Self Responses Along Cingulate Cortex Reveal Quantitative Neural Phenotype For High Functioning Autism

Background: Typical social interaction requires the ability to recognize one's role in an interpersonal exchange. In particular, attributing behavioral outcomes correctly to oneself or to other agents is essential for productive social interaction.

Objectives: The capacity to attribute social outcomes to the appropriate agents may be missing or perturbed in individuals with autism. We approach this issue in high-functioning males with autism spectrum disorder (ASD) using functional magnetic resonance imaging (fMRI).

Methods: First, using a visual imagery task, we extract a basis set for responses along the cingulate cortex of control subjects that reveals an agent-specific eigenvector (self eigenmode) associated with imagining oneself executing a specific motor act. Second, we show that the same self eigenmode arises in controls during one’s own decision (the self phase) in an interpersonal exchange game (iterated trust game). Third, we assessed hemodynamic activations as high-functioning adolescents with autism engaged in the iterated trust game with a social partner.

Results: Using the iterated trust game, we show that ASD males exhibit a severely diminished self eigenmode when playing the game with a human partner. This diminished response covaries parametrically with their behaviorally assessed symptom severity suggesting its value as an objective endophenotype.

Conclusions: The perturbed neural response in autism, evoked within an active interpersonal exchange, provides a quantitative neural phenotype that may identify new subtypes of autism and further be used to seek covariates in genetic databases.