(RESEARCH PROJECT- EARLY PREDICTORS OF COGNITIVE/LANGUAGE DEVELOPMENT) PROJECT SUMMARY This project aims to identify electrophysiological markers (using magnetoencephalography, MEG) that predict future intellectual ability in infants and toddlers at risk for intellectual and developmental disability (IDD). To this end, we will use a suite of MEG paradigms developed in the previous IDDRC cycle that show differential sensitivity to general cognitive and language-specific ability. Paradigms focus on assessment of primary (pure tones) through higher-order (lexical access) auditory cortex activity. With the obtained auditory cortex neural measures used (singly and combined) we will predict future functional status (cognitive and language). Infant- optimized versions of these paradigms are applied to infants at genetic risk of a subsequent intellectual disability diagnosis. Hence, we hypothesize that early assessment of electrophysiological activity in at-risk infants will not only quantitatively indicate the degree of risk but will also predict and specify the nature of impairment. Given that most clinical diagnoses of intellectual disability are not made until at least school-age years, an accelerated longitudinal design is invoked. First, an Infant phase studies babies at 6, 12 and then 18 months in an attempt to predict functional status at 36 months. A simultaneously recruited Preschool phase recruits toddlers at age 3 years with similar genetic diagnoses (at-risk for IDD) to predict functional outcome assessment obtained at age 6 years. Via this research design, the interim functional follow-up of 3 year olds initially scanned as 6, 12 and 18-month infants can be better interpreted with respect to prediction of outcome at age 6 years. Through serial MEG examination, instantaneous (e.g., 6, 12 or 18 months) assessments as well as developmental trajectories (6- to 12- to 18-month interval change) are interrogated for their predictive value. With respect to innovation, given the temporal and spatial resolution of brain activity that is almost unique to MEG, MEG is poised to greatly enhance our understanding of normal and abnormal infant and toddler brain development. Specially, in addition to noted use of exams that directly target a range of primary/secondary auditory cortex neural processes, analyses that provide measures of brain activity in source space allow for focused assessment of activity at brain regions of a priori interest versus examining a composite measure of whole-brain activity. It is anticipated that early repeated assessment of brain activity of infants at risk for an IDD diagnosis will provide actionable information to parents and caregivers and, where needed, allow earlier tailored interventions.