Source: Washingtoin Post
Date: 6 March 2004

The Potential of 'Brain Pacemakers'

Implanted Devices May Alter Treatment of Many Disorders

By Rob Stein
Washington Post Staff Writer

A handful of scientists around the world have begun cautiously experimenting with devices implanted in patients' bodies to deliver precisely targeted electrical stimulation to the brain in hopes of treating otherwise hopeless behavioral, neurological and psychiatric disorders.

While stressing that the ethically sensitive research with "brain pacemakers" has just begun, the scientists say the results so far have been so promising that it could mark the beginning of a new era in treating often intractable cases. The approach builds on rapid recent advances in understanding how the brain works, on high-tech imaging technologies that allow surgeons to pinpoint targets with unprecedented precision, and on the miniaturization of computerized electronic devices that can safely be inserted under the skin.

"I believe we have opened up a totally new field of research," said Alim-Louis Benabid, a neurosurgeon who pioneered the field at the University of Grenoble in France. "The number of labs which are entering the field is increasing extremely quickly. We will probably see in the next five to 10 years a number of exciting new applications."

Brain pacemakers are already widely used to treat Parkinson's disease and other movement disorders, and now several neurological centers have begun trying them to relieve several forms of previously untreatable pain, including rare but excruciating "cluster headaches."

Large trials are planned in Europe and the United States to control the worst cases of epilepsy. Small pilot studies have begun for patients with the most devastating, resistant forms of depression and for obsessive-compulsive disorder, a sometimes disabling psychiatric condition marked by repetitive thoughts and routines.

French researchers have begun testing on monkeys to see whether the devices might suppress appetite, and perhaps boost metabolism, in obese people. Some researchers are thinking about how they might use the technique to overcome addictions.

The research is shadowed, however, by one of the most reviled episodes of medical history -- the psychiatric surgery boom of the early and mid-20th century, when lobotomies and abuses of electroshock therapy became synonymous with horrendous mistreatment depicted in books and films such as "One Flew Over the Cuckoo's Nest." The sinister images of mind control conjured up by the notion of implanting electrodes into people's brains only adds to the potential for controversy.

Chastened by that dark legacy, the researchers say they are moving exceedingly carefully, testing the approach only on hopelessly ill people who otherwise would face irreversible brain surgery or risk side effects from shock therapy, and creating layers of protections to ensure that all patients are fully informed and shielded from abuse. Although the procedure carries risks, so far it appears fairly safe. Moreover, researchers say, the treatment has the advantage of being able to be simply turned off or removed if it does not work or if problems occur.

Nevertheless, the research arouses fears of reviving the reckless use of brain surgery, about the wisdom of poking around in what some consider the font of a person's humanity, about oversimplifying mental illness as a purely biological problem, and the temptation to move too quickly to try out new technologies.

"Any time you start messing with the brain and start treating it as, quote-unquote, just another organ, we're going to have questions of the propriety of doing this kind of thing," said Raymond De Vries, a medical sociologist at the Institute for Advanced Study in Princeton, N.J. "This is the brain. This is the seat of who we are."

Modeled on heart pacemakers routinely implanted in people's chests to automatically regulate heart rhythms, brain pacemakers were first developed in the late 1980s to treat Parkinson's, a devastating brain disorder in which victims inexorably lose control of their muscles.

In a painstaking six-hour procedure, surgeons drill two small holes into a patient's skull. Then, using computerized scans and electrical monitoring of the firing of nerve cells to precisely guide them, they carefully thread two electrodes, each about the diameter of a piece of spaghetti, to specific areas on each side of the brain, depending on the nature of the disorder.

Because brain surgery is painless, the operation is done while the patient is conscious so his responses can help guide the surgeons. The electrodes are attached to wires embedded under the skin that lead down the side of the patient's head, neck and shoulder to battery-operated, adjustable pacemakers implanted under the collarbone.

Known technically as "deep brain stimulation," the approach has been used on tens of thousands of patients with Parkinson's, as well as patients with two other movement disorders, essential tremor and dystonia. Encouraged by the success and safety of the treatment for those disorders, researchers began exploring its potential for other conditions.

About two dozen people worldwide have undergone the procedure in a handful of small experiments testing brain pacemakers for depression and obsessive-compulsive disorder, or OCD.

Psychiatrists started with obsessive-compulsive disorder, because OCD can be so severe and because the brain pathways involved are fairly well understood. Neurosurgeons are implanting the electrodes into parts of the brain called the anterior limbs of the internal capsules, which are believed to be relay stations for signals to and from other parts of the brain that create the repetitive thoughts.

Before her operation, Kelly Fahrenkrug was tormented by such thoughts -- pounding, relentless fears of being contaminated by some ominous but amorphous threat outside her home.

"It's like your own brain torturing you. It's just constant repetitive thoughts and routines, and being very afraid all the time," said Fahrenkrug, 34, a housewife and mother in Davenport, Iowa.

Today, her obsessive thoughts have quieted. They are not gone. But they are hushed. Fahrenkrug can do things that once seemed impossible -- run errands, ferry her daughter around town, entertain friends.

"It just sort of eased up is how I'd describe it. It was gradual. I just noticed a lift in my mood. I just started to notice things were better," she said.

Scientists do not understand exactly how electrical stimulation may work. The brain uses tiny electrical and chemical impulses to transmit messages. The external stimulation may either turn on or amplify -- or perhaps turn off or diminish -- certain electrical signals, ameliorating the symptoms.

"The brain is an electrical organ with circuitry that carries messages. It's like having an orchestra playing a symphony, with various areas playing different parts. They have to play together," said Ali R. Rezai, director of functional neurosurgery at the Cleveland Clinic Foundation in Ohio. "In some cases, some parts aren't playing in synchrony. You hear chaotic music. That's what's happening -- it's chaotic activity. We can get in there and modulate that chaotic activity."

While researchers caution that the studies done so far are small and preliminary, the results appear promising, apparently providing at least some benefit for about half of OCD patients. Patients experience a reduction in paralyzing fears, which reduces their compulsion to engage in often debilitating repetitive routines. In some, improvement has been dramatic, enabling people who had been incapacitated for years to return to work and develop personal relationships. The approach appears to be producing similar results for people devastated by depression.

"It's very exciting," said Andres Lozano, a neurosurgeon at the University of Toronto working with colleagues at Emory University in Atlanta to test the approach for depression. "These are patients who have failed all other therapies."

To rule out the placebo effect, scientists have evaluated some patients when they were unaware the stimulators were not delivering current.

While the surgery carries risks such as infection and hemorrhage, so far no serious problems have been reported, the researchers said. Some experts, however, are troubled by the move to start testing the approach on people with other disorders, particularly depression, without more preliminary research.

"Our knowledge of the functional anatomy of depression is not as good as it is for OCD. I'm a little bit more reserved about that and think they should be waiting a bit more," said Mark S. George, director of the brain-stimulation laboratory at the Medical University of South Carolina in Charleston. "Our first rule is to first do no harm, and it would seem that something as invasive as deep brain stimulation should be tested on animal models for depression first."

Raj Persaud, a psychiatrist at the Maudsley Hospital in London, said he has reservations. "Looking at yourself and making the changes that may be necessary takes some time," he said. "Neurosurgery is the quick fix."

But researchers involved in the work say they are proceeding slowly, only offering the treatment to people who otherwise would continue to suffer.

"This would be a last resort," said Wayne K. Goodman, a psychiatrist at the University of Florida, who treated Fahrenkrug.

All the centers testing the procedure have established elaborate programs and oversight to make sure no patients are accepted for treatment until they have been thoroughly screened to make sure they have no other options, might benefit, and are capable of giving informed consent.

"What happened during the era of lobotomy was those techniques were heralded as miraculous cures for patients," said Benjamin D. Greenberg, a psychiatrist at Brown University and Butler Hospital in Providence, R.I. "The procedure over time became applied indiscriminately. The overall consequences were tragic for many patients. It's all that history that makes us as careful as we are."

As part of that effort, the researchers have enlisted Joseph J. Fins, a medical ethicist at the Weill Medical College of Cornell University.

"They are very sensitive to the historical legacy of psychosurgery," Fins said. "Today's iteration is far more discreet, less toxic and easier to study than its predecessor." Given the pivotal role the brain plays in the body, Rezai predicts a much broader spectrum of patients will eventually benefit.

"I think we're really in the beginning of a new era for the treatment of neurological and psychological disorders that are intractable to medication and other treatments," Rezai said.

Eventually, Rezai said, "smart brain pacemakers" will be able to sense aberrant brain cell firings and correct the problem with "a burst of therapeutic activity."

"With time, it will become a more routine part of the armamentarium of therapies for patients," he said. "In the future, neural prostheses and smart systems for the brain will be applied more and more."
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