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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?

MARIO DELLA GROTTA IS 36 years old, with a buzz cut and a tattoo of a rose on his right bicep. He wears a gold chain around a neck that is thick as a thigh. He's the kind of guy you might picture in a bar in a working-class neighborhood, a cigarette wedged in the corner of his lip and a shot glass full of something amber. He seems, on first appearance, like the kind of guy who swaggers his way through the world, but that is not true of Mario. There was a time when rituals to ward off panic consumed 18 hours of his day. He couldn't stop counting and checking. Fearful of dirt, he would shower again and again. He searched for symmetries. His formal diagnosis was obsessive-compulsive disorder, which is just a fancy way of saying scared. Had he remembered to lock the car door? Did he count that up correctly? The French call obsessive-compulsive disorder folie du doute, a much more apt title than our clinical OCD; folie du doute, a phrase that gets to the existential core of worry, a clenched, demonic doubting that overrides evidence, empiricism, plain common sense. For Mario, his entire life was crammed into a single serrated question mark.

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Mario's anxiety was so profound, and so impervious to other treatments, that six years ago his psychiatrists at Butler Hospital in Providence, Rhode Island, suggested psychosurgery, or what—in an effort to avoid the stigmatization associated with lobotomies and cingulotomies—is now being labeled more neutrally: neurosurgery for psychiatric disorders. Medtronic, a Minneapolis-based company, has adapted implants it originally developed to treat movement disorders in Parkinson's patients for use in the most intractable but common psychiatric problems: anxiety and depression. These neural pacemakers, composed of eight bilateral implanted electrodes, four per hemisphere, emit an electrical current that, theoretically, jams pesky brain circuits, the ones that say you suck you suck you suck or oh no oh no oh no. This idea made sense to Mario. His experience of mental illness was one of a terrible loop de loop. So he said yes to surgery. He said yes in part because he knew that if he didn't like the neural implants, he could simply have them switched off.

And so, Mario became one of the first American psychiatric patients to undergo this highly experimental procedure. Worldwide there have so far been only some 50 implantations for OCD and 15 for depression, but the technology suggests a not-too-distant future when options other than drugs may be available to sufferers of serious mental illness. Industry analysts predict that the entire "neurostimulation market"—already worth $550 million and growing 20 percent a year—could top $5 billion and that the technology will be adapted to combat everything from addiction to obesity.

Such fervor has critics nervous that rather than curing problems antidepressants have been unable to address, the implant industry could repeat the problems that have scandalized the pharmaceutical world (see "War of the Wires," page 66). And psycho-surgery, by its very nature, brings with it a thicket of ethical twisters. Whose head is it? By directly manipulating the brain might we turn ourselves into Maytag technicians, programming speed cycles and rinses? Could it be possible to actually control the content of another's thinking, as opposed to merely their affective states? Even setting aside these sci-fi concerns, should doctors wade into apparently healthy brain tissue when they have yet to precisely locate mental pathology?

THE FIRST RESEARCHER to confirm that brain function, and by extension dysfunction, could be localized was French neurologist Paul Broca, in 1861. Autopsying a patient who could say only one word—"tan"—Broca identified organic damage to what he theorized was the speech center. But it took 75 years, and a Portuguese neurologist by the name of Egas Moniz, to take Broca's theory of speech localization and apply it to madness. Moniz, who would win a Nobel Prize for his invention of lobotomy, used to stride through the hallways of Lisbon's insane asylums looking for patients suitable for the frontal lobe surgery, which Moniz's surgical colleagues performed, first via ether injections, the alcohol essentially burning away the brain, and later with a leucotome, an ice-pick-shaped device with a retractable wire to whisk out gray matter.

In 1936, shortly after the first lobotomies were performed in Lisbon, the procedure came to our side of the sea, where it was adapted with all-American vigor. By the late 1950s, more than 30,000 patients had had lobotomies and the surgery was being used to "cure" everything from mental retardation to homosexuality to criminal insanity. Its most fervent promoter, Dr. Walter Freeman, eventually performed surgeries on multiple patients in an assembly-line fashion. Post-surgery, it was common for a lobotomy recipient to be perpetually placid, a carbon copy of themselves, faint and fuzzy.

While Moniz and his protégés were sawing through skulls, Robert Heath was studying an alternate form of psychosurgery—deep brain stimulation, or DBS—at the Tulane University School of Medicine. Heath took patients culled from the back wards of Louisiana's mental hospitals, slit open their skulls, and dropped electrodes down deep inside them. With the use of a handheld stimulator, Heath discovered that electrodes placed in the hippocampus, the thalamus, or the tegmentum could produce states of rage or fear, while electrodes placed in the brain's septal area and part of the amygdala could produce feelings of pleasure. Heath "treated" a homosexual man (identified as B-19) by firing electrodes in his pleasure center while having him watch movies of heterosexual encounters, and within 17 days B-19 was a newly made man. He proved it to Heath by sleeping with a prostitute Heath himself had hired for this demonstration.

Neural implants dramatically illustrated Broca's notions of localization, and, in so doing, changed the way we thought of the brain. Prior to localists like Broca, people believed thoughts and emotions were carried through the head via hollow tunnels. Now, however, diffuse tunnels were out and in their place, an image of discrete segments, real estate, if you will, some of it swampland, some of it stately, but all of it perhaps subject to human renovation.

And unlike lobotomies, those renovations did not have to be permanent. In a public demonstration at a bullring in Spain, another researcher, Yale's Jose Delgado, provoked an implanted bull with a matador's red cape. The enraged animal raced toward him, head down, stopping only at the very last second, when Delgado, with a push of a button, fired the implant and the bull, its aggression eradicated, trotted away. The potential uses and abuses of neural implants were obvious: You could control prison populations; you could effectively wipe out violence.

By the late 1960s, implants appealed to those in the medical and law enforcement communities who believed that urban riots were born not of poverty or oppression but of "violent tendencies" that could be monitored or altered. The federal Law Enforcement Assistance Administration handed out large sums to researchers studying implants and other behavior-modification techniques. Under one such grant proposal, in 1972 Dr. Louis Jolyon West of UCLA was to form the Center for the Study and Reduction of Violence and conduct research at various California prisons. The plan was to take inmates, implant them, and then monitor their brain activity after discharge. When a Washington Post reporter investigated this scheme, he discovered a precedent: In 1968 officials at California's Vacaville prison performed electrode surgery on three inmates (including a minor) with the assistance of military doctors.

A series of Senate hearings in the mid-1970s brought these and other government forays into behavior modification to the public's attention, and the public, particularly African Americans, were more than a little perturbed at the thought that mind control was seen as a viable solution to social injustice or crime. Meanwhile, the CIA was rumored to be experimenting with implants to break down POWs and discredit rebellious citizens (Heath admitted he'd been approached by the agency), and Michael Crichton's The Terminal Man, in which the main character receives implants to control his epilepsy and turns psychotic, became a best-seller.

All this, concomitant with the rise of the antipsychiatry movement, ensured that neural implants fell into disrepute. They were resurrected in 1987 when a French neurosurgeon, Alim-Louis Benabid, operating on a Parkinson's patient, discovered that if he touched the patient's thalamus with an electrical probe, the patient's shaking stopped. A decade later, Medtronic's neural implants were approved by the FDA for treating tremors, and some 30,000 patients worldwide have since been implanted for movement disorders. But something else was observed. Those implanted Parkinson's patients, a few brightened right up. It appeared the circuits controlling physical shaking were somehow connected to mental quaking as well. "It's how a lot of medicine happens," says neurosurgeon Jeff Arle of the Lahey Clinic in Burlington, Massachusetts. "It's by extrapolating backwards. Someone then has to have the chutzpah to say 'Gee, maybe we ought to try this for certain psychiatric problems.' You believe it's worth the risk. You don't know until you try it."

By the mid-1990s a small, international group of psychiatrists, neurologists, and neurosurgeons was considering using the implants for mental illness. One of their primary questions: Where, precisely, in a psychiatric patient, would one put the electrodes? While Heath and Delgado demonstrated that you can crudely trigger generalized states of affect—like terror and rage—by stimulating areas of the limbic system, no one has so far found those millimeter-sized snarls of circuitry where researchers hope the more nuanced forms of human mental health, or illness, reside. "We want more than anything," says Dr. Helen Mayberg of Emory University, a DBS depression researcher, "to find that sweet spot, and go there." Dr. Ben Greenberg, one of Mario's psychiatrists, notes that it took a long time to hone in on the targets with Parkinson's. "We are several years into that process," he says. "We will find the circuitry involved in psychiatric conditions. I think it's going to happen."

Some scientists question the very premise that despair can be localized. "Psychosurgery is based on a flawed and impoverished vision of the relationship between brain tissue and psychological disorder. It is extremely unlikely that any psychiatric problem can be located in one so-called 'abnormal' brain region," says Dr. Raj Persaud, a consulting psychiatrist at London's Maudsley Hospital. "The notion of abnormality remains deeply problematic given the huge overlap between psychiatric and normal populations in all contemporary measurements of brain structure and function. Instead, dysfunction is much more likely to result from a change in relationships between several areas, and so psychosurgery is based on a flawed attempt to carry over the same physicalist thinking that has been so powerful in bodily medicine, inappropriately to the medicine of the mind."

If finding the exact loci of depression or obsession proves to be problematic, couldn't scientists simply override people's psychic pain by stimulating their pleasure centers? That would be too crude, neuroscientists say, akin to getting patients high. Adds Harold Sackheim of the New York State Psychiatric Institute, "If you can get relief without invasive surgery"—this procedure comes with up to a 5 percent chance of hemorrhage; a 2 to 25 percent chance of infection—"you might want to pursue that other avenue first."

Pills. That's the other avenue we should supposedly pursue first. And we have. For all our consumption, though, the risk of suicide associated with antidepressants is now considered dangerous enough to adolescents that the FDA has mandated black-box warnings on labels alerting doctors and patients of the dangers. Equally compelling is data that suggests that antidepressants leave a staggering number of users without any relief at all. "We have searched and searched," says depression researcher Dr. William Burke of the University of Nebraska Medical Center, "for the Holy Grail, and we have never found it." That's true. Thirty percent of people who take an antidepressant are not helped by it. Of the 70 percent who are helped, only 30 percent feel robust relief; the other 40 percent get some symptom relief and limp along. Doctors advise the limpers to switch or combine drugs, but between 10 and 20 percent of patients never improve no matter what pills they take.

Mario, who'd tried some 40 different combinations of medications, knows this all too well. He wanted a shot at the ordinary, a lawn he might mow just once a week. The ability to endure the mess and touch of children. He decided the implants were well worth the risk.

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