Sensory Perception of Threat in Anxiety

描述(由申请者提供)：焦虑的特征是对威胁的反应增强。然而，焦虑症的确切病因仍不清楚。与目前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，这一应用程序提出了一种神经感觉解释，强调了一条通往焦虑的感觉路径。基于我们实验室和其他研究小组积累的新证据，我们假设刺激的生物学意义可以存储在感觉系统中，这样一旦输入与感觉大脑登记，情感价值就会被解码，这与基于边缘的威胁评估平行并往往先于此。作为认知流中的首批操作之一，对威胁的有偏见的感觉随后会影响下游过程，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处理研究的第一线，将为基本威胁分析和焦虑产生提供新的见解，从而有助于创新焦虑症的临床治疗。为此，本提案将采用认知-情感神经科学的方法，首先定义焦虑中威胁的感觉编码，并强调两个概念上的重点：1)强调高度专业化的个体威胁亚型的感觉表征，这可以为对不同威胁的不同和有时相互矛盾的反应和反射提供神经基础，并解释焦虑症的不同症状(具体目标1)；2)评估多和跨模式(与单峰)感觉输入的威胁感知，通过优化模拟现实生活的感觉体验，极有希望揭示焦虑中威胁的新的多方面和特定形态的感觉偏差(具体目标2)。其次，计划中的研究将机械地规定最初对威胁的知觉偏差对随后的情绪和认知过程的影响，导致各种焦虑症状(特别是负面解读、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，我们将利用一系列独特和全面发展的专业知识和技术(功能磁共振成像、脑事件相关电位、自主神经生理学、心理物理学；以及焦虑评估和激发)来确定感觉威胁及其行为后果的神经基础，这些神经基础随焦虑而变化。该项目的发现将创造一个知识体系，可能会挑战占主导地位的以边缘为中心的焦虑概念化，推动向多系统、多路径理论化的转变。

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.