume so that normal stimuli become painful, Byl says.

No one has yet looked at the brain maps of people who are suffering from overuse syndrome, where the only symptom is diffuse pain, to see if they too are abnormal. "It would be interesting to do these brain mappings," says Candia. "If there is a relation between massive practice and brain reorganisation [in dystonia], the same could be true for other problems, too." Byl and Merzenich plan to begin work soon on monkeys with sore hands but no dystonia.

In the meantime, Byl can dangle one tantalising preliminary result, still unpublished. She tested her sensory retraining method on eight patients-four computer users and four sign-language interpreters-who had had severe, lingering pain from overuse. Within the first hour, several patients reported that their pain had eased, at least temporarily, and within three months all had improved dramatically enough to return to work. Coincidence, placebo effect, or repaired brain map? Byl still isn't sure-but an army of RSI sufferers would love to know the answer.

Further reading:

A primate model for studying focal dystonia and repetitive strain injury by Nancy N. Byl and others, Physical Therapy, vol 77, p 269 (1997)

Abnormal somatosensory homunculus in dystonia of the hand by William Bara-Jimenez and others, Annals of Neurology, vol 44, p 828 (1998)

Constraint-induced movement therapy for focal hand dystonia in musicians by Victor Candia and others, The Lancet, vol 353, p42 (1999)

From New Scientist magazine, vol 162 issue 2181, 10/04/1999, page 26

© Copyright New Scientist, RBI Limited 2001

Contact Tadpole Music Studio at:

Thomas Beckner
Tadpole Music Studio
516-939-0717
beckner@tadmusic.com

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