Brain and Mental Health RECOVERY

描述(由申请人提供)： 创伤后应激障碍(PTSD)是一个重大的公共和退伍军人健康问题，给从阿富汗和伊拉克部署归来的多达20%的士兵带来巨大负担。认知和情感神经科学方法的证据表明，内侧额叶皮质(MFC)在恐惧处理和情绪调节过程中的功能障碍在创伤后应激障碍的病理生理学中处于中心地位。然而，这些证据中有很大一部分来自对几十年前战场上年纪较大的退伍军人的研究，以及相对昂贵的脑成像技术，这些技术在临床环境中的应用有限。对NeuRA参与疾病康复的机制知之甚少。本申请的总体目标是通过使用事件相关电位(ERP)的脑电(EEG)测量来推进研究脑功能的替代方法，事件相关电位(ERP)是一种便携技术，可以部署在真实世界的办公室环境中，并提供可靠的时间锁定刺激神经反应度量。我们最近的许多工作集中于MFC事件相关电位，反映了神经对威胁/危险的社会信号的反应，以及通过重新评估策略对负面情绪的认知、意志调节过程中的神经参与-这些过程与避免威胁/危险和情绪调节失调密切相关，这些都是创伤后应激障碍的标志症状。这项拟议的前瞻性、自然主义的纵向研究将评估和跟踪两项有效的ERP任务中的临床状态、轨迹和脑功能，这两项任务涉及威胁处理和情绪调节，涉及患有创伤后应激障碍的退伍军人(n=120)在部署期间的战斗创伤，以及具有类似战斗暴露水平的退伍军人(n=60)没有患上创伤后应激障碍(CEC)。此外，将在研究开始时、6个月后和12个月后进行全面的临床评估，包括密切跟踪治疗情况，以确定创伤后应激障碍的持久性或康复情况。在研究开始时、6个月和一年后，还将进行事件相关电位成像，以解决4个目标：1)与研究开始时的CEC相比，研究开始时PTSD患者在威胁感知和情绪调节过程中的神经生理功能特征；2)比较持续性PTSD患者和一年后康复和战斗暴露对照组(CEC)的神经生理功能；3)将神经生理功能的变化与PTSD症状学的变化联系起来；以及4)检查神经生理功能和PTSD症状学之间假设关系的临床和心理社会调节因素和调节因素。这项研究的结果将为创伤后应激障碍评估社会威胁和情绪调节信号的潜在大脑机制以及这种大脑功能障碍与创伤后应激障碍的维持和康复的临床相关性提供新的线索。这些知识对于确定适当的大脑目标以指导当前的干预措施和创新新的干预措施至关重要，目的是在我们返回的士兵中对创伤后应激障碍进行一级和二级预防。

DESCRIPTION (provided by applicant): Posttraumatic stress disorder (PTSD) is a major public and VA health concern and exerts substantial burden on as many as 20% of soldiers returning from deployment in Afghanistan and Iraq. Evidence of cognitive and affective neuroscience approaches suggest that the medial frontal cortex (MFC) dysfunction during fear processing and emotion regulation is central in the pathophysiology of PTSD. However, much of this evidence comes from studies of older veterans from combat theaters from decades ago, and from brain imaging techniques that are relatively expensive with limited translation to clinical settings. Little is known about the neura mechanism involved in recovery from the disorder. The overarching goal of the present application is to advance an alternative approach to the study of brain function through the use of electroencephalography (EEG) measures of event-related potentials (ERP), a portable technique that can be deployed in the 'real world' office setting and provides time-locked stimulus neural response metrics that are reliable. Much of our recent work focuses on MFC ERPs reflecting neural reactivity to social signals of threat/danger and neural engagement during cognitive, volitional regulation of negative affect through reappraisal strategies - processes tightly related to avoidance of threat/danger and dysregulated affect, hallmark symptoms of PTSD. The proposed prospective, naturalistic longitudinal study will assess and follow the clinical status, trajectory and brain function during two validated ERP tasks involving threat processing and emotion regulation in veterans with PTSD (n=120) related to their combat trauma during deployment and in veterans (n=60) with similar levels of combat exposure who did not develop PTSD (CEC). Moreover, comprehensive clinical assessments, including close tracking of treatment, will be conducted at study entry, 6 months later and 12 months later to ascertain persistence of or recovery from PTSD. ERP imaging will also occur at entry, 6 months and one year later in order to address 4 Aims: 1) Characterize neurophysiological function during threat perception and emotion regulation in PTSD patients compared to CECs at study entry; 2) Compare neurophysiological function of patients with persistent PTSD and patients who recover and combat-exposed controls (CEC), one year later; 3) Relate change in neurophysiological function to change in PTSD symptomatology; and 4) Examine clinical and psychosocial moderators and mediators of the hypothesized relationship between neurophysiological function and PTSD symptomatology. The findings of this study will shed new light on the brain mechanisms underlying disturbances in appraising social signals of threat and emotion regulation in PTSD and the clinical relevance of this brain dysfunction to the maintenance of and recovery from PTSD. Such knowledge is critically important to identifying the appropriate brain targets to guide current interventions and innovating new interventions, aimed at primary and secondary prevention of PTSD in our returning soldiers.