Social interaction and communication begin in early infancy, and, although these are fundamental humanfunctions, little is known about the underlying neural mechanisms that regulate them particularly in AutismSpectrum Disorder (ASD). ASD is a neurodevelopmental disorder characterized by significant disabilities inlanguage and social skills, and the specific neural mechanisms that lead to these disabilities remain active topicsfor investigation. Emerging theoretical directions converge on problems with eye-contact as a salient componentof these communication and social disabilities. Technical limitations, however, associated with imaging of two ormore individuals during natural communication and mutual eye contact have been a primary obstacle to theseinvestigations. To overcome this technical impasse, we employ a rapidly developing brain imaging technology,functional near-infrared spectroscopy (fNIRS) allowing simultaneous neural imaging of two individuals duringvalid interactions to observe the neural effects of eye-to-eye contact and actual dialogue. Functional NIRSdetects active neural tissue based on the blood-oxygen-level-dependent (BOLD) signal by measuring variationsin the absorption spectra associated with oxyhemoglobin and deoxyhemoglobin. Because detectors andemitters are surface mounted on the head, they are relatively insensitive to head movement, and, as such, fNIRSis well suited for investigations of neural events engaged during active interpersonal interactions between twoparticipants. The neural mechanisms that underlie atypical interpersonal interactions and eye contact in adultASD are the focus of this proposal. Pilot studies confirm the feasibility of all aspects of this research project.Dyads consisting of a confederate and a participants with typical development (TYP) or ASD will be comparedduring neuroimaging while engaged in natural interaction and communication. We introduce a computationalapproach based on wavelet analysis to quantify regional cross-brain coherence between the two participantsand hypothesize that cross-brain coherence associated with speech and eye contact will be reduced in ASDrelative to the TYP cohort. Cross-brain computations also form the basis for a model of dynamic neuralprocesses based on neural “send and receive” functions during communication. We hypothesize that thesedynamic “cross-brain communication” systems unify and coordinate the roles of language production andreception (Broca's and Wernicke's Areas), respectively, with visual reception involving face specializations(fusiform gyrus). Computational comparison of cross-brain connectivity effects as well as conventional functionalconnectivity and segregation/contrast effects during live communication both with and without direct eye contactprovides a transformational technical, empirical, computational, and theoretical advance toward understandingthe dynamic neural mechanisms associated with social and communication disabilities in ASD.