A Neurosensory Account of Posttraumatic Stress Disorder

创伤后应激障碍的神经感觉学解释

基本信息

批准号：
10607183
负责人：
Wen Li
金额：
$ 39.23万
依托单位：
FLORIDA STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-01-01 至 2027-10-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10607183
关键词：
Advocate Agitation Amygdaloid structure Arousal Attenuated Behavior Behavioral Biological Assay Cephalic Clinical Cognitive Cues Detection Disease Disinhibition Down-Regulation Food Frequencies Fright Functional disorder Galvanic Skin Response Impairment Individual Investigation Memory Mental disorders Methodology Modality Noise Odors Output Participant Pathologic Pathology Patients Perception Phase Physiological Play Post-Traumatic Stress Disorders Prefrontal Cortex Reaction Time Regulation Rest Role Sensory Severities Stimulus Symptoms System Task Performances Testing Thalamic structure Up-Regulation active control affective neuroscience functional magnetic resonance imaging/electroencephalography innovation insight neural neuropsychiatric disorder neuroregulation neurosensory novel recruit response sensory cortex sensory integration sensory mechanism vigilance visual search

项目摘要

ABSTRACT Posttraumatic stress disorder (PTSD) is a common and highly disabling psychiatric disorder. Pathological fear is at the core of PTSD, and accordingly, neural accounts of PTSD have emphasized dysfunctions of the fear system (primarily, the amygdala-prefrontal-cortex fear circuit). Motivated by recent expansion of the fear circuit into the sensory cortex and growing recognition of rich sensory anomalies in PTSD, we have proposed a neurosensory account of PTSD, integrating basic sensory cortical pathophysiology with amygdala-prefrontal-cortex dysfunctions into a tripartite Sensory-Prefrontal-cortex-Amygdala (SPA) pathology of PTSD. Specifically, we propose that PTSD involves sensory cortical disinhibition that exacerbates amygdala-prefrontal-cortex dysfunctions, which in turn impairs top-down regulation, resulting in a vicious cycle of SPA pathology. The current project seeks to elucidate three specific mechanisms in this account: (Aim 1) Intrinsic (tonic) sensory cortical disinhibition that maintains SPA pathology in PTSD (by sustaining intrinsic amygdala- prefrontal-cortex dysfunctions with excessive spontaneous sensory afferents); (Aim 2) Novelty-related (phasic) sensory cortical disinhibition that drives SPA pathology in PTSD (by heightening sensory cortical reactivity to novel cues, resulting in excessive sensory output that drives amygdala-prefrontal-cortex dysfunctional response to novelty); and (Aim 3) Threat-related sensory cortical disinhibition that exacerbates SPA pathology and threat biases in PTSD (by heightening sensory cortical reactivity to threat stimuli and synergizing with biased sensory cortical encoding of threat, resulting in excessive, threat-laden sensory output that exacerbates amygdala-prefrontal-cortex dysfunctional response to threat). This project will leverage our fully-developed cutting-edge methodology of simultaneous EEG-fMRI combined with non-invasive neuromodulation (specifically, transcranial alternating current stimulation/tACS to enhance sensory cortical inhibition), thereby permitting integrative spatial and temporal assays and causal inferences. This mechanistic investigation has the potential to break new theoretical ground by revealing a tripartite SPA pathology of PTSD. Clinically, identification of sensory cortical disinhibition as a fundamental mechanism that is malleable (via neuromodulation) would open a new line of mechanism- based treatments for PTSD.

抽象的创伤后应激障碍（PTSD）是一种常见且高度致残的精神疾病。病理性的恐惧是 PTSD 的核心，因此，PTSD 的神经解释强调了恐惧系统（主要是杏仁核-前额叶-皮层恐惧回路）。受近期扩张的推动随着恐惧回路进入感觉皮层，并且越来越多地认识到 PTSD 中丰富的感觉异常，我们提出了 PTSD 的神经感觉解释，将基本的感觉皮层病理生理学与杏仁核-前额皮质-杏仁核功能障碍变成三重感觉-前额皮质-杏仁核 (SPA) PTSD 的病理学。具体来说，我们认为 PTSD 涉及感觉皮质去抑制，加剧杏仁核-前额叶-皮质功能障碍，进而损害自上而下的调节，导致处于 SPA 病理的恶性循环中。当前的项目旨在阐明该帐户中的三个具体机制：（目标 1）内在（补品）感觉皮质去抑制，维持 PTSD 中的 SPA 病理（通过维持内在的杏仁核- 前额皮质功能障碍伴有过度的自发感觉传入）；（目标 2）新颖性相关（阶段性）感觉皮质去抑制，驱动 PTSD 中的 SPA 病理学（通过增强感觉皮质对新线索的反应，导致过度的感觉输出，驱动杏仁核前额皮质对新鲜事物的反应失调）；（目标 3）与威胁相关的感觉皮质去抑制加剧 PTSD 中的 SPA 病理学和威胁偏见（通过增强感觉皮层对威胁的反应性）刺激和与威胁的有偏见的感觉皮层编码协同作用，导致过度的、充满威胁的感觉输出加剧杏仁核前额皮质对威胁的功能失调反应）。这项目将利用我们完全开发的同步脑电图-功能磁共振成像相结合的尖端方法通过非侵入性神经调节（特别是经颅交流电刺激/tACS 增强感觉皮层抑制），从而允许综合空间和时间分析以及因果分析推论。这项机制研究有可能通过揭示一个新的理论基础来开辟新的理论基础 PTSD 的三方 SPA 病理学。临床上，将感觉皮质去抑制鉴定为可延展的基本机制（通过神经调节）将开辟一条新的机制路线—— PTSD 的基础治疗。