Social interaction deficits are at the crux of autism spectrum disorder (ASD) and contribute to significant functional impairment, including poorer relationship quality and low employment rates in individuals with ASD. Despite an enormous amount of research dollars invested and thousands of research papers published on the topic, we remain far from understanding the basic neural computations underlying social processes in ASD. In the current proposal, we posit that this information gap is due in part to the rarity with which computational model- based analyses are used in ASD neuroimaging research. Additionally, most studies use passive paradigms (e.g. face perception) rather than examining brain functioning while participants engage in ecologically-relevant, interactive social tasks more akin to the type of interactions with which people with ASD struggle in their daily lives. This proposal takes an innovative computational psychiatry approach to understanding aberrant neural computations of social interactions in ASD, using high-resolution (7T) functional magnetic resonance imaging (fMRI) and virtual reality-like tasks that test individuals? abilities to proactively and dynamically engage in simulated social interactions. In particular, we focus on the ability of individuals with ASD to: 1) discriminate and track levels of closeness and power when navigating social interactions in a choose-your-own-adventure style interactive paradigm, and 2) understand and adapt to social norms and exert control over social others in the context of a proactive social exchange paradigm. We use novel computational models to examine the neural computations and connectivity underlying proactive social behavior, focusing on brain regions (e.g., hippocampus) that have been understudied in the context of social deficits in ASD. Finally, we use machine learning approaches to explore ASD heterogeneity along dimensions of dynamic and proactive social interactions and apply these indices to make clinically-meaningful predictions. We hypothesize that: 1) hippocampal tracking of social space will be less robust in ASD as compared to neurotypical controls and will correlate with social symptoms; 2) ASD individuals will show slower norm adaptation rate, greater aversion to norm violation, and reduced social controllability, accompanied by reduced neural encoding of social values in anterior insula and ventral striatum; and 3) these parameters will help identify subtypes of ASD and predict ASD- relevant outcomes (e.g. social skills, adaptive social functioning, quality of life). We expect that findings from this project will break new ground and fill critical knowledge gaps regarding the neurobiology of ASD. In particular, we expect our findings will greatly enhance understanding of the neural and computational mechanisms underlying deficits in proactive social behavior in ASD and will allow us to identify distinct, neurobiologically- driven clusters. In so doing, the results of this project could offer new tools by which to subtype the ASD phenotype and provide novel insights into treatment targets.

Public Health Relevance

Despite social deficits being core features of autism spectrum disorder (ASD) and contributing to relationship difficulties and low employment rates, their neurobiological underpinnings are poorly understood. The goal of this study is to gain new knowledge about the brain mechanisms underlying social deficits in autism using computational modeling, novel brain imaging tools, and interactive experimental tasks that simulate dynamic social interactions. In contributing to our understanding of the brain basis of ASD, this study may unveil new directions for intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH122611-01A1
Application #
10130086
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Gilotty, Lisa
Project Start
2020-09-15
Project End
2025-06-30
Budget Start
2020-09-15
Budget End
2021-06-30
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Psychiatry
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029