Fixing Your Brain
When pills fail, electrical implants can mend brains damaged by Parkinson's, stroke, and depression
ATLANTA--Mickey Lawson's brain is talking. The 63-year-old picture framer from Lawrenceville, Ga., is strapped to a surgical table in operating room 15 at Emory University Hospital. He is also trapped in the rigid embrace of Parkinson's disease, which in the past decade has robbed him of speech and muscle control. Yet his brain is quite lively, and in the OR this afternoon in late January, everyone can hear it.
A loud popping begins echoing from a speaker. "You can hear it's pretty active," says neurosurgeon Robert Gross. He is gingerly guiding an electrode--a wire only a few millionths of an inch thick--into Lawson's brain through a nickel-size hole in his skull. It's picking up the sounds of neurons firing electrical impulses, the very stuff of thoughts and commands. Gross has pushed into part of an essential motor circuit that's damaged in Parkinson's. By putting a battery-powered device like a pacemaker in Lawson's chest and hooking it up to an implanted electrode, via a wire under the skin of his neck and scalp, Gross intends to stimulate that circuit and get Lawson moving smoothly again.
His brain feels no pain from the implant. But Lawson does, awake while under a local anesthetic so doctors can ask him about sensations evoked by the electrode. His head is squeezed in a metal brace to keep it from moving, his body racked by spasms from his disease. "Mr. Lawson?"asks an anesthetist, "Are you OK?" He squeezes her hand hard in reply.
This is deep brain stimulation, and Lawson is among the latest of about 30,000 people in the United States to get it. Drugs have failed him, so this is the next step. Lawson hopes to end up like Lucian Kent, 69, who had the procedure last November. "Once they turned the electrode on, it was like a magic wand," says the retired police
officer who lives in Philadelphia, Tenn. "I used to be in a wheelchair. Now I'm walking, and my balance is better. I do water aerobics."
Welcome to the new science of brain repair. Doctors are now using tiny electrical devices to help mend broken brains--and not only those injured by Parkinson's. Neurologists at several hospitals have just started a major trial of a promising implant that can fix brain damage caused by strokes. Last year, the Food and Drug Administration also approved a nerve stimulator to treat serious depression. And at a neuroscience meeting in Washington, D.C., in November, scientists showcased a brand-new implant that allows a quadriplegic to control a remote robotic arm with, literally, his mind. Says Harold Sackheim, a brain stimulation expert at the New York State Psychiatric Institute: "There's a ton of stuff going on."
It's all being pushed by tremendous advances in brain mapping, allowing doctors to target tiny areas, and new implants with computer chips to control them that can fit in these small spaces. "But the big thing is that our understanding of targets has changed," Sackheim says. "The brain is an electrical organ. And there is no more efficient way of getting it to act than by using a tiny electrical current. You can't get drugs, for example, to target just one region. That's why you see all sorts of bad side effects. We're seeing the start of a whole new class of medicine."
It is not a class of miracles, however. This is brain surgery, after all, a last resort. And these patients are the most challenging to treat, so the success rates are often lower than those with other groups that are not as sick. Low numbers make it harder to figure out the amount of electric current or site of an implant that leads to the best results. So a lot still depends on the skill of the individual doctor.
The field began to take shape about a decade ago, when researchers traced out brain circuits controlling movement. Previously, doctors treating disorders like Parkinson's--which afflicts about 1.5 million people in the United States--had tried to intervene with a pill. Cells in a part of the brain called the substantia nigra produce dopamine, a chemical essential for movement. When the cells die off, Parkinson's symptoms appear: rigidity, wild trembling, and a wooden, blank face. But the pill, levodopa, can replenish dopamine and restore normality.
At least for a while. "There's a honeymoon period of about five years," says Mahlon Delong, an Emory neurologist and specialist in movement disorders. "But then in some people the freezing symptoms re-emerge. People have 'on'states when the drug works and they can move and 'off' states when they can't. The 'off' periods become more frequent," says Delong. "This is a dreadful problem."
Delong and several colleagues discovered that there are other spots in this circuit where they can intervene, such as the subthalamic nucleus, or STN. "In Parkinson's, there's an abnormal signal. By stimulating STN, we seem to be replacing it with a more tolerable pattern," Delong says. "You can drown out the bad actors."
Back in the OR, Gross is trying to do that for Lawson. Finding the nucleus, a sliver of cells that's at most 8 millimeters thick and hidden in the center of the brain, is not easy. In fact, surgeons missed it in Lawson a year ago--something, Gross says, that happens in perhaps 1 in 100 patients--so this is his second go-round. Brain scans can help with approximate landmarks. Better accuracy comes with the mapping electrode Gross is using. This isn't the stimulating wire--that gets inserted later--but a thinner wire designed for listening. It has now traveled 36.33 millimeters through Lawson's brain, according to a digital display. "Each region has a characteristic firing pattern, and we can see it and hear it," Gross says. "Here we're in the STN. In the next area down, the substantia nigra, there's not as many neuron connections, so the background noise drops off." No sooner are the words out of his mouth than the sound level quiets down. The depth display reads 42.
During the next half-hour, Gross makes two more runs with the electrode, outlining the boundaries of his target. It's not long before he finds the sweet spot. Neurosurgeons replace the mapping electrode with the thicker stimulating one and anchor it to the skull with a plastic cap.
Buzzing. Later this month, after his brain has healed, Lawson will return to the hospital to have a neurologist turn on the pulse generator near his collarbone. It will buzz his brain 24 hours a day. The pulses should make his "on" periods much longer.
About 70 percent of patients who get the procedure get some benefit. Lawson still responds to levodopa for short periods, and that's a big predictor of success, according to Matthew Stern, director of the Parkinson's Disease and Movement Disorders Center at Pennsylvania Hospital in Philadelphia. "It means the circuits are still working to some extent." Another key is using those mapping electrodes in surgery. Some hospitals instead rely on brain scans alone, and Stern says that makes it less likely that they will hit the target.
Deep brain stimulation can hit the target for another movement disorder that can contort the entire body: dystonia. When 52-year-old Michael Withey was an auto-assembly-line worker in Michigan about 15 years ago, his neck started to twist around to the right. His back went in the opposite direction--and stayed there. "The pain," Withey recalls, "was tremendous." Nothing really helped. Not painkillers, not Botox injections to relax his muscles. "Basically," he says, "I became a shut-in."In 2002, he had brain stimulation surgery on part of the movement circuit called the globus pallidus. "It wasn't like I got better right away. But after about three months," he recalls, "I noticed the pain was going. Then my posture got better. I'm back to doing normal things."
Not everyone gets back to normal, however. Pat Brogan, 38, had an electrode implant in 2004. Today, he's still hurting and still on lots of medications that make him woozy. "It has helped some," says Brogan, who lives in Hazleton, Pa. "The pain is down. But I'm not where I want to be."
Stroke is yet another disease in which brain stimulation, albeit a less invasive kind, seems to help people recover movement. "What's amazing is that we can see changes in the brain, and in people's abilities, several years after their strokes," says Helmi Lutsep, a neurologist at Oregon Health and Science University in Portland. Lutsep has been testing an implant called a cortical stimulator on people with partial paralysis after a stroke caused by a blood clot. The electrode is placed just above the brain surface over the motor cortex. "We don't have to go deeper," Lutsep says, "because that's where the damage is."
During the six-week trial, the 16 patients had been doing intensive physical and occupational therapy, along with a matched group of stroke patients without stimulators. At the end, the stimulator group showed motion improvements ranging from 15 to 30 percent; those without the device ranged from 0 to 12 percent.
Those small numbers can mean a huge difference. June Wallace, 77, tried regular rehab after her stroke but still struggled. Then, as part of an earlier trial, she got an implant. "I had pretty much switched to my left hand for everything," she says, "because I couldn't do much with the right. But after three weeks with the implant, I noticed I could pick things up with the right. Now I drive my car. I'm at least 90 percent back to normal." A larger study, now underway, may bring the device closer to FDA approval in the next few years.
There are those with even more severe paralysis who may be aided by implant technology. Quadriplegics, for instance, often have no movement from the neck down. But an experimental device called a BrainGate offers a little more control. At Massachusetts General Hospital in Boston, two patients have had an electrode grid, about the size of a baby aspirin, planted in a brain area that controls voluntary hand movement. The wires come out to a small plug on the scalp, which, in turn, is connected to a small computer sitting next to the patient's wheelchair. The grid tracks patterns of brain activity as the patient thinks "move to the left" or "move to the right." It turns out those patterns are different, and the computer can tell them apart. It can use the patterns to run devices that move left or right, like a computer screen cursor.
"Within the first three days, I was able to control the cursor. When I think back on it, it was kind of a trip," says Matthew Nagle, 26, the first patient to have the implant. (He had it removed after 13 months because he needed an MRI, which is dangerous with metal in the brain.) Nagle was also able to control a robotic arm on the other side of his room.
Going beyond motion to emotion, brain repairmen have also set their sights on treatment-resistant depression. This is not the blues. This is not a low mood. "This is a living hell," says Charles Conway, a St. Louis University psychiatrist who works with these patients.
Lana Sanderson has passed through this torment. The 55-year-old Seattle resident had been battling depression ever since her 20s. "I just couldn't function,"says Sanderson. "I felt like weights were tied to my legs all the time. Just going across the room was hard, and frankly I didn't even want to try." During bad periods, she was stuck in her house, and she lost her pharmaceutical sales job. And there was the pain, an ache that permeated her body and mind with no obvious cause. "I tried virtually every class of medication available, in every combination. And finally I had ECT." The electroconvulsive therapy--large shocks to the brain, delivered in a hospital--didn't work either. There are about 4 million Americans like Sanderson. Many consider suicide. Quite a few go through with it.
Sanderson finally did get help from vagus nerve stimulation. VNS was originally developed to treat epilepsy in the late 1990s, and about 35,000 epileptics have the implant. One advantage is that it doesn't involve cutting into the skull. Instead, it uses a major highway to the brain called the left vagus nerve, located in the neck. A surgeon places electrical coils around the nerve and hooks them up to a pacemakerlike device, implanted in the skin of the chest. Pulses of electricity travel into the brain, short-circuiting epileptic seizures. Researchers noticed that patients' moods improved, probably because some of these signals stimulated parts of the brain's limbic system, which affects emotions.
Energy. In 2000, as part of a clinical trial, Sanderson got such an implant. "A week after the surgery, I was able to hook up my daughter's stereo speakers," says Sanderson. "It seems like a small thing, but days earlier it had been too difficult to think about. In about six months, I started walking every day. I finally felt I had some energy."
About 550 people with this kind of depression now have VNS implants. There are small side effects. The device emits a pulse every five minutes, and many people get hoarse for the 30-second duration because the vagus nerve is near the vocal cords. And as with deep brain stimulation, not everyone benefits; just over half, in fact. Physicians are quick to point out that these people have not been helped by anything else. More important, of those who do respond, 60 to 70 percent hold that better mood--including complete remissions--for at least two years.
Another, more experimental technique for serious depression, which doesn't involve surgery, is transcranial magnetic stimulation, or TMS. In a doctor's office, a small paddle-shaped magnet is held over the patient's left prefrontal cortex, which is tied to mood-control areas. The current produced by the magnet prompts greater activity in these regions. "You can start outside and affect inside," says Mark George, a psychiatrist and TMS expert at the Medical University of South Carolina in Charleston. There have not been a lot of big studies of the technique, which is usually applied for several minutes a day over four weeks. But so far, research shows an improvement that's slightly greater than that seen with antidepressants alone.
Brain repair still has rough edges. For instance, in deep brain stimulation, there's a lot of trial and error in picking pulse voltages and some debate about the optimum sites and even the number of implants. That may be one reason why Pat Brogan is still crippled. And with transcranial magnetic stimulation, even the best brain repairmen admit they are not exactly sure how it exerts its therapeutic effects. "We really need a better understanding of the science," says Sackheim. Plus, insurance companies are balking at paying the $20,000 price tag for VNS, claiming it is investigational despite its FDA approval.
Patients have, however, been able to appeal some of these denials successfully. And if the medical science turns out to support the continuing technical advances, brain fixes will increasingly rely on plugs instead of just pills.
5 WAYS TO REPAIR A BROKEN BRAIN
The brain is electric and doesn't work properly when damaged cells interrupt the circuit connections. New implants can jump-start these circuits with tiny electric currents.
VAGUS NERVE STIMULATION
Resistant depression, epilepsy
Periodic battery-driven pulses from an implant on the nerve travel into the brain and drown out irregular activity.
TRANSCRANIAL MAGNETS
Resistant depression
The left prefrontal cortex leads to an underactive mood area. A magnet outside the head sends a current inside, rousing the region.
DEEP BRAIN STIMULATION
Parkinson's, dystonia, other motion disorders
An electrode wired to an implanted battery overrides abnormal movement signals from this or near- by areas.
BRAINGATE
Spinal cord injury
In quadriplegics, an implant picks up motor control signals and passes them to a computer that commands remote devices.
CORTICAL STIMULATOR
Stroke
Damage in this area causes partial paralysis. An electrode hooked to an implanted battery excites new activity.
VAGUS NERVE
Goes to areas of mood and body control
MOTOR CORTEX
Starts voluntary movements
SUBTHALAMICNUCLEUS
Affects muscle control
PREFRONTAL CORTEX
Affects emotional responses
This story appears in the February 20, 2006 print edition of U.S. News & World Report.