Source: Wired
Date: 16 September 2006

Back From the Dead

A small but passionate group of doctors say that electricity applied deep in the brain can jolt patients out of irreversible comas. That's when the real problems begin.

By Gary Greenberg

For someone left for dead 12 years ago, Candice Ivey seems to be doing pretty well. She's still got her homecoming queen looks and A-student smarts. She has earned a college degree and holds a job as a recreational therapist in a retirement community. She has, however, lost her ballerina grace and now walks a bit like her feet are asleep. She slurs her words a little, too, which sometimes leads to trouble. "One time I got pulled over," she says in her North Carolina twang. "The cop looked at me and said, 'What have you been drinking?' I said, 'Nothing.' He said, 'Get out here and walk the line.' I was staggering all over the place. He said, 'All right, blow into this.' Of course I blew a zero, and he had to let me go."

In November 1994, when Ivey was 17, a log truck T-boned her Chevy Blazer. She remembers nothing of the next two months. But it's all seared into the memory of her mother, Elaine, especially the part where the doctors told her that Candice, who was in a coma and breathing by respirator, should be pronounced dead. Her brain, they said, was entirely and irreversibly destroyed by a week of swelling and bleeding and being pushed up against the inside of her skull like a ship scuttled on a reef.

A few days later, however, Candice proved the doctors wrong. Unhooked from the respirator, she continued to breathe on her own – something she couldn't have done if she were truly brain-dead. Now Elaine faced the horrible decision of whether or not to feed her child. The doctors warned her that Candice would probably never wake up, and if she did, she almost certainly would be unable to live independently. In the worst case, she would enter the permanent twilight known as a persistent vegetative state, in which she might sleep and wake and move her limbs, yawn and sneeze and utter sounds, but not in a way that was purposeful. Elaine decided to keep the feeding tube in place, which, she recalls, made the neurosurgeon furious. "He thought I was just prolonging her agony and that I would have a vegetable on my hands," she says. "But when it's your child lying there, you'll do anything."

In this case, anything included letting an orthopedic surgeon named Edwin Cooper try an experimental treatment. He approached Elaine out of the blue soon after the accident and urged her to let him put an electrified cuff on Candice's wrist. It sent a 20-milliampere charge – enough to make her hand clench and her arm tremble a little – into her median nerve, a major pathway to the brain. It might rouse her from her coma, he said.

"I thought it was hokey, if you want to know the truth," Elaine says. She agreed nonetheless – she was, she says, "drunk as a coot" from a combination of "nerve pills and a full glass of whisky" – and the cuff went on. Within a week, Elaine was sure that Candice was stirring. Her doctors doubted it. "They kept telling me it was just reflexes, but a momma knows." Then, just before New Year's Day, a month after the accident, Cooper asked Candice how many little pigs there were. She held up three fingers.

Now 29, Candice Ivey is thrilled to see the 64-year-old Cooper when he shows up at her door. She gives him a big, warm hug and sits close to him on the couch. They chat about the presentation on traumatic brain injury that she recently gave to nurses at Cooper's hospital, and how hearing the story of her ordeal again brought him to tears. As she tells me of her injury and its aftermath, she comes back time and again to her gratitude. "The wreck was my fault," she says. "But getting better, that was God's doing. He sent Dr. Cooper to my momma, didn't he?"

Edwin Cooper has been sent, or has sent himself, to about 60 severely brain-injured people since the mid-1980s, when he first made the accidental discovery that electrical stimulation had effects on arousal. He was using a neuro-stimulator to relieve spasticity in the limbs of microcephalics, people with abnormally small skulls who often have reduced mental capacity and poor muscle control. During the treatment, he recalls, one patient started looking around his room and smiling when people walked in, instead of staring blankly. Cooper had already observed that when he placed the stimulator on one arm of a quadriplegic patient to strengthen the muscles there, the opposite arm also got stronger. He concluded that the electricity was making its way to the brain, crossing to the opposite hemisphere, and stimulating arousal centers in the process. He began to wonder about the effect this might have on unconscious people. "I thought, if someone were normal and able-bodied but in a coma, maybe this would make a difference, maybe help wake them up," Cooper says. "It was like maybe we could reboot the brain."

Cooper started testing this hypothesis in 1993. Candice Ivey was one of his first research subjects, and her recovery remains the most spectacular. But Cooper has gathered data on 37 other patients in two studies (at the University of Virginia and East Carolina University). The results indicate that people given electrical stimulation emerge from comas sooner and then regain function more quickly than if they are given only traditional treatment. They're more likely to leave the hospital under their own steam, with less-severe disabilities than would be predicted by the nature and extent of their injuries.

Still, Cooper knows that 38 patients is a tiny sample, especially in a field where so little is understood and in which unexplained spontaneous awakenings, even after long periods of unconsciousness, are not uncommon. But despite being published in the peer-reviewed journals Brain Injury and Neuropsychological Rehabilitation, his work has yet to attract the attention of mainstream researchers. So, in the meantime, he hustles for every patient. He heard about Candice while at a friend's wake, waiting to view the body. Another mourner mentioned that there was a girl in a coma at ECU's Pitt County Memorial Hospital. "I got right out of that line and went to find her," he says. He adds that he has Google news trackers set up for "brain stem injury" and "teenage coma." But the patients and doctors he contacts rarely respond, and Cooper and his stimulator remain on the margins of medicine, frustrated. "It's so easy. Why don't people just use it?"

Cooper's best hope may lie overseas in Japan, where over the last two decades doctors have used electrical stimulation on hundreds of patients – some of whom have been unconscious for many years. The evidence that the Japanese doctors have amassed could confirm Cooper's claims and bring hope to the families of patients most American doctors consider beyond cure. But it may also undermine the hard-won yet fragile consensus on what, neurologically speaking, makes someone alive and when it is acceptable to pull the plug.

Cooper may be without honor in his own home, but mention his name at the Fujita Health University Hospital, just outside the industrial city of Nagoya, Japan, and surgeons light up with recognition. He's been there a few times, collaborated with them on a book chapter, and told them about Candice Ivey and his other patients. They're glad to have a fellow traveler in the US, but they're quick to point out – politely, of course – that they've been doing this work longer than Cooper and have treated many more patients.

The Japanese also use a more spectacular method: They implant the electrodes right into the spine. That's what Isao Morita is doing today. Trained at the Cleveland Clinic, he's a neurosurgeon who wears his hair in a brush cut and speaks passable English. The patient, Katsutomo Miura, lies facedown on the table. He's anesthetized, even though he was already unconscious when he was passed through the doors separating the sterile surgical wing from the rest of the hospital. He's been unconscious for nearly eight years. He was 23 when an ambulance crew found him bleeding and unresponsive on the road near his home in Osaka, next to his wrecked motorbike and his helmet. His legs were shattered, and one of them is now permanently bent at the knee, like he was frozen in place as he was about to run away. It sticks up from the table, making a little pup tent of the blue surgical drapes.

"Yoroshiku onegai shimasu" ("Thank you in advance for your cooperation"), Morita says, and waits for the five-person surgical team to respond in kind before he slices into Miura's neck. It takes 20 minutes of cutting and cauterizing, of spreading muscle and clearing away blood and gristle, for Morita to burrow down to Miura's spine. "C-5," he announces to me, a little triumphantly, as he points into the cavity he has created. Peering over his shoulder, I can see the vertebra that was his target. It is pure white and glistening. Morita takes a pneumatic drill and tunnels along the spine, toward Miura's head, explaining that, so far, this is exactly how a disc surgery would go. I resolve to take better care of my back.

Morita tries to thrust an inch-and-a-half-long, quarter-inch-wide flat metal bar into the tunnel, but it won't go. He drills and pushes four more times until the electrode finally settles into place along the second and third cervical vertebrae. He snakes a wire from there under Miura's skin to a second incision he has made between the shoulder blades. Meanwhile, another doctor has been working at Miura's waist to create an internal pouch for the battery pack that will power the electrode on his spine. Now she runs a wire up to the opening in his back, and Morita, using four tiny screws, splices it to the lead to complete the circuit. Once the swelling goes down and they switch the implant on, it will send a train of electrical pulses through his spinal column and into his brain. The hard part over, the surgeons begin to chat easily as they close up Miura, even laughing a little bit about the anesthesiologist, who has dozed off at his station.

I've already seen this kind of operation. It was part of the PowerPoint presentation I got the day before from Tetsuo Kanno, Morita's mentor and the originator of the surgery. Kanno discovered the virtues of the dorsal column implant accidentally, he says, when he was using it to stimulate muscles in stroke patients. He shows me statistics on the 149 people he and his staff have treated. He cites one study of patients who had been unconscious for an average of 19 months. A vegetative state is considered permanent after one year, but 42 percent of Kanno's patients showed significant improvement. He explains that even a guy like Miura stands a chance. If the electric current keeps flowing into his brain for long enough, maybe years, Miura is likely to make "some recovery."

Which is either good news or bad news, depending on how you feel about Kanno's definition of recovery. Most of the implant recipients, he says, move up a notch in their level of consciousness, from a persistent vegetative state to a "minimally conscious state," a condition in which people are able to muster small but unmistakable signs of awareness. "Maybe the patient just smiles or follows with their eyes," Kanno says. Other Japanese doctors using deep brain stimulation – in which electrodes are implanted directly in brain tissue – have reported similar results: patients who improve to the point where they are severely disabled rather than entirely unresponsive.

But this is enough for Mariko Miura, who spent $30,000 on her son's implant. The day after the surgery, she declares through a translator that she senses her son is calm and comfortable. "If he could just show what he feels," she adds, "yes or no, maybe blinking once or twice, maybe holding hands, maybe a smile, that would be great." The doctors say this is exactly their goal, even though the patient's MRI shows that the right hemisphere of his brain is almost entirely atrophied. "There is no medical indication in this case," Morita says. "This surgery is socially indicated. It is the family's decision if they want to go on, and our job to do what they wish."

These doctors know how strange this kind of reasoning sounds to American ears. "US doctors say that it doesn't mean anything. But even if the patients can't talk," Kanno says, "if they just look up when the family comes in the room, it makes the family very happy." Then again, he says, "you are very dry people in America, dry and cool. Here we are very wet and warm. You see just a body; you say, OK, stop feeding it. But we think a person in a vegetative state has a soul."

No one is sure exactly why electrical stimulation works, but there is strong evidence that it has undefined but profound effects on the brain. We know that electricity can rouse unconscious animals and that deep brain stimulation is widely used to treat Parkinson's disease and dystonia, a disorder in which muscles twist and contract uncontrollably. Kanno and his team have also recorded that patients receiving stimulation have higher levels of dopamine and norepinephrine, as well as increased blood flow in the brain – both conditions are associated with arousal. This increased activity could well lead to nerve cells in the brain forming new connections more quickly, which a recent paper in The Journal of Clinical Investigation showed can lead to minimally conscious patients reawakening.

There are critics, of course. Electrical stimulation as a treatment for vegetative state "is junk science," according to the recently deceased Ronald Cranford, an expert in the clinical and ethical aspects of prolonged unconsciousness. Joseph Giacino, a rehabilitation psychologist at New Jersey's JFK Johnson Rehabilitation Institute who has led efforts to define the minimally conscious state, says that he thinks much of the "success" reported by Kanno occurred because his patients were minimally conscious, not vegetative, to begin with.

Giacino does agree, however, with Cooper and the doctors in Japan that there is enough evidence to warrant further investigation. But the doctors who would like to conduct the necessary research are finding the scientific and political climate inhospitable to their work. Among the obstacles they face is the consensus that emerged following the 1976 New Jersey Supreme Court ruling that Karen Ann Quinlan, a 22-year-old who had suffered severe brain damage, was beyond hope of regaining sentience and could be allowed to die of starvation. According to bioethicist Joseph Fins, who directs the medical ethics division at Cornell's Weill Medical College, this has led doctors to abandon severely brain-injured patients too quickly. The result: statistics indicating that these patients don't get better. Families and doctors then give up, and researchers are discouraged from pursuing possible treatments – a vicious circle that Fins calls therapeutic nihilism. He says this approach ought to be reconsidered. "We've spent a long time allowing people to die. Maybe they deserve more intellectual, diagnostic, and therapeutic engagement than we have acknowledged."

To Fins, that engagement could well include electrical stimulation. He and a Weill colleague, neurosurgeon Nicholas Schiff, have laid out a framework for testing deep brain stimulation on the severely brain-injured, but they're a long way from actually doing any treatment. Fins knows, however, that they're up against "proponents of the right to die who have been concerned about … the hard-won right to forgo life-sustaining therapy," and that getting the research under way may be difficult as a result.

Things will get especially complicated if firm evidence shows, as Cooper believes it will, that electrical stimulation often pushes people out of a persistent vegetative state and into a minimally conscious state. If it becomes clear that a PVS is not entirely hopeless and irreversible, then the diagnosis, which has functioned as a rationale for ending life support, will no longer provide moral clarity. If that happens, Giacino says, "people are going to have to really think about what this all means before nonchalantly pulling the plug."

Of course, it is hard to imagine that anyone makes that monumental decision nonchalantly. But perhaps people do take as certain some things that might not be quite true – namely, that vegetative states cannot be treated. This, of course, was the pivot on which the Terri Schiavo spectacle turned: People argued that her doctors were wrong about the hopelessness of her condition, that maybe that little smile meant starving her might be murder, rather than mercy. As it happens, she would have been unlikely to respond to any form of electrical stimulation; cases in which the brain has been deprived of oxygen, rather than injured by force, are the hardest to treat. But accident victims fill emergency rooms, and it is hard to picture how much more tortuous our decisions will get if new truths about electrical stimulation displace old certainties about hopelessness.

Even with current guideposts, the complexities seem mind-bending. Just ask Candice Ivey. She has impaired short-term memory, a lack of stamina, and difficulty with impulse control that makes it tough to keep friends. Because of that, her life – one of the best possible outcomes after so severe an injury – is still immeasurably harder than it was before her accident. "God's allowed me to do a lot of good things," she says. "But I remember what life used to be like and what I used to do mentally and physically, and I wouldn't want to do this again. If this ever happens again, I want them to terminate me." Later, her mother draws deeply on her cigarette when I ask her about this. "It goes through my head every day," Elaine says. "If I had let her die, she'd at least be at peace. And I keep thinking there has to be a reason for this – her life will turn around. But when it doesn't happen … I mean, it's been 12 years now."

Things are no simpler in Katsutomo Miura's hospital room the day after his surgery. He's entirely still except for his lips, which are rooting ceaselessly like a hungry infant's. His mother, who is bustling over him, leans into his face, squeezes his cheek, and talks to him. I realize she is introducing me to him. "My son and I, we are one person," she told me earlier, and, as if to prove her point, she picks up his right hand and extends it for me to shake. It is warm and wet.

Not for the first time in my three days at Fujita, I'm reminded of another doctor who more famously applied electricity to a lifeless body to animate it. Of course, Victor Frankenstein's wish to cheat mortality lies behind all medicine, but you don't often see its monstrous implications displayed as clearly as in this poor man suspended by good intentions between two worlds. "We produce these patients," Kanno says. "It is the dark side of neurosurgery."

Unintended consequences, and the impossibility of unraveling them, are on my mind as I finish my visits with Japanese implant patients and their mothers. No one seems to be much concerned about what this is like for the patients ("We have no discussion with them," Kanno says), and I'm wondering why these women can't see that their children are gone forever, why they can't move on. I want to say something like this to my translator as we get into the elevator, but there are tears in her eyes. "They're so well loved," she says, and I can't help but think that I am not only on the other side of the world, but on the other side of our beliefs about what makes a life worth living, that I am grasping the moral chaos that will ensue if science proves these doctors right.

Gary Greenberg ( is a Connecticut-based writer and psychotherapist.

and further reading

Thought control?
First Brain Prosthesis?
The Orgasm Command-Center
Electrodes in Brain to Switch Off Pain
The Transcranial Magnetic Stimulator
Brain Stimulation and the Shadow Self
Wireheads and Wireheading in Science Fiction
Addicted brains; the chemistry of pain and pleasure
Pleasure Evoked by Electrical Stimulation of the Brain

pair of rats