Until recently, severe spinal cord injuries came with a fairly definite diagnosis of paralysis, whether partial or complete. But new developments in both stem-cell therapy and electronic stimulation have begun to provide hope, however distant, that paralysis may not be a life sentence. Complicated muscle stimulation devices can enable limited standing and walking, and the first embryonic stem-cell trials began last year. Other techniques, however, may provide an even simpler solution.
In his lab at the University of California, Los Angeles, V. Reggie Edgerton is developing an electronic neural bridge, one that helps impulses jump from one side of a severed spinal cord to the other to take advantage of neural “circuitry” that remains intact even after it’s been cut off from the brain. In research presented two weeks ago at the Society for Neuroscience meeting in San Diego, Edgerton and graduate student Parag Gad used this approach, combined with electromyography (EMG), to help rats with severed spinal cords and completely paralyzed hind legs to run on all fours again. When their front legs began to run, the movement triggered a small current that prompted their rear legs to keep up.
Edgerton has been working on a system that employs preëxisting abilities of the spinal cord: neural pathways that, after an injury, may be blocked but don’t disappear. Although the brain may control the impulse that initiates walking, the sequential muscle-by-muscle movement is not under our conscious command. “The signal coming down from the brain isn’t to activate this muscle and then this muscle and then this muscle,” Edgerton says. “It’s to activate a program that’s built into the circuitry. A message comes down from the brain that says step. The spinal cord knows what stepping is; it just has to be told to do that.”
Rather than connecting electrodes to neurons or muscles, Edgerton attaches his neural bridge to electrodes on the outside membrane of the severed spinal cord. Slow pulses of electricity fire up the spinal circuitry associated with stepping, and, once the legs start to bear weight, the spinal cord recognizes the resulting sensory information and generates stepping motions on its own—no brain connection required.
With the flick of a switch, Edgerton and his colleagues made the rat’s paralyzed hind limbs break into a trot. The result—an even, rhythmic gait controlled by the researchers—is something that stimulation of individual muscles can’t yet replicate.
Gad took this system one step further, creating a technique that monitors movement of the animal’s front legs and uses this information to generate electrical pulses that prompt the rear legs to move. First, he developed an algorithm that can distinguish walking activity—constant, alternating movement in both forelegs. Then, he implanted EMG wires into the front and rear legs, to detect the activity of skeletal muscles. The EMG wires connect to a small backpack containing a microcontroller that, upon detecting walking in the forelimbs, sends out a constant pulse to the spinal cord, triggering the hind limbs to join in.
“They’re demonstrating, in a practical sense, many of the concepts that have been tossed around for some time,” says Vivian Mushahwar, a biomedical engineer at the University of Alberta. “It is really refreshing.” Mushahwar and physiologist Richard Stein, also at the University of Alberta, have been working on another system that takes advantage of the spinal cord’s innate circuitry.
“The work is really neat, and is a nice proof of principle in the animal,” Stein says. “But I’d need a little more evidence to be convinced it would be useful in a person.”
The researchers still have much to do before the EMG technique can be moved into humans. The rats have only been tested on a treadmill, rather than more varied terrain. And translating Gad’s feedback loop from a rat’s four-legged stance to the human’s two-legged one won’t be simple, since humans don’t use their forelimbs in a way that could predictably act as a trigger for walking.
The EMG trigger, Edgerton says, is just the start of determining how to put movement control back in the patient’s hands. “We want to see what kind of strategies could be used for a patient to be able to control when to turn it on and when to turn it off.” EMG electrodes are already being used to help amputees control prosthetic limbs: activating a particular muscle, in combination with an EMG wire, can signal a prosthetic arm to move up and down or a prosthetic hand to open and close.
“This isn’t particularly remarkable—yet,” says Eberhard Fetz, a biophysiologist at the University of Washington. “Triggering the hind limbs by using the activity of the forelimbs is new, and I would be interested to check back next year to see if they’ve been able to create a more dynamic, continually interactive interface”—one that could incorporate feedback from the EMG electrodes in the hind limbs to create a fully functional system.
Gad is already on the case. He believes there could be other ways to get people to trigger stimulation, whether it’s a switch controlled by hand or something more akin to the muscle-activated prosthetics. “This is the first effort in trying to develop an interface that would go with epidural stimulation,” Edgerton says. “[Gad] has developed a system so that the rat has control. It doesn’t necessarily know that it has control, but when it moves the forelimbs, the hind limbs are going to be turned on. The idea is to get the animal more in control of what happens.”