A multi-scale modelling framework combining musculoskeletal rigid-body simulations with adaptive finite element analyses, to evaluate the impact of femoral geometry on hip joint contact forces and femoral bone growth.

Multi-scale simulations, combining muscle and joint contact force (JCF) from musculoskeletal simulations with adaptive mechanobiological finite element analysis, allow to estimate musculoskeletal loading and predict femoral growth in children. Generic linearly scaled musculoskeletal models are commonly used. This approach, however, neglects subject- and age-specific musculoskeletal geometry, e.g. femoral neck-shaft angle (NSA) and anteversion angle (AVA). This study aimed to evaluate the impact of proximal femoral geometry, i.e. altered NSA and AVA, on hip JCF and femoral growth simulations. Musculoskeletal models with NSA ranging from 120° to 150° and AVA ranging from 20° to 50° were created and used to calculate muscle and hip JCF based on the gait analysis data of a typically developing child. A finite element model of a paediatric femur was created from magnetic resonance images. The finite element model was morphed to the geometries of the different musculoskeletal models and used for mechanobiological finite element analysis to predict femoral growth trends. Our findings showed that hip JCF increase with increasing NSA and AVA. Furthermore, the orientation of the hip JCF followed the orientation of the femoral neck axis. Consequently, the osteogenic index, which is a function of cartilage stresses and defines the growth rate, barely changed with altered NSA and AVA. Nevertheless, growth predictions were sensitive to the femoral geometry due to changes in the predicted growth directions. Altered NSA had a bigger impact on the growth results than altered AVA. Growth simulations based on mechanobiological principles were in agreement with reported changes in paediatric populations.

Physics-Based Simulations to Predict the Differential Effects of Motor Control and Musculoskeletal Deficits on Gait Dysfunction in Cerebral Palsy: A Retrospective Case Study.

Physics-based simulations of walking have the theoretical potential to support clinical decision-making by predicting the functional outcome of treatments in terms of walking performance. Yet before using such simulations in clinical practice, their ability to identify the main treatment targets in specific patients needs to be demonstrated. In this study, we generated predictive simulations of walking with a medical imaging based neuro-musculoskeletal model of a child with cerebral palsy presenting crouch gait. We explored the influence of altered muscle-tendon properties, reduced neuromuscular control complexity, and spasticity on gait dysfunction in terms of joint kinematics, kinetics, muscle activity, and metabolic cost of transport. We modeled altered muscle-tendon properties by personalizing Hill-type muscle-tendon parameters based on data collected during functional movements, simpler neuromuscular control by reducing the number of independent muscle synergies, and spasticity through delayed muscle activity feedback from muscle force and force rate. Our simulations revealed that, in the presence of aberrant musculoskeletal geometries, altered muscle-tendon properties rather than reduced neuromuscular control complexity and spasticity were the primary cause of the crouch gait pattern observed for this child, which is in agreement with the clinical examination. These results suggest that muscle-tendon properties should be the primary target of interventions aiming to restore an upright gait pattern for this child. This suggestion is in line with the gait analysis following muscle-tendon property and bone deformity corrections. Future work should extend this single case analysis to more patients in order to validate the ability of our physics-based simulations to capture the gait patterns of individual patients pre- and post-treatment. Such validation would open the door for identifying targeted treatment strategies with the aim of designing optimized interventions for neuro-musculoskeletal disorders.

Pre-treatment EMG can be used to model post-treatment muscle coordination during walking in children with cerebral palsy.

When treating children with Cerebral Palsy (CP), computational simulations based on musculoskeletal models have a great potential in assisting the clinical decision-making process towards the most promising treatments. In particular, predictive simulations could be used to predict and compare the functional outcome of a series of candidate interventions. In order to be able to benefit from these predictive simulations however, it is important to know how much information about the post-treatment patient's motor control could be gathered from data available before the intervention. Within this paper, we quantified how much of the muscle activity measured after a treatment could be explained by subject-specific muscle synergies computed from EMG data collected before the intervention. We also investigated whether generic synergies could be used, in case no EMG data is available when running predictive simulations, to reproduce both pre- and post-treatment muscle activity in children with CP. Subject-specific synergies proved to be a good indicator of the patient's post-treatment motor control, explaining on average more than 85% of the post-treatment muscle activity, compared to an average of 94% when applied to the original pre-treatment data. Generic synergies explained 84% of the pre-treatment and 83% of the post-treatment muscle activity on average, but performed relatively well for patients with low selective motor control and poorly in patients with more selectivity. Our results suggest that subject-specific muscle synergies computed from pre-treatment EMG data could be used with confidence to represent the post-treatment motor control of children with CP during walking. In addition, when performing simulations involving patients with a low selective motor control, generic synergies could be a valid alternative.

SimCP: A Simulation Platform to Predict Gait Performance Following Orthopedic Intervention in Children With Cerebral Palsy.

Gait deficits in cerebral palsy (CP) are often treated with a single-event multi-level surgery (SEMLS). Selecting the treatment options (combination of bony and soft tissue corrections) for a specific patient is a complex endeavor and very often treatment outcome is not satisfying. A deterioration in 22.8% of the parameters describing gait performance has been reported and there is need for additional surgery in 11% of the patients. Computational simulations based on musculoskeletal models that allow clinicians to test the effects of different treatment options before surgery have the potential to drastically improve treatment outcome. However, to date, no such simulation and modeling method is available. Two important challenges are the development of methods to include patient-specific neuromechanical impairments into the models and to simulate the effect of different surgical procedures on post-operative gait performance. Therefore, we developed the SimCP framework that allows the evaluation of the effect of different simulated surgeries on gait performance of a specific patient and includes a graphical user interface (GUI) that enables performing virtual surgery on the models. We demonstrated the potential of our framework for two case studies. Models reflecting the patient-specific musculoskeletal geometry and muscle properties are generated based solely on data collected before the treatment. The patient's motor control is described based on muscle synergies derived from pre-operative EMG. The GUI is then used to modify the musculoskeletal properties according to the surgical plan. Since SEMLS does not affect motor control, the same motor control model is used to define gait performance pre- and post-operative. We use the capability gap (CG), i.e., the difference between the joint moments needed to perform healthy walking and the joint moments the personalized model can generate, to quantify gait performance. In both cases, the CG was smaller post- then pre-operative and this was in accordance with the measured change in gait kinematics after treatment.

Selective dorsal rhizotomy improves muscle forces during walking in children with spastic cerebral palsy.

BACKGROUND: Selective dorsal rhizotomy aims to reduce spasticity in children with cerebral palsy. Early investigations indicated postoperative weakness, whereas more recent studies showed that selective dorsal rhizotomy either does not change or improves muscle strength. All previous studies assessed muscle strength in a static position, which did not represent the walking situation. The aim of this study was to analyze the influence of selective dorsal rhizotomy on muscle forces during gait. METHODS: Motion capture data of 25 children with spastic cerebral palsy and 10 typically developing participants were collected. A musculoskeletal OpenSim model was used to calculate joint kinematics, joint kinetics and muscle forces during gait. Static optimization and an electromyography-informed approach to calculate muscle forces were compared. A Muscle-Force-Profile was introduced and used to compare the muscle forces during walking before and after a selective dorsal rhizotomy. FINDINGS: Independent of the approach used (electromyography-informed versus static optimization), selective dorsal rhizotomy significantly normalized forces in spastic muscles during walking and did not reduce the contribution of non-spastic muscles. INTERPRETATION: This study showed that selective dorsal rhizotomy improves dynamic muscle forces in children with cerebral palsy and leads to less gait pathology, as shown in the improvement in joint kinematics and joint kinetics. Individual muscle force analyses using the Muscle-Force-Profile extend standard joint kinematics and joint moment analyses, which might improve clinical-decision making in children with cerebral palsy in the future. The reference data of our participants and MATLAB code for the Muscle-Force-Profile are publicly available on simtk.org/projects/muscleprofile.

Modulation of gluteus medius activity reflects the potential of the muscle to meet the mechanical demands during perturbed walking.

Mediolateral stability during walking can be controlled by adjustment of foot placement. Reactive activity of gluteus medius (GM) is modulated during the gait cycle. However, the mechanisms behind the modulation are yet unclear. We measured reactive GM activity and kinematics in response to a mediolateral platform translation during different phases of the gait cycle. Forward simulations of perturbed walking were used to evaluate the isolated effect of the perturbation and the GM response on gait stability. We showed that the potential of GM to adjust lateral foot placement and prevent collisions during swing varies during the gait cycle and explains the observed modulation. The observed increase in stance, swing or combined GM activity causes an outward foot placement and therefore compensates for the loss of stability caused by a perturbation early in the gait cycle. GM activity of the swing leg in response to a platform translation late in the gait cycle counteracts foot placement, but prevents collision of the swing foot with the stance leg. This study provides insights in the neuromechanics of reactive control of gait stability and proposes a novel method to distinguish between the effect of perturbation force and reactive muscle activity on gait stability.

Relationship between bone adaptation and in-vivo mechanical stimulus in biological reconstructions after bone tumor: A biomechanical modeling analysis.

BACKGROUND: Biomechanical interpretations of bone adaptation in biological reconstructions following bone tumors would be crucial for orthopedic oncologists, particularly if based on quantitative observations. This would help plan for surgical treatments, rehabilitative programs and communication with the patients. We aimed to analyze the biomechanical adaptation of a femoral reconstruction after Ewing sarcoma according to an increasingly-used surgical technique, and to relate in-progress bone resorption to the mechanical stimulus induced by different motor activities. METHODS: We created a multiscale musculoskeletal and finite element model from CT scans and motion analysis data at a 76-month follow-up of a patient, to analyze muscle and joint loads, and to compare the mechanical competence of the reconstructed bone with the contralateral limb, in the current real condition and in a possible revision surgery that removed proximal screws. FINDINGS: Our results showed strategies of muscle coordination that led to differences in joint loads between limbs more marked in more demanding motor activities, and generally larger in the contralateral limb. The operated femur presented a markedly low ratio of physiological strain due to load-sharing with the metal implant, particularly in the lateral aspect. The possible revision surgery would help restore a physiological strain configuration, while the safety of the reconstruction would not be threatened. INTERPRETATION: We suggest that bone resorption is related to load-sharing and to the internal forces exerted during movement, and the mechanical stimulus should be improved by adopting modifications in the surgical treatment and by promoting physical therapy aimed at specific muscle strengthening.

Effect of lower-limb joint models on subject-specific musculoskeletal models and simulations of daily motor activities.

Understanding the validity of using musculoskeletal models is critical, making important to assess how model parameters affect predictions. In particular, assumptions on joint models can affect predictions from simulations of movement, and the identification of image-based joints is unavoidably affected by uncertainty that can decrease the benefits of increasing model complexity. We evaluated the effect of different lower-limb joint models on muscle and joint contact forces during four motor tasks, and assessed the sensitivity to the uncertainties in the identification of anatomical four-bar-linkage joints. Three MRI-based musculoskeletal models having different knee and ankle joint models were created and used for the purpose. Model predictions were compared against a baseline model including simpler and widely-adopted joints. In addition, a probabilistic analysis was performed by perturbing four-bar-linkage joint parameters according to their uncertainty. The differences between models depended on the motor task analyzed, and there could be marked differences at peak loading (up to 2.40 BW at the knee and 1.54 BW at the ankle), although they were rather small over the motor task cycles (up to 0.59 BW at the knee and 0.31 BW at the ankle). The model including more degrees of freedom showed more discrepancies in predicted muscle activations compared to measured muscle activity. Further, including image-based four-bar-linkages was robust to simulate walking, chair rise and stair ascent, but not stair descent (peak standard deviation of 2.66 BW), suggesting that joint model complexity should be set according to the imaging dataset available and the intended application, performing sensitivity analyses.

Are subject-specific musculoskeletal models robust to the uncertainties in parameter identification?

Subject-specific musculoskeletal modeling can be applied to study musculoskeletal disorders, allowing inclusion of personalized anatomy and properties. Independent of the tools used for model creation, there are unavoidable uncertainties associated with parameter identification, whose effect on model predictions is still not fully understood. The aim of the present study was to analyze the sensitivity of subject-specific model predictions (i.e., joint angles, joint moments, muscle and joint contact forces) during walking to the uncertainties in the identification of body landmark positions, maximum muscle tension and musculotendon geometry. To this aim, we created an MRI-based musculoskeletal model of the lower limbs, defined as a 7-segment, 10-degree-of-freedom articulated linkage, actuated by 84 musculotendon units. We then performed a Monte-Carlo probabilistic analysis perturbing model parameters according to their uncertainty, and solving a typical inverse dynamics and static optimization problem using 500 models that included the different sets of perturbed variable values. Model creation and gait simulations were performed by using freely available software that we developed to standardize the process of model creation, integrate with OpenSim and create probabilistic simulations of movement. The uncertainties in input variables had a moderate effect on model predictions, as muscle and joint contact forces showed maximum standard deviation of 0.3 times body-weight and maximum range of 2.1 times body-weight. In addition, the output variables significantly correlated with few input variables (up to 7 out of 312) across the gait cycle, including the geometry definition of larger muscles and the maximum muscle tension in limited gait portions. Although we found subject-specific models not markedly sensitive to parameter identification, researchers should be aware of the model precision in relation to the intended application. In fact, force predictions could be affected by an uncertainty in the same order of magnitude of its value, although this condition has low probability to occur.

Neural correlates of motor learning and performance in a virtual ball putting task.

Learning to move skillfully requires that the motor system adjusts motor commands based on ongoing performance, until the task is executed satisfactorily. Robots can be used to emulate motor tasks that involve haptic interaction with objects. These studies may provide useful insights on how humans acquire a novel motor skill. Here we address motor skill learning in a 2D ball putting task, by looking at both kinematic and EEG correlates of learning and performance. Participants grasped the handle of a manipulandum and had to hit a virtual ball in order to put it into a target region (hole). The robot was used to render the contact force with the ball during impact. At every trial, with respect to the initial ball position, the hole appeared in one of three different directions and two distances, selected randomly. The experimental protocol included a total of 300 movements. In movement kinematics we looked at the effects of learning and target distance. In EEG signals, we looked at the effect of learning and the effect of success/failure on the ongoing brain activity. Subjects managed to improve their performance through practice, in all directions and at both target distances. Direction did not affect the performance much, but greater target distance induced greater errors. With regards to the EEG activity, we found that (i) practice led to an increased theta synchronization in the frontal areas; (ii) successful trials were preceded by higher theta synchronization, and alpha and beta desynchronization. These results suggest that EEG signals can be used to monitor the learning process and to predict the outcome (success/failure) of individual trials. These findings open possibilities to develop new schemes to promote and facilitate learning, which integrate EEG and robots.