Kanner's (1943) original characterization of autism as a """"""""Disturbance of Affective Contact"""""""" encompassed the lack of the capacity to connect from an early age emotionally to people, reflecting broad impairments in the experience, perception, regulation, and expression of emotion as well as in synchronizing and sharing it to form relationships. Since then, researchers have started to characterize these deficits at the behavioral level. In addition, a few studies have begun to explore the brain mechanisms underlying the deficits in adults with autism. Despite these important efforts, the characterization of the development of brain mechanisms for emotion processing remains a critical and largely unmet challenge, with few studies exploring this in individuals with and without autism throughout childhood. Further studies are required to examine the relationship between the development of emotion processing and that of underlying neural systems, particularly subcortical, temporal, and prefrontal cortical structures and their interactions. Such studies will inform the understanding of the neural bases of atypical emotional development in children with autism and of normal emotional development in children without autism, and the results will aid the development of earlier and better behavioral interventions and management for children and adults with autism. In this application, we propose to study samples of 6- to 11-year-old children with and without autism and adults with and without autism using a multiple methodology approach to characterize the development of brain mechanisms for emotion processing. We will investigate the perception, understanding, experience, and expression of emotion using eye tracking and behavioral measurements. We will also chart the functional development of the underlying neural substrates for emotion processing using functional magnetic resonance imaging (fMRI) and paradigms designed to probe atypical patterns in autism both in the functioning of specific brain regions and in the functional connectivity between key emotional brain structures. Finally, we will adopt an imaging genetics approach to examine gene-brain-behavior interactions in shaping the development of the emotional brain and as inter-individual modifiers of behavioral expression. Specifically, we will examine the role of the 5-HTTLPR S allele in the development of amygdala dysfunction and in reduced functional connectivity between limbic and prefrontal structures in autism. Research on the behavioral and neural mechanisms underlying the development of emotion processing deficits in autism, as proposed in this application, will provide important new insights into the development of the emotional brain in autism and will provide behavioral and brain phenotypes for genetics studies to investigate important genetic modifiers of behavioral expression that may be amenable to rational pharmacotherapy. Improved understanding of the behavioral, cognitive, and neural mechanisms of emotional processing in autism will improve the recognition and treatment of the profound emotional immaturity in ASD that is associated with problematic behavior at all ages and contributes to poor function in adulthood. This research addresses Autism Research Matrix goals # 16, 19, 22, 23, 26, 31, and 34.
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