Project Summary Difficulties with pragmatic (i.e., social) language are a highly clinically significant feature of autism spectrum disorder (ASD) that can impose a significant burden on autistic individuals throughout the lifespan. Strong evidence suggests that pragmatic language can also be subtly impacted among clinically unaffected first-degree relatives, constituting a principal feature of the broad autism phenotype (BAP) believed to reflect ASD-related genetic influence. Understanding the causes of pragmatic difficulties in ASD is therefore critically important for improving clinical care (e.g., by tailoring interventions to target underlying mechanistic factors), and for informing gene-brain-behavior connections. Importantly, research on pragmatic language in ASD has primarily focused on English speakers, and no studies have examined the pragmatic language features of the BAP cross-linguistically. Because pragmatic language is fundamentally cultural, understanding how pragmatic profiles, and their mechanistic underpinnings, might differ across languages and cultures is critical, especially in increasingly multilingual societies (including the US). In this proposal, our multidisciplinary international team of investigators will employ an armamentarium of cutting-edge analytic platforms and innovative deep behavioral and targeted neural phenotyping methods to delineate similarities and differences in pragmatic language profiles in ASD and the BAP, across speakers of Cantonese and English. By examining how pragmatic profiles may differentially express in these two typologically distinct languages (including how pitch processing and related pragmatic language mechanisms differ across speakers of tone and non-tone languages), analyses will provide insights into the complex biological and environmental influences on ASD pragmatic profiles. Our prior work and new preliminary data strongly indicate that neuro-auditory, speech rhythmic, and articulatory contributors to pragmatic language are robustly impacted in both Cantonese- and English-speaking ASD groups, supporting our hypothesis that core pragmatic features are subserved by fundamental and biologically deep mechanistic processes with strong genetic etiology. Using a family-study design, this project will not only comprehensively characterize pragmatic language profiles across speakers of Cantonese and English, but importantly, also examine the mechanistic underpinnings of these pragmatic language profiles that may be common across languages, or language-specific. Further, complementary light phenotyping is applied in tandem with machine-learning data- driven analyses, including natural language processing, in a larger verification sample. Findings will highlight both those pragmatic features under strong biological influence, as well as those that are potentially more malleable to environmental influences, such as linguistic structure and cultural features.