Neural mechanisms of reactive aggression in adolescence: Altered reactivity during threat and reinforcement conditioning

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PROJECT SUMMARY/ABSTRACT Reactive aggression (RA) is a transdiagnostic indicator that permeates nearly all psychiatric disorders, and its persistence into adolescence is linked to severe and intractable forms of psychopathology. Research suggests this etiologically distinct form of aggression - defined as an impulsive, enraged attack triggered by perceived threat (provocation or withdrawal of expected reward) - can be differentiated from other forms of aggression by high levels of emotional reactivity. Yet, the underlying neural process by which heightened emotional reactivity increases risk for RA remains unknown. While theoretical models link RA to heightened reactivity during two fundamental learning processes - threat conditioning and reinforcement conditioning - threat- and reinforcement- based dysfunction are typically examined in isolation and often outside the context of learning as predictors of aggression, broadly defined. Further, aggression has typically been examined in disorder-specific samples (e.g., externalizing disorders), precluding the advancement of a transdiagnostic mechanistic model of RA. The current proposal seeks to address these limitations by integrating neural and behavioral levels of analysis to examine the independent and synergistic effects of threat and reinforcement conditioning on trajectories of RA in an at- risk heterogenous sample of adolescents (n=105; 50% female). Specifically, this study will sample along a continuum of risk for RA by recruiting youth (13-15 years) with low, moderate, and high emotional reactivity. The central hypothesis of this proposal is that higher limbic activation, coupled with lower activation in prefrontal, regulatory regions during fundamental learning processes will predict the persistence and exacerbation of RA over time. Characterizing the neural underpinnings of fundamental learning processes that contribute to RA has the potential to illuminate transdiagnostic neural processes critical to the development of mental illness. This project will be the first in a larger program of research that will contribute to NIMH Strategic Priorities 2.1 by 1) focusing on individual differences in neurobiological processes underlying RA as a transdiagnostic indicator of risk and 2) improving our ability to detect youth at heightened risk for RA and related psychopathology. This application details a comprehensive research and training plan that allows this candidate to address these questions and develop the foundation necessary to become an independent investigator. Specifically, this candidate will receive training in 1) a developmental neuroscience approach to the study of learning models contributing to RA; 2) intensive training in neuroimaging acquisition and analytic methods among adolescent populations; and 3) advanced longitudinal design and data analysis. This candidate has assembled a mentorship team of senior investigators (Stepp, Luna) along with expert consultants, who possess stellar track records of training junior scientists and supporting their development into highly successful independent investigators. This expertise, combined with the resources afforded by the University of Pittsburgh, strongly position this candidate to achieve her proposed training, research, and career goals.