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

患有创伤后应激障碍 (PTSD) 的退伍军人和服役人员与认知控制相关的大脑激活

• 批准号: 10426231
• 负责人: Randall S. Scheibel
• 金额: --
• 依托单位: MICHAEL E DEBAKEY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426231
• 关键词: Address; Amygdaloid structure; Anterior; Area; Autonomic nervous system; Behavior Therapy; Bilateral; Biological; Brain; Catecholamines; Clinical; Clinical Trials; Cognitive; Common Data Element; Cross-Sectional Studies; DSM-V; Data; Development; Diagnosis; Differential Diagnosis; Disease; Emotional; Event; Exhibits; Failure; Freedom; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Health; Human Resources; Image; Impaired cognition; Impairment; Inferior; Inferior frontal gyrus; Insula of Reil; Investigation; Left; Lobule; Measures; Medial; Mediating; Mental Depression; Middle frontal gyrus structure; Modeling; Motor; Neurobiology; Neuronal Dysfunction; Neurophysiology - biologic function; Outcome Measure; Parietal; Participant; Pathway interactions; Patients; Pattern; Pharmacology; Post-Traumatic Stress Disorders; Prefrontal Cortex; Procedures; Prognosis; Publications; Recording of previous events; Regression Analysis; Regulation; Reporting; Research; Resources; Rest; Risk; Role; Sampling; Sensory; Severities; Sleep; Sleeplessness; Social Problems; Structure; Substance abuse problem; Symptoms; System; Temporal Lobe; Veterans; anatomic imaging; association cortex; blast exposure; cingulate cortex; cingulate gyrus; cognitive control; cognitive skill; combat; combat trauma; combat veteran; comorbid depression; comorbidity; comparison group; conditioned fear; daily functioning; design; diagnostic criteria; disability; effectiveness evaluation; emotion regulation; executive function; experience; imaging modality; mild traumatic brain injury; mortality; neuroimaging; neuroimaging marker; operation; participant enrollment; post-traumatic symptoms; psychosocial; relating to nervous system; service member; stress related disorder; symptom cluster; tool; trauma exposure; treatment trial

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.

创伤后应激障碍（PTSD）的潜在神经生物学一直是 假设在介导恐惧条件的神经系统中涉及功能障碍， 情绪控制和自主神经系统的中心调节。但是，功能性 神经影像学研究检查认知技能也已开始确定内部的变化 其他神经系统。在最近的出版物中，我们报告了功能性的初步结果 磁共振成像（fMRI）认知控制范式，箭头任务， 用于检查创伤后应激症状升高（PTSS）和大脑功能之后 持久自由/行动伊拉克自由/新黎明（OEF/OIF/OND）战斗 部署。这些发现与神经资源的转变一致 关联领域并支持创伤后应激障碍（PTSD）的概念模型 这强调了中央儿茶酚胺中高音和改变的作用。以前的 使用执行功能fMRI范式研究PTSD和PTSS的调查，包括我们 自己的研究都遭受了一个或多个限制，例如 不符合PTSD的完整诊断标准的参与者，使用fMRI范式的参与者 联合执行功能和症状挑衅程序，检查 没有作战创伤的样本，并且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。当前的应用程序 提出了一项精心设计的功能神经影像学研究，该研究将集中于战斗有关 实施此类控件时的PTSD。 拟议的研究的主要目标是检查与PTSD相关的变化 与认知控制相关的神经功能以及这种激活与这种激活之间的关系 临床症状，日常功能（即睡眠，社会心理功能）和外部措施 执行职能。这项研究的另一个重要目的是检查 静止状态功能连接性，并将它们与认知控制过程中的激活联系起来。它 将作为OEF/OIF/OND退伍军人的横截面研究，并确认 PTSD诊断，将包括一个外伤裸露的比较组和其他 比较组检查PSTD与Coborbid MTBI结合使用。合并 抑郁症也将被解决，所有参与者将完成正式评估 针对PTSD及相关条件（例如滥用药物），包括临床医生辅助PTSD DSM-5和其他PTSD共同数据元素作为关键度量的比例。项目 持续时间为三年半，它将获得与事件有关的静止状态 FMRI数据，解剖成像以及来自症状和结果指标的数据以表征 样本。我们假设认知控制在PTSD患者中的参与将 与箭头任务激活模式相关，该模式相对于比较组 将包括杂种缔合皮质内的激活减少，并增加 情绪调节以及主要感觉或运动功能涉及的其他结构。图像 还将进行回归分析，这些激活变化预计为 与异常连通性，临床症状，认知障碍以及问题有关 日常功能。