A Multi-Modal Investigation of Neurophysiological Deficits in PTSD

PTSD 神经生理缺陷的多模式研究

• 批准号: 10597088
• 负责人: Antonia Seligowski
• 金额: $ 5.58万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2023-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10597088
• 关键词: Address; Anterior; Aversive Stimulus; Behavior; Biological Assay; Blood specimen; Brain; Complex; Data; Dorsal; Electrodes; Electroencephalography; Electromagnetics; Emotional; Emotions; Estradiol; Event; Exhibits; Frequencies; Fright; Goals; Hormones; Individual; Investigation; Learning; Luteal Phase; Measures; Menstrual cycle; Mentorship; Methods; Modeling; National Institute of Mental Health; Participant; Phase; Physiological; Population; Post-Traumatic Stress Disorders; Prefrontal Cortex; Progesterone; Research; Resolution; Rest; Risk; Role; Sampling; Scalp structure; Serum; Sex Differences; Signal Transduction; Source; Standardization; Stimulus; Strategic Planning; System; Techniques; Testing; Training; Woman; brain circuitry; cingulate cortex; comparison control; conditioned fear; conditioning; density; emotion regulation; experience; improved; individualized medicine; men; multimodality; neural; neural circuit; neurophysiology; paired stimuli; personalized approach; proliferative phase Menstrual cycle; response; source localization; temporal measurement; tomography; translational research program; trauma exposure

Project Summary Posttraumatic stress disorder (PTSD) is a debilitating condition characterized by altered neural circuitry underlying threat and emotion processing. PTSD is twice as prevalent in women than men, and menstrual cycle phase has been implicated in sex differences, but the neural circuitry of PTSD is poorly characterized in women. A consistent finding is that PTSD is associated with increased resting state activity of dorsal anterior cingulate cortex (dACC) and decreased activity of ventromedial prefrontal cortex (vmPFC), reflecting exaggerated emotional responding and dampened emotion regulation, respectively. PTSD is also associated with decreased functional connectivity in the theta frequency range (4-7 Hz). The dACC appears to be a generator of theta range brain activity, which has been implicated in PTSD; however, no prior research has probed theta-based resting state dACC and vmPFC activity, or theta-based dACC-vmPFC connectivity in PTSD. Further, no prior research has examined these effects in women based on menstrual cycle phase. In addition to resting state deficits, fear conditioning studies have shown that PTSD is associated with increased late positive potential (LPP) amplitudes in response to fearful stimuli, reflecting exaggerated emotional encoding. While there are well-established effects of menstrual cycle phase on the LPP, no prior research has tested these effects in women with PTSD. Characterization of this neural circuitry and the moderating role of menstrual cycle phase represent critical gaps in understanding how women experience greater risk for PTSD. To address these unmet needs, we will take a multi-modal approach to PTSD brain circuitry by testing resting state and event-related neurophysiological deficits in trauma-exposed women with and without PTSD. We will use high-density EEG to probe theta-based resting state activity of the dACC and vmPFC, as well as dACC-vmPFC functional connectivity in PTSD. We will then probe event-related deficits by measuring the LPP and its underlying cortical sources during fear conditioning. Finally, we will collect estradiol and progesterone to determine menstrual cycle phase and test its moderating effects on these phenomena. The applicant will learn to use state-of-the-art physiological methods such as standardized Low Resolution Electromagnetic Tomography (sLORETA), power envelope connectivity analyses, ERPs with source localization, and serum hormone assays. Using the temporal resolution of high-density EEG, this study will provide a more nuanced and mechanistic understanding of fear circuitry deficits in women with PTSD. Our overall goal is directly in line with Objective 1 of the NIMH’s Strategic Plan: “Define the Mechanisms of Complex Behaviors.” Specifically, the proposal will further elucidate the neurophysiological circuits and mechanisms underlying PTSD in women. By leveraging advanced EEG techniques, this study will ultimately contribute to the improvement of PTSD treatments by improving our understanding and informing individualized approaches (e.g., stimulation of the vmPFC to regulate dACC activity, adjusting approaches based on menstrual cycle phase).

项目摘要 创伤后应激障碍（PTSD）是一种衰弱的疾病，其特征是神经回路改变 潜在的威胁和情感处理。 PTSD在女性中的普遍是男性的两倍，月经周期是 性别差异中隐含了阶段，但PTSD的神经回路在女性中的特征很差。 一个一致的发现是，PTSD与背扣带回的静息状态增加有关 皮层（DACC）和腹前额叶皮层（VMPFC）的活性改善，反映了夸张的 情感反应和该死的情绪调节。 PTSD也与改进有关 Theta频率范围内的功能连通性（4-7 Hz）。 DACC似乎是Theta范围的发电机 大脑活动，已在PTSD中暗示；但是，尚无先前的研究证明基于theta的休息 PTSD中的状态DACC和VMPFC活动，或基于theta的DACC-VMPFC连接。此外，没有先前的研究 已经根据月经周期阶段检查了女性的这些影响。除了安息状态定义，恐惧 调节研究表明，PTSD与晚期积极电位（LPP）放大器的增加有关 为了回应可怕的刺激，反映了夸张的情感编码。虽然有良好的效果 在LPP上的月经周期阶段，没有先前的研究在PTSD女性中测试了这些影响。 这种神经回路的表征和月经循环阶段的调节作用代表临界差距 在了解女性如何经历PTSD风险更大的过程中。 为了满足这些未满足的需求，我们将通过测试采用多模式的方法来解决PTSD脑电路 患有和没有PTSD的静止状态和事件相关的神经生理缺陷。 我们将使用高密度脑电图来探测DACC和VMPFC的基于theta的静息状态活动，以及 PTSD中的DACC-VMPFC功能连接。然后，我们将通过测量LPP来探测事件相关的定义 及其在恐惧调节过程中的基本皮质来源。最后，我们将收集雌二醇和孕酮 确定月经周期阶段，并测试其对这些现象的调节作用。申请人将学习 使用最先进的物理方法，例如标准化低分辨率电子 断层扫描（Sloreta），功率信封连接分析，具有源定位的ERP和串行 使用高密度脑电图的临时分辨率，本研究将提供更细微的细微差别和 对PTSD女性的恐惧电路防御的机械理解。我们的总体目标直接符合 NIMH战略计划的目标1：“定义复杂行为的机制”。具体来说， 提案将进一步阐明女性PTSD的神经生理回路和机制。经过 利用高级脑电图技术，这项研究最终将有助于改善PTSD 通过提高我们的理解和告知个性化方法来治疗（例如，刺激 VMPFC调节DACC活性，根据月经周期阶段调整方法）。