Biology subjects

Simha, S. N.

Publications and source records attributed to Simha, S. N..

8 recordsLinked to original sources

bioRxiv2026

The mammalian muscle spindle as a tunable feedback controller in locomotion

Although muscle spindle sensory signals have been extensively studied, little is known about how and why muscle spindle firing is modulated by the central nervous system during movement. Specialized motor neurons to the muscle spindle, i.e. gamma motor neurons, can profoundly alter spindle firing during behavior, but technological limitations hinder our ability to record gamma motor and muscle spindle sensory signals during most behaviors. We used a biophysical model of a muscle spindle within a muscle-tendon unit to simulate how gamma drive may modulate muscle spindle Ia firing during locomotion. Based on a few available recordings from decerebrate animals, we demonstrate that our model, tuned to passive stretch conditions, can reproduce profound changes in muscle spindle firing in response to identical joint motions in locomotor vs. relaxed stretch conditions. Our model can discover phasic patterns of two types of gamma motor neuron drive based on recorded muscle spindle Ia firing and joint motion. By simulating perturbations, we conclude that: 1) sinusoidal activation of static gamma motor neurons during locomotion, encoding intended movement, modulates muscle spindle signals such that they act as sensorimotor feedback signals based on errors from the intended muscle fascicle length; 2) phasic on/off activation of dynamic gamma motor neurons during locomotion acts as an event detector, heightening muscle spindle Ia responses to discrete perturbations. As such, their muscle-within-muscle structure allows the muscle spindle to act as a highly tunable physical internal model of muscle state to guide movement. Our model supports proposed but as-yet-untested theories of muscle spindle function and offers a framework for extending the testing of muscle spindle function to active, behavioral conditions.

neuroscience↗

bioRxiv2025

Influence of exoskeleton stiffness on primary afferent feedback during stretch perturbations of isolated muscle-tendon unit

Exoskeletons assist and augment movement, but their effects on proprioceptive feedback remain poorly understood due to challenges in making direct measures of sensory signals in humans. Here, we leveraged a benchtop animal model to begin to explore how mechanical context akin to an elastic exoskeleton operating on a human lower limb joint may influence primary muscle spindle firing. In an anesthetized rat preparation, we applied controlled stretches to the medial gastrocnemius with engineered springs (0-0.5 N/mm) attached in parallel to the muscle-tendon unit (MTU) while modulating muscle activation to maintain overall system stiffness. Fascicle length was measured with sonomicrometry, force and MTU length with a servo motor, and spindle instantaneous firing rate (IFR) using dorsal root recordings. Trading off increases in parallel exoskeleton stiffness with reductions in muscle activation decreased biological muscle force (3.1 {+/-} 0.6 N to 1.6 {+/-} 0.6 N, p < 0.001) and stiffness (4.4 {+/-} 1.5 N/mm to 2.3 {+/-} 1.3 N/mm, p < 0.01), and increased fascicle length (7.9 {+/-} 1.3 mm to 8.3 {+/-} 1.5 mm, p < 0.005). We found significant correlations between spindle firing and each independent muscle fascicle kinematic and kinetic factor we investigated (p < 0.005). Thus, parallel stiffness emulating a passive elastic exoskeleton modifies muscle fascicle dynamics but does not alter spindle firing, possibly due to internal trade-offs in the salient muscle fascicle kinetic and kinematic features that drive spindle behavior. Leveraging in situ experimental frameworks that enable monitoring of primary afferent feedback during active contractions in complex mechanical contexts such as added parallel stiffness can provide a window into the effects of wearable devices on underlying sensory systems.

neuroscience↗

bioRxiv2025

Biophysical model for predicting muscle short-range stiffness during movement

Musculoskeletal simulations can offer valuable insight into how the properties of our musculoskeletal system influence the biomechanics of our daily movements. One such property is muscles history-dependent initial resistance to stretch, also known as short-range stiffness, which is key to stabilizing movements in response to external perturbations. Short-range stiffness is poorly captured by existing musculoskeletal simulations since they employ phenomenological Hill-type muscle models that lack the mechanisms underlying short-range stiffness. While it has been previously shown that biophysical cross-bridge models can reproduce muscle short-range-stiffness, it is unclear which specific biophysical properties are necessary to capture history-dependent muscle force responses in behaviorally relevant conditions. Here, we tested the ability of various biophysical cross-bridge models to reproduce empirical short-range stiffness and its history-dependent changes across a broad range of behaviorally relevant length changes and activation levels, using an existing dataset on permeabilized rat soleus muscle fibers (N = 11). We found that a biophysical cross-bridge model with cooperative myofilament activation reproduced the effects of muscle activation (R2 = 0.86), stretch amplitude (R2 = 0.71) and isometric recovery time (R2 = 0.79) on history-dependent changes in short-range stiffness after shortening. Similar results were obtained when the cross-bridge distribution of the biophysical model was approximated by a Gaussian (R2 = 0.73 - 0.88), but at a 20 times lower computational cost. These effects could not be reproduced by either a biophysical cross-bridge model without cooperative myofilament activation or a Hill-type model (R2 < 0.5). The reduced computational demand of the Gaussian-approximated models facilitates implementing biophysical cross-bridge models with cooperative myofilament activation in musculoskeletal simulations to improve the prediction of short-range stiffness during movements.

physiology↗

bioRxiv2023

Attenuation of muscle spindle firing with artificially increased series compliance during stretch of relaxed muscle

Muscle spindles relay vital mechanosensory information for movement and posture, but muscle spindle feedback is coupled to skeletal motion by a compliant tendon. Little is known about the effects of tendon compliance on muscle spindle feedback during movement, and the complex firing of muscle spindles make these effects difficult to predict. Our goal was to investigate changes in muscle spindle firing using added series elastic elements (SEEs) to mimic a more compliant tendon, and to characterize the accompanying changes in firing with respect to muscle-tendon unit (MTU) and muscle fascicle displacements (recorded via sonomicrometry). Sinusoidal, ramp-hold-release, and triangular stretches were analyzed to examine potential changes in muscle spindle instantaneous firing rates (IFRs) in locomotor-and perturbation-like stretches as well as history dependence. Added SEEs effectively reduced overall MTU stiffness and generally reduced muscle spindle firing rates, but the effect differed across stretch types. During sinusoidal stretches, peak firing rates were reduced and IFR was strongly correlated with fascicle velocity. During ramp stretches, SEEs reduced the dynamic and static responses of the spindle during lengthening but had no effect on initial bursts at the onset of stretch. Notably, IFR was negatively related to fascicle displacement during the hold phase. During triangular stretches, SEEs reduced the mean IFR during the first and second stretches, affecting the history dependence of mean IFR. Overall, these results demonstrate that tendon compliance may attenuate muscle spindle feedback during movement, but these changes cannot be fully explained by reduced muscle fascicle length and velocity. New FindingsO_ST_ABSWhat is the central question of the study?C_ST_ABSLittle is known about the effects of tendon compliance on muscle spindle function. We asked whether increasing the series compliance the muscle-tendon unit muscle spindle Ia responses to stretch. We also test the relationship between muscle spindle firing rates and muscle fascicle biomechanics. What is the main finding and its importance?Muscle spindle firing was generally attenuated with added series compliance, with the exception of the initial burst at the onset of stretch. Overall, the changes depended upon stretch profiles, and could not be fully explained by muscle fascicle length and velocity.

physiology↗

bioRxiv2022

History-dependent muscle resistance to stretch remains high after small, posturally-relevant pre-movements

The contributions of intrinsic muscle fiber resistance during mechanical perturbations to standing and other postural behaviors are unclear. Muscle stiffness, a traditional metric for estimating muscles intrinsic resistance to stretch, is known to vary depending on the current level and history of the muscles activation, as well as the muscles recent movement history; this property has been referred to as history dependence or muscle thixotropy. However, we currently lack sufficient data about the degree to which muscle stiffness is modulated across posturally-relevant characteristics of muscle stretch and activation. Here, we characterized the history dependence of muscles resistance to stretch in single, permeabilized, activated, muscle fibers in posturally-relevant stretch conditions and activation levels. We used a classic paired muscle stretch paradigm, varying the amplitude of a "conditioning" triangular stretch-shorten cycle followed by a "test" ramp-and-hold imposed after a variable inter-stretch interval. We tested low (<15%), intermediate (15-50%) and high (>50%) muscle fiber activation levels, evaluating short-range stiffness and total impulse in the test stretch. Muscle fiber resistance to stretch remained high at conditioning amplitudes of <1% L0 and inter-stretch intervals of >1 s, characteristic of healthy standing postural sway. A ~70% attenuation of muscle resistance to stretch was reached at conditioning amplitudes of >3% L0 and inter-stretch intervals of <0.1s, characteristic of larger, faster postural sway in balance-impaired individuals. Overall, amplitude and inter-stretch interval interact to disrupt myofilaments such that intrinsic resistance to stretch is attenuated if the stretch is large enough and/or frequent enough. Summary StatementIntrinsic muscle fiber resistance to stretch is preserved after small, slow pre-movements based on healthy postural sway, but markedly reduced as pre-movements increase to emulate abnormal postural sway.

physiology↗

bioRxiv2021

The Split-Belt Rimless Wheel

Split-belt treadmill training, common in stroke rehabilitation and motor learning experiments, reveals a mechanism through which energy can be extracted from the environment. People can extract net positive work from a split-belt treadmill by lengthening their step onto the fast belt. To understand how leg angles and belt speed differences affect energy transfer between the treadmill and the person during split-belt walking, we simulated a split-belt rimless wheel that alternates rotating on fast and slow treadmill belts. We found that the split-belt rimless wheel can passively walk steadily forward under a range of conditions, extracting enough energy from the treadmill to overcome losses during collisions. The simulated wheel can tolerate both speed disturbances and ground height variability, and it can even capture enough energy to walk uphill. We also built a physical split-belt rimless wheel robot, demonstrating the feasibility of energy extraction during split-belt treadmill walking. In comparing the wheel solutions to human split-belt gait, we found that humans do not maximize positive work performed by the treadmill; costs associated with balance and free vertical moments likely limit adaptation. This study characterizes the mechanics and energetics of split-belt walking, demonstrating that energy capture through intermittent contacts with the two belts is possible when the belt speed difference is paired with an asymmetry in leg angles at step-to-step transitions. This study demonstrates a novel way of harnessing energy through individual rotations rather than continuous contact and offers a simple model framework for understanding human choices during split-belt walking.

bioengineering↗

bioRxiv2020

Increasing the gradient of energetic cost does not initiate adaptation in human walking

When in a new situation, the nervous system may benefit from adapting its control policy. In determining whether or not to initiate this adaptation, the nervous system may rely on some features of the new situation. Here we tested whether one such feature is salient cost savings. We changed cost saliency by manipulating the gradient of participants energetic cost landscape during walking. We hypothesized that steeper gradients would cause participants to spontaneously adapt their step frequency to lower costs. To manipulate the gradient, a mechatronic system applied controlled fore-aft forces to the waist of participants as a function of their step frequency as they walked on a treadmill. These forces increased the energetic cost of walking at high step frequencies and reduced it at low step frequencies. We successfully created three cost landscapes of increasing gradients, where the natural variability in participants step frequency provided cost changes of 3.6% (shallow), 7.2% (intermediate) and 10.2% (steep). Participants did not spontaneously initiate adaptation in response to any of the gradients. Using metronome-guided walking-- a previously established protocol for eliciting initiation of adaptation--participants next experienced a step frequency with a lower cost. Participants then adapted by -1.41{+/-}0.81 (p=0.007) normalized units away from their originally preferred step frequency obtaining cost savings of 4.80{+/-}3.12%. That participants would adapt under some conditions, but not in response to steeper cost gradients, suggests that the nervous system does not solely rely on the gradient of energetic cost to initiate adaptation in novel situations.

neuroscience↗

bioRxiv2018

A mechatronic system for studying energy optimization during walking.

A general principle of human movement is that our nervous system is able to learn optimal coordination strategies. However, how our nervous system performs this optimization is not well understood. Here we design, build, and test a mechatronic system to probe the algorithms underlying optimization of energetic cost in walking. The system applies controlled fore-aft forces to a hip-belt worn by a user, decreasing their energetic cost by pulling forward or increasing it by pulling backward. The system controls the forces, and thus energetic cost, as a function of how the user is moving. In testing, we found that the system can quickly, accurately, and precisely apply target forces within a walking step. We next controlled the forces as a function of the users step frequency and found that we could predictably reshape their energetic cost landscape. Finally, we tested whether users adapted their walking in response to the new cost landscapes created by our system, and found that users shifted their step frequency towards the new energetic minima. Our system design appears to be effective for reshaping energetic cost landscapes in human walking to study how the nervous system optimizes movement.

neuroscience↗