Supplement to: Examining the interplay between resting oscillations, novelty processing, and attention in PTSD

对创伤后应激障碍的更有效和更有针对性的治疗存在大量未满足的需求 （PTSD）。PTSD的终生患病率在人群中很高，估计为6.7%。一个屏障， 开发更好的治疗方法是我们缺乏对PTSD神经机制的理解，没有经过验证的 创伤后应激障碍的生物标志物除了PTSD的情感症状外，注意力缺陷也是持续的， 直接影响生活质量，破坏人际关系和就业。虽然重要，现在和过去 神经成像研究主要集中在对威胁性刺激的注意力改变上。然而，非威胁性 在平民生活中，每天都要经历刺激，一些研究表明，对非刺激的神经反应， 在创伤后应激障碍中，威胁性刺激也会改变。一项独立的研究表明， 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，我们预期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，目前的研究主要是研究任务诱发反应或静息网络，而不是两者。 合取这个差距是一个重大的问题，因为了解大脑如何从休息过渡到任务 预计将在注意力分配中发挥重要作用。本申请的目的是利用 脑磁图（MEG）检查静息状态网络的上级时空分辨率， 使用听觉古怪（auditory oddball，AOD）任务对中性的、新颖的听觉刺激的反应。核心假设是， 与战斗有关的PTSD患者会表现出休息MEG的改变，这将影响他们正确地 对日常生活中的非威胁性刺激做出反应，这些关联将与PTSD症状有关 严重性和注意力措施。中心假设将通过三个具体目标进行检验：1）确定任务- PTSD相关者听觉网络发生器的振幅和潜伏期的变化 非PTSD战斗控制（CC）通过AOD范式; 2）确定与 创伤后应激障碍与CC。PTSD和CC之间注意力表现的差异预计与以下因素有关： 静息神经振荡和3）检查静息网络之间的关系，基于任务的神经 激活、症状严重程度和神经认知测试中的注意力表现。方法是创新的 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 与新奇和目标P3相关的处理相关联，然后将联合收割机与以下评估相结合 静息状态网络，以将静息状态网络功能和任务相关功能彼此链接，并且 注意措施和症状严重程度。这项研究是重要的，因为目前的治疗方法 PTSD虽然有效，但具有已知的局限性，并且缺乏PTSD的生物标志物。了解 PTSD中突出的和破坏性的注意力症状的病理生理学将最终指导 发展更有针对性和更有效的评估和治疗。

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.