A monkey sits on a bench, wires running from its head
and wrist into a small box of electronics. At first the wrist lies
limp, but within 10 minutes the monkey begins to flex its muscles
and move its hand from side to side. The movements are clumsy, but
they are enough to justify a rewarding slug of juice. After all, it
shouldn't be able to move its wrist at all.
A nerve connection in the monkey's upper arm had previously been
blocked with an anaesthetic that prevented signals travelling from
its brain to its wrist, leaving the muscles temporarily paralysed.
The monkey was only able to move its arm because the wires and the
black box bypassed the broken link.
The monkey was in Eberhard Fetz's lab at the University of
Washington in Seattle. The experiment, performed last year, was the
first demonstration of a new treatment that might one day cure
paralysis, which is typically caused by a broken connection in the
spinal cord. Though much work has focused on using stem cells to
regrow damaged nerve fibres, some researchers believe that an
electronic bypass like this is equally viable.
The idea is to implant electronic chips in the relevant regions
of the brain to record neural activity. Then a decoder deciphers
the neural chatter, often from thousands of neurons, to figure out
what the brain wants the body to do. These messages must then be
relayed - ideally wirelessly - to electrodes that deliver a pulse
of electricity to stimulate the muscles into action. Such "brain
chips" are already restoring hearing to the deaf and vision to the
blind, and helping to stave off epileptic fits, so the idea isn't
as far-fetched as it might sound (see "Bionic medicine").
Every step of progress in tackling paralysis has been hard won.
One of the early demonstrations that it may be possible emerged in
2003, when José Carmena, then at Duke University in Durham, North
Carolina, successfully created an interface between brain and
machine that allowed his lab monkeys to play a computer game using
only their minds.
To gain a juice reward, the monkeys had to move a cursor -
initially with a joystick - to hit a target on the computer screen.
Beforehand, Carmena and his colleagues had implanted several chips
throughout the parietal and frontal lobes of the monkeys' brains -
regions known to plan and control movement. Each chip held up to 64
electrodes, which recorded the firing of the surrounding neurons as
the monkeys manipulated the joystick.
Once the system had successfully decoded the chatter from the
monkeys' neurons, the program stopped responding to the joystick's
movement altogether and relied solely on the monkeys' thoughts to
control the cursor. Eventually even the animals worked this out and
stopped holding the joysticks as they completed the task (PLoS
Biology, vol 1, p 42).
Manipulating a cursor on a computer screen is one thing, but
whether such brain chips could translate the more complicated tasks
of daily life remained an open question until 2004, when John
Donoghue and colleagues from Cyberkinetics in Providence, Rhode
Island, implanted a 100-electrode chip in the brain of a
25-year-old man known as MN, who had been left paralysed from the
neck down by a knife wound.
Over the subsequent nine months, MN successfully used this
BrainGate chip to open emails, operate a television and even
control a robotic arm (Nature, vol 442, p 164). It was a promising
step, but the technology was far from perfect. "Although BrainGate1
worked well in many ways, at times the control was not
satisfactory," says Donoghue. And by the end of the trial, fluids
from the brain had degraded the chip. The team are now solving
these problems, and earlier this year announced the start of a
clinical trial for an improved version of the chip.
With a chip implanted in his brain, a paralysed man was able to
open emails, operate the TV and even control a robotic arm
The ultimate hope for many paralysed people, of course, is to
regain movement in their own limbs. Until Fetz's experiment last
year, no one had successfully used an implant to bridge a broken
connection between the brain and the body. Trials of functional
electrical stimulation (FES), in which implanted electrodes
directly stimulate muscles into action, had hinted that this might
be possible. But these impulses had been activated by external
triggers, such as a switch controlled by one of the patient's
healthy limbs, and not directly by brain signals.
Not only did Fetz's work demonstrate that the electronics could
descramble neural signals and relay appropriate instructions to the
limbs using FES, he also showed that the brain makes the job easier
than one might expect. Although the motor neurons that connected to
the chip did not naturally control the wrist, in a short time they
adapted to the task and controlled complex actions (Nature, vol
456, p 639). "All neurons could be used equally well for control
regardless of their original association to movement," says team
member Chet Moritz.
That could have an important implication for humans hoping to
use similar implants in the future. "It underscores the impressive
flexibility of the brain in learning to adapt to novel connections,
which may play a key role in allowing neural prostheses to be
adopted by patients," he says.
So could the same approach work in humans? There seem to be no
fundamental obstacles, and Donoghue plans to test the proposition
in the new BrainGate trials, using his chip to control a limb using
FES. If successful, it will represent a milestone in the
development of such treatments.
Direct electrical stimulation of muscles using FES is unlikely
to be the final solution, however. This direct approach uses a
relatively powerful electric current applied to large areas of
tissue, producing fairly clumsy movements. A more elegant method,
some claim, is to send the impulse along the existing healthy
nerves. That would require smaller local currents, delivered with
greater precision, to finer regions of the muscle tissue, which
should allow more subtle control.
Coordination
As a bonus, nerve stimulation could simplify some of the demands
placed on a brain chip. That's because for many rhythmic
activities, such as breathing, walking and crawling, the brain
simply sends a command signal and it is the spinal cord's in-built
systems that orchestrate the fine movements of each muscle. So if
the healthy sections of a damaged spinal cord have retained their
ability to control movement, the electronic chip could transmit the
brain signal around the broken connection but leave the muscular
orchestration to the spinal cord. In this case, a brain chip would
just beam the message to a second device implanted in the spine
below the break, which would then stimulate the spinal cord.
The chips could simply transmit the information around the break,
leaving the undamaged sections of the spinal cord to orchestrate
the muscles
That could "dramatically simplify the control signals needed
from the brain", says Moritz, since for these repetitive tasks the
brain chip would just decode and transmit an umbrella command. Such
simplification should make the chips less likely to fail - an
important consideration when the only way to replace the chips is
through invasive surgery - and also reduce their power
consumption.
Using this principle in 2002, Vivian Mushahwar, now at the
University of Alberta in Edmonton, Canada, plugged four electrodes
into a cat's spinal cord and delivered signals that mimicked the
brain's command to walk. Sure enough, the cat made stepping
motions.
Simply relaying the messages across a break in this way would
not help the worst injuries, however, in which the spinal cord has
lost its ability to coordinate muscles. In these cases, to minimise
the size of the brain chip, and the burden placed on it, the
muscular orchestration would need to come from either the chip
implanted in the spinal cord, or an external device that
communicates wirelessly with the chips in the brain and the
spine.
Calculating exactly which nerves to stimulate and in what
pattern is no easy task, but the first demonstration of an
artificial "central pattern generator" was reported last year, when
Mushahwar and colleagues at Johns Hopkins University in Baltimore,
Maryland, successfully tested such a chip on a cat. With
coordination coming solely from an external CPG chip connected to a
handful of electrodes that stimulated the cat's spine, the animal
was able to walk (IEEE Transactions on Biomedical Circuits and
Systems, vol 2, p 212). In this experiment, the team were simply
testing the CPG's ability to orchestrate movement as an alternative
to FES, so the trigger came from a manual switch and not the cat's
brain. The next hurdle will be to use the CPG in conjunction with a
neural chip.
While this CPG chip only dealt with the action of walking, in
humans an additional external chip might also offload some of the
processing from the brain chip for non-repetitive motions like
clenching a fist or raising a hand. The brain doesn't necessarily
produce an umbrella command for all of these movements, so the
neural implant would still need to detect a more complicated
signal, but the external chip could at least perform some of the
processing to decode and relay these comands to the relevant
electrodes.
For many patients, technology like this would only solve half
the problem, however. Paralysed people who have lost feeling as
well as movement in their limbs would need two-way systems to pass
sensations back to their brain. This information could come from
artificial sensors, but ideally the chip would read sensations from
existing nerves and relay them to chips that stimulate the areas of
the brain that process tactile information.
Although work has been slower in this area, there's good
evidence it will one day be possible. Carmena, for instance, who is
now at the University of California, Berkeley, recently stimulated
a rat's brain to feel sensations from some "virtual whiskers",
causing it to move as if its own whisker's had really brushed
against an object. Similar technology could one day relay tactile
information to human brains.
If these advances in brain-chip capability are to be exploited,
the researchers still need to ensure that the chips are safe and
durable. Biocompatibility, for instance, is a huge challenge,
because tissue in the brain can react badly to an implant, killing
off the very neurons that the electronics are trying to connect to.
Recent efforts suggest a coating of growth hormones might mitigate
this problem, while others have shown chips that slowly exude stem
cells might also work.
Then there's the problem of powering the devices. Most existing
implants - like cochlear implants, for example - are connected to a
battery outside the head that can be replaced regularly. The
electrodes in the spine and limbs could be powered this way, but
it's less practical for a chip deep within the skull. Instead, such
chips will need to be recharged by electromagnetic fields generated
by a device outside the head, so power consumption will have to be
minimal.
One solution might be to offload the more difficult processing
to a portable computer outside the body, before passing the
information back to the chips that stimulate the nervous system. In
this way, Reid Harrison at the University of Utah in Salt Lake City
has produced a neural chip that uses just 8 milliwatts. That's less
than the "standby" LED on the front of a TV set.
Security risks
All the pieces are gradually coming together, but whatever
happens it will be a long time before these chips can become a
mainstream treatment: the US Food and Drug Administration requires
as much as 10 years of animal testing before a chip can be deemed
safe enough to be implanted in human brains. That means the latest
technology, such as chips that stimulate tactile sensations in the
brain, will need extensive testing before clinical trials can
begin.
Yet even once the technology has proven itself, the social
issues surrounding the treatment will need to be solved. Take the
question of security, for example. Last year, a team of researchers
successfully hacked into a heart pacemaker and defibrillator
through the wireless communication that allows doctors to adjust
its performance. Although the device wasn't implanted in anyone at
the time, it raised the possibility that hackers could disrupt a
patient's treatment (New Scientist, 22 March 2008, p 23).
To make matters worse, there is currently no obvious way of
protecting a defibrillator or pacemaker from a hacker without
inhibiting a doctor from accessing it during an emergency. Since
neural prostheses will rely so heavily on wireless links to
communicate between the different components, the risk to these
chips may be even greater.
Perhaps most perplexing is the question of legal responsibility.
If someone wearing a neural prosthesis were to punch someone, who
is to blame? The action may have been deliberate, in which case the
patient is to blame, or the chip may have been malfunctioning and
the responsibility would lie with the manufacturer. Discovering
where the truth lay would be no easy task. The law has had trouble
catching up with the self-parking car, never mind an electronically
controlled limb gone wild.