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Alzheimer's, addiction, obesity — maladies for future brain implants

Photo Credit: COURTESY OF REED HUTCHINSON - Musician Brad Carter played his guitar as surgeons as UCLA placed an implant inside his brain, helping surgeons locate the right spot for their electrodes. OHSU neurosurgeon Kim Burchiel is pioneering a technique which allows patients to remain under asleep during surgery.In 1990, Oregon Health & Science University neurosurgeon Kim Burchiel pioneered the use of a technique called Deep Brain Stimulation in the United States as a last chance therapy for patients with Parkinson’s disease. Burchiel implanted a thin electrical wire into the brains of Parkinson’s patients who had lost much of their ability to control their bodies and for whom therapeutic drugs no longer worked.

By hitting just the right spot in the brain with 180 electrical impulses a second sent from a battery pack implanted near the patient’s shoulder, Burchiel was able to help his Parkinson’s patients regain motor control, some for five or more hours a day.

“This is a success story,” Burchiel says. “It’s a rare procedure in surgery that has proved to the highest level of evidence. There are very few procedures that are proven to this level.”

Throughout the world today, more than 100,000 people afflicted with Parkinson’s and similar movement disorders have received brain implants, about one-tenth the number who might benefit, according to Burchiel. But the idea of hitting tiny targets in the brain as a means of overriding misfiring neurological circuits created intriguing possibilities for neurosurgeons everywhere.

As scientists have begun mapping the brain, experiments using brain implants for people suffering from depression, obsessive-compulsive disorder, obesity, addiction and Alzheimer’s disease have begun to proliferate. But for the last 24 years, Burchiel, the pioneer, was forced to watch as scientists in other states and countries pursued new uses for brain implants.

An obscure Oregon statute enacted in 1973, in reaction to the mind-control horrors detailed in Ken Kesey’s Oregon-based novel “One Flew Over the Cuckoo’s Nest,” restricted the use of brain surgery here. Burchiel wanted to join other neurosurgeons across the country in experimenting with brain implants for depression and obsessive-compulsive disorder, but couldn’t get approval from the state medical board.

“People are so paranoid about the idea of psychosurgery,” Burchiel says. “It was like a third rail. They wouldn’t touch it.”

In 2013, Burchiel finally convinced the medical board that brain implantation was not the psychosurgery of “Cuckoo’s Nest” fears. No brain matter is removed, or even changed. Take the implant out and the brain is as it always was.

Yet Burchiel remains very much aware that a green light from the medical board does not dispel public squeamishness about the idea of planting electrodes in brains, and that the moral and ethical questions that kept him from pursuing his research now are going to become more, not less, prominent.

Northeast Portland resident Robert O’Neal was diagnosed with Parkinson’s five years ago, but he’d known something was wrong with his body for awhile before that. When his right hand began to tremor uncontrollably, a neurologist delivered the news, explaining that Parkinson’s is a progressive disease that would slowly rob him of motor control and energy and for which there is no cure.

Five years of medication has helped slow the progression of the disease, but brought with it a common side effect, what O’Neal calls “mental fogginess.” As time has passed, he has had to increase the dosage of drugs that increasingly aren’t working as well.

O’Neal, 67, has been told a brain implant might significantly help him regain motor functions and eliminate the mental fogginess. Still, he says he’s inclined to put off his decision.

“It’s kind of a scary deal,” O’Neal says. “Electrodes in your brain, nickel-sized holes in your skull. They talk about one of the downfalls can be infection, and infection in the brain doesn’t sound good.”

Hope for other disorders

While OHSU’s Burchiel is just beginning to look at using deep brain stimulation for maladies beyond movement disorders such as Parkinson’s, during the past 15 years Emory University neurologist Helen Mayberg has experimented with implants to help patients suffering from depression.

Depression is a much more complicated disease than Parkinson’s, not only because it involves a psychological component, but also because it appears to involve numerous areas of the brain. Yet stimulating one tiny spot in the brain with an electrode has greatly relieved the symptoms of severe depression in well more than half of her patients, Mayberg asserts.

Mayberg uses an analogy to describe her work — the brain as a city’s electrical grid. “Take out a transformer of the electrical grid in a city, and sometimes you’re surprised,” she says. “You might think (only) contiguous neighbors will lose their power. A lot of times you see it’s actually spread out in a pattern you hadn’t anticipated.”

Mayberg found that one spot on the brain, the transformer, in Area 25, which is connected to a number of different brain regions that are involved in depression, from cognition and motivation to sleep and libido. Depressed patients who improved after taking medication showed decreased activity in Area 25.

Mayberg’s work has its detractors. A study called BROADEN was halted this year at its halfway mark, apparently because the Area 25 stimulation wasn’t working on depressed patients. But Mayberg remains undeterred. Deep brain stimulation is still a poorly understood procedure using a road map — the brain’s circuitry — that is far from completed, she says.

Mayberg doesn’t anticipate a day when hundreds of thousands of people submit to brain implants to deal with psychiatric diseases such as depression. Ironically, she expects her work will someday lead to new drugs that can target small areas of the brain to help depressed patients.

“I can envision a day where if you know there’s a problem at a particular hub, you might be able to alter it permanently and fix it,” she says.

At Ohio State University, neurosurgeon Dr. Ali Rezai is predicting that 20 years from now more than a million people will be walking around with brain implants. Rezai has put brain implants in 10 patients suffering from Alzheimer’s disease, and he says in some of them he is noticing behavioral and cognitive improvements.

Rezai isn’t alone in his belief in the future of brain implants. The U.S. Department of Defense announced a year ago that it will invest more than $70 million to find deep brain targets that might be involved in aggression and post-traumatic stress disorder.

Ohio State neurosurgeons also are experimenting with deep brain stimulation for obsessive-compulsive disorder, and Rezai says he’s excited about the work being done using implants with obesity and addiction as well.

Yes, Rezai says, there is a fear factor involved with opening up the brain, but he says initially, the same reluctance greeted heart pacemakers when they were introduced 50 years ago. Today, more than 3 million people have pacemakers helping their hearts beat consistently. In fact, some neurosurgeons call brain implants pacemakers for the brain.

“Fundamentally, the era of brain implants is here to stay,” Rezai says.

Impulse to resist implants

Using brain implants to treat diseases such as depression, Alzheimer’s and addiction gets to the heart of the reason Oregon limited the use of deep brain stimulation for so many years — fear of mind control. Specifically, the Oregon statute limited the use of any form of psychosurgery “for the primary purpose of altering the thoughts, emotions or behavior of a human being.”

Those sorts of limitations don’t apply to any of the medications used to treat people for psychiatric diseases such as depression. And that may be the product of an irrational, but very human, response to the idea of brain implants, says Erik Parens, a bioethicist at the New York-based Hastings Center and author of “Shaping Our Selves: On Technology, Flourishing and a Habit of Thinking.”

Burchiel says his new surgical approach to brain implants (see sidebar) lowers the risk of complications to 1 percent or less. Parens says if that’s true, people might need to reconsider their resistance to brain implants.

“Sticking an electrical pulse in the brain seems yuckier than sticking a capsule in the mouth, but in principle I can’t see the difference, assuming the side effect profiles are the same,” he says, noting that at present, brain implants are only being used in patients for whom drugs already have been tried and have failed.

Concerns about mind control or changing patients’ personalities are almost archaic in a world of freely dispensed Prozac, Parens says. “Pharmacology is a form of mind control, but mind control in the service of treating a psychiatric disorder,” he says. “All of these drugs are a form of changing our minds.”

For his part, OHSU’s Burchiel is viewing the rush to try deep brain stimulation for a variety of psychiatric maladies with a little bit of distrust.

“It’s sort of become this snowball,” he says. “People get overenthusiastic about technology that’s the next big thing.”

Nevertheless, he’s enthusiastic about pushing forward with trials for new uses, even as he declines to say which diseases he’s looking at. He says he’s hoping that within the next year or two his team will be announcing new technologies that will push brain implants beyond the “primitive” stage that he says is the status quo.

Burchiel looks to the pacemaker model, where the most advanced devices don’t just send out the same signal at the same pace over and over. Instead, they are part of a feedback loop, the electrical impulses sent to the heart changing based on what is happening with the heart or breathing rate. As neuroscientists become better at decoding the brain’s signals, Burchiel says, deep brain stimulation will enter a truly modern age.

“We don’t understand the message,” Burchiel says. “If you had that ability, we would have the next generation of neurostimulation, and we’d be able to do many things. That to me is the excitement factor.”

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Photo Credit: PHOTO COURTESY OHSU/JOHN VALLS - Using advanced imaging techniques OHSU neurosurgeon Kim Burchiel implants electrodes while patients remain under an anesthetic.

Surgery while patient sleeps reduces risk

One of the weirder aspects of deep brain stimulation is that, traditionally, the surgery takes place while the patient is awake. Surgeons use thin wire electrodes to touch as many as five spots in the brain trying to find the precise target for their implant. One millimeter off and the implant may be useless, or worse. By having the patient awake, the surgeons can monitor the patient’s response as they touch different targets.

But that technique often keeps the patient in surgery up to six hours. And, according to Oregon Health & Science University neurosurgeon Kim Burchiel, who pioneered the technique in the United States, it increases the risk of complications.

“The more times you push a sharp object into the brain, the more likely it is you’re going to get a hemorrhage in the brain,” Burchiel says.

While other neurosurgeons have been pushing ahead with new uses for brain implants, Burchiel in recent years has been focused on new surgical techniques he thinks make the implant operations safer. Last year he announced what he thinks is a breakthrough — brain implant surgery with the patient asleep.

Burchiel’s new technique involves using medical imaging before and during surgery to find the right targets for electrodes. The surgeries take about half as long as when patients are awake. So far, he has done 300 of the surgeries and not one has resulted in a brain hemorrhage, he says. The traditional implant surgery has a hemorrhage rate of about 1 percent.

An added bonus, according to Burchiel, is that once patients were told they could have brain implant surgery under anesthesia, twice as many were willing to submit to the surgery.

Ironically, given the reluctance of the public to accept the idea of any type of brain implants, surgeons around the country so far have been slow to adopt Burchiel’s new surgery.

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