Search bioRxiv⌕ Search

bioRxiv · 10.1101/2021.12.20.473515

Simulated hemiparesis increases optimal spatiotemporal gait asymmetry but not metabolic cost

Abstract

Several neuromuscular impairments, such as weakness (hemiparesis), occur after an individual has a stroke, and these impairments primarily affect one side of the body more than the other. Predictive musculoskeletal modeling presents an opportunity to investigate how a specific impairment affects gait performance post-stroke. Therefore, our aim was to use to predictive simulation to quantify the spatiotemporal asymmetries and changes to metabolic cost that emerge when muscle strength is unilaterally reduced. We also determined how forced spatiotemporal symmetry affects metabolic cost. We modified a 2-D musculoskeletal model by uniformly reducing the peak isometric muscle force in all left-limb muscles. We then solved optimal control simulations of walking across a range of speeds by minimizing the sum of the cubed muscle excitations across all muscles. Lastly, we ran additional optimizations to test if reducing spatiotemporal asymmetry would result in an increase in metabolic cost. Our results showed that the magnitude and direction of effort-optimal spatiotemporal asymmetries depends on both the gait speed and level of weakness. Also, the optimal metabolic cost of transport was 1.25 m/s for the symmetrical and 20% weakness models but slower (1.00 m/s) for the 40% and 60% weakness models, suggesting that hemiparesis can account for a portion of the slower gait speed seen in people post-stroke. Adding spatiotemporal asymmetry to the cost function resulted in small increases (~4%) in metabolic cost. Overall, our results indicate that spatiotemporal asymmetry may be optimal for people post-stroke, who have asymmetrical neuromuscular impairments. Additionally, the effect of speed and level of weakness on spatiotemporal asymmetry may explain the well-known heterogenous distribution of spatiotemporal asymmetries observed in the clinic. Future work could extend our results by testing the effects of other impairments on optimal gait strategies, and therefore build a more comprehensive understanding of the gait patterns in people post-stroke. Author SummaryA stroke causes damage to the brain. This typically results in several changes to the nervous and muscular (neuromuscular) system that change how people post-stroke tend to walk and perform other tasks. Individuals post-stroke tend to walk with an asymmetrical motion and expend more energy while walking than other age-matched individuals. We still do not understand how each specific change to the neuromuscular system is linked with changes in walking patterns, in part because it is difficult to test one individual change at a time in people. Instead, we can use a mathematical model of the musculoskeletal system that represents the individual changes to the muscular system that occur in people post-stroke. In this study, we modeled how a common change in people post-stroke (muscle weakness) can impact walking patterns. We found that the level of weakness and the walking speed affect the asymmetrical walking patterns of our models, but do not change the total energy cost. Overall, our study is one step towards better understanding how neuromuscular changes in people post-stroke affects walking patterns. This knowledge could be applied to identify rehabilitation strategies that are most likely to improve walking in people post-stroke.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Johnson, R. T., Bianco, N. A., Finley, J.. 2021-12-21. Simulated hemiparesis increases optimal spatiotemporal gait asymmetry but not metabolic cost. https://doi.org/10.1101/2021.12.20.473515

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Comparative study of chlorophyll measurement in Physcomitrium patens moss using a conventional microscope adapted for combined 2D+1D imaging and spectral analysis

Imaging spectroscopy often requires expensive and complex equipment. Here we show a simple procedure for attaching a standard miniature fiber spectrometer to a conventional microscope, allowing easy integration of 2D imaging with 1D high-resolution spectral measurements. This combination provides much of the benefit of a full imaging spectrometer without the large equipment investment, and we provide instructions for modifying microscopes to this setup and the present measurements of living cells that demonstrate their performance. Using this setup, we compare the quantitative measurement of chlorophyll concentration in Physcomitrium patens moss using color imaging and spectral sampling.

bioengineering↗

De novo designed single-domain antibodies protect against lethal cobra venom neurotoxicity in vivo

Generative protein design can now rapidly produce de novo binders with high affinity and functional activity against a wide range of targets, including lethal snake venom toxins. However, so far most reported successes rely on new-to-nature scaffolds with limited therapeutic precedent. Single-domain antibodies (VHHs) offer a clinically validated alternative scaffold that can bind and neutralize long-chain -neurotoxins, which are some of the most lethal components in snake venoms. Here we compare three recently established de novo design models with VHH-design capabilities (Germinal, RFantibody, and BoltzGen) for their ability to generate VHHs against the neurotoxin -cobratoxin from the monocled cobra (Naja kaouthia). Using standardized model inputs and evaluation criteria based on AlphaFold3 interface confidence (ipTM) and RMSD self-consistency, we find that Germinal was the only method to generate designs passing stringent in silico criteria for experimental testing. We therefore performed a larger Germinal design campaign employing three different VHH frameworks and experimentally validated 46 designs in vitro. Of these, 42 expressed as soluble proteins and we identified four binding hits derived from two of the three tested frameworks. Of the four binders, two lead candidates were further characterized and demonstrated high affinity (KDs of 4.1 nM and 10.8 nM), monomeric behavior and low polyreactivity, indicating favorable biophysical and developability properties, as well as functional toxin neutralization in vitro. To assess their therapeutic potential we investigated their ability to protect against -cobratoxin toxicity in vivo. Both candidates fully protected mice after -cobratoxin challenge, with 100% survival compared to a lethal control. One candidate also retained notable neutralization capacity against whole venom of Naja kaouthia with a survival of 56%, while the other protected 22% when tested in a rescue setting. Together, we demonstrate that de novo VHH design can generate high affinity single-domain antibodies with in vivo protection against lethal cobra venom neurotoxicity, and provide practical insights into method- and framework-dependent performance.

bioengineering↗

Simple Feedback for Complex Movement: Capturing Whole-Limb Reorganization during Single-IMU Gait Retraining

Clinical gait retraining typically relies on multi-sensor arrays and high-dimensional feedback displays, imposing setup and interpretation burdens that limit routine clinical deployment. We developed a single-IMU visual biofeedback system that delivers real-time feedback of Lower Limb Trajectory Error (LLTE), a composite kinematic error metric integrating knee position and shank angle across the stance phase. Twenty able-bodied adults walked on a treadmill under two visual biofeedback targets (flexed-knee, extended-knee) while receiving either corrected (n=10) or uncorrected (n=8) feedback, where the correction accounted for limb orientation at initial contact. LLTE and stance-phase knee kinematics adapted consistently under the flexed-knee target for both feedback groups, with feedback formulation moderating the temporal trajectory of change. Adaptation toward the extended-knee target was limited, likely because participants were already operating near terminal knee extension and because the scalar error metric provided limited directional information for correction. Ankle range of motion (ROM) changed significantly across the stance phase under both target conditions, while hip ROM did not. Multiscale multivariate sample entropy (MSMVSE) increased monotonically with time scale across all conditions, with no statistically distinguishable difference between corrected and uncorrected feedback. These results suggest that single-IMU LLTE biofeedback can modify gait mechanics and that adaptation was expressed across multiple lower-limb segments rather than through changes at a single joint.

bioengineering↗