The ‘Timed Up and Go’ test (TUG) is a widely used clinical tool for assessing gait and balance, relying primarily on timing as a measure. However, there are more observable biomechanical compensation strategies within TUG that are indicative of underlying neuromuscular issues and movement priorities. In individuals with unilateral knee osteoarthritis, an increased trunk flexion during TUG is a common phenomenon, often attributed to muscle weakness and/or pain avoidance. Unfortunately, it is difficult to differentiate between these underlying causes using experimental studies alone. This study aimed to distinguish between muscle weakness and pain avoidance as contributing factors, using predictive neuromuscular simulations of the sit-to-walk movement. Muscle weakness was simulated by reducing the maximum isometric force of the vasti muscles (ranging from 20% to 60%), while pain avoidance was integrated as a movement objective, ensuring that peak knee load did not exceed predefined thresholds (2–4 times body weight). The simulations demonstrate that a decrease in muscular capacity led to greater trunk flexion, while pain avoidance led to slower movement speeds and altered muscle recruitments, but not to greater trunk flexion. Our predictive simulations thus indicate that increased trunk flexion is more likely the result of lack of muscular reserve rather than pain avoidance. These findings align with reported differences in kinematics and muscle activations between moderate and severe knee osteoarthritis patients, emphasizing the impact of severe muscle weakness in those with advanced knee osteoarthritis. The simulations offer valuable insights into the mechanisms behind altered movement strategies, potentially guiding more targeted treatment.@en

Standing up from a chair is a key daily life activity that is sensitive to functional limitations as we age and associated with falls, frailty, and institutional living. Predictive neuromusculoskeletal models can potentially shed light on the interconnectivity and interdependency of age-related changes in neuromuscular capacity, reinforcement schemes, sensory integration, and adaptation strategies during stand-up. Most stand-up movements transfer directly into walking (sit-to-walk). The aim of this study was to develop and validate a neuromusculoskeletal model with reflex-based muscle control that enables simulation of the sit-to-walk movement under various conditions (seat height, foot placement). We developed a planar sit-to-walk musculoskeletal model (11 degrees-of-freedom, 20 muscles) and neuromuscular controller, consisting of a two-phase stand-up controller and a reflex-based gait controller. The stand-up controller contains generic neural pathways of delayed proprioceptive feedback from muscle length, force, velocity, and upper-body orientation (vestibular feedback) and includes both monosynaptic an antagonistic feedback pathways. The control parameters where optimized using a shooting-based optimization method, based on a high-level optimization criterium. Simulations were compared to recorded kinematics, ground reaction forces, and muscle activation. The simulated kinematics resemble the measured kinematics and muscle activations. The adaptation strategies that resulted from alterations in seat height, are comparable to those observed in adults. The simulation framework and model are publicly available and allow to study age-related compensation strategies, including reduced muscular capacity, reduced neural capacity, external perturbations, and altered movement objectives@en

Humans walk differently on the Moon, risking musculoskeletal injuries affecting the safety of all crew members. Jesse Rhoades and Thomas Geijtenbeek explain how a new approach to data analysis could reduce this risk for astronauts in NASA’s current Moon exploration programme Artemis.@en

Neuromuscular disorders often lead to ankle plantar flexor muscle weakness, which impairs ankle push-off power and forward propulsion during gait. To improve walking speed and reduce metabolic cost of transport (mCoT), patients with plantar flexor weakness are provided dorsal-leaf spring ankle-foot orthoses (AFOs). It is widely believed that mCoT during gait depends on the AFO stiffness and an optimal AFO stiffness that minimizes mCoT exists. The biomechanics behind why and how an optimal stiffness exists and benefits individuals with plantar flexor weakness are not well understood. We hypothesized that the AFO would reduce the required support moment and, hence, metabolic cost contributions of the ankle plantar flexor and knee extensor muscles during stance, and reduce hip flexor metabolic cost to initiate swing. To test these hypotheses, we generated neuromusculoskeletal simulations to represent gait of an individual with bilateral plantar flexor weakness wearing an AFO with varying stiffness. Predictions were based on the objective of minimizing mCoT, loading rates at impact and head accelerations at each stiffness level, and the motor patterns were determined via dynamic optimization. The predictive gait simulation results were compared to experimental data from subjects with bilateral plantar flexor weakness walking with varying AFO stiffness. Our simulations demonstrated that reductions in mCoT with increasing stiffness were attributed to reductions in quadriceps metabolic cost during midstance. Increases in mCoT above optimum stiffness were attributed to the increasing metabolic cost of both hip flexor and hamstrings muscles. The insights gained from our predictive gait simulations could inform clinicians on the prescription of personalized AFOs. With further model individualization, simulations based on mCoT minimization may sufficiently predict adaptations to an AFO in individuals with plantar flexor weakness.@en

Background: Most cases of toe walking in children are idiopathic. We used pathology-specific neuromusculoskeletal predictive simulations to identify potential underlying neural and muscular mechanisms contributing to idiopathic toe walking. Methods: A musculotendon contracture was added to the ankle plantarflexors of a generic musculoskeletal model to represent a pathology-specific contracture model, matching the reduced ankle dorsiflexion range-of-motion in a cohort of children with idiopathic toe walking. This model was employed in a forward dynamic simulation controlled by reflexes and supraspinal drive, governed by a multi-objective cost function to predict gait patterns with the contracture model. We validated the predicted gait using experimental gait data from children with idiopathic toe walking with ankle contracture, by calculating the root mean square errors averaged over all biomechanical variables. Findings: A predictive simulation with the pathology-specific model with contracture approached experimental ITW data (root mean square error = 1.37SD). Gastrocnemius activation was doubled from typical gait simulations, but lacked a peak in early stance as present in electromyography. This synthesised idiopathic toe walking was more costly for all cost function criteria than typical gait simulation. Also, it employed a different neural control strategy, with increased length- and velocity-based reflex gains to the plantarflexors in early stance and swing than typical gait simulations. Interpretation: The simulations provide insights into how a musculotendon contracture combined with altered neural control could contribute to idiopathic toe walking. Insights into these neuromuscular mechanisms could guide future computational and experimental studies to gain improved insight into the cause of idiopathic toe walking.

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The myocutaneous anterolateral thigh (ALT) and vastus lateralis (VL) flaps include a large muscle mass and a sufficient vascular pedicle, and they have been used for decades to reconstruct traumatic and acquired defects of the head and neck and extremities. In spite of these benefits, musculoskeletal dysfunction was reported in nearly 1 out of 20 patients at follow-up. It is unclear whether the recently proposed muscle-sparing flap-raising approach could preserve VL muscle function and whether patients at increased risk could benefit from such an approach. Therefore, we performed a predictive dynamic gait simulation based on a biological motion model with gradual weakening of the VL during a self-selected and fast walking speed to determine the compensable degree of VL muscle reduction. Muscle force, joint angle, and joint moment were measured. Our study showed that VL muscle reduction could be compensated up to a certain degree, which could explain the observed incidence of musculoskeletal dysfunction. In elderly or fragile patients, the VL muscle should not be reduced by 50% or more, which could be achieved by muscle-sparing flap-raising of the superficial partition only. In young or athletic patients, a VL muscle reduction of 10%, which corresponds to a muscle cuff, has no relevant effect. Yet, a reduction of more than 30% leads to relevant weakening of the quadriceps. Therefore, in this patient population with the need for a large portion of muscle, alternative flaps should be considered. This study can serve as the first basis for further investigations of human locomotion after flap-raising.

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Background: The stiffness of a dorsal leaf AFO that minimizes walking energy cost in people with plantarflexor weakness varies between individuals. Using predictive simulations, we studied the effects of plantarflexor weakness, passive plantarflexor stiffness, body mass, and walking speed on the optimal AFO stiffness for energy cost reduction. Methods: We employed a planar, nine degrees-of-freedom musculoskeletal model, in which for validation maximal strength of the plantar flexors was reduced by 80%. Walking simulations, driven by minimizing a comprehensive cost function of which energy cost was the main contributor, were generated using a reflex-based controller. Simulations of walking without and with an AFO with stiffnesses between 0.9 and 8.7 Nm/degree were generated. After validation against experimental data of 11 people with plantarflexor weakness using the Root-mean-square error (RMSE), we systematically changed plantarflexor weakness (range 40–90% weakness), passive plantarflexor stiffness (range: 20–200% of normal), body mass (+ 30%) and walking speed (range: 0.8–1.2 m/s) in our baseline model to evaluate their effect on the optimal AFO stiffness for energy cost minimization. Results: Our simulations had a RMSE < 2 for all lower limb joint kinetics and kinematics except the knee and hip power for walking without AFO. When systematically varying model parameters, more severe plantarflexor weakness, lower passive plantarflexor stiffness, higher body mass and walking speed increased the optimal AFO stiffness for energy cost minimization, with the largest effects for severity of plantarflexor weakness. Conclusions: Our forward simulations demonstrate that in individuals with bilateral plantarflexor the necessary AFO stiffness for walking energy cost minimization is largely affected by severity of plantarflexor weakness, while variation in walking speed, passive muscle stiffness and body mass influence the optimal stiffness to a lesser extent. That gait deviations without AFO are overestimated may have exaggerated the required support of the AFO to minimize walking energy cost. Future research should focus on improving predictive simulations in order to implement personalized predictions in usual care. Trial Registration Nederlands Trial Register 5170. Registration date: May 7th 2015. http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=5170.

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To maximize effects of dorsal leaf ankle foot orthoses (AFOs) on gait in people with bilateral plantarflexor weakness, the AFO properties should be matched to the individual. However, how AFO properties interact regarding their effect on gait function is unknown. We studied the interaction of AFO bending stiffness with neutral angle and footplate stiffness on the effect of bending stiffness on walking energy cost, gait kinematics and kinetics in people with plantarflexor weakness by employing predictive simulations. Our simulation framework consisted of a planar 11 degrees of freedom model, containing 11 muscles activated by a reflex-based neuromuscular controller. The controller was optimized by a comprehensive cost function, predominantly minimizing walking energy cost. The AFO bending and footplate stiffness were modelled as torsional springs around the ankle and metatarsal joint. The neutral angle of the AFO was defined as the angle in the sagittal plane at which the moment of the ankle torsional spring was zero. Simulations without AFO and with AFO for 9 bending stiffnesses (0–14 Nm/degree), 3 neutral angles (0–3-6 degrees dorsiflexion) and 3 footplate stiffnesses (0–0.5–2.0 Nm/degree) were performed. When changing neutral angle towards dorsiflexion, a higher AFO bending stiffness minimized energy cost of walking and normalized joint kinematics and kinetics. Footplate stiffness mainly affected MTP joint kinematics and kinetics, while no systematic and only marginal effects on energy cost were found. In conclusion, the interaction of the AFO bending stiffness and neutral angle in bilateral plantarflexor weakness, suggests that these should both be considered together when matching AFO properties to the individual patient.

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Spasticity is a common impairment within pediatric neuromusculoskeletal disorders. How spasticity contributes to gait deviations is important for treatment selection. Our aim was to evaluate the pathophysiological mechanisms underlying gait deviations seen in children with spasticity, using predictive simulations. A cluster analysis was performed to extract distinct gait patterns from experimental gait data of 17 children with spasticity to be used as comparative validation data. A forward dynamic simulation framework was employed to predict gait with either velocity- or force-based hyperreflexia. This framework entailed a generic musculoskeletal model controlled by reflexes and supraspinal drive, governed by a multiobjective cost function. Hyperreflexia values were optimized to enable the simulated gait to best match experimental gait patterns. Three experimental gait patterns were extracted: (1) increased knee flexion, (2) increased ankle plantar flexion, and (3) increased knee flexion and ankle plantar flexion when compared with typical gait. Overall, velocity-based hyperreflexia outperformed force-based hyperreflexia. The first gait pattern could mostly be explained by rectus femoris and hamstrings velocity-based hyperreflexia, the second by gastrocnemius velocity-based hyperreflexia, and the third by gastrocnemius, soleus, and hamstrings velocity-based hyperreflexia. This study shows how velocity-based hyperreflexia from specific muscles contributes to different spastic gait patterns, which may help in providing targeted treatment.

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Background: Bilateral plantarflexor muscle weakness is a common impairment in many neuromuscular diseases. However, the way in which severity of plantarflexor weakness affects gait in terms of walking energy cost and speed is not fully understood. Predictive simulations are an attractive alternative to human experiments as simulations allow systematic alterations in muscle weakness. However, simulations of pathological gait have not yet been validated against experimental data, limiting their applicability. Research question: Our first aim was to validate a predictive simulation framework for walking with bilateral plantarflexor weakness by comparing predicted gait against experimental gait data of patients with bilateral plantarflexor weakness. Secondly, we aimed to evaluate how incremental levels of bilateral plantarflexor weakness affect gait. Methods: We used a planar musculoskeletal model with 9 degrees of freedom and 9 Hill-type muscle-tendon units per leg. A state-dependent reflex-based controller optimized for a function combining energy cost, muscle activation squared and head acceleration was used to simulate gait. For validation, strength of the plantarflexors was reduced by 80 % and simulated gait compared with experimental data of 16 subjects with bilateral plantarflexor weakness. Subsequently, strength of the plantarflexors was reduced stepwise to evaluate its effect on gait kinematics and kinetics, walking energy cost and speed. Results: Simulations with 80 % weakness matched well with experimental hip and ankle kinematics and kinetics (R > 0.64), but less for knee kinetics (R < 0.55). With incremental strength reduction, especially beyond a reduction of 60 %, the maximal ankle moment and power decreased. Walking energy cost and speed showed a strong quadratic relation (R²>0.82) with plantarflexor strength. Significance: Our simulation framework predicted most gait changes due to bilateral plantarflexor weakness, and indicates that pathological gait features emerge especially when bilateral plantarflexor weakness exceeds 60 %. Our framework may support future research into the effect of pathologies or assistive devices on gait.

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Accurate predictive simulations of human gait rely on optimisation criteria to solve the system's redundancy. Defining such criteria is challenging, as the objectives driving the optimization of human gait are unclear. This study evaluated how minimising various physiologically-based criteria (i.e., cost of transport, muscle activity, head stability, foot–ground impact, and knee ligament use) affects the predicted gait, and developed and evaluated a combined, weighted cost function tuned to predict healthy gait. A generic planar musculoskeletal model with 18 Hill-type muscles was actuated using a reflex-based, parameterized controller. First, the criteria were applied into the base simulation framework separately. The gait pattern predicted by minimising each criterion was compared to experimental data of healthy gait using coefficients of determination (R²) and root mean square errors (RMSE) averaged over all biomechanical variables. Second, the optimal weighted combined cost function was created through stepwise addition of the criteria. Third, performance of the resulting combined cost function was evaluated by comparing the predicted gait to a simulation that was optimised solely to track experimental data. Optimising for each of the criteria separately showed their individual contribution to distinct aspects of gait (overall R²: 0.37–0.56; RMSE: 3.47–4.63 SD). An optimally weighted combined cost function provided improved overall agreement with experimental data (overall R²: 0.72; RMSE: 2.10 SD), and its performance was close to what is maximally achievable for the underlying simulation framework. This study showed how various optimisation criteria contribute to synthesising gait and that careful weighting of them is essential in predicting healthy gait.

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Wearable actuators in lower-extremity active orthoses or prostheses have the potential to address a variety of gait disorders. However, whenever conventional joint actuators exert moments on specific limbs, they must simultaneously impose opposing reaction moments on other limbs, which may reduce the desired effects and perturb posture. Momentum exchange actuators exert free moments on individual limbs, potentially overcoming or mitigating these issues. We simulate unperturbed gait to compare conventional joint actuators placed on the knee or hip of the swing leg, and equivalent angular momentum exchange actuators placed on the shank or thigh. Our results indicate that, while conventional joint actuators excel at increasing toe clearance when assisting knee flexion, free moments can yield greater increases in stride length when assisting knee extension or hip flexion.@en

Deficits in the ankle plantarflexor muscles, such as weakness and contracture, occur commonly in conditions such as cerebral palsy, stroke, muscular dystrophy, Charcot-Marie-Tooth disease, and sarcopenia. While these deficits likely contribute to observed gait pathologies, determining cause-effect relationships is difficult due to the often co-occurring biomechanical and neural deficits. To elucidate the effects of weakness and contracture, we systematically introduced isolated deficits into a musculoskeletal model and generated simulations of walking to predict gait adaptations due to these deficits. We trained a planar model containing 9 degrees of freedom and 18 musculotendon actuators to walk using a custom optimization framework through which we imposed simple objectives, such as minimizing cost of transport while avoiding falling and injury, and maintaining head stability. We first generated gaits at prescribed speeds between 0.50 m/s and 2.00 m/s that reproduced experimentally observed kinematic, kinetic, and metabolic trends for walking. We then generated a gait at self-selected walking speed; quantitative comparisons between our simulation and experimental data for joint angles, joint moments, and ground reaction forces showed root-mean-squared errors of less than 1.6 standard deviations and normalized cross-correlations above 0.8 except for knee joint moment trajectories. Finally, we applied mild, moderate, and severe levels of muscle weakness or contracture to either the soleus (SOL) or gastrocnemius (GAS) or both of these major plantarflexors (PF) and retrained the model to walk at a self-selected speed. The model was robust to all deficits, finding a stable gait in all cases. Severe PF weakness caused the model to adopt a slower, "heel-walking" gait. Severe contracture of only SOL or both PF yielded similar results: the model adopted a "toe-walking" gait with excessive hip and knee flexion during stance. These results highlight how plantarflexor weakness and contracture may contribute to observed gait patterns.@en

Predictive simulations of human walking have great potential to expand our understanding of locomotion. For instance, they can isolate the effect of specific impairments on observed gait pathologies or aid in designing assistive devices by modeling human-device interactions. Introducing simulated impairments or adding augmentation devices to a model may change kinematics, including preferred walking speed. Experimental studies have characterized cost of transport over a wide range of walking speeds, and have shown that humans prefer walking at a speed that minimizes their cost of transport [1]. The purpose of this study was to use a predictive simulation framework to reproduce experimental energetic cost of transport. We trained a model to walk at speeds between 0.5 and 2.0 m/s and compared our simulated cost of transport to experimental data.@en