Maturation of Social and Non-Social Reward Processing in the Adolescent Amygdala and Orbitofrontal Cortex - ABSTRACT Adolescence is a time of substantial development attributed to the maturation of brain circuits that underlie the acquisition of new cognitive, emotional, and social skills. It is also a time of maximum vulnerability for mental disorders. In the past decade, the incidence of anxiety, depression, and suicide increased by ~60% in adolescents, remarkably more in females than in males. The social isolation during the COVID-19 pandemic added to the severity of the national and international statistics. To fully address the current youth mental health crisis, we need to understand how and why the dramatic reorganization of the adolescent brain contributes to the increased vulnerability to mental disorders. The studies proposed here rest on the assumption that the remodeling of the reward circuits of the brain creates the shared foundation of cognitive, affective, and social maturation during adolescence. Our multifaceted project addresses foundational gaps in our knowledge on how reward-driven motivational states inform adolescent behaviors such as risk-taking, pleasure-seeking, impulsivity, and a range of emotional responses to challenges of the social environment. We designed a within-subject, longitudinal study that spans the 2.5 - 3-year duration of adolescence in non-human primates. During this period, we will obtain repeated samplings of neurophysiological data recorded from the amygdala and orbitofrontal cortex in the context of the same behavioral tasks. In parallel, we will longitudinally monitor morphometric and microstructural changes in the gray and white matter of the brain through serial MRI scans, complemented by physical and hormonal measures of pubertal maturation. The three specific aims address the neural basis of three different aspects of reward processing in the subcircuit of the amygdala and orbitofrontal cortex. First, we will use a delay discounting task to determine the cellular and circuit level changes that underlie the increasing tolerance (or lack thereof) for delayed rewards. Second, we use a social reward-allocation task to test the neural underpinning of social reward processing in a self-oriented and an other-oriented social frame of reference. Finally, we will determine where and how social status is processed in the adolescent brain. Understanding social status relies on the ability to form abstract representations and is also a prerequisite for the successful integration of the individual into a hierarchical adult social group. The team, with combined expertise in human and non-human primate social behavior, neurophysiology, neuroimaging, and endocrinology, will apply conceptually and technically innovative approaches to generate unique and translational data, at both cellular and circuit levels, that account for the emerging cognitive, affective, and social skills acquired during adolescence.
