How Deep-Brain Stimulation Works

By Sora Song Sunday, July 16, 2006
    • The practice of psychosurgery has long been dormant — tarnished by the notorious brain-scrambling lobotomies of the 1940s and '50s — but it has recently reclaimed a bit of its luster, thanks to a relatively new and much more benign technique called deep-brain stimulation. Researchers believe the treatment, which has made remarkable strides in the care of Parkinson's patients, may hold huge potential as a therapy for many other disorders.

    Deep-brain stimulation (DBS) was first developed in France in 1987 and evolved out of the so-called ablative, or lesioning, surgeries in which doctors use heat probes to burn and permanently damage small regions of the brain — in the case of Parkinson's, regions where patients' tremors and quakes are known to arise. These same brain areas are targeted with DBS, but instead of destroying tissue, doctors implant slender electrodes that pump steady pulses of electricity — think of it as a sort of pacemaker for the brain.

    DBS electrodes measure just a millimeter thick, and implanting them is a painstaking procedure that begins with the indelicate task of boring a hole through the skull. Once inside, surgeons thread the electrodes deep into the brain, aiming for a spot, usually on the subthalamic nucleus in Parkinson's patients, a fraction of the size of a pea. The electrodes are then connected to wires that snake from the skull, behind the ear and down to a small battery-run power pack installed in the chest. The settings on the unit, which is patient controlled, must be fine-tuned after the operation — an exercise that may take weeks or months, given that the device can be programmed up to 60,000 different ways.

    When switched on, the generator delivers continuous low-voltage electrical pulses to the brain. Doctors aren't sure exactly how the pulses work, but they appear to block the abnormal firing of neurons — caused in Parkinson's by a lack of dopamine, a brain chemical crucial for the proper transmission of nerve-cell signals. Overall, DBS reduces 50% to 60% of the symptoms that characterize Parkinson's disease, including tremors, stiffness, slowness, gait problems and uncontrollable writhing, allowing patients extraordinary gains in movement and control. And for most patients, who typically have to take dozens of pills a day, it means a significant reduction in medication.

    DBS is not a cure for Parkinson's. Though the surgery can help improve patients' movement, DBS does nothing for non-motor symptoms of the disease, such as depression, anxiety, balance problems, cognitive decline and memory loss. In some cases, the procedure can make these issues worse; in others, it can cause problems where there were none. In all cases, patients need sustained medical care after surgery, as their disease continues to progress. "Parkinson's is a chronic, neurological disease," says Dr. Michael Okun, a University of Florida neurologist and medical director of the National Parkinson Foundation, "so that means you still have to manage it over the long term."

    To date, more than 35,000 patients around the world have had DBS electrodes implanted in their brains, and there are 250 centers in the U.S. that perform the operation. Though it's no longer considered experimental, DBS is, for now, still used as a second- or third-line treatment, reserved for patients with relatively advanced cases of the disease and those for whom medication alone is inadequate or can't be adjusted precisely enough to keep their tremors and writhing under control. "This surgery was a last resort, but that's an evolving concept," says Dr. Ali Rezai, a neurosurgeon and chairman of the Center for Neurological Restoration at the Cleveland Clinic. "Ten years ago we were only operating on the most severe, disabled, wheelchair-dependent patients, but now we're operating on patients with moderate to severe Parkinson's. They're saying, 'Instead of waiting another five or 10 years until I'm at my end stage with medications, why don't I deal with this now and get more control over my life?'"

    Inspired by its success with Parkinson's and movement disorders like dystonia and essential tremor, Rezai and others have launched several trials studying the effect of DBS on a variety of neurological and psychiatric conditions. By embedding electrodes in different parts of the brain, researchers have brought about different results.

    In a study published in the journal Neuron in March 2005, researchers at Emory University School of Medicine performed the surgery on six patients with extreme, intractable depression. Electrodes were implanted in the subgenual cingulate region of the volunteers' brains, and as soon as the device was turned on, the authors wrote, "All patients spontaneously reported acute effects including 'sudden calmness or lightness,' 'disappearance of the void' ... 'connectedness,' and sudden brightening of the room." Four patients continued to experience heightened mood during the six-month study, and for three patients the severe depression that had failed to respond to drugs, psychotherapy and repeated bouts of electroconvulsive shock therapy disappeared into remission or near-remission.

    In another trial Rezai and colleagues at Brown University implanted DBS electrodes in 10 patients with obsessive-compulsive disorder. Three years after surgery, says Rezai, two-thirds of those patients are still showing significant improvement in what were once debilitating and immovable symptoms. So far, some 50 patients worldwide have received experimental DBS therapy for depression and OCD — and that's just the beginning.

    At about 20 U.S. centers, researchers are leading trials on these and other new applications of DBS, including as treatment for epilepsy and chronic pain. In other experiments DBS has quelled 75% of the tics in patients with Tourette's syndrome, findings that have prompted the establishment of larger studies that will begin next year. Meanwhile, in small studies in Asia, scientists have found that DBS may lessen the grip of addiction in heroin and opium abusers. And still more studies involving stimulation therapy on the surface of the brain suggest it can improve the hearing disorder tinnitus as well as movement deficits associated with strokes.

    Though larger studies still need to be done, many researchers believe this new concept — of a pacemaker for the brain — may well mark the beginning of a revolution in psychiatric and neurological treatment. "We can thank the patients with Parkinson's disease for helping us develop these therapies because what we learned from them we're applying to other disorders," Okun says. "It's a very exciting time for brain science."

    "Parkinson's," says Rezai, "was the tip of the iceberg."