Elizabeth S. Norton, Ph.D. - US grants

PROJECT SUMMARY Autism spectrum disorder (ASD) is a common neurodevelopmental disorder, affecting social communication in approximately 1 out of 68 children (CDC, 2016). Because dyadic interactions are central to language and social development, the brain basis of these social communication and engagement processes are of interest. In children with ASD or parents with subclinical language and personality features similar to defining symptoms of autism (known as the broader autism phenotype, BAP), social communication may be interrupted. Despite the dynamic, dyadic nature of social communication, most neuroimaging studies examine individuals one at a time, and often study social communication and engagement during artificial experimental situations, such as listening to recorded speech or viewing faces on a screen. Studying dyadic engagement in natural context is important because engaged, reciprocal interactions promote language and social communication development. This study uses cutting-edge ?social EEG? techniques in order to measure responses in two brains simultaneously and assess their synchrony. Toddlers with and without ASD and their mothers both wear EEG caps and their EEG is recorded during naturalistic interactions designed to elicit (a) joint engagement with and without communication, (b) parallel attention (no communication), or (c) no joint engagement. Behavior is microcoded in to these four mutually-exclusive states. Neural synchrony is then compared across each state, after carefully removing and controlling for motion artifacts. This study breaks new ground in 3 ways, by assessing parent-child synchrony (1) in ASD vs. TD groups, (2) in toddlers, and (3) in relation to dyadic social communication and joint engagement. Because ASD is known to begin early in life and arise from differences in the brain, understanding brain differences in dyadic social communication and joint engagement via the assessment of neural synchrony could provide insight into the mechanisms underlying the disorder. It could also lead to a potential objective marker of brain processes useful for diagnosis and assessment of ASD and of intervention response. Specific aims are as follows: Specific Aim 1. Examine the extent to which different levels of observed behavioral engagement are reflected in differences in EEG neural synchrony among typically-developing (TD) toddler-mother dyads. Hypothesis 1: Dyadic neural synchrony (mother-toddler EEG phase coherence and power similarity) will be greater during periods of dyadic social communication and joint engagement than during parallel attention; synchrony will be lowest during periods of no joint engagement. Specific Aim 2. Determine the extent to which neural synchrony in different dyadic engagement states differs in children with ASD and mothers with BAP traits. Hypothesis 2: Dyads with a child with ASD or a parent with BAP traits will have reduced neural synchrony relative to TD dyads while engaged in social communication and joint engagement but will not differ during parallel attention or no engagement states.

PROJECT SUMMARY ? Original Submission Primary language impairment (PLI) begins early in life and affects 6-8% of children. Although language intervention is maximally effective the earlier it is delivered, normative variation in language acquisition across toddlerhood (here 24-36 months) impedes accurate identification of PLI prior to late preschool age. The proposed study introduces a novel, theoretically- grounded, neurodevelopmental framework designed to generate a sensitive and specific model to identify PLI as early as possible. Our developmentally- sensitive, translational approach introduces multiple innovations including: (1) characterizing the developmental patterning of toddler emergent language beginning at 24 mos. using state-of-the-art methods, within a large community sample; (2) incorporating EEG/ERP neural biomarkers of language into PLI risk assessment; (3) using a novel paradigm to assess the protective effects of both behavioral and neural synchronization within parent-child language transactions; and (4) consideration of irritability, a robust developmental marker of early mental health risk, to enhance identification of those language delayed toddlers at highest risk for persistence. For the proposed When to Worry about Language Study (W2W-L), we capitalize on our funded study of 350 infants (50% irritable and 50% non-irritable) (R01MH107652, Wakschlag, PI) and enrich it via recruitment of a sub-sample of 200 late talking toddlers. This will yield a large and diverse sample of 550 24-month-olds. Our key predictors will be toddler emergent language patterns (24-36 months), their neural biomarkers and synchrony within the transactional language environment. Our central outcome is primary language impairment (PLI) status at preschool age (54 mos., when PLI can be reliably evaluated), assessed via clinical gold standard expressive and receptive language abilities. SPECIFIC AIMS: AIM 1a. Evaluate accuracy of PLI prediction based on multi-component measures of language including intensive longitudinal assessments of toddler developmental precursors of key language functions at older ages, neural biomarkers. We will assess neural and linguistic processing via quantitative EEG during parent-child interaction and ERPs to speech sounds as well as during eye tracking tasks and 1b. Evaluate feasibility of creating an algorithm for early identification of PLI that can be applied in clinical practice, using cross-validation and machine learning. AIM 2: Test the hypothesis that parent-child dyadic synchrony buffers PLI risk For the first time, we combine behavioral and novel social EEG measures of parent-child synchrony during natural interaction and a custom-designed word learning task to directly test how observed (behavioral) and neural (EEG) dyadic synchrony impact word learning. AIM 3: Test whether consideration of toddler irritability enhances PLI prediction. In sum, PLI confers sustained negative effects on a variety of personal-social and academic outcomes. Pinpointing children at highest risk for PLI is critical for reducing the public health burden of PLI for children, families, and the systems supporting them, and enhancing targeted allocation of resources.