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

补充：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: 10409301
• 负责人: JULIA MARIE STEPHEN
• 金额: $ 16.41万
• 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/10409301
• 关键词: Address; Affective Symptoms; Anterior; Attention; Attentional deficit; Auditory; Auditory area; Automobile Driving; Behavior; Biological Markers; Brain; Brain region; Combat Disorders; Complex; Control Groups; Data; Detection; Development; Electroencephalography; Employment; Event-Related Potentials; Executive Dysfunction; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impairment; Individual; Insula of Reil; Intervention; Lead; Life; Link; Magnetoencephalography; Measures; Mission; National Institute of Mental Health; Neurocognitive; Neurologic; Neurons; Participant; Patient Self-Report; Patients; Pattern; Performance; Pilot Projects; Play; Population; Post-Traumatic Stress Disorders; Prevalence; Process; Quality of life; Reporting; Research; Resolution; Rest; Risk; Risk Factors; Role; Sampling; Severities; Short-Term Memory; Source; Stimulus; Symptoms; Task Performances; Testing; United States National Institutes of Health; auditory stimulus; base; biomarker identification; cingulate cortex; cognitive function; combat; combat trauma; effective therapy; executive function; experience; innovation; neurocognitive test; neuroimaging; neuromechanism; novel; novelty processing; relating to nervous system; response; service member; side effect; spatiotemporal; success; sustained attention; temporal measurement; theories; trauma exposure

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.

对于创伤后应激障碍的更有效和更有针对性的治疗，还有大量未得到满足的需求 (创伤后应激障碍)。创伤后应激障碍在人群中的终生患病率很高，估计为6.7%。一个障碍是 开发更好的治疗方法是我们对创伤后应激障碍的神经机制缺乏了解，没有得到证实的 创伤后应激障碍的生物标志物。除了创伤后应激障碍的情感症状外，注意力缺陷也是持久的和相关的 直接影响到生活质量，破坏人际关系和就业。虽然很重要，但现在和过去 神经成像研究主要集中在对威胁刺激的注意力改变上。然而，不具威胁性 刺激在平民生活中每天都有体验，一些研究表明，对非刺激的神经反应 威胁性刺激在创伤后应激障碍中也会发生变化。另一项单独的研究表明，改变休息方式 网络也与创伤后应激障碍有关。基于静息连通性对神经元放电的影响 根据阈值，我们预计休息网络也在异常的任务诱发反应(如注意力)中发挥作用。 然而，目前的研究在很大程度上考察了任务诱发的反应或休息网络，而不是 连词。这一差距是一个重要的问题，因为了解大脑如何从休息状态转换到任务状态 有望在注意力分配中发挥重要作用。此应用程序的目标是利用 超高时空分辨率的脑磁图(MEG)检查静息状态网络和 使用听觉古怪(AOD)任务对中性的、新的听觉刺激的反应。中心假设是 与战斗相关的创伤后应激障碍患者的静息脑磁图将出现改变，这将影响正常的 在日常生活中对非威胁性刺激做出反应，这些联系将与创伤后应激障碍症状相关 严重度和注意措施。中心假设将通过三个具体目标进行检验：1)确定任务- 创伤后应激障碍患者听觉网络产生器诱发的波幅和潜伏期改变 通过AOD范例提供给非创伤后应激障碍战斗控制(CC)；2)识别与以下相关的静息脑磁图模式 创伤后应激障碍与CC。创伤后应激障碍和慢性精神障碍患者的注意表现差异可能与以下因素有关 静息神经振荡和3)考察静息网络、任务型神经 神经认知测试中的激活、症状严重程度和注意力表现。这种方法是创新的 因为它将利用脑磁图出色的时空分辨率来确定潜在的大脑网络 与新颖性和目标P3相关的处理相关联，然后将其与 休眠状态网络，将休眠状态网络功能和任务相关功能彼此链接，并 注意措施和症状严重程度。这项拟议的研究意义重大，因为目前的治疗方法是 创伤后应激障碍虽然有效，但也有已知的局限性，而且缺乏创伤后应激障碍的生物标志物。了解 创伤后应激障碍的显著和破坏性注意症状背后的病理生理学将最终指导 制定更有针对性和更有效的评估和治疗。