Physics-based predictive simulations of human movement have the potential to support personalized medicine, but large computational costs and difficulties to model control strategies have limited their use. We have developed a computationally efficient optimal control framework to predict human gaits based on optimization of a performance criterion without relying on experimental data. The framework generates three-dimensional muscle-driven simulations in 36 min on average—more than 20 times faster than existing simulations—by using direct collocation, implicit differential equations and algorithmic differentiation. Using this framework, we identified a multi-objective performance criterion combining energy and effort considerations that produces physiologically realistic walking gaits. The same criterion also predicted the walk-to-run transition and clinical gait deficiencies caused by muscle weakness and prosthesis use, suggesting that diverse healthy and pathological gaits can emerge from the same control strategy. The ability to predict the mechanics and energetics of a broad range of gaits with complex three-dimensional musculoskeletal models will allow testing novel hypotheses about gait control and hasten the development of optimal treatments for neuro-musculoskeletal disorders.

Musculoskeletal simulations are used in many different applications, ranging from the design of wearable robots that interact with humans to the analysis of patients with impaired movement. Here, we introduce OpenSim Moco, a software toolkit for optimizing the motion and control of musculoskeletal models built in the OpenSim modeling and simulation package. OpenSim Moco uses the direct collocation method, which is often faster and can handle more diverse problems than other methods for musculoskeletal simulation. Moco frees researchers from implementing direct collocation themselves—which typically requires extensive technical expertise—and allows them to focus on their scientific questions. The software can handle a wide range of problems that interest biomechanists, including motion tracking, motion prediction, parameter optimization, model fitting, electromyography-driven simulation, and device design. Moco is the first musculoskeletal direct collocation tool to handle kinematic constraints, which enable modeling of kinematic loops (e.g., cycling models) and complex anatomy (e.g., patellar motion). To show the abilities of Moco, we first solved for muscle activity that produced an observed walking motion while minimizing squared muscle excitations and knee joint loading. Next, we predicted how muscle weakness may cause deviations from a normal walking motion. Lastly, we predicted a squat-to-stand motion and optimized the stiffness of an assistive device placed at the knee. We designed Moco to be easy to use, customizable, and extensible, thereby accelerating the use of simulations to understand the movement of humans and other animals.

Algorithmic differentiation (AD) is an alternative to finite differences (FD) for evaluating function derivatives. The primary aim of this study was to demonstrate the computational benefits of using AD instead of FD in OpenSim-based trajectory optimization of human movement. The secondary aim was to evaluate computational choices including different AD tools, different linear solvers, and the use of first-or second-order derivatives. First, we enabled the use of AD in OpenSim through a custom source code transformation tool and through the operator overloading tool ADOL-C. Second, we developed an interface between OpenSim and CasADi to solve trajectory optimization problems. Third, we evaluated computational choices through simulations of perturbed balance, two-dimensional predictive simulations of walking, and three-dimensional tracking simulations of walking. We performed all simulations using direct collocation and implicit differential equations. Using AD through our custom tool was between 1.8 ± 0.1 and 17.8 ± 4.9 times faster than using FD, and between 3.6 ± 0.3 and 12.3 ± 1.3 times faster than using AD through ADOL-C. The linear solver efficiency was problem-dependent and no solver was consistently more efficient. Using second-order derivatives was more efficient for balance simulations but less efficient for walking simulations. The walking simulations were physiologically realistic. These results highlight how the use of AD drastically decreases computational time of trajectory optimization problems as compared to more common FD. Overall, combining AD with direct collocation and implicit differential equations decreases the computational burden of trajectory optimization of human movement, which will facilitate their use for biomechanical applications requiring the use of detailed models of the musculoskeletal system. Algorithmic differentiation speeds up trajectory optimization of human movement PLOS ONE | https://doi.Fig 2.Flowchart depicting the optimal control framework. We developed two approaches (AD-ADOLC and AD-Recorder) to make an OpenSim function F and its forward (F fwd) and reverse (F rev) directional derivatives available within the CasADi environment for use by the NLP solver during the optimization. In the AD-ADOLC approach (top), ADOL-C's algorithms are used in a C++ code to provide F fwd and F rev. In the AD-Recorder approach (bottom), Recorder provides the expression graph of F as MATLAB source code from which CasADi's C-code generator generates C-code containing F, F fwd, and F rev. The AD-Recorder approach combines operator overloading, when generating the expression graph, and source code transformation, when processing the expression graph to generate C-code for F, F fwd, and F rev. In both approaches, the code comprising F, F fwd, and F rev is compiled as a Dynamic-link Library (DLL), which is imported as an external function within the CasADi environment. In our application, F represents the multi-body dynamics and is called when formulating the optimal control problem. The latte...

Locomotion results from complex interactions between the central nervous system and the musculoskeletal system with its many degrees of freedom and muscles. Gaining insight into how the properties of each subsystem shape human gait is challenging as experimental methods to manipulate and assess isolated subsystems are limited. Simulations that predict movement patterns based on a mathematical model of the neuro-musculoskeletal system without relying on experimental data can reveal principles of locomotion by elucidating cause–effect relationships. New computational approaches have enabled the use of such predictive simulations with complex neuro-musculoskeletal models. Here, we review recent advances in predictive simulations of human movement and how those simulations have been used to deepen our knowledge about the neuromechanics of gait. In addition, we give a perspective on challenges towards using predictive simulations to gain new fundamental insight into motor control of gait, and to help design personalized treatments in patients with neurological disorders and assistive devices that improve gait performance. Such applications will require more detailed neuro-musculoskeletal models and simulation approaches that take uncertainty into account, tools to efficiently personalize those models, and validation studies to demonstrate the ability of simulations to predict gait in novel circumstances.