PROJECT SUMMARY/ABSTRACT Long-term goals of this application are to develop safe, effective, and scalable interventions with a strong basis in neuroscience, to improve the upper extremity (UE) function of children with cerebral palsy (CP). Our UE intervention called “APPLES” is parent-administered, medical team-directed, uses soft constraint and “sticky-mittens” and bimanual therapy. Our first R01 showed that it effectively improved UE function, cortical somatosensory processing, and reach smoothness, while being safe for the developing brain and body in infants (6-24 months) with CP. Our competing renewal addresses remaining gaps in knowledge: is there an earliest age at which APPLES is most effective, can APPLES be successfully delivered through telehealth, and because parents are delivering APPLES, are there evidence-based supports that we can offer them to be more effective, and do all parents need these supports equally. We also specifically address new NCMRR priorities for: (1) “multimodal approaches that promote plasticity and sensorimotor function”, (2) “patient-reported outcomes as ... secondary endpoints in trials”, and (3) “development of scalable strategies”. We call our new intervention APPLES-tele, as it will be delivered through telehealth and start in infants as young as 3 months. In addition, we test the relative efficacy of APPLES-tele vs. standard care group and vs. a novel parent-centered approach (PCA) that is infant- and CP-specific. PCA consists of education in infant motor learning, adaptive strategies for CP, and positive psychology in parenting (from the scientifically-proven Triple P Positive Parenting Program model). PCA will help parents develop “authoritative parenting”, an optimal parenting style proven to promote better long-term developmental outcomes. The design is a randomized controlled trial with both business-as-usual and active treatment comparisons; two groups receive PCA and APPLES-tele, but in different order. The other receives standard care. Both 6- week interventions will have the same weekly-telehealth schedule. Assessments are at baseline, at 6- weeks and 12 weeks. We use standardized tests of hand function and development, validated measures of parent-treatment fidelity, and parent-relevant measures of performance. Interventions and assessments are protocolized and monitored to ensure rigor and reproducibility. We leverage a large cohort of parents and children across 4 centers already linked through our successful implementation network for early detection of CP, with diverse socioeconomic and geographic conditions in an area > 11% of the US. We aim to demonstrate improvements in UE function are greater in the APPLES-tele-first group than in both control groups after the first 6-weeks of intervention. Conversely, we will show parent CP-specific knowledge and parent-child emotional connection are greater in the PCA-first group than the other 2 groups. We will then explore whether relative efficacy o...