Light-activated muscles fight fatigue – news from neuroscience

Summary: Researchers have developed a new approach to muscle control using light instead of electricity. This optogenetic technique enables more precise muscle control and significantly reduces fatigue in mice. Although this approach is not currently feasible in humans, it could revolutionize prosthetics and help people with limited limb function.

Important facts:

  • Optogenetic muscle stimulation offers more precise control than electrical stimulation.
  • This method significantly reduces muscle fatigue compared to traditional approaches.
  • Researchers are working on ways to safely transport light-sensitive proteins into human tissue.

Source: WITH

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 widely used because it leads to 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.

One hurdle that researchers now want to overcome is the safe introduction of light-sensitive proteins into human tissue. Image credit: Neuroscience News

“It turns out that by using light, i.e. through optogenetics, you can control muscles more naturally. In terms of clinical application, this type of interface could be very versatile,” 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 McGovern Institute for Brain Research of MIT.

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 Mr., MIT graduate student Guillermo Herrera-Arcos and her 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 RoboticsHerrera-Arcos is the lead author of the article.

Optogenetic control

For decades, researchers have been studying the use of functional electrical stimulation (FES) to control the muscles in the body. In this method, electrodes are implanted that stimulate the nerve fibers and thus trigger 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 fidelity of control that is achieved through a natural recruitment of the muscle, where small motor units, then medium-sized motor units, and finally large motor units are recruited in that order as the signal strength increases,” says Herr. “With FES, when you artificially apply current to the muscle, the largest units are recruited first. So if you increase 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 see 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 amount of muscle force they could generate using the traditional FES approach to the forces generated using their optogenetic method. For the optogenetic studies, they used mice that had already been genetically engineered 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.

“If we change the optical stimulation we give to the nerve, we can control the force of the muscle proportionally and almost linearly. This is similar to the way our brain’s signals control our muscles. This makes the muscle easier to control compared to 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 muscle’s output (how much force is produced).

This mathematical model allowed the researchers to develop a closed-loop control system. In such a system, the controller sends a stimulating 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 over an hour before they became fatigued, whereas with FES stimulation the muscles became fatigued after just 15 minutes.

One hurdle researchers are currently trying 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 can 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 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, researchers hope their strategy could help 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 change the clinical care of individuals with limb pathologies,” says Herr.

Financing: The research was funded by the K. Lisa Yang Center for Bionics at MIT.

About this news from optogenetics and neuroscience research

Author: Melanie Grados
Source: WITH
Contact: Melanie Grados – MIT
Picture: The image comes from Neuroscience News

Original research: Closed access.
“Closed-loop optogenetic neuromodulation enables fatigue-resistant, high-fidelity muscle control” by Hugh Herr et al. Science Robotics


Abstract

Closed-loop optogenetic neuromodulation enables highly precise and fatigue-resistant muscle control

Closed-loop neuroprostheses show promise in restoring movement in individuals with neurological diseases.

However, conventional activation strategies based on functional electrical stimulation (FES) cannot precisely modulate muscle strength and lead to rapid fatigue due to their unphysiological recruitment mechanism.

Here, we present a closed-loop control system that utilizes physiological force modulation under functional optogenetic stimulation (FOS) to enable highly precise muscle control for extended periods (> 60 min) in vivo.

We first uncovered the force modulation characteristic of FOS, which shows stronger physiological recruitment and significantly higher modulation areas (> 320%) compared to FES.

Second, we developed a neuromuscular model that accurately describes the highly nonlinear dynamics of optogenetically stimulated muscles.

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 neuroprostheses and optogenetically controlled biohybrid robots with high-precision force modulation.

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