A Multi-Modal Investigation of Neurophysiological Deficits in PTSD

PTSD 神经生理缺陷的多模式研究

基本信息

批准号：
10392455
负责人：
Antonia Seligowski
金额：
$ 15.21万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10392455
关键词：
Address Anterior Aversive Stimulus Behavior Biological Assay Blood specimen Brain Complex Data Dorsal Electrodes Electroencephalogram Electromagnetics Emotional Emotions Estradiol Event Exhibits Frequencies Fright Goals Hormones Individual Investigation Lead 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 base brain circuitry cingulate cortex conditioned fear conditioning density emotion regulation experience improved individualized medicine men multimodality neural circuit neurophysiology paired stimuli personalized approach proliferative phase Menstrual cycle relating to nervous system response source localization temporal measurement tomography translational research program trauma exposure

项目摘要

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).

项目概要创伤后应激障碍 (PTSD) 是一种以神经回路为特征的衰弱性疾病潜在威胁和情绪处理以及月经周期在女性中的患病率是男性的两倍。创伤后应激障碍（PTSD）阶段与性别差异有关，但女性创伤后应激障碍（PTSD）的神经回路特征却很少。一致的发现是 PTSD 与背侧前扣带回静息状态活动增加有关皮层（dACC）和腹内侧前额叶皮层（vmPFC）活动减少，反映了夸大的情绪反应和情绪调节减弱也分别与创伤后应激障碍（PTSD）下降有关。 dACC 似乎是 theta 频率范围（4-7 Hz）内的功能连接。大脑活动，这与创伤后应激障碍有关；然而，之前没有研究探讨过基于θ的休息状态 dACC 和 vmPFC 活动，或 PTSD 中基于 θ 的 dACC-vmPFC 连接此外，没有先前的研究。除了静息状态赤字之外，还根据月经周期阶段检查了这些对女性的影响。条件反射研究表明，PTSD 与晚期正电位 (LPP) 振幅增加有关对恐惧刺激的反应，反映了夸张的情绪编码，同时也有明确的影响。月经周期阶段对 LPP 的影响，之前没有研究测试过这些对患有 PTSD 的女性的影响。这种神经回路的特征和月经周期阶段的调节作用代表了关键的差距了解女性如何经历更大的 PTSD 风险。为了解决这些未满足的需求，我们将通过测试对 PTSD 大脑回路采取多模式方法患有或不患有创伤后应激障碍（PTSD）的遭受创伤的女性的静息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 θ 的静息状态活动，以及然后，我们将通过测量 LPP 来探究与事件相关的缺陷。及其在恐惧调节过程中的潜在皮质来源最后，我们将收集雌二醇和黄体酮。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了解。使用最先进的生理方法，例如标准化低分辨率电磁法断层扫描 (sLORETA)、功率包络连接分析、具有源定位的 ERP 和血清利用高密度脑电图的时间分辨率，这项研究将提供更细致和更详细的分析。对患有创伤后应激障碍 (PTSD) 的女性恐惧回路缺陷的机械理解我们的总体目标与此直接一致。 NIMH 战略计划的目标 1：“定义复杂行为的机制。” 该提案将进一步阐明女性 PTSD 的神经生理回路和机制。利用先进的脑电图技术，这项研究最终将有助于改善创伤后应激障碍通过提高我们的理解和告知个性化方法（例如，刺激 vmPFC 调节 dACC 活动，根据月经周期阶段调整方法）。