GLOW: Gleaning Language trajectories and Outcomes in autistic toddlers using Wearable brain imaging - PROJECT SUMMARY During toddlerhood (18–36 months), children seamlessly progress from communicating with single words to using increasingly complex sentences, yet many autistic toddlers remain minimally verbal even after receiving years of early intervention services. Consequently, there is an urgent need to elucidate the mechanisms underlying these heterogeneous language profiles and trajectories during toddlerhood to inform the development of more personalized, neurobiologically informed early interventions (NIDCD Strategic Plan; Theme 3). However, relatively few studies have examined language-related brain-behavior dynamics during the 18–36 month window. This is partly because conventional neuroimaging requires stillness or sleep, which can be difficult for toddlers, both with and without autism. The interactive specialization model posits that broad, bilateral engagement of cortical temporal and frontal regions narrows into a more focal, left-lateralized temporal–frontal network as language proficiency improves over the first three years of life. Here, we test the central hypothesis that disruptions to this process may lead to persistent language delays in autism. This Stephen I. Katz Early Stage Investigator R01 leverages High-Density Diffuse Optical Tomography (HD-DOT), a motion-tolerant, child- friendly imaging technique offering high-quality spatial resolution, to address these gaps. We will recruit 222 toddlers (autistic with language delay, autistic without language delay, and neurotypical; n=74/group) to complete HD-DOT imaging at four time points (18, 24, 30, 36 months) alongside a comprehensive battery of spoken language assessments. Aim 1 examines whether 18-month neural activation in bilateral temporal and frontal regions distinguishes autistic toddlers with and without language delay from neurotypical age and sex-match peers. Aim 2 characterizes longitudinal trajectories of neural activation from 18 to 36 months and examines whether distinct developmental trajectories predict subsequent spoken language outcomes. Aim 3 examines whether child active engagement and parent responsiveness measured at 24 and 30 months mediate the influence of 18-month neural activation patterns on 36-month spoken language abilities. By identifying the neural correlates and predictors of spoken language outcomes throughout toddlerhood, this work will lay the groundwork for the development of more personalized, neurobiologically informed interventions.