A Neurosensory Account of Posttraumatic Stress Disorder

摘要 创伤后应激障碍（PTSD）是一种常见的高度致残性精神疾病。病理 恐惧是创伤后应激障碍的核心，因此，创伤后应激障碍的神经帐户强调了功能障碍， 恐惧系统（主要是杏仁核-前额皮质恐惧回路）。由于最近的扩张， 恐惧回路进入感觉皮层，以及对PTSD中丰富的感觉异常的日益认识， 提出了一种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-前额叶-皮层功能障碍为三重感觉-前额叶-皮层-杏仁核（SPA） PTSD的病理学具体来说，我们认为创伤后应激障碍涉及感觉皮层去抑制， 加重杏仁核-前额叶皮层功能障碍，进而损害自上而下的调节， 陷入SPA病理学的恶性循环 目前的项目旨在阐明三个具体机制在这个帐户：（目的1）内在（滋补） 感觉皮层去抑制，维持创伤后应激障碍的SPA病理（通过维持内在杏仁核， 前额叶皮质功能障碍伴自发感觉传入过多）;（目的2）新奇相关 （阶段性）感觉皮层去抑制驱动创伤后应激障碍中的SPA病理（通过提高感觉皮层 对新线索的反应，导致过度的感觉输出，驱动杏仁核-前额叶皮层 对新奇事物的功能障碍反应）;和（目标3）与威胁相关的感觉皮层去抑制， 加剧了创伤后应激障碍中的SPA病理和威胁偏见（通过提高感觉皮层对威胁的反应性 刺激和协同与偏见的感觉皮层编码的威胁，导致过度的，充满威胁的 加重杏仁核-前额皮质对威胁的功能障碍反应的感觉输出）。这 该项目将利用我们完全开发的尖端方法，同时脑电图功能磁共振成像结合 使用非侵入性神经调节（特别是经颅交流电刺激/tACS， 增强感觉皮层抑制），从而允许整合的空间和时间分析和因果关系分析。 推论这种机制的调查有可能打破新的理论基础，揭示了一个 创伤后应激障碍的病理学在临床上，感觉皮层去抑制被认为是 一种可延展的基本机制（通过神经调节）将开辟一条新的机制路线- 创伤后应激障碍的基础治疗

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.