Brain mechanisms supporting the generalization of learned fear

描述（由申请人提供）：条件学习研究的主要目标是了解生物体如何获得和表达习得行为的基本原理。例如，巴甫洛夫恐惧条件反射，已经成为研究人类如何通过中性提示和生物厌恶刺激之间的偶然性学习过程来学习恐惧无害刺激的模型系统。在揭示恐惧学习的神经生物学基础方面取得了重大进展，认知神经科学的最新进展为临床焦虑症（从特定恐惧症到创伤后应激障碍）的行为治疗提供了信息。本提案中的具体目标旨在通过直接调查支持习得性恐惧泛化的过程来扩展涉及人类恐惧学习的行为和大脑机制的知识。这些研究将探索人类如何利用心理生理学和功能磁共振成像（fMRI）方法将中性物体概括为近似恐惧刺激。我们将揭示生物行为和大脑机制参与概括恐惧，试图更好地描述临床障碍，以夸大恐惧反应为特征的中性线索。在这些研究中，参与者将使用巴甫洛夫恐惧条件反射方法了解特定对象与恐惧相关。随后，参与者将被暴露在一系列偏离恐惧条件的物体上，这些物体沿着感知相似性（目标1）或语义相关性（目标2和目标3）的维度。恐惧泛化的个体差异将通过行为心理生理学测量来限制我们对大脑活动的解释来评估。此外，这三个目标的一个主要目标不仅是研究人类是如何概括恐惧的，而且还研究如何控制对与恐惧刺激在感知上或概念上相关的物体的恐惧反应。

DESCRIPTION (provided by applicant): A primary goal in conditioned learning research is to understand the principles underlying how organisms acquire and express learned behaviors. Pavlovian fear conditioning, for instance, has served as a model system for the study of how humans learn to fear otherwise innocuous stimuli through the process of contingency learning between a neutral cue and a biologically aversive stimulus. Significant progress has been made in unraveling the neurobiological basis of fear learning, and recent advances in cognitive neuroscience have informed behavioral treatments for clinical anxiety disorders ranging from specific phobias to posttraumatic stress disorder. The Specific Aims within this proposal are designed to extend knowledge of the behavioral and brain mechanisms involved in human fear learning by directly investigating processes supporting the generalization of learned fears. These investigations will explore how humans generalize to neutral objects that approximate a feared stimulus using psychophysiology and functional magnetic resonance imaging (fMRI) methods. We will uncover the biobehavioral and brain mechanisms involved in generalizing fear in the attempt to better characterize clinical disorders marked by exaggerated fear responses to neutral cues. In these studies, participants will learn that a particular object is fear relevant using Pavlovian fear conditioning methods. Subsequently, participants will be exposed to a range of objects that deviate from the fear conditioned object along a dimension of perceptual similarity (Aim 1) or semantic relatedness (Aim 2 and Aim 3). Individual differences in fear generalization will be assessed by constraining our interpretations of brain activity with behavioral psychophysiology measures. Furthermore, a primary goal in all three Aims is to investigate not only how humans generalize fear, but also learn to control fear responses to objects that are perceptually or conceptually related to a feared stimulus. PUBLIC HEALTH RELEVANCE: The proposed research contributes to a greater understanding of mental health disorders marked by heightened expression of fear. These neuroimaging investigations attempt to uncover the brain mechanisms supporting the generalization of fear from a known fear-relevant stimulus to emotionally neutral stimuli that approximate the feared stimulus, either perceptually or semantically. A greater recognition of how generalization modulates the cognitive processes involved in fear expression will strengthen understanding of certain mental health disorders (e.g. specific phobias and posttraumatic stress disorder) and may lead to model systems important for the treatment and prevention of these disorders.