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Who Holds the Clicker?

Neuroscientists hope that brain implants can treat intractable mental illness. But who would control those brave new minds?

ON A MONDAY in early February 2001, as Mario woke up next to his pregnant wife, neurosurgeons at Rhode Island Hospital were suiting up for his operation. A week or so before, Mario had gone to a tattoo artist and had the Chinese sign for "child" inked into his wrist. "If I didn't make it, if I never got to see my daughter be born, then at least I would have this tattoo," he says. "Child. With it on my skin, I knew I could go to the grave with some meaning."

As it is impossible to use animal testing to gauge whether or not DBS can treat depression and anxiety, the only guinea pigs available are people like Mario. To be eligible for neural implants he had to exhaust every available pharmacological option at either optimal or above-optimal doses and undergo at least 20 hours of behavior therapy. He had to understand the risks and implications of the procedure and provide his consent. His case was reviewed by three review boards. The FDA, which regulates medical devices, gave its blessing to this experiment. "We don't want to repeat the mistakes of the past," says Dr. Greenberg, his psychiatrist. "We want to be sure this therapy is not only not used indiscriminately, but that it is reserved for the group of people who have failed trials of everything else."

Once in the OR, Mario was given a local anesthetic. His head had been shaved, his brain targeted to millimeter precision by MRIs. Attached to his head was a stereotactic frame to provide surgeons with precise coordinates and mapping imagery. He'd undergone extensive neuropsychological testing to determine where to put the implants and to provide a preoperative baseline of functioning. After surgery, a DBS patient will be retested with these core questions in mind: Have the symptoms improved or deteriorated or stayed the same? By implanting these electrodes, how has cognitive functioning changed, if at all?

DBS doctors choose their targets—in Mario's case, the anterior limb of the internal capsule, an area that connects the thalamus with the orbital and medial prefrontal cortex—based on past lobotomies and cingulotomies that were deemed to provide some relief for the symptoms at hand. There is a problem, however, in using past lo- botomy lesions as one's DBS guidebook: All sorts of surgical lesions have attenuated anxiety and depression in desperate patients, lesions on the cingulate gyrus or the caudate nucleus, lesions to the left or right, up or down, here or there. Without a single sweet spot, the possibilities are disturbingly numerous.

Doctors are anxious to separate DBS from the psychosurgeries of the past, when ice-pick-like instruments were thrust up under open eyes, blades swished through the brain. While the finer points of brain functionality are still hazy, the surgery itself is conducted with far more precision and technological finesse than Moniz or Heath could have ever hoped for. But some facts remain the same. There is a gruesome quality to any brain surgery. The drill is huge; its twisted bit grinds through bone, making two burr holes on either side of the skull.

The drilling was over in a few minutes; surgeons then took a couple of hours to get the implants in place. As is the practice with brain surgery, Mario remained awake throughout and he was repeatedly questioned: "Are you okay? Are you alert?" His head was in the steel halo screwed to his skull. The operating room was cold, despite the relentless surgical sun. The surgeon threaded two 1.27-millimeter wires through the burr holes, wires on which the tiny platinum/iridium electrodes were strung. Picture it as ice fishing. There is the smooth bald lake, the hole opening up, dark water brimming like blood within the aperture, and then the slow lowering of string, the searching, searching, for where the fish live.

Mario could feel none of this because the brain, the seat of all sensation, itself has no sensory nerves. Next the surgeons implanted two two-inch by three-inch battery packs beneath each of Mario's clavicles and ran wires from the packs (the batteries of which have to be replaced every few months) up under the skin of his neck to the implants. The packs, controlled by a remote programming device, power the electrodes when the doctor flips the switch and adjusts the current. Mario lay there, waiting.

He would have to wait awhile. Psychiatrists do not turn the electrodes on right after surgery. That happens later, when the swelling in the head has gone down, when the bruised brain has had a chance to heal itself and the burr holes have sealed with skin. Then Ben Greenberg would pass a programmer over Mario's chest, and the wires would leap to life.

AFTER THREE WEEKS, Mario went back to Greenberg's office. The men sat facing each other, Greenberg with the programmer on his lap. He snapped open the laptoplike device and, using a handheld controller inside, activated the implants. Mario remembers the exact moment they went on. "I felt a strange sadness go all through me," he says. Mario recalls Greenberg's fingers tapping on the keyboard, adjusting the current, the pulse duration, and the frequency. After a few taps, the sadness went away. "With DBS the thing has a certain immediacy to it," says Dr. Steven Rasmussen, Mario's other psychiatrist. "You can change behavior very, very rapidly. On the flip side of it there's a danger too. This really is a kind of mind control, you know what I mean."

This is the rare admission. For the most part, researchers insist DBS has nothing to do with mind control or social shaping; they are simply psychiatrists targeting symptoms. These doctors have seen severe psychiatric anguish and know its remission is always a blessing. But anytime a psychiatrist tries to tweak a patient's mind, he does so in accordance with social expectations.

Tap tap. Now Mario felt a surge inside of him. Later, outside, Mario peered at the world turned on, turned up, and indeed it did look different, the grass a cheerful lime green, the yellow-throated daffodils. Mario went home. He wanted to talk. He had things to do. Who needed sleep? "You're like the Energizer Bunny," his wife said to him. "I felt revved," Mario says.

Mario is not the only person to become a little too happy on the wire. "That's one of the dangers," says Greenberg. Dr. Don Malone of the Cleveland Clinic says, "We don't want hypomania. Some patients like that state. It can be pleasurable. But this is just like having a drug prescription. We decide how much, when, and how."

But it's not the same as with a drug prescription. A patient can decide to take no drugs, or five drugs. A patient can split his drugs with his spouse, feed them to the dog, or just switch psychopharmacologists. Despite prescription regulations, there is tremendous freedom in being a pill popper. But not so for those with implants. True, no one any longer is dragged to the operating table in terror. No one is cut without exquisitely careful consideration. Instruments have been honed, imaging devices advanced. And yet, patients do not, cannot, fully understand, or appreciate, the degree to which, after the surgery, they will be under their doctor's control. Once a month OCD patients must visit their psychiatrist for what are called adjustments. (Emory's Dr. Mayberg says that for her depression patients, the rule is "set it and forget it.") Adjustment decisions, altering the "stimulation parameters," reflect how the patient scores on a paper-and-pencil test of symptom intensity, and they take into account the family's and the patient's subjective report, but the final and ultimately complete control lies with the treatment provider. At a 2004 meeting of the President's Council on Bioethics, Massachusetts General neurosurgeon and Harvard professor Dr. G. Rees Cosgrove gave a presentation on the issues surrounding DBS. At the end, another Harvard professor asked: "Who holds the clicker?"

Cosgrove's answer: "The doctor."

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