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It had been more than six hours since Joan Sikkema first laid her shaven head on the operating table, six hours since a 14-millimeter hole was drilled in her skull and a thin electrode inserted deep inside her brain. Now, swaddled in blankets in the cold operating room and wide awake, Joan (pronounced joe-ann) looked up at half a dozen physicians in surgical gowns, all of whom seemed to be shouting orders at her simultaneously.

“Put your hands out steady!” one said.

“Touch your finger to your nose!”

“Puff out your cheeks!” said another. Pairs of eyes met over surgical masks, and half-nods were exchanged.

This was supposed to be the climactic moment of a surgical session that had begun around 9:00 a.m., when Ali R. Rezai, an Iranian-born and Western-trained neurosurgeon, opened the tiny porthole in the left side of Joan’s skull, about five centimeters behind the hairline. Rezai and a team of functional neurosurgeons, neurologists and nurses at the Cleveland Clinic Foundation in Ohio had spent the next few hours electronically eavesdropping on single cells in Joan’s brain, attempting to pinpoint the precise trouble spot that caused a persistent, uncontrollable tremor in her right hand. Once confident they had found the spot, the doctors had guided the electrode itself deep into her brain, into a small duchy of nerve cells within the thalamus. The hope was that when they sent an electrical current to the electrode, in a technique known as deep-brain stimulation, her tremor would diminish, and perhaps disappear altogether.

“Any tingling in the area?” asked neurologist Erwin B. Montgomery Jr., standing over Joan and tweaking the knob on a device that controls the voltage, frequency and duration of electrical stimulation. He was both testing the electrode’s effectiveness and making sure it wasn’t in a place where a burst of electricity could cause problems. Several millimeters too far back could cause a tingling sensation known as parathesis and possibly speech problems. Several millimeters too far forward, and the electrode might miss the target and have no therapeutic effect at all. Every question the doctors fired at Joan elicited a geographical answer about the exact position of the electrode inside her brain.

“Hold out your hands.” Joan held her hands straight out. There was nary a tremor or shake. “Boy, that looks pretty steady,” Montgomery announced. “Okay, open your mouth.” Joan slowly opened her mouth. “Say, Today is a lovely day.’”

“Todayis,” Joan said, very slowly, “alovelyday.”

If functional neurosurgeons like Rezai are correct, this collaborative medical scene, where patients lie awake in the operating room and help doctors implant a kind of neurological pacemaker, could soon be commonplace. Similar to heart pacemakers, which are surgically implanted in the chest and use electrical stimulation to maintain optimal cardiac rhythm, brain pacemakers consist of an electrode permanently implanted in the brain to maintain neural equilibrium. The electrode emits electric pulses from a power pack in the chest.

Brain pacemakers were first successfully implanted in humans nearly 15 years ago in France, and in 1997, the U.S. Food and Drug Administration approved the first U.S. use of pacemakers to treat essential tremor and Parkinsonian tremor-currently, the only approved indications. But until very recently, the procedure had been performed relatively infrequently, and not surprisingly, it has been viewed with great caution. “Historically, the field has been hindered-appropriately-by the problematic memory of things like the lobotomy, where the science wasn’t there and many of the outcomes were horrific,” says Joseph J. Fins, chief of the Division of Medical Ethics at Weill Medical College of Cornell University.

But now, as the science of brain circuitry has become better understood, and as the long-term outcomes of brain pacemakers have shown the technology to be both effective and safe, that could be about to change. The FDA is now considering-or soon will be asked to consider-several applications that could ultimately open up the technology to tens of thousands of patients with disabling neurological conditions. For instance, the FDA was expected this summer to approve the use of brain pacemakers for the treatment of a number of other Parkinson’s-related symptoms, such as stiffness. The agency recently authorized investigational use of the devices to treat certain forms of epilepsy and approved testing of pacemakers in the treatment of obsessive-compulsive disorder; the first three patients with obsessive-compulsive disorder received implants earlier this year at Butler Hospital in Providence, RI. Within a year, surgeons at the Cleveland Clinic expect to test the devices as a treatment for severe depression. And by the end of this year, the group hopes to begin using deep-brain electrical stimulation to try and “awaken” patients who have suffered severe brain damage and live in a cognitive limbo known as a “minimally conscious state.” In the more distant future, laboratory research suggests that pacemakers may even have a role in controlling behavioral disorders, such as obesity, anorexia and addiction.

Doctors estimate that brain and neurological conditions afflict more than 50 million Americans. “For all these conditions, conservative therapy like drugs helps, but basically 10 to 20 percent of patients are refractory to these therapies,” says Rezai. “Surgery is not for everybody. At this point, we really have to reserve it for end-stage patients for whom nothing else works. But that’s evolving. I equate it to where heart pacemakers were in the 1950s. Back then, you would tell someone, I’m having a pacemaker put in,’ and people would go, What’s that?’ Now everyone knows what a heart pacemaker is. I think that it will be a similar situation for brain pacemakers in 10 or 20 years.”

The recent operation on Joan Sikkema at the Cleveland Clinic may well be a harbinger of this coming revolution in brain surgery. But like any new medical procedure, it wasn’t without its worrisome moments. Six hours in, the slowness of Joan’s speech began to sound like something other than weariness. The words were mushy and slurred. Someone asked Joan how she felt, and she mumbled a reply that, although hard to hear, didn’t sound cheerful.

“What did she say?” someone asked. “What did she say?” The neurosurgeons were aiming for a target roughly the size of the eraser on a pencil, and clearly they weren’t there yet.


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