Neurobiobehavioral markers of stress, saliency, and multisensory dysfunction in autism - PROJECT SUMMARY Sensory abnormalities are commonly observed in children with autism spectrum disorders (ASD). In early interactions with caregivers, visual, auditory, and somatosensory processing is integral to social interchanges and helps direct attention toward important cues. The integration of sensory information aids in detecting salient features of the external environment. In ASD, however, there is evidence of atypical multisensory integration and disrupted salience processing. Ineffective integration and saliency detection of sensory information likely contribute to cognitive and emotional overload and uncertainty, and increased stress reactivity. Elevated stress (e.g., cortisol) associated with sensory dysfunction in ASD may further compound core symptomatology and contribute to later development of internalizing symptoms (e.g., anxiety) frequently co-occurring in ASD. Sensory abnormalities are often correlated with internalizing symptoms in ASD children, although the underlying neural and behavioral mechanisms are unclear. Therefore, this research project will investigate the relationship between multisensory integration, salience processing, and stress reactivity, and establish how abnormalities in these domains are associated with internalizing symptoms in ASD. These relations will be examined in ASD children (n=115) and typically developing peers (n=115) between 7 and 10 years of age, when complex multisensory integration begins to stabilize and risk of developing internalizing symptoms increases. We theorize that deficits in low-level sensory processing disrupt both high-level multisensory integration and saliency detection, which are linked to internalizing symptoms; we further hypothesize these links to be moderated by stress reactivity in ASD. The proposed research aims to: (1) characterize multisensory integration in the context of saliency detection of sensory information in children with ASD; (2) map activity and functional connectivity of the neural circuits underlying multisensory integration and salience processing; (3) examine associations between subjective measures of reported sensory responsivity, quantitative measures of multisensory integration and saliency detection, and stress reactivity; and (4) relate neural and behavioral measures of multisensory integration and salience processing, as well as indices of stress reactivity, to co-occurring internalizing symptoms reported in children with ASD. This project will implement a multimodal approach, including the collection of quantitative psychophysical discrimination response thresholds (to visual, auditory, somatosensory, and multisensory stimulation), biological indicators of stress reactivity (i.e., salivary cortisol), magnetic resonance imaging (MRI) data (i.e., task and resting state functional connectivity MRI, anatomical MRI), subjective caregiver-report questionnaires, and cognitive and psychodiagnostic assessments. The findings will elucidate the links between neurobiobehavioral mechanisms underpinning multisensory integration, salience processing, and manifestations of stress, as well as internalizing conditions in children with autism.