MIT controls muscles with optogenetics

05 Jun 2024

Optical method could be better than electrical stimulation for treatment after paralysis.

A project at MIT has investigated whether optogenetics could be a better way to drive muscle contraction in clinical treatments than traditional electrical stimulation.

Published in Science Robotics, the findings may prove to be good news for people dealing with muscle paralysis or amputation, where using neuroprosthetic systems to supply electrical stimulation can help regain muscle function, but also lead to fatigue or poor control.

In a study using mice, MIT has now found that applying an optogenetic approach instead offered measurably more precise muscle control, along with a dramatic decrease in fatigue.

"It turns out that by using light, through optogenetics, one can control muscle more naturally," commented Hugh Herr, co-director of the K. Lisa Yang Center for Bionics at MIT. "In terms of clinical application, this type of interface could have very broad utility."

Optogenetic modulation, whereby light is used to fire or inhibit specific neurons labelled with light-activated enzymes, is a rapidly advancing and prize-winning field of biophotonics, especially for studies of the brain. A functional optogenetic stimulation approach has also shown promise for muscle stimulation, but the details of its effects have not previously been studied.

"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," said Herr. "With electrical stimulation, 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."

To test whether optogentics can provide finer control, MIT compared the amount of muscle force it could generate using the traditional electrical approach with forces generated by an optogenetic method.

Game-changing clinical care for patients with limb pathology

For its optogenetic studies, the team used mice that had been genetically engineered to express the light-sensitive protein channelrhodopsin-2. They implanted a small light source near the tibial nerve, which controls muscles of the mouse's lower leg.

The researchers then measured muscle force as they gradually increased the amount of light stimulation, and found that optogenetic control produced a steady and gradual increase in contraction of the muscle, which is not the case with electrical stimulation.

“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," commented MIT's Guillermo Herrera-Arcos. "This is similar to how the signals from our brain control our muscles. Because of this, it becomes easier to control the muscle."

After assessing how the amount of light going into the system relates to the output force of the muscle, the project was able to stimulate muscles for more than one hour before fatiguing, as opposed to the 15 minutes possible using electrical stimulation.

Translating this approach to human patients could offer a route to treating people who have experienced strokes, limb amputation, and spinal cord injuries. But this translation may not be straightforward, since the light-sensitive proteins likely to be employed are thought to cause an unwanted immune response in some test animals, leading to muscle atrophy and cell death.

"A key objective of the K. Lisa Yang Center for Bionics is to solve that problem," said Hugh Herr. "A multipronged effort is underway to design new light-sensitive proteins and strategies to deliver them, without triggering an immune response. This could lead to a minimally invasive strategy that would change the game in terms of clinical care for persons suffering from limb pathology."