How did the bodies of animals, including ours, become such fine-tuned movement machines? How vertebrates coordinate the eternal tug-o-war between involuntary reflexes and seamless voluntary movements is a mystery that Francisco Valero-Cuevas' Lab in USC Alfred E. Mann Department of Biomedical Engineering, set out to understand.

The Lab's newest computational paper published in the Proceedings of the National Academy of Sciences (PNAS) adds to the thought leadership about the processing of sensory information and control of reflexes during voluntary movements-;with implications as to how its disruption could give rise to motor disorders in neurological conditions like stroke, cerebral palsy, and Parkinson's disease. 

Do you remember the pediatrician tapping your knee to see if you had a strong involuntary knee-jerk reaction? This was to test the stretch reflexes in your spinal cord, which resist muscle stretching to give you muscle tone to hold your body up against gravity for example, fast corrections after tripping. So, how exactly those reflexes are modulated or inhibited to allow smooth, voluntary movement has been debated since Charles Scott Sherrington's foundational work in the 1880s (yes, the 1880s!). This new work cuts directly into critical debates about how the ancient spinal cord and the relatively new human brain interact to produce smooth movements and how some neurological conditions disrupt this fine balance and produce slow, inaccurate, jerky, etc. movements in neurological conditions.

The study, led by Biomedical engineering doctoral student Grace Niyo, sheds light on a possible undiscovered system or circuitry at play within the spinal cord that, when working properly, "modulates" reflexes during voluntary movements. The study, Niyo says, proposes "a theoretically new mechanism to modulate spinal reflexes at the same spinal cord level as stretch reflexes."

Valero-Cuevas, Professor of Biomedical Engineering, Aerospace and Mechanical Engineering, Electrical and Computer Engineering, Computer Science, and Biokinesiology and Physical Therapy at USC, is the corresponding author of the paper "A computational study of how α- to γ-motoneurone collateral can mitigate velocity-dependent stretch reflexes during voluntary movement. 

Reflexes are sophisticated and ancient low-level information exchange mechanisms that co-evolved and co-adapted with later developments like the human brain…understanding their collaboration with the brain is critical to understanding movement in health and disease."

Valero-Cuevas, Professor, University of Southern California

Valero-Cuevas says, "We are constantly benefiting from, and modulating stretch reflexes, whether we realize it or not as we stand, move and act."

Professor Valero-Cuevas' lab is dedicated to understanding neuromuscular control in animals and robots, with implications for clinical rehabilitation for human mobility. 

He explains, "Although our brain is highly sophisticated, we need to recognize the value and power of the ancient spinal cord-;which has allowed all vertebrates to thrive for millions of years before large brains were even possible. We would like to understand how the spinal cord is able to regulate smooth movements, even with minimal brain control, as we know happens in amphibians and reptiles. This perspective could have important implications for understanding, and possibly treating, movement disorders in neurological conditions that affect the brain, spinal cord, or both-;and also for creating biologically-inspired prostheses or robots that move smoothly using simulated spinal cords."

The simulation experiment: To test whether and how a spinal circuit can allow voluntary movements by modulating or inhibiting movement perturbations that arise from stretch reflexes, the team, led by Niyo, created a biomechanical model of the arm of a macaque monkey in the physics simulator software called MuJoCo, generating over one thousand reaching movements. The simple stretch reflex rule is that muscles being stretched will tend to oppose the stretch, while muscles that are shortening do not show stretch reflexes. They first demonstrated that unmodulated stretch reflexes indeed produce a self-perturbation that disrupts voluntary arm movements. They then implemented a simple spinal circuit whereby the same neurons in the spinal cord that control muscle force (called alpha motoneurons) also scale (i.e., modulate) the stretch reflex proportionally to their level of muscle excitation. That is, highly excited muscles would have strong stretch reflex responses if stretched, and vice versa. They found that this simple rule-;that it is physiologically possible given the known projections from alpha motoneurones (also called collaterals) to the reflex circuitry can-;by itself-;largely correct the self-perturbations from stretch reflexes to produce smooth and accurate voluntary movements. 

From a modern engineering perspective, one might compare this to "edge computing," says Valero-Cuevas, which is the idea that information processing is done at the source (limb sensors and the spinal cord) instead of exclusively at the central command center (the brain)-;much like some apps in your phone that pre-processes information to be sent to a cloud server. Valero-Cuevas makes the mechanical analogy to these low-level connections to the reflex circuitry being like the "training wheels on a bicycle that are there to allow you to have fun, and catch you should you make a mistake while you learn to ride your bicycle." 

These circuits may help you produce novel voluntary movements with minimal perturbations but leave open the possibility of the brain and cerebellum to also refine and learn to control reflexes as your nervous system matures or gains enough experience. 

Implications: Beyond better understanding movement disorders, Niyo says this knowledge could be a starting point for experimentalists to start looking for and testing for such spinal circuits. "This work could also inspire and guide new therapies at the appropriate level of the nervous system for treatment of movement disorders like stroke and cerebral palsy," say Niyo and Valero-Cuevas. 

The study's additional co-authors include Lama I. Almofeez, a PhD student in the USC Alfred E Man Department of Biomedical Engineering and Andrew Erwin, who at the time of the study was a Post-doctoral scholar in the USC Division of Biokinesiology and Physical Therapy.

Source:

Journal reference:

Niyo, G., et al. (2024) A computational study of how an α- to γ-motoneurone collateral can mitigate velocity-dependent stretch reflexes during voluntary movement. PNAS. doi.org/10.1073/pnas.2321659121.