Brain mechanisms supporting the generalization of learned fear

描述(由申请人提供)：条件性学习研究的一个主要目标是了解生物体如何获得和表达学习行为的基本原理。例如，巴甫洛夫恐惧条件作用已成为研究人类如何通过在中性提示和生物厌恶刺激之间进行偶然性学习的过程来学习恐惧原本无害的刺激的模型系统。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的行为治疗提供了信息，从特定的恐惧症到创伤后应激障碍。这项建议的具体目的是通过直接研究支持习得性恐惧泛化的过程来扩展人类恐惧学习中涉及的行为和大脑机制的知识。这些研究将探索人类如何使用心理生理学和功能磁共振成像(FMRI)方法对接近令人恐惧的刺激的中性物体进行概括。我们将揭示泛化恐惧的生物行为和大脑机制，试图更好地描述以对中性线索的夸大恐惧反应为标志的临床疾病。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到特定对象与恐惧相关。随后，参与者将接触到沿感知相似性(目标1)或语义关联(目标2和目标3)的维度偏离恐惧条件对象的一系列对象。通过用行为心理生理学方法限制我们对大脑活动的解释，来评估恐惧概括性的个体差异。此外，这三个目标的一个主要目标不仅是研究人类如何概括恐惧，而且还要学习控制对感知上或概念上与令人恐惧的刺激有关的物体的恐惧反应。 公共卫生相关性：拟议的研究有助于更好地理解以高度表达恐惧为标志的精神健康障碍。这些神经成像研究试图揭示支持将恐惧从已知的与恐惧相关的刺激概括为情感中性刺激的大脑机制，这些刺激在感知上或语义上与令人恐惧的刺激相似。对概括性如何调节恐惧表达所涉及的认知过程的更多认识将加强对某些心理健康障碍(例如，特定恐惧症和创伤后应激障碍)的理解，并可能导致对这些障碍的治疗和预防至关重要的模型系统。

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.