Sensory Perception of Threat in Anxiety

描述（由申请人提供）：焦虑的特征是对威胁的高度反应。然而，焦虑障碍的确切病因基础仍然不清楚。与流行的以杏仁核为中心的威胁处理和焦虑病理生理学观点不同，本应用程序提出了一种神经感觉解释，强调了焦虑的感觉途径。基于我们实验室和其他团队积累的新证据，我们假设刺激的生物学意义可以存储在感觉系统中，这样，一旦输入被感觉大脑记录下来，情感价值就会被解码，这与基于边缘的威胁评估是平行的，而且通常是在此之前。作为认知流的第一个操作之一，对威胁的有偏见的感觉知觉会影响下游过程，直接或间接地导致焦虑中观察到的各种认知和情绪异常。该项目代表了焦虑中威胁的基本感觉加工研究的第一线，将为基本威胁分析和焦虑发生提供新的见解，从而有助于创新焦虑障碍的临床治疗。为此，本研究将采用认知-情感神经科学方法，首先从两个概念重点来定义焦虑中威胁的感觉编码：1)强调个体威胁亚型的高度专门化的感觉表征，这可以为不同威胁的不同反应和反射提供神经基础，并解释焦虑障碍的异质症状（Specific Aim 1）；2)评估多模态和跨模态（相对于单模态）感官输入的威胁感知，通过优化模拟现实生活中的感官体验，这对揭示焦虑中新的多方面和模态特定的威胁感官偏见有很大的希望（具体目标2）。其次，计划中的研究将机械地具体说明最初对威胁的知觉偏见对随后的情绪和认知过程的影响，从而产生各种焦虑症状（特别是负面解释、过度社交回避和对威胁的选择性注意；具体目标3）。在六个独立的实验中，我们将采用独特和充分发展的专业知识和技术（功能性磁共振成像，fMRI；脑事件相关电位，erp；自主生理学；心理物理学；焦虑评估和挑衅）来确定威胁的感官知觉及其行为后果的神经基础，这些后果随着焦虑的功能而变化。该项目的研究结果将创造一个知识体系，有可能挑战以大脑边缘为中心的主流焦虑概念化，促进向多系统、多路径理论的转变。

DESCRIPTION (provided by applicant): Anxiety is characterized by heightened response to threat. However, the precise etiologic basis of anxiety disorders remains obscure. Differing from prevailing amygdala-centric views of threat processing and anxiety pathophysiology, this application proposes a neurosensory account, highlighting a sensory pathway to anxiety. Based on accruing new evidence from our laboratory and other groups, we posit that the biological significance of a stimulus can be stored in the sensory system such that the affective value is decoded as soon as the input registers with the sensory brain, paralleling and often preceding limbic- based threat evaluation. As one of the first operations in the cognitive stream, biased sensory perception of threat can then influence downstream processes, directly or indirectly contributing to a variety of cognitive and emotional anomalies observed in anxiety. Representing one of the first lines of research on basic sensory processing of threat in anxiety, this program would provide new insights into basic threat analysis and anxiety genesis, and thus help to innovate clinical treatment for anxiety disorders. Towards that end, this proposal will employ a cognitive-affective neuroscience approach to firstly define sensory encoding of threat in anxiety with two conceptual emphases: 1) to accentuate highly specialized sensory representations of individual threat subtypes, which could inform the neural basis for distinct and sometimes contradictory responses and reflexes to different threats, and account for the heterogeneous symptomology of anxiety disorders (Specific Aim 1); and 2) to evaluate threat perception of multi- and cross-modal (vs. unimodal) sensory input, which, by optimally simulating real-life sensory experience, holds great promise for revealing novel multifaceted and modality-specific sensory biases of threat in anxiety (Specific Aim 2). Secondly, the planned research will mechanistically specify the impact of initial perceptual bias to threat on subsequent emotional and cognitive processes, giving rise to various anxiety symptoms (in particular, negative interpretation, excessive social avoidance and selective attention to threat; Specific Aim 3). In six independent experiments, we will employ a unique and fully developed constellation of expertise and techniques (functional magnetic resonance imaging, fMRI; brain event- related potentials, ERPs; autonomic physiology; psychophysics; and anxiety assessment and provocation) to determine the neural underpinnings of sensory perception of threat and its behavioral consequences, varying as a function of anxiety. The project findings will create a body of knowledge that is likely to challenge the dominant limbic-centered conceptualization of anxiety, promoting a shift to a multi-system, multi-path theorization. PUBLIC HEALTH RELEVANCE: Anxiety disorders are the most common psychiatric illness, causing a great deal of devastation and suffering for the patients. However, the etiology of anxiety remains obscure. Traditional accounts for anxiety genesis typically implicate exaggerated amygdala reactivity as the primary mechanism, but the proposal here points to a novel alternative-a neurosensory model of anxiety. The proposed investigation will elucidate aberrant sensory representation of threat in the sensory brain and consequent threat perception bias in anxiety, which intensifies and perpetuates anxiety symptoms directly or indirectly via its impact on downstream information processing. As such, this research program will generate significant new insights into anxiety etiology and greatly contribute to clinical prevention and intervention of this illness.