TRANSFER Examining the interplay between resting oscillations, novelty processing, and attention in PTSD

转移 检查 PTSD 中静息振荡、新奇处理和注意力之间的相互作用

• 批准号: 10452084
• 负责人: JULIA MARIE STEPHEN
• 金额: $ 9.85万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10452084
• 关键词: TRANSFER; Examining; interplay; between; resting

There is a substantial unmet need for more effective and targeted treatments for posttraumatic stress disorder (PTSD). The lifetime prevalence of PTSD is high in the population at an estimated 6.7%. One barrier for developing better therapies is our lack of understanding of the neural mechanisms in PTSD, with no validated biomarkers for PTSD. In addition to the affective symptoms in PTSD, attention deficits are persistent and linked directly to quality of life, disrupting relationships and employment. While important, current and past neuroimaging studies have largely focused on altered attention to threatening stimuli. However, non-threatening stimuli are experienced daily in civilian life and a few studies have demonstrated that neural responses to non- threatening stimuli are also altered in PTSD. A separate line of research demonstrates that altered resting networks are also associated with PTSD. Based on the influence of resting connectivity on neuronal firing thresholds, we expect that resting networks also play a role in abnormal task-evoked responses (e.g. attention). However, current studies largely examine either task-evoked responses or resting networks, but not the two in conjunction. This gap is a significant problem, because understanding how the brain transitions from rest to task is expected to play an important role in attention allocation. The objective in this application is to utilize the superior spatio-temporal resolution of magnetoencephalography (MEG) to examine resting state networks and responses to neutral, novel auditory stimuli using the auditory oddball (AOD) task. The central hypothesis is that individuals with combat-related PTSD will show alterations in rest MEG that will impact the ability to properly respond to non-threatening stimuli in day-to-day life and these associations will be related to PTSD symptom severity and attention measures. The central hypothesis will be tested via three Specific Aims: 1) Identify task- induced changes in amplitude and latency of the auditory network generators in participants with PTSD relative to non-PTSD combat controls (CC) via the AOD paradigm; 2) Identify resting MEG patterns associated with PTSD versus CC. Differences in attention performance between PTSD and CC are expected to be related to resting neural oscillations and 3) Examine the relationship between resting networks, task-based neural activation, symptom severity, and attention performance on neurocognitive tests. The approach is innovative because it will harness the excellent spatio-temporal resolution of MEG to determine underlying brain networks associated with Novelty and Target P3-related processing and then will combine this with an assessment of resting state networks to link resting state network functioning and task-related functioning to each other and to attention measures and symptom severity. The proposed research is significant because current treatments for PTSD, while effective, have known limitations and biomarkers for PTSD are lacking. Understanding the pathophysiology underlying prominent and disruptive attention symptoms in PTSD will ultimately guide the development of more directed and effective assessment and treatment.

对创伤后应激障碍更有效、更有针对性的治疗的需求还有很大未得到满足 （创伤后应激障碍）。人群中 PTSD 的终生患病率很高，估计为 6.7%。一个障碍 开发更好的治疗方法是我们对 PTSD 的神经机制缺乏了解，没有经过验证的 PTSD 的生物标志物。除了 PTSD 的情感症状外，注意力缺陷也是持续存在且相互关联的 直接影响生活质量，扰乱人际关系和就业。虽然现在和过去都很重要 神经影像学研究主要集中在对威胁性刺激的注意力改变上。不过，不具威胁性 平民生活中每天都会经历刺激，一些研究表明，对非刺激的神经反应 创伤后应激障碍（PTSD）中威胁性刺激也会发生改变。另一项研究表明，改变休息方式 网络也与创伤后应激障碍有关。基于静息连接对神经元放电的影响 阈值，我们预计静息网络也在异常任务诱发反应（例如注意力）中发挥作用。 然而，目前的研究主要考察任务诱发反应或静息网络，而不是两者 连词。这种差距是一个重大问题，因为了解大脑如何从休息状态过渡到任务状态 预计在注意力分配中发挥重要作用。该应用程序的目标是利用 脑磁图 (MEG) 的卓越时空分辨率可检查静息状态网络和 使用听觉奇怪（AOD）任务对中性的、新颖的听觉刺激做出反应。中心假设是 患有与战斗相关的创伤后应激障碍 (PTSD) 的人会表现出静息 MEG 的变化，这将影响正确处理问题的能力 对日常生活中的非威胁性刺激做出反应，这些关联与 PTSD 症状有关 严重程度和注意措施。中心假设将通过三个具体目标进行测试：1）确定任务- 诱发 PTSD 相关参与者听觉网络发生器振幅和延迟的变化 通过 AOD 范式实现非 PTSD 战斗控制 (CC)； 2) 识别与相关的静息 MEG 模式 PTSD 与 CC。 PTSD 和 CC 之间注意力表现的差异预计与 静息神经振荡 3) 检查静息网络、基于任务的神经网络之间的关系 神经认知测试中的激活、症状严重程度和注意力表现。该方法具有创新性 因为它将利用 MEG 出色的时空分辨率来确定潜在的大脑网络 与Novelty和Target P3相关的处理相关联，然后将其与评估结合起来 静息状态网络将静息状态网络功能和任务相关功能相互连接起来 注意措施和症状严重程度。拟议的研究意义重大，因为目前的治疗方法 PTSD 虽然有效，但也有其局限性，并且缺乏 PTSD 的生物标志物。了解 PTSD 中突出和破坏性注意力症状背后的病理生理学将最终指导 制定更直接、更有效的评估和治疗。