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

项目总结/摘要 反应性攻击（RA）是一种跨诊断指标，几乎渗透到所有精神疾病，其 持续到青春期与严重和棘手的精神病理学形式有关。研究表明 这种在病因学上独特的攻击形式--被定义为一种冲动的、愤怒的攻击， 威胁（挑衅或收回预期奖励）-可以通过以下方式与其他形式的攻击区分开来： 高水平的情绪反应。然而，增强情绪反应的潜在神经过程 RA的风险仍然未知。虽然理论模型将RA与两个期间的高反应性联系起来， 基本学习过程-威胁条件反射和强化条件反射-威胁和强化- 基础功能障碍通常被孤立地检查，并且通常在学习背景之外作为 侵略，广义上的。此外，攻击性通常在疾病特异性样本中进行检查（例如， 外化障碍），排除了RA的跨诊断机制模型的进展。当前 一项提案试图通过整合神经和行为层面的分析来解决这些限制， 威胁和强化条件作用对RA轨迹的独立和协同作用， 青少年风险异质性样本（n=105; 50%女性）。具体而言，本研究将沿着沿着 通过招募具有低、中、高情绪反应性的青年（13-15岁）来评估RA的连续风险。的 该提议的中心假设是，较高的边缘系统激活，加上较低的前额叶激活， 基础学习过程中的调节区域将预测RA的持续和加重 随着时间表征有助于RA的基本学习过程的神经基础， 有可能阐明对精神疾病发展至关重要的跨诊断神经过程。这 该项目将是一个更大的研究计划，将有助于NIMH战略优先事项2.1由1） 关注RA神经生物学过程的个体差异，作为RA的转诊断指标。 风险和2）提高我们检测RA和相关精神病理学高危青年的能力。这 申请详细说明了一个全面的研究和培训计划，使该候选人能够解决这些问题 问题和发展成为独立调查员所需的基础。具体来说， 候选人将接受以下培训：1）学习模型研究的发展神经科学方法 对青少年进行神经影像学采集和分析方法的强化培训 3）先进的纵向设计和数据分析。这位候选人组建了一个导师团队 高级调查员团队（Stepp，Luna）与专家顾问一起沿着，他们拥有 培训初级科学家，并支持他们发展成为非常成功的独立调查人员。这 专业知识，结合匹兹堡大学提供的资源，强烈定位这位候选人 以实现她提出的培训、研究和职业目标。

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.