In cases of paralysis or amputation, neuroprosthetic systems that artificially stimulate muscle contraction with electrical current can help regain limb functionality. However, despite many years of research, this type of prosthesis is not commonly used because it causes rapid muscle fatigue and poor control.
MIT researchers have developed a new approach that they hope could one day enable better muscle control with less fatigue. Instead of using electricity to stimulate muscles, they used light. In a study on mice, researchers showed that this optogenetic technique allows for more precise muscle control as well as a dramatic reduction in fatigue.
“It turns out that by using light and optogenetics you can control muscles more naturally. “In terms of clinical application, this type of interface could have very broad utility,” says Hugh Herr, professor of media arts and sciences, co-director of the K. Lisa Yang Center for Bionics at MIT and associate member of the MIT McGovern Institute for Brain research.
Optogenetics is a method based on genetically engineering cells to express light-sensitive proteins, which allows researchers to control the activity of these cells by exposing them to light. This approach is not currently feasible in humans, but Herr, MIT graduate student Guillermo Herrera-Arcos and their colleagues at the K. Lisa Yang Center for Bionics are currently working on ways to safely and effectively deliver light-sensitive proteins into human tissue.
Herr is the lead author of the study, which appears today in Science Robotics. Herrera-Arcos is the lead author of the paper.
Optogenetic control
For decades, researchers have been studying the use of functional electrical stimulation (FES) to control muscles in the body. This method involves implanting electrodes that stimulate nerve fibers, thereby causing muscle contraction. However, this stimulation usually activates the entire muscle at once, which is not the natural way the human body controls muscle contraction.
“Humans have this incredible precision of control that is achieved through a natural recruitment of the muscle, where as the signal strength increases, small motor units are recruited, then medium-sized, and then large motor units are recruited in that order,” says Herr. “In FES, when you artificially irradiate the muscle with electricity, the largest units are recruited first. So when you amplify the signal, you get no power at first and then suddenly you get too much power.”
This great force not only makes it more difficult to achieve precise muscle control, but it also tires the muscle quickly, within five or ten minutes.
The MIT team wanted to find out if the entire interface could be replaced with something else. Instead of electrodes, they wanted to control muscle contraction using optical molecular machines via optogenetics.
Using mice as an animal model, the researchers compared the muscle force they could generate with the conventional FES approach with the force they generated with their optogenetic method. For the optogenetic studies, they used mice that had already been genetically modified to express a light-sensitive protein called channelrhodopsin-2. They implanted a small light source near the tibial nerve, which controls the muscles of the lower leg.
The researchers measured muscle strength while gradually increasing the amount of light stimulation and found that, unlike FES stimulation, optogenetic control resulted in a steady, gradual increase in muscle contraction.
“By changing the optical stimulation we deliver to the nerve, we can control the force of the muscle proportionally, in an almost linear way. This is similar to the way our brain signals control our muscles. This makes it easier to control the muscle than with electrical stimulation,” says Herrera-Arcos.
Fatigue resistance
Using data from these experiments, the researchers created a mathematical model of optogenetic muscle control. This model relates the amount of light entering the system to the output of the muscle (how much force is produced).
This mathematical model allowed researchers to design a closed-loop controller. In this type of system, the controller provides a stimulation signal, and after the muscle contracts, a sensor can detect how much force the muscle is exerting. This information is sent back to the controller, which calculates whether and how much the light stimulation needs to be adjusted to achieve the desired force.
Using this type of control, the researchers found that the muscles could be stimulated for more than an hour before they became fatigued, whereas with FES stimulation the muscles became fatigued after just 15 minutes.
One hurdle that researchers are now working to overcome is how to safely deliver light-sensitive proteins into human tissue. A few years ago, Herr’s lab reported that these proteins can trigger an immune response in rats that inactivates the proteins and could also lead to muscle wasting and cell death.
“A key goal of the K. Lisa Yang Center for Bionics is to solve this problem,” says Herr. “Multifaceted efforts are underway to develop new light-sensitive proteins and strategies for their delivery without triggering an immune response.”
As further steps toward reaching human patients, Herr’s lab is also working on new sensors that can measure muscle strength and length, as well as new ways to implant the light source. If successful, the researchers hope their strategy could benefit people who have suffered strokes, limb amputations and spinal cord injuries, as well as others whose ability to control their limbs is limited.
“This could lead to a minimally invasive strategy that would fundamentally transform the clinical care of people with limb diseases,” says Herr.
The research was funded by the K. Lisa Yang Center for Bionics at MIT.