Sensory Project in Infant/Toddler Siblings of Children with Autism (Project SPIS) - Abstract Individuals with autism experience challenges in developing language that impact their long-term social, academic, and vocational success. Previous research has identified several predictors of language in children with autism, but even when these predictors are considered, a large amount of the variance in language remains unexplained. Importantly, many children with autism still do not develop “useful speech” or language ability, despite receiving interventions that target these previously-identified predictors. Thus, there is a pressing need to identify novel predictors of language in children with autism. It has been proposed that differences in sensory responsiveness may emerge early in life from altered brain states and impact a child's ability to engage with others in their environment, thereby producing “cascading effects” on language acquisition in children affected by autism. If this is the case, intervening upon early sensory responsiveness may translate to improved language outcomes, by influencing brain states and boosting engagement in this population. Although intuitively appealing, given our understanding of the precedence and possible “foundational” nature of early sensory development relative to the emergence of “higher-level” language skill, evidence for the cascading effects theory to date has been rather limited. A primary challenge to establishing the aforementioned links is that autism cannot always be reliably diagnosed in the earliest stages of life (i.e., in infancy and toddlerhood). A potential solution is to prospectively follow infants and toddlers known to be at high likelihood for a future diagnosis of autism and language disorder. The Sensory Project in Infant/Toddler Siblings of Children with Autism (Project SPIS) scales up a prior NIDCD-funded R21 (R21DC016144; PI: Woynaroski) in a comprehensive test of the cascading effects framework in infant and toddler siblings of children with autism (Sibs-AUT), approximately one-third of whom will go on to be diagnosed with autism or language disorder, and infants at relatively lower, general population- level likelihood of these conditions (younger siblings of typically developing children; Sibs-TD). NOVELTY AND IMPACT: This innovative and interdisciplinary project is expected to further elucidate the nature of longitudinal links between a potentially tractable, but relatively understudied factor (early sensory responsiveness) and language in infants at elevated and lower, general population-level likelihood of autism. If our hypotheses are born out, findings of the study will lay the foundation for a clinical trial that will examine the efficacy of a targeted treatment of sensory function for distal effects on language as mediated by more proximal effects on resting brain states and engagement in infants at high likelihood for autism. This work is expected to facilitate earlier identification of language impairments and point towards novel targets of early “preventative” interventions, thereby improving the long-term outcomes of children who are diagnosed with, or at heightened risk for, autism and language disorder.