There's a hand lying on the blanket on Matt Nagle's desk and he's staring at it intently, thinking "Close, close," as the scientists gathered around him look on. To their delight, the hand twitches and its outstretched fingers close around the open palm, clenching to a fist. In that moment, Nagle made history. Paralyzed from the neck down after a vicious knife attack four years ago, he is the first person to have controlled an artificial limb using a device implanted into his brain.
The experiment took place a few months ago as part of a broader trial into what are known in the business as brain-computer interfaces. Although it is early days, aficionados of the technology see a world where brain implants return ability to those with disability, allowing them to control all manner of devices by thought alone. There are huge hurdles ahead. No one knows how much information we can usefully decipher from the electrical fizz of the brain's 100 billion neurons. More important, scientists are still in the dark as to what effect, if any, long-term implants will have on the human brain, or how its circuitry will cope with the new tasks demanded of it.
Nagle got involved in the latest trial after hearing about John Donoghue, a professor of neuroscience at Brown University in Rhode Island, whose company Cyberkinetics has developed an implant called BrainGate. Under Donoghue's instruction, Nagle was given a general anesthetic before a disk the size of a poker chip was cut from his skull. After making an incision in the brain's protective membrane, a tiny array of 96 hair-thin electrodes, each protruding about a millimeter, was pressed onto the surface of his brain, just above a region of the sensory motor cortex that is home to the neuronal circuitry governing arm and hand movement. With the electrodes in position, the bony disk was replaced, leaving room for a tiny wire to connect the electrodes to a metal plate the size of a 10-pence piece that sits on Nagle's head like a button.
To read brain signals from Nagle's motor cortex, Donoghue's researchers attach an amplifier to the metallic button on his head and run a cable to a computer. When he's hooked up, the tiny voltages of the sparking neurons beneath the electrodes produce a series of brainwaves that dance on the computer screen.
Since having the electrodes implanted in June last year, Nagle has been test-driving the technology, seeing what he, and it, are capable of. "We're evaluating his ability to do a whole range of things. We've hooked him to a computer that lets him turn a TV on and off, change channels and turn the volume up and down," says Donoghue.
The success of the technology relies on being able to decipher accurately the electrical activity within Nagle's brain and turn it into useful actions. The trials started tentatively. Nagle had been unable to move any of his limbs for nearly four years. The scientists had no idea how this would have affected the brain signals that normally control movement. Would they have fizzled out through lack of use, much as muscles waste away for those in the wheelchairs? "No one knew if it would work in someone with these injuries, but simply by asking him to imagine moving we got useful signals and it was amazing. I was overwhelmed by how beautifully the cells were still working," says Donoghue.
Getting the signals is one thing; deciphering them is another. But Donoghue's team found that some simple rules held -- if the brain wanted to move the hand to the right, certain cells would fire a rapid series of impulses. If the brain was willing the hand to move left, the cells fired a different number of times. Other information, such as where the hand should end up, what trajectory it should take, and how quickly it should move, is also embedded in the electrical signals.
Part of the difficulty in reading brain signals is that while even a simple movement such as raising a hand requires electrical signals from many regions of the brain, the implanted electrodes pick up just a tiny fraction of those that fire. "We're recording only a dozen or so, when a million might be active," says Donoghue, who likens the process to dropping a microphone into a crowded room and trying to get the gist of all the conversations going on.
The limitations of taking signals from just a few active neurons have become apparent in the trial. Many of the tasks Nagle is given involve moving a cursor around a screen by thinking which way it should move. But the cursor jiggles, making it difficult to select icons on the screen with any precision. "We could smooth it out using software, but at the moment, we want to see if Matthew can learn to control the wobble," says Donoghue, who is recruiting four other patients to complete the trial. "If he can do that, he could use computer software to answer e-mails, and if he can do that, he could be employed."
Ultimately, Donoghue says there should be no need to connect cables to people's heads to read their minds. Miniaturization should bring smaller devices that can be powered through unbroken skin and transmit signals wirelessly from the brain to a processor worn on a belt that triggers the intended device.
If all goes according to plan, Donoghue's trial, designed to explore how well a variety of people can control different devices by the power of thought, will be completed in about 18 months. He's not the only one keen to find out just how useful such devices could be. At Duke University in North Carolina, Miguel Nicolelis is in the final stages of getting permission to fit 16 quadriplegic patients -- half in the United States, half in Brazil -- with brain implants for a period of 30 days. Initially the trial will look at whether the patients' brains still produce useful motor signals. "Then, we want to see if these patients can control a robotic arm that can reach and grab objects, and how well their brains get used to it," says Nicolelis.
In previous studies, his team showed that when monkeys had their brains hooked up to robotic arms, they assimilated the arm, effectively making it their own. "Their brains actually incorporated the robotic arm by dedicating neuronal space to it. We want to see if the same thing happens in humans," he adds.
For all the promise brain implants hold, there are some who believe they are not the best bet for many patients. Implants suffer from a number of drawbacks, the first being that they demand invasive surgery, with attendant risks. Second, implanted electrodes cause at least some inflammation of the brain tissues they push into. As well as obvious medical concerns, if the inflammation is significant, it can smother any signals the electrodes might pick up.
"Every one you put in gives some inflammation, but it's minor. We're still working on making electrodes more biocompatible, but we've got monkeys who have so far survived for nearly five years with implants and they are fine," says Nicolelis. "The thing is, to do what we want to do, to get that level of control, you have to get into the brain."
Nicolelis says his goal is to use brain implants to allow the disabled to walk again. He has already started designing a wearable robotic "exoskeleton" that could help power paralyzed legs -- think Wallace and Gromit's "The Wrong Trousers," only with better control. Nicolelis is also developing something called "shared control" in which a robotic limb is triggered by a basic command from the brain, but refines and carries out the movement itself, using preprogrammed intelligence. "The hurdles ahead, after finding even better electrodes, are developing prosthetics that are more amenable to brain control," he says.
Many of the labs looking at brain implants started out doing basic research into understanding how small numbers of neurons worked. The research required the development of thin wire electrodes that could cozy up to individual neurons, a legacy that led to fully implantable devices. But for many applications, simpler signals, which can be picked up without undergoing major surgery, may suffice.
At the Wadsworth Center, the laboratory arm of the New York State Health Department, John Wolpaw and his team recently proved that a hat not unlike a swimming cap peppered with electrodes could pick up clear enough signals to allow the wearer to move a cursor around a computer screen. "There was an unsupported assumption that to get that kind of control, you needed to implant, but our work showed that's not the case. These systems can do better than a lot of people give them credit for," says Wolpaw.
Instead of tapping into the brain's natural signals for moving limbs, Wolpaw's system picks up changes in general brain activity that the patient must learn to control. "We look at rhythms on the EEG that are normally just idling, but we've shown that by using mental imagery, people can learn to make the signals stronger or weaker, and we can translate that into cursor movement," says Wolpaw.
Wolpaw's patients are trained over 10 sessions, during which about 80 percent learn to control their brainwaves well enough to move a cursor around a screen. In time, most can do other things, such as think of answers to questions to select on-screen, without it interrupting their control. The risks of the technique are undoubtedly fewer than for full brain implants, though questions remain about the effects of forcing the brain to change its activity, in a way the electrodes can pick up. "It's probably just like learning anything else. There's been no indication that any of this does anything harmful, and it's hard to see how it could, but we can't say for sure," says Wolpaw.
While Wolpaw has achieved control many thought impossible without implanting electrodes directly into the brain, he feels a third technique, called electrocorticography, or Ecog, might have the brightest future. Ecog involves a smaller operation to place a small sheet of electrodes on the surface of the brain. "With this, you get strong signals, you can pick them up from smaller areas, but you're not sticking something into the brain," he says. Preliminary trials show patients can learn to use Ecog devices much faster than electrodes placed on their scalps.
More than likely is that all three techniques will co-develop, each finding its own niche. Full implants may only be worthwhile for the severely disabled, who need to control complex machinery, such as prosthetic limbs, with their thoughts. For many, though, regaining even the most minor level of independence would help. "One fellow said to me, 'I just want to be able to scratch my nose,'" says Donoghue. "It's easy to forget the kinds of extraordinary things people can't accomplish. If you can do something that lets them reach out to the world even a little, it can make a huge difference."