PROJECT SUMMARY Mid-substance Achilles tendinopathy is a painful, debilitating, and chronic tendon pathology. Rehabilitation exercises are the first treatment option for patients, but clinical studies have reported 20-60% of patients continue to experience pain and symptoms 5-years later. Despite these poor outcomes, rehabilitation protocols remain standardized because of insufficient evidence to support precision care. Our Parent R01 project will determine similarities in tendon loading and biomechanics in patients with mid-substance Achilles tendinopathy and how these similarities affect tendon healing, pain, and functional outcomes. In this Ancillary R01, we will leverage our innovative High-Density surface ElectroMyoGraphy (HDsEMG) interface to measure the plantar flexor neuromechanics during isolated ankle testing using dynamometry and functional tasks during walking on differing grades. Our preliminary data demonstrate that the relative contributions of the primary plantar flexor muscles can be modified by changing the knee angle during isolated and functional tasks. We will use this experimental model system to test the mechanistic link between plantar flexor neuromechanics, Achilles tendon loading biomechanics, and patient outcomes. In Aim 1, we will define neuromechanical profiles across Achilles tendinopathy disease progression. In Aim 2, we will link neuromechanical profiles with Achilles tendon loading profiles and stress imaging. By leveraging our large and well-characterized cohort of individuals with Achilles tendinopathy, this Ancillary R01 will establish how neuromechanical mechanisms (Ancillary R01) mediate complex biomechanical loading profiles of pathologic Achilles tendinopathy (Parent R01). This is a necessary next step to develop precision rehabilitation that factor patient-specific neuromechanics and Achilles tendon biomechanics. After successfully completing our proposed aims, we will test the clinical efficacy of precision neuromechanical rehabilitation in a randomized clinical trial.