Abstract There is a growing translational research effort to understand the brain mechanisms of dysfunction in neurodevelopmental disorders including Down syndrome (DS) and other conditions that cause intellectual and developmental disability (IDD). Targeted treatments under development, often supported by animal studies, have the potential to normalize, or at least substantially mitigate, the neurobiological, cognitive, and behavioral problems associated with DS. However, several controlled clinical trials focused on DS and other IDDs (such as fragile X syndrome) in the past decade have been completed with limited success. Although the medications may actually be ineffective or inadequately provide clinical benefit, other explanations for trial failures include limited brain plasticity in the adults or adolescents studied, robust placebo effects that may obscure true benefits of active drug, and outcome measures that are inadequately sensitive to changes occurring in daily life. Optimization of ecologically valid, reliable and sensitive outcome measures for these conditions will facilitate the evaluation and identification of effective and clinically meaningful interventions. Executive dysfunction (ED), spanning processes and behaviors of planning and goal-directed behavior, cognitive flexibility, working memory, inhibitory control, and several forms of attention, has been emphasized by NIH DS working groups and other investigators as a key domain to target in trials. ED is a key component of the cognitive phenotype of DS, is predictive of limitations in adaptive functioning, and may be associated with risk for later dementia in this population. The primary aim of this project is to refine and develop the preliminary feasibility, reliability and validity of a smartphone-based electronic Ecological Momentary Assessment (eEMA) tool (iBehavior) for caregiver and teacher ratings of behaviors associated with ED in the daily lives (home and classroom environments) of children and adolescents with DS and IDD. The second aim of the project is to utilize the tool in the context of an already planned and funded (R01HD076189) double-blind placebo- controlled crossover trial of extended release methylphenidate in children and adolescents with DS and other forms of IDD with comorbid ADHD. This aim will determine iBehavior’s sensitivity to treatment and relative susceptibility to placebo effects compared to other rating scales and cognitive tests. The empirical validation of an eEMA app appropriate for use as an outcome measure in future DS trials will provide a technologically novel method for use in the home and classroom setting that has the potential to detect treatment-related changes in daily life, changes that may not be adequately captured by laboratory tests or retrospective caregiver questionnaires and interviews.