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TBI: Minds over motion

Imagine you're paralyzed. A catastrophic accident or disease has trapped you inside a body that refuses to follow your brain's instructions. Your brain, meanwhile, functions normally, although you are unable to move your limbs or speak. You cannot pet your dog, hug your child or wave to the paperboy. You cannot articulate even the simplest request, desire or feeling. I'm hungry. My nose itches. I'm cold. The television is too loud. I love you.

Now, imagine you could manipulate objects around you - open e-mail, play a video game, adjust the volume on the television set, even lift a cup of coffee to your lips or propel your paralyzed body across the room - using only your thoughts. That's more difficult to imagine, isn't it?

Scientists at Brown University in Providence, R.I., are operating beyond most imaginations. They have developed data that show how a tiny sensor can allow a quadriplegic human to control a robotic limb, open a prosthetic hand and move a computer cursor using brain activity alone. The device that makes these actions possible is called BrainGate, created and tested by Cyberkinetics Neurotechnology Systems. It is capable of recording multiple brain cells simultaneously, decoding signals in real time to control computers or other external devices.

The research behind BrainGate is largely credited to neuroscientist John Donoghue, director of the Brown University Brain Science Program. Donoghue, his colleagues and students were interested in how the brain constructs movement. They knew that individual brain cells communicating to each other produce signals that result in movement. To understand how that happens, they needed a way to record multiple brain cells simultaneously. By using a sensor planted in the brain of a primate, the team decoded signals and demonstrated that the monkey could move a computer cursor merely by thinking about it.

"We taught a monkey to control a cursor on the screen with his hand just as you would control the arrow on a desktop with a mouse," Donoghue says. "We used sensors to pick up brain signals as the monkey moved the cursor. We then ran the data through a computer, bypassing the monkey's hand movement to see if the brain signals - not the hand - could move the cursor. And it worked."
What about paralyzed humans? "We wanted to know what happens when there is a disconnection of the brain from the body," Donoghue says. "So a number of colleagues and I started a company that could forge a way to take our laboratory device and turn it into something beneficial to humans."

Four human subjects have participated in two trials using the device: two with spinal-cord injuries, one who suffered a brain-stem stroke and another with ALS, a degenerative disease that impairs motor movement. Initial human trials concluded that the implanted device is safe, movement-controlling brain activity is present, and indeed, people can perform useful tasks by their thoughts alone.
"It was really striking to me that the brain activity was still there," Donoghue says. "In fact, it was even more surprising that the mere suggestion to subjects to imagine moving their arms right or left immediately triggered brain-cell activity."

While encouraging, the early results were less than perfect. The quality of control from raw brain signals was not very good. Initial movements were wobbly, and the cursor did not stay still.
"When you and I move our hands we're using millions of neurons," Donoghue says. "In the trials, we were trying to replicate movement by using input from only a few dozen cells. We learned right away that short-term practice didn't improve quality, and while I believed long-term practice might improve results, I had little data to prove that."

To improve quality of movement, Brown University's Dr. Michael Black took the raw signals and applied additional computations. Donoghue and his team then added the capability to click on an icon on a computer screen, giving the person the ability to make a selection using an on-screen keyboard, to control a television, and to operate other external devices.

Cursors to Muscles. Neurotechnology is not limited to helping motor-impaired humans move cursors on computer screens or to manipulate remote appliances by thoughts alone. Cutting-edge biomedicine, neuroscience, mathematics, computer science and engineering have paved the way for the development of closed-loop neuromotor prostheses that may enable interaction between the brain, paralyzed limbs and external devices, such as robotic limbs. Simply put, scientists are confident that neural activity transmitted by tiny devices implanted in the brain could soon command motion over paralyzed muscles or the actions of prosthetic limbs or electric wheelchairs.

"Our long-term goal is to restore lost function as naturally as possible," says physician Leigh Hochberg, a Brown University alumnus and lead author of a 2006 article in the science journal Nature, detailing clinical trials involving the BrainGate device. "If someone with advanced ALS or brain-stem stroke is unable to speak, we'd like to restore the ability to communicate through external devices. For someone with a spinal-cord injury or lost limb, we'd like to restore the ability to control one's own limb or prosthetic limb as naturally as people without injury or disease do."

There are several potential ways to restore lost function, Hochberg says. The simplest may be to try to reconnect the two parts of the system that are still working across the part that is injured. For example, the brain still works, and the limb still works, but the connection between them - the spinal cord - is broken. By connecting the signal in the brain that says "move my limb" to a prosthetic device, or by using functional electric stimulation, it may be possible one day to move the prosthetic limb or natural limb by simply thinking about it.

More than 15 years of research and development have yielded astonishing results at the Cleveland Functional Electrical Stimulation Center, a consortium whose partners include the Cleveland VA Medical Center, Case Western Reserve University and the public hospital system of MetroHealth Medical Center. FES trials have shown that people with spinal-cord injuries can regain some mobility when electrodes are placed in the muscles or nerves of an immobile limb and stimulated by another uninjured muscle group. Subjects with strategically placed electrodes have been able to perform tasks such as lifting cups of liquid to their mouths. But the technology has its limits.

"A limitation of FES is that the available controllers - the signals that tell the device how to move a limb - are limited to activities that are still possible, such as moving a shoulder or turning the head," Hochberg says. "Ideally, the signal that drives a limb would be the same signal that is coming out of the brain that caused movement in the limb in the first place."

The BrainGate device also has limitations; size and connectivity are two. The device consists of a recording array of electrodes about the size of a baby aspirin. It is surgically implanted in the motor cortex of the brain. The electrodes transmit brain activity along fine wires to a small pedestal attached externally to the top of the skull. A large plug is attached to the connector, and the signal is transmitted to a computer. The implanted device must be physically tethered to an external computer. "Much like brain stimulators for Parkinson's disease or a heart pacemaker, the BrainGate device is eventually going to have to become fully implanted," Hochberg says. "Arto Nurmikko and colleagues here at Brown University are developing methods to fully implant the device so brain activity can be transmitted wirelessly to a receiver. Brain signals could also be run under the skin to drive a limb. The key is to change brain signals into control signals, and that requires an external computer or implanted chip."

Amazing as BrainGate may be, Hochberg acknowledges the infancy of its technology. "We know a lot less than we want to know, but what we do know is that it's indeed possible to effect movement through thought alone," Hochberg says. "This is exciting and important science. Development and application of this technology will, I believe, enable disabled people to control the environment around them, and in the future move prosthetic or robotic limbs and even their own paralyzed limbs - through brain signals."

Mixing and Matching. The Center for Restorative Regenerative Medicine is also playing a pivotal role in improving function for individuals with limb trauma by developing high-tech solutions for the restoration of limbs. The center, directed by Dr. Roy K. Aaron, is a collaboration between the Providence VA Medical Center and Brown University. Aaron says he would like to eventually see prosthetics activated by a junction of some sort between the body of the user and the prosthetic device. The signals might travel the nervous system, the muscles or come directly from the brain and perform subtle motion, even have artificial skin with touch pads that can actually feel. Ten years ago, such ideas might have seemed like science fiction, but VA and university researchers at Providence, Cleveland, Chicago and other centers give Aaron confidence that his dream is obtainable.

"Our challenge here is to use what progress we achieve and what progress people deliver to us," Aaron says. "There is a healthy creative tension in orthopedic research between biologists and engineers. Sometimes the biologists get ahead of the engineers, and sometimes the engineers get ahead of the biologists. The job of the clinician is to choose for a patient those solutions that are most appropriate."
The Providence center is working on a number of prosthetic technologies intended to provide independence to users of the devices. Research there is breaking new ground in tissue engineering, orthopedics, neurotechnology, prosthetic design and rehabilitation. The various techniques converge to create the concept of a bio-hybrid limb - composed of both biological and non-biological materials - enabling researchers to transcend the limitations of biological tissue and prosthetic materials alone.

For those who have lost the use of limbs - due to spinal-cord injury, brain-stem stroke, ALS, amputation or other reasons - the BrainGate device and other state-of-the-art prosthetic technologies are more than scientific breakthroughs. They represent hope that someday, somehow, science will find a way to restore movement - and the freedom that comes with it - to those affected.
"It's my hope that day comes sooner than later," Aaron says.

– James V. Carroll



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