Using optogenetics, MIT researchers developed a neuromodulation method that could someday help people with amputations, paralysis, and other conditions that restrict movement to regain muscle control for extended periods of time. The researchers showed that functional optogenetic stimulation (FOS) can enable fatigue-resistant control of muscles with higher accuracy and higher generated force than functional electrical stimulation (FES). For decades, researchers have explored the potential of FES to control muscles in the body. This method uses electrodes implanted in the body to stimulate nerve fibers, causing a muscle to contract. FES tends to activate the entire muscle at once, which inhibits fine muscle control and tires out the muscle quickly. “Humans have this incredible control fidelity that is achieved by a natural recruitment of the muscle, where small motor units, then moderate-sized, then large motor units are recruited, in that order, as signal strength is increased,” professor Hugh Herr said. “With FES, when you artificially blast the muscle with electricity, the largest units are recruited first. So, as you increase signal, you get no force at the beginning, and then suddenly you get too much force.” MIT researchers developed a way to help people with amputation or paralysis regain limb control. Instead of using electricity to stimulate muscles, they used light. Here, researcher Guillermo Herrera-Arcos looks at light shining from an optical neurostimulator. Courtesy of Steph Stevens. Instead of using electrodes to control muscle movement, the MIT team chose to explore the use of light to control muscle contraction. To this end, they conducted experiments to compare the metrics of force modulation and control performance of FOS and FES. The team implanted a small light source near the tibial nerve, which controls the muscles of the lower leg, in mice that were genetically engineered to express channelrhodopsin-2, a light-sensitive protein. They gradually increased the amount of light stimulation to the nerve while measuring muscle force and found that optogenetic control produced a steady, gradual increase in the contraction of the muscle. “As we change the optical stimulation that we deliver to the nerve, we can proportionally, in an almost linear way, control the force of the muscle,” researcher Guillermo Herrera-Arcos said. “This is similar to how the signals from our brain control our muscles. Because of this, it becomes easier to control the muscle compared with electrical stimulation.” Using the data obtained from this experiment, the researchers created a mathematical model to relate the amount of light input to the nerve to the output of muscle force. Based on this model, they designed a closed-loop controller to deliver a stimulatory signal to the muscle. After the muscle contracts, a sensor detects how much force the muscle is exerting. The recording of muscle force is sent back to the controller, which calculates any adjustments that need to be made to the optogenetic stimulation to reach the desired force. The researchers evaluated the performance of the closed-loop controller over short and extended durations. With the closed-loop system for FOS, the researchers were able to stimulate muscles for more than an hour before the muscles became fatigued. In contrast, muscles became fatigued after only 15 minutes of stimulation using FES. Professor Hugh Herr (left) and researcher Guillermo Herrara-Arcos (right) developed a minimally invasive strategy based on optogenetics that could transform clinical care for persons suffering from limb pathology. Courtesy of Steph Stevens/MIT. The experimental results provide a comprehensive characterization of FOS muscle dynamics; enable the development of an optogenetically stimulated muscle model; demonstrate accurate, fatigue-resistant muscle control with FOS; and lay the foundation for neural controllers for optogenetically modulated motor prostheses. “It turns out that by using light, through optogenetics, one can control muscle more naturally,” Herr said. “In terms of clinical application, this type of interface could have very broad utility.” The researchers are now working on how to safely deliver light-sensitive proteins into human tissue. Several years ago, Herr’s lab reported that in rats, these proteins can trigger an immune response that inactivates the proteins and potentially could lead to muscle atrophy and cell death. “A multipronged effort is underway to design new, light-sensitive proteins, and strategies to deliver them, without triggering an immune response,” Herr said. To help prepare for the use of FOS in humans, Herr’s lab is also working on new sensors that can be used to measure muscle force and length and on new ways to implant the light source. In the future, optogenetic stimulation technology integrated with real-time sensing could help restore motion in people who have experienced strokes, limb amputation, and spinal cord injuries, or who have lost the ability to control their limbs through other means. Neuroprostheses could replace the missing neuronal input by delivering precise commands for using artificial stimulation to restore muscle function. “This could lead to a minimally invasive strategy that would change the game in terms of clinical care for persons suffering from limb pathology,” Herr said. The research was published in Science Robotics (www.doi.org/10.1126/scirobotics.adi8995).