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

项目摘要/摘要 反应性攻击(RA)是一种渗透到几乎所有精神障碍的跨诊断指标，其 坚持到青春期与严重和棘手的精神病理形式有关。研究表明 这种病因学上不同的攻击形式--定义为由感知到的 威胁(挑衅或撤回预期报酬)-可通过以下方式与其他形式的攻击区分开来 高度的情绪反应。然而，增强情绪反应的潜在神经过程 增加类风湿性关节炎的风险目前尚不清楚。虽然理论模型将类风湿关节炎与两年中的高反应性联系在一起 基本学习过程.威胁条件作用和强化条件作用.威胁和强化 基性功能障碍通常是孤立地检查的，通常是在学习环境之外作为预测因素 攻击性，广义的。此外，攻击性通常在特定于障碍的样本中被检查(例如， 外在化障碍)，排除了类风湿关节炎跨诊断机制模型的发展。海流 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运动轨迹的独立作用和协同作用。 青少年风险异质性样本(n=105；50%为女性)。具体地说，这项研究将沿着一个 通过招募具有低、中、高情绪反应的年轻人(13-15岁)来持续增加RA的风险。这个 这一理论的中心假设是，边缘激活程度较高，加上前额叶激活程度较低， 基础学习过程中的调控区域将预测类风湿关节炎的持续和恶化 随着时间的推移。表征有助于类风湿性关节炎的基本学习过程的神经基础 阐明对精神疾病发展至关重要的跨诊断神经过程的潜力。这 该项目将是一个更大的研究计划中的第一个，该计划将对NIMH战略优先事项2.1至1做出贡献) 关注RA潜在神经生物学过程的个体差异作为RA的跨诊断指标 风险和2)提高我们发现患类风湿性关节炎和相关精神疾病风险增加的年轻人的能力。这 申请详细说明了全面的研究和培训计划，使应聘者能够解决这些问题 提出问题，并为成为独立调查员奠定必要的基础。具体地说，这 应聘者将接受1)学习模型研究的发展神经科学方法的培训 促进类风湿性关节炎；2)加强青少年神经影像获取和分析方法的培训 3)先进的纵向设计和数据分析。这位候选人已经召集了一位导师 高级调查团队(Stepp，露娜)以及专家顾问，他们拥有出色的 培训初级科学家，支持他们发展成为非常成功的独立调查人员。这 专业知识，加上匹兹堡大学提供的资源，有力地证明了这位候选人的地位 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.