Successful social exchanges, from date nights to peace talks, fundamentally rely on coordination and trust between individuals who have different goals or preferences. Such conflict between individual goals can be harmonized by long-time-scale strategies, such as turn-taking behaviors. However, this requires establishing the trust that forgoing preference will be reciprocated in the future. Indeed, building trust and preserving long-timescale social coordination that is essential for forming and maintaining relationships is achieved by flexible, dynamic re-evaluation of the other?s behavior and renegotiation processes of navigating preference distances. Recent evidence suggests that the implicit processes of interpersonal coordination are closely related to the core impairments in psychiatric disorders such as Autism. Despite the immense importance of trust and strategic social coordination to both normal and abnormal cognition and our existence as a society, its single-neuronal basis and causal underpinnings remain almost completely unknown. While this level of cellular and mechanistic investigation is not readily accessible in humans, non-human primates, who closely model human social cognition, are particularly powerful model for understanding the implementations of core neuronal computations underlying human strategic social interactions. Here, we leverage principles of game theory to provide a novel framework that operationally encapsulates long-term social coordination, and adapt it to be compatible with neurophysiological investigation in primates. Equipped with these non-human primate models of social interaction, large-scale single-neuron recordings across multiple brain regions, and advanced mathematical modeling approaches my goal is to systematically dissect the brain-wide neuronal underpinnings of social coordination. Key to this effort is developing and implementing new tools for large-volume, long-term use compatible, spatially specific and temporally precise perturbation in primates through the use of new generation neural effectors. With these new precision-perturbations we will simultaneously investigate the contributions of the proposed major hubs of the ?social brain? in encoding and modulating trust and strategic social coordination. Understanding gleaned from this work will illuminate the neural architecture and circuits mediating trust and strategic social coordination. Given that impaired interpersonal coordination is associated with various neurological and psychiatric disorders (such as autism spectrum disorders and schizophrenia), these results also will help set the path to transform clinical treatments for widespread neurological and psychiatric medically-intractable disorders.

Public Health Relevance

Our lack of understanding of the basis of social interactions presents a major roadblock to developing neural circuit-based therapies for disorders such as major depression, schizophrenia, and autism spectrum disorders, which are marked by debilitating deficits in social interactions. We propose to investigate the single-neuron and circuit basis of long- timescale strategic social behaviors using rhesus macaques, and we will develop a novel tool for neural perturbation that represents a step towards a minimally invasive approach to treat brain dys function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
NIH Director’s New Innovator Awards (DP2)
Project #
1DP2MH126142-01
Application #
10003074
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Ferrante, Michele
Project Start
2020-09-15
Project End
2025-05-31
Budget Start
2020-09-15
Budget End
2025-05-31
Support Year
1
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Stanford University
Department
Neurology
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305