Summary: Researchers have developed a new approach to muscle control using light rather than electricity. This optogenetic technique allows more precise muscle control and significantly reduces fatigue in mice. Although currently not feasible in humans, this approach could revolutionize prosthetics and help people with impaired limb function.
Highlights:
- Optogenetic muscle stimulation provides more precise control than electrical stimulation.
- This method significantly reduces muscle fatigue compared to traditional approaches.
- Researchers are working on ways to safely deliver light-sensitive proteins to human tissues.
Source: WITH
For people who are paralyzed or amputee, neuroprosthetic systems that artificially stimulate muscle contraction with an electrical current can help them regain function in their limbs. However, despite many years of research, this type of prosthesis is rarely used because it causes rapid muscle fatigue and poor control.
MIT researchers have developed a new approach that they hope can one day provide better muscle control with less fatigue. Instead of using electricity to stimulate muscles, they used light. In a mouse study, researchers showed that this optogenetic technique provides more precise muscle control, as well as a dramatic reduction in fatigue.
“It turns out that by using light, through optogenetics, we 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 an MIT associate member. 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 deliver proteins sensitive to light safely and effectively into human tissues.
Herr is the lead author of the study, which appears today in Scientific robotics. Herrera-Arcos is the lead author of the article.
Optogenetic control
For decades, researchers have explored the use of functional electrical stimulation (FES) to control the body’s muscles. This method involves implanting electrodes that stimulate nerve fibers, causing a muscle to contract. However, this stimulation tends to activate the entire muscle at once, which is not how the human body naturally controls muscle contraction.
“Humans have this incredible fidelity of control that is achieved by natural recruitment of the muscle, where small, then medium-sized, then large motor units are recruited, in that order, as signal strength increases “, explains Herr. “With FES, when you artificially explode the muscle with electricity, the largest units are recruited first. So as you increase the signal you get no strength at first and then all of a sudden you get too much strength.
This significant force not only makes precise muscle control more difficult, but it also wears out the muscle quickly, within five or ten minutes.
The MIT team wanted to see if they could replace that entire interface with something different. Instead of electrodes, they decided to try controlling muscle contraction using molecular optical machines via optogenetics.
Using mice as an animal model, the researchers compared the amount of muscle force they could generate using the traditional FES approach with the forces generated by their optogenetic method. For the optogenetic studies, they used mice that had already been genetically modified to express a light-sensitive protein called canalrhodopsin-2. They implanted a small light source near the tibial nerve, which controls the muscles in the lower leg.
The researchers measured muscle strength as they gradually increased the amount of light stimulation and found that, unlike FES stimulation, optogenetic control produced a steady, gradual increase in muscle contraction.
“As we change the optical stimulation we deliver to the nerve, we can proportionally, almost linearly, control the strength of the muscle. This is similar to how signals from our brain control our muscles. As a result, it becomes easier to control the muscle compared to electrical stimulation,” explains 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 (the amount of force generated).
This mathematical model allowed researchers to design a closed-loop controller. In this type of system, the controller delivers a stimulation signal and, once the muscle contracts, a sensor can detect the force exerted by the muscle. 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 strength.
Using this type of control, researchers found that muscles could be stimulated for more than an hour before tiring, whereas muscles fatigued after just 15 minutes using FES stimulation.
One of the hurdles researchers are currently working to overcome is how to safely introduce light-sensitive proteins into human tissues. Several years ago, Herr’s lab reported that in rats, these proteins can trigger an immune response that inactivates the proteins and could also lead to muscle atrophy and cell death.
“One of the key goals of the K. Lisa Yang Center for Bionics is to solve this problem,” says Herr. “A multi-pronged effort is underway to design new light-responsive proteins, and strategies to deliver them, without triggering an immune response.”
As additional steps to reach human patients, Herr’s lab is also working on new sensors that can be used to 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 a stroke, limb amputation, or spinal cord injury, as well as others whose ability to control their limbs is reduced.
“This could lead to a minimally invasive strategy that would be a game-changer in terms of clinical care for people with limb pathology,” says Herr.
Funding: The research was funded by MIT’s K. Lisa Yang Center for Bionics.
About this latest research in optogenetics and neuroscience
Author: Melanie Grados
Source: WITH
Contact: Mélanie Grados – MIT
Picture: Image is credited to Neuroscience News
Original research: Closed access.
“Closed-loop optogenetic neuromodulation enables high-fidelity, fatigue-resistant muscle control” by Hugh Herr et al. Scientific robotics
Abstract
Closed-loop optogenetic neuromodulation enables high-fidelity, fatigue-resistant muscle control
Closed-loop neuroprosthetics show promise for restoring movement in people with neurological disorders.
However, conventional activation strategies based on functional electrical stimulation (FES) fail to accurately modulate muscle force and exhibit rapid fatigue due to their nonphysiological recruitment mechanism.
Here we present a closed-loop control framework that exploits physiological force modulation under functional optogenetic stimulation (FOS) to enable high-fidelity muscle control for prolonged periods (>60 minutes) in vivo.
We first discovered the force modulation characteristic of FOS, showing more physiological recruitment and significantly higher modulation ranges (>320%) compared to FES.
Second, we developed a neuromuscular model that accurately describes the highly nonlinear dynamics of optogenetically stimulated muscle.
Third, based on the optogenetic model, we demonstrated real-time control of muscle force with improved performance and fatigue resistance compared to FES.
This work lays the foundation for fatigue-resistant neuroprosthetics and optogenetically controlled biohybrid robots with high-fidelity force modulation.