Though walking impairments are prevalent in society, clinical treatments are often ineffective at restoring lost function. For this reason, researchers have begun to explore the use of patient-specific computational walking models to develop more effective treatments. However, the accuracy with which models can predict internal body forces in muscles and across joints depends on how well relevant model parameter values can be calibrated for the patient. This study investigated how knowledge of internal knee contact forces affects calibration of neuromusculoskeletal model parameter values and subsequent prediction of internal knee contact and leg muscle forces during walking. Model calibration was performed using a novel two-level optimization procedure applied to six normal walking trials from the Fourth Grand Challenge Competition to Predict In Vivo Knee Loads. The outer-level optimization adjusted time-invariant model parameter values to minimize passive muscle forces, reserve actuator moments, and model parameter value changes with (Approach A) and without (Approach B) tracking of experimental knee contact forces. Using the current guess for model parameter values but no knee contact force information, the inner-level optimization predicted time-varying muscle activations that were close to experimental muscle synergy patterns and consistent with the experimental inverse dynamic loads (both approaches). For all the six gait trials, Approach A predicted knee contact forces with high accuracy for both compartments (average correlation coefficient r = 0.99 and root mean square error (RMSE) = 52.6 N medial; average r = 0.95 and RMSE = 56.6 N lateral). In contrast, Approach B overpredicted contact force magnitude for both compartments (average RMSE = 323 N medial and 348 N lateral) and poorly matched contact force shape for the lateral compartment (average r = 0.90 medial and −0.10 lateral). Approach B had statistically higher lateral muscle forces and lateral optimal muscle fiber lengths but lower medial, central, and lateral normalized muscle fiber lengths compared to Approach A. These findings suggest that poorly calibrated model parameter values may be a major factor limiting the ability of neuromusculoskeletal models to predict knee contact and leg muscle forces accurately for walking.

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