Humans have been using electric current as a therapeutic agent at least since the Romans employed the Mediterranean torpedo-a kind of stingray that discharged electricity-in treating, presumably, gout and pain in the lower extremities. Electroconvulsive or shock therapy has been used for decades, predominantly as a treatment for severe depression. Nor is electrical stimulation of the brain, strictly speaking, new. The first recorded attempt occurred in 1874, when a doctor in Ohio inserted a needle into the brain of a patient with cancer and applied electricity. In 1948, J. Lawrence Pool of Columbia University tried using electrical stimulation against depression.
By the mid-20th century, electrical stimulation of the brain fell mostly into disuse-in part because of the rise of neuropharmacology, and in part because of a social and ethical hangover from the first, swashbuckling era of psychosurgery. Indeed, the recent evolution and practice of elective neurosurgery, especially for the treatment of psychiatric disorders, has been haunted by the chilling history of the lobotomy. The severing of nerve connections in the prefrontal cortex was first attempted in 1935 by a Portuguese neurologist, Antnio Egas Moniz. The procedure was popularized in this country by Walter J. Freeman in Washington, DC, and commonly used as a treatment for depression until the late 1950s.
Despite the horrific consequences of this crude form of neurosurgery, there was a kernel of scientific merit to lobotomies. Freeman believed the operations disrupted neural connections between the frontal cortex of the brain and the thalamus, which consists of two walnut-sized structures deep in the brain, one in each hemisphere, each composed of 120 distinct neural clusters, or nuclei. The thalamus influences not only emotion but things like movement and sensation, and it is clusters of neural tissue in and around the thalamus that neurosurgeons are now revisiting-not with knives or ice-picks, but with electrodes.
The renaissance in deep-brain stimulation began, serendipitously, toward the end of 1985, in an operating room in France. At the University of Grenoble, neurosurgeon Alim-Louis Benabid was preparing to ablate, or destroy, a portion of the thalamus in a patient whose hand flapped uncontrollably with the condition known as essential tremor. This drastic form of surgery, involving heat or radiation, is typically the last therapeutic option for patients with motor disorders who have exhausted all other treatments. “Before making a lesion on the target,” Benabid says, “you must make sure you are not in a place where the lesion would be inappropriate and cause a permanent deficit.” The way to determine the location, then and now, is to send a short burst of electricity through an electrode and observe the effect. In this case, the effect stunned everyone in the operating room, including the patient.
“What I saw,” Benabid recalls, “was that his hand stopped flapping. I turned off the stimulation, and the tremor came back. So I apologized to the patient and said, That was unfortunate. Was it painful?’ And the patient said, No, no, it was nice. Can I try it again?’ So we tried again, and the tremor stopped. My first thought was, I was relieved that it wasn’t a complication. The concomitant thought was, That’s interesting!’”
Armed with this intriguing chance observation, Benabid jerry-rigged some existing electrical stimulation equipment to attempt deep-brain stimulation experimentally. The first opportunity presented itself in 1987, with a Parkinson’s patient who had already undergone the surgical destruction of the thalamus on one side of the brain. The patient had developed a tremor on the other side, but destroying thalamic tissue on both sides of the brain is exceedingly undesirable, so Benabid offered to implant an electrode instead as a last-gap measure. The patient agreed, and thus began the modern era of deep-brain stimulation.
Nearly 15 years later, the technology has become much more refined. The Grenoble group has reported on the largest group of patients to date; in 148 Parkinson’s-disease patients treated since 1993, the average rate of improvement, measured according to a traditional scale used to assess Parkinson’s symptoms, was 65 percent. And the benefits have not diminished.
“We’re at the cusp of a new era in terms of therapy,” says Montgomery, who with Rezai codirects the Center for Functional and Restorative Neuroscience at the Cleveland Clinic. “Up to now, the field has been dominated by pharmacology. But deep-brain stimulation is going to have a tremendous impact on neurology. Basically, the brain is an electrical device, so it stands to reason that we should be able to influence the brain electrically. And we can offer a specificity and precision that drugs will never be capable of.”
Brain pacemakers also offer significant advantages over traditional neurosurgery, in which, Rezai says, portions of the deep brain are irreversibly destroyed. Implanting electrodes, while minimally invasive, does not destroy chunks of tissue. “In this day and age,” Rezai says, “there’s no reason to have destructive brain surgery. It’s a one-shot deal and you can have side effects that are permanent. With stimulation, you can turn it off and you’re back to where you started, so it’s fully reversible. And you can adjust it, tailor the device to the patient’s needs.”