Cognitive control-related brain activation in veterans and service members with PTSD

创伤后应激障碍(PTSD)的神经生物学基础是 假设涉及调节恐惧条件反射的神经系统功能障碍， 情绪控制和自主神经系统的中枢调节。然而，功能性的 检测认知技能的神经成像研究也开始识别大脑中的 其他神经系统。在最近的一篇文章中，我们报道了一项功能 磁共振成像(FMRI)认知控制范式，箭头任务，这是 用于检查创伤后应激症状(PTSS)的升高和以下脑功能 持久自由行动/伊拉克自由/新黎明行动(OEF/OIF/OND)战斗 部署。这些发现与神经资源从更高水平转移一致 并支持创伤后应激障碍(PTSD)的概念模型 这强调了过度觉醒和中枢儿茶酚胺的变化所起的作用。上一首 使用执行功能fMRI范式研究创伤后应激障碍和创伤后应激障碍，包括我们的 都受到了一个或多个限制，例如 不符合创伤后应激障碍完全诊断标准的参与者，使用功能磁共振成像范式 结合执行功能和症状激发程序，检查 没有战斗创伤的样本，以及未能充分筛查或控制合并症 抑郁症和轻度创伤性脑损伤(MTBI)等疾病。当前应用程序 提出了一项设计良好的功能神经成像研究，将重点放在与战斗有关的 在实施此类控制措施时应对创伤后应激障碍。 拟议的研究的主要目标将是检查与创伤后应激障碍相关的变化 与认知控制相关的神经功能及其激活与神经功能的关系 临床症状、日常功能(即睡眠、心理社会功能)和外部措施 执行职能。这项研究的另一个重要目标是检查 静息状态的功能连接，并将其与认知控制过程中的激活联系起来。它 将对OEF/OIF/OND退伍军人进行横断面研究，并确认 创伤后应激障碍诊断，将包括一个创伤暴露对照组和一个额外的 对照组检测PSTD合并mTBI。共病 抑郁症也将被解决，所有参与者都将完成正式评估 对于创伤后应激障碍和相关情况(例如，药物滥用)，包括临床医生协助的创伤后应激障碍 将DSM-5和其他创伤后应激障碍通用数据元素作为关键衡量标准。该项目的 持续时间将为三年半，并将获得与事件相关的休息状态 FMRI数据、解剖成像以及来自症状和结果测量的数据来表征 样本。我们假设创伤后应激障碍患者的认知控制参与 与箭头任务激活模式相关联，相对于比较组， 将包括异模联结皮质内的激活减少和在 其他涉及情绪调节和初级感觉或运动功能的结构。图像 还将执行回归分析，这些激活更改预计将 与连接异常、临床症状、认知障碍和 日常运作。

The underlying neurobiology of posttraumatic stress disorder (PTSD) has been hypothesized to involve dysfunction within neural systems that mediate fear conditioning, emotional control, and central regulation of the autonomic nervous system. However, functional neuroimaging research examining cognitive skills has also started to identify alterations within other neural systems. In a recent publication we reported preliminary results from a functional magnetic resonance imaging (fMRI) cognitive control paradigm, the Arrows Task, which was used to examine elevated posttraumatic stress symptoms (PTSS) and brain function following Operation Enduring Freedom/Operation Iraqi Freedom/New Dawn (OEF/OIF/OND) combat deployment. Those findings were consistent with a neural resource shift away from higher-level association areas and supported a conceptual model of posttraumatic stress disorder (PTSD) that emphasizes the role of hyperarousal and alterations in central catecholamines. Previous investigations using executive function fMRI paradigms to study PTSD and PTSS, including our own research, have all suffered from one or more limitations such as the enrollment of participants who did not meet full diagnostic criteria for PTSD, use of fMRI paradigms that combined both executive function and symptom provocation procedures, examination of samples without combat trauma, and the failure to screen or control adequately for co-morbid disorders such as depression and mild traumatic brain injury (mTBI). The current application proposes a well-designed functional neuroimaging study that would focus on combat-related PTSD while implementing such controls. The proposed study's primary objective would be to examine PTSD-related changes in neural function associated with cognitive control and the relationship between this activation and clinical symptoms, daily functioning (i.e., sleep, psychosocial function), and external measures of executive functions. Another important aim of this study would be to examine alterations in resting state functional connectivity and to relate these to activation during cognitive control. It would be conducted as a cross sectional study of OEF/OIF/OND veterans with a confirmed PTSD diagnosis and would include a trauma exposed comparison group and an additional comparison group to examine PSTD in combination with co-morbid mTBI. Co-morbid depression would also be addressed and all participants would complete a formal assessment for PTSD and related conditions (e.g., substance abuse), including the Clinician-Assisted PTSD Scale for DSM-5 and other PTSD common data elements as key measures. The project's duration would be three and a half years and it would acquire event-related and resting state fMRI data, anatomical imaging, and data from symptom and outcome measures to characterize the sample. We hypothesize that the engagement of cognitive control in patients with PTSD will be associated with an Arrows Task activation pattern which, relative to the comparison groups, will include decreased activation within heteromodal association cortex and increases within other structures involved in emotional regulation and primary sensory or motor functions. Image regression analyses would also be performed and these activation changes are expected to be related to abnormal connectivity, clinical symptoms, cognitive impairment, and problems with daily functioning.