Closed-loop Optogenetic Neuromodulation Enables High-Fidelity Fatigue-Resistant Muscle Control

Neurology Genetics Basic Medical Sciences Bioengineering Biophysics Life Sciences Medicine
closed-loop control optogenetic stimulation fatigue-resistant neuroprostheses muscle control

High-Fidelity Fatigue-Resistant Muscle Control Through Closed-Loop Optogenetic Neural Modulation

Research Flowchart

Background Introduction

Skeletal muscle is the biological actuator for almost all movements in animals and humans. However, under various neurological conditions, the communication pathways between the central nervous system and neuromuscular components are severed, resulting in motor disorders such as paralysis. Neural prosthetics (NP) can replace the missing neural input by delivering precise commands through artificial stimulation to restore muscle function. However, existing functional electrical stimulation (FES) is challenging to regulate muscle force accurately due to its non-physiological muscle unit recruitment mechanism and demonstrates rapid fatigue. This compels researchers to seek new stimulation methods to provide reliable long-term gradual muscle regulation.

In recent years, functional optogenetic stimulation (FOS) has emerged as a technique that uses light to genetically modify neural cells, showing potential for sequentially recruiting motor units, thus offering a new neural modulation strategy for neural prosthetics. However, the relationship between stimulation parameters and force generation remains unclear and needs further study.

Paper Source

This paper was authored by Guillermo Herrera-Arcos, Hyungeun Song, Seong Ho Yeon, Omkar Ghenand, Samantha Gutierrez-Arango, Sapna Sinha, and Hugh Herr. This study belongs to the Massachusetts Institute of Technology (MIT) K. Lisa Yang Center for Bionics, Media Lab, McGovern Institute for Brain Research, and Harvard-MIT Division of Health Sciences and Technology. The paper was published in the journal “Science Robotics” on May 22, 2024.

Research Process and Details

Detailed Experimental Procedure

The study verified whether optogenetic stimulation (FOS) can achieve high-fidelity and fatigue-resistant muscle force control through three main experiments:

  1. Open-Loop Stimulation Experiment: First, the authors performed open-loop stimulation to mechanistically characterize force modulation characteristics. By comparing FES and FOS, they found that the latter showed higher force modulation accuracy during longer interval pulses and could sequentially recruit motor units.

  2. System Identification Experiment: Next, they stimulated the muscle with dynamically rich signals to conduct a system identification procedure, accurately describing the highly nonlinear dynamics of optogenetic muscle stimulation. This process involves establishing an optogenetic neuromuscular model that includes a static nonlinear (SNL) component, a opsin dynamic system (ODS), and a linear dynamic system (LDS).

  3. Closed-Loop Control Experiment: Finally, based on the above model, they designed a closed-loop controller and evaluated its performance over short and long periods. Experiments proved that FOS in closed-loop control outperformed FES, achieving high-fidelity and fatigue-resistant muscle force control.

Main Research Findings

Phase One: Open-Loop Stimulation Experiment

In the open-loop experiments, the research team revealed the force modulation characteristics of FOS, which exhibited a more physiological recruitment and significantly higher modulation range (over 320%) compared to FES. FOS showed different mechanical behavior during proximal and distal stimulations, with distal stimulation displaying more sustained force generation and consistent steady-state values, indicating that optogenetic stimulation might be more suitable for distal locations.

Phase Two: Construction of the Neuromuscular Model

Based on the results above, the research team developed a biophysical model accurately describing the highly nonlinear dynamics of optogenetic muscle stimulation. This model includes static nonlinear (SNL) properties, opsin dynamic systems (ODS), and linear dynamic systems (LDS). By quantifying the recruitment characteristics of optogenetic and electrical stimulation, FOS demonstrated higher resolution and more linear force modulation.

Phase Three: Closed-Loop Control Experiment

Researchers designed a closed-loop controller incorporating feedback and feedforward elements to evaluate muscle force controllability. Experimental results showed that under square wave and sine wave trajectories, the model-based controller achieved significantly lower errors in the FOS group (errors of 13.8% and 33.5%, respectively) compared to feedback-only controllers. In long-term stimulation experiments, FOS exhibited significant fatigue resistance, able to maintain force adjustments for up to 62 minutes, much longer than FES’s approximately 15 minutes.

Conclusion and Research Value

This study proposes, for the first time, a complete framework for achieving high-fidelity, fatigue-resistant muscle control through optogenetic neural modulation. FOS not only demonstrates a more physiological force modulation mechanism but also has excellent long-term fatigue resistance, laying the foundation for functional neural prosthetics and optogenetic control of biohybrid robots.

This research significantly advances the application potential of optogenetic technology in neural prosthetics and biohybrid systems, proposing key directions and challenges for future research, especially in practical clinical applications. These findings provide new insights for fundamental research in neuroscience and bioengineering and are crucial for developing next-generation high-performance neural prosthetics and biohybrid systems!