Our collaborative team is currently advancing a randomized controlled trial at five different sites in the United States with 12-36 month-old children, diagnosed with mild-to-moderate spastic cerebral palsy (CP) (N=110). The study is designed to evaluate the effectiveness of an intense protocol of physical (PT) and occupational (OT) therapies versus the current standard of care. The therapists are using the Perception-Action approach (P-AA), a child-driven, active, dynamic, task-oriented therapy. P-AA is based on concepts of neuroplasticity and takes advantage of the young brain’s ability to reorganize and stimulate dormant neurons to influence the acquisition of motor skills and neurodevelopment. Previous work strongly suggests that a protocol of intense therapy is feasible and may substantially improve function in young children with CP (Duncan, Shen, Zou, Han, Lu, Zheng, et al., 2012; Pottinger, Rahlin, Voigt, Walsh, Fregosi, & Duncan, 2018). The study employs a crossover design that provides all children an equal number of therapies over a 48-week period. Children are randomized to either early intense therapy (Group 1) or delayed intense therapy (Group 2). Children randomized to Group 1 receive PT and OT five days a week for 12 weeks followed by 36 weeks of PT and OT once a week (standard of care); children randomized to Group 2 start with 36 weeks of PT and OT once a week and finish with 12 weeks of PT and OT five days a week. The primary outcome measure is an assessment of clinical changes in motor function after 12, 24, 36 and 48 weeks using the Gross Motor Function Measure-66, the most widely used evaluation tool to assess the effectiveness of interventions for CP. Parental/caregiver-reported changes in function are captured with the Pediatric Evaluation of Disability Index-Functional Skills assessment at the same time points. Comparison of changes from baseline to 12 weeks will be used to evaluate impact of daily versus weekly protocols; 24- and 36-week evaluations will be used to determine whether gains made during the intense phase are maintained even after reverting to standard treatment; and 48-week evaluations will be used to assess whether intense therapy is equally effective independently of the time of administration, or if there is a greater benefit in earlier administration. In a subgroup of children with hemiplegia presentation (n=20), clinical findings will be correlated with magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) that assess white matter and high angular resolution diffusion imagining (HARDI). This will provide an objective analysis of anatomical changes that will be correlated with clinical functional changes. The results of this project will offer insight in the management of young children diagnosed with spastic CP, a highly limiting condition in which current standard of care delivers less than optimal results. We anticipate that our findings will significantly improve children’s functional independent abilities and in so doing will improve their quality of life and that of their families. We also believe that the identification of signature changes in neuroimaging will lead to recognizing MRI/DTI/HARDI as a clinical tool for evaluating the effectiveness of interventions of patients with CP.