Using Light to Better Control Muscles While Reducing Fatigue Could Help People with Paralysis or Amputations Regain Limb Function

Recently, a research team at the Massachusetts Institute of Technology (MIT) developed a new method that uses light signals instead of electrical signals to stimulate muscles. Compared to electrical stimulation, this optogenetic technology provides more precise muscle control while significantly reducing muscle fatigue. Relevant research was recently published in the journal Science Robotics, titled "Closed-loop optogenetic neuromodulation enables high-fidelity fatigue-resistant muscle control."

Previous studies have shown that the ChR2 light-sensitive protein can be stably and safely expressed in mammalian neurons and can drive neuronal depolarization. When activated with a series of brief light pulses, ChR2 can control excitatory or inhibitory synaptic transmission with millisecond temporal resolution. This technology provides neuroscientists and biomedical engineers with a universal tool and marks the official arrival of optogenetics.

Scientists have long explored the use of functional electrical stimulation (FES) to control body muscles, a method that involves implanting electrodes that stimulate nerve fibers, releasing electrical signals to cause muscles to contract. However, this electrical stimulation tends to activate the entire muscle at once, which is not the way the body naturally controls muscle contraction.

In fact, the human body is a complex and sophisticated system with incredible control fidelity. This is achieved through the natural recruitment of muscles - starting with small motor units first, then medium-sized motor units, and finally large motor units as the intensity of the stimulus signal increases. Step by step, it's like an army gathering and mobilizing.

Professor Hugh Herr, the corresponding author of the paper, said that in functional electrical stimulation (FES), when muscles are artificially stimulated with electricity, the maximum motor unit will be directly activated, making it impossible to achieve precise control, and the muscles will easily fall into fatigue or even damage. Therefore, there is an urgent need for a new method that can precisely control muscles to overcome the various disadvantages of FES.

In this latest study, the research team tried to replace functional electrical stimulation (FES) with a different signaling method. They used optical molecular machines based on optogenetics to control muscle contraction. Optogenetics is a method based on genetically engineering cells to express light-sensitive proteins and controlling their activity by exposing these cells to specific wavelengths of light, so optogenetics can allow for more natural control of muscles.

Using mice as an animal model, the research team compared the muscle force they produced using traditional functional electrical stimulation (FES) methods and functional optogenetic stimulation (FOS). For the optogenetic study, they used mice that had been genetically engineered to express the ChR2 light-sensitive protein and implanted a small light source in the mouse model near the tibial nerve, which controls the calf muscles.

Figure 1. Experimental framework for muscle characterization and control.

The team measured muscle strength while gradually increasing the amount of light stimulation. They found that unlike electrical stimulation-based FES, optogenetics-based FOS controlled muscle contraction was more stable and could proportionally control muscle force in an almost linear manner. This is closer to the way real brain signals control muscle contraction. Because of this, it becomes easier to control muscles with FOS compared to FES.

Using these experimental data, the research team created a mathematical model of optogenetics-based muscle control that relates the amount of light entering the system to the muscle's output (how much force it produces). This mathematical model therefore allowed the researchers to design a closed-loop controller that sends a stimulus signal and, after the muscle contracts, a sensor that detects the force exerted by the muscle.

This information is sent back to the controller, which calculates whether and how much light stimulation needs to be adjusted to achieve the desired force. Using this closed-loop controller, the research team found that muscles did not fatigue after more than an hour of FOS stimulation, compared to just 15 minutes of FES stimulation.

One hurdle the research team is currently working to overcome is how to safely deliver the light-sensitive protein into human tissue. A few years ago, a study by the same team showed that in mice, these light-sensitive proteins can trigger an immune response that leads to protein inactivation and may also lead to muscle atrophy and cell death. They are designing new light-sensitive proteins and new strategies for delivery without triggering an immune response. In addition, they are working on new sensors that can be used to measure muscle strength and length, as well as new ways to implant light sources.

Overall, this study, published in Science Robotics , provides a comprehensive characterization of functional optogenetic stimulation (FOS) muscle dynamics using biophysical models to design closed-loop controllers. Neural modulation strategies for coordinated motor recruitment are elucidated, enabling the development of optogenetically stimulated muscle models and the demonstration of accurate fatigue-resistant muscle control. This work lays the foundation for optogenetically modulated neural controllers of motor prostheses.

Figure 2. Optogenetically stimulated muscle model.

In terms of clinical applications, optogenetics-based controllers may have very broad uses, and the research team plans to apply this treatment strategy to patients with stroke, paralysis, limb amputation, spinal cord injury, and other patients with impaired limb control. This could lead to a minimally invasive strategy that changes clinical care for people with limb pathology.

Reference

Herrera-Arcos G, et al. Closed-loop optogenetic neuromodulation enables high-fidelity fatigue-resistant muscle control. Science Robotics, 2024, 9(90): eadi8995.