Neural Circuitry of Social Cognition in the Broad Autism Phenotype

DESCRIPTION (provided by applicant): For over 15 years, our research team has taken Kanner's original observations about behavioral features characteristic of some parents of autistic individuals and developed standardized, valid, and reliable clinical measures to define what is now referred to as the Broad Autism Phenotype (BAP). The BAP is thought to represent the phenotypic expression of the underlying genetic liability to autism in non-autistic relatives of autistic individuals and is defined by characteristics that are milder but qualitatively similar to the defining features of autism. In our current UNC STAART Autism Research Center, we have identified abnormalities of social cognition (on tasks linked in previous studies to specific brain regions in the neural circuitry of social cognition) that occur more commonly in 'autism parents'with the social behavioral characteristics of the BAP (i.e., aloof personality) than in either 'autism parents'without aloof personality or community controls. We have developed fMRI paradigms that identify abnormalities in key components of the neural circuitry of social cognition in autism (amygdala, superior temporal sulcus, and fusiform gyrus) and developed a novel approach for probing the complex processing of social information from faces - the Bubbles Method that allows us to integrate simultaneous measurement of eye tracking data, skin conductance response, and BOLD responses on fMRI to isolate which features of the face drive behavioral, autonomic, and neural discrimination of social information from faces. In this revised application, we propose to use fMRI, neuropsychological, behavioral, and psychophysiological measures to characterize the neural circuitry of abnormal social cognition in parents of autistic individuals and to elucidate the stage of information processing at which dysfunctional social cognition arises in the BAP. This application is a collaboration of three investigators with a track record of collaboration and complementary experience in autism and the BAP (J. Piven at UNC), fMRI of social cognition (G. McCarthy at Duke), and novel approaches to elucidating the neural basis of social cognition (R. Adolphs at Caltech). Study of the behavioral and neural mechanisms underlying the social behavioral component of the BAP, as proposed in this application, will provide important new insights into the forme fruste of the autism brain and behavioral phenotype for use in future genetics, brain, and behavioral studies of autism and the BAP.