Neural Mechanisms of Attention in PTSD and Comorbid TBI

PTSD 和共病 TBI 中注意力的神经机制

• 批准号: 8774107
• 负责人: Michael Esterman
• 金额: --
• 依托单位: VA BOSTON HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2018-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8774107
• 关键词: Affective; Afghanistan; Attention; Attentional deficit; Behavioral; Biological Neural Networks; Boston; Brain; Brain region; Center for Translational Science Activities; Classification; Clinical; Cognitive; Cognitive deficits; Collaborations; Data; Development; Diagnostic; Dorsal; Emotional; Face; Facial Injuries; Failure; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Goals; Impairment; Individual; Intervention; Iraq; Leadership; Life; MRI Scans; Maintenance; Measures; Memory; Methods; Mind; Modeling; Nature; Neurobiology; Neurocognitive; Outcome; Participant; Patient Self-Report; Pattern; Performance; Post-Traumatic Stress Disorders; Principal Investigator; Procedures; Process; Quality of life; Research; Research Personnel; Resources; Rest; Risk Factors; Role; Sampling; Scientist; Severities; Stimulus; Symptoms; Task Performances; Testing; Therapeutic; Thinking; Time; Training; Training Programs; Translating; Trauma; Treatment Efficacy; Veterans; base; career; clinical Diagnosis; cognitive control; cohort; daily functioning; distraction; emotion regulation; fusiform face area; improved; innovation; mindfulness; neuroimaging; neuromechanism; neuropsychological; next generation; novel; psychologic; public health relevance; relating to nervous system; research study; skills; social; spatiotemporal; standard care; stress disorder; sustained attention

This project will seek to characterize attentional and inhibitory dysfunction in PTSD using innovative psychological and neuroimaging methods, and will focus on a central unanswered question: are increased attentional/inhibitory failures in PTSD driven by an inability to consistently engage task-positive cognitive control networks of the brain, or rather are they due to inappropriate engagement of task-negative brain networks associated with distraction? Thus, this project will identify the neural networks responsible for attentional disruption in PTSD, by using spatiotemporal patterns of brain activity to predict attentional lapses in real time, as well as to predict clinical diagnosis and severity. The proposal systematically explores sustained attention and inhibitory control in the context of fearful stimuli, as well as in more neutral, everyday contexts, using novel behavioral and fMRI methods developed by the principal investigator. This characterization of attentional and inhibitory control in PTSD will help explain difficulties that these individuals have in everyday life, and will be translatable to therapeutic augmentation and improved neurocognitive-based interventions. The project will also provide training in neuropsychological, psychiatric, and neuroimaging aspects of PTSD. This will facilitate the applicant's career goal to become a full-time, fully-funded independent investigator researching the neurocognitive injuries facing veterans, and allow the applicant to assume a leadership role as a VA scientist and to help train the next generation of researchers. The applicant is wholly committed to expanding his skills to better the lives of veterans. He intends to continue his career within the VA indefinitely. DESIGN: First, the project consists of a task-based fMRI experiment, which investigates the neural signature of sustained attention and inhibitory control deficits in individuals with PTSD. Participants (n=96) will be drawn from a RR&D TBI Center of Excellence at VA Boston- a large, extremely well-behaviorally characterized sample of OEF/OIF veterans with varying degrees of PTSD. Second, the project includes functional connectivity analyses of resting fMRI data, including multivariate pattern analyses, in an expanded set of individuals from the TBI Center. METHODS: The first set of experiments uses a novel continuous performance task and concurrent fMRI, in order to assess sustained attention and inhibitory control, and the effects of both affective and non-affective distractions. Second, an expanded cohort of participants will undergo MRI scans to examine resting state functional connectivity in core attentional and inhibitory control networks of the brain. Pattern classification (decoding) models of functional connectivity will potentially reveal neurobiological markers of PTSD. OBJECTIVES: Aim 1. Neurally and behaviorally characterize sustained attention and inhibitory deficits in PTSD. Hypothesis 1A. Sustained attention deficits in PTSD+ vs. PTSD- will be exacerbated by distraction, and emotional distraction in particular (neutral and fearful faces). Hypothesis 1B. Sustained attention deficits in PTSD+ vs. PTSD- will be characterized by increased distraction (distraction model) as reflected by inappropriate engagement of the default mode network (mind-wandering) and face-specific brain regions associated with neutral face distractors, and in particular, fearful face distractors. Hypothesis 1C. Independent of distraction, sustained attention deficits in PTSD+ vs. PTSD- will be characterized by failure to consistently engage task- positive brain networks, including the salience and dorsal attention networks (depletion model). Aim 2. Examine PTSD-related alterations in intrinsic functional brain connectivity, using multivariate pattern analysis (MVPA). Hypothesis 2. PTSD will be associated with abnormal connectivity in the 1) Salience network and 2) Dorsal attention network, associated with attentional, inhibitory and emotional control and 3) Default mode network, associated with mind-wandering and task-unrelated thoughts. These connectivity patterns will reliably predict the presence and severity of PTSD.

该项目将寻求利用创新方法来描述 PTSD 中的注意力和抑制功能障碍。 心理学和神经影像学方法，并将重点关注一个未解答的核心问题：增加 创伤后应激障碍 (PTSD) 患者的注意力/抑制失败是由于无法持续参与任务积极认知而导致的 大脑的控制网络，或者更确切地说，它们是由于任务消极大脑的不适当参与造成的 网络与分心有关？因此，该项目将确定负责的神经网络 PTSD 中的注意力中断，通过使用大脑活动的时空模式来预测 PTSD 中的注意力缺失 实时，以及预测临床诊断和严重程度。该提案系统地探讨了可持续 在恐惧刺激以及更中性的日常环境中的注意力和抑制控制， 使用由主要研究者开发的新颖的行为和功能磁共振成像方法。这种表征 PTSD 中的注意力和抑制控制将有助于解释这些人在日常生活中遇到的困难 生命，并将转化为治疗增强和改善的基于神经认知的干预措施。 该项目还将提供创伤后应激障碍（PTSD）的神经心理学、精神病学和神经影像学方面的培训。 这将有助于申请人实现成为全职、资金充足的独立调查员的职业目标 研究退伍军人面临的神经认知损伤，并允许申请人担任领导角色 弗吉尼亚州科学家并帮助培训下一代研究人员。申请人完全致力于 扩展他的技能以改善退伍军人的生活。他打算无限期地继续在退伍军人管理局的职业生涯。 设计：首先，该项目包括基于任务的功能磁共振成像实验，该实验研究神经特征 PTSD 患者持续注意力和抑制控制缺陷的研究。参与者 (n=96) 将是 来自 VA 波士顿的 RR&D TBI 卓越中心 - 一个大型的、行为特征极其良好的中心 患有不同程度 PTSD 的 OEF/OIF 退伍军人样本。二、项目包括功能 静息功能磁共振成像数据的连通性分析，包括多变量模式分析，在一组扩展的 来自 TBI 中心的个人。 方法：第一组实验使用新颖的连续性能任务和并发功能磁共振成像， 为了评估持续注意力和抑制控制，以及情感和非情感的影响 干扰。其次，更多的参与者将接受核磁共振扫描来检查静息状态 大脑核心注意力和抑制控制网络的功能连接。图案分类 功能连接的（解码）模型将有可能揭示 PTSD 的神经生物学标记。 目标：目的 1. 从神经和行为上表征持续注意力和抑制缺陷 创伤后应激障碍。假设1A。 PTSD+ 与 PTSD- 相比，持续的注意力缺陷会因分心而加剧，并且 尤其是情绪分心（中立和恐惧的面孔）。假设1B。持续注意力缺陷 PTSD+ 与 PTSD- 的特点是分心增加（分心模型），如不适当的行为所反映 默认模式网络（走神）和与面部相关的特定大脑区域的参与 中性的面部干扰因素，特别是可怕的面部干扰因素。假设1C。不受干扰， PTSD+ 与 PTSD- 相比，持续注意力缺陷的特点是无法持续参与任务 - 积极的大脑网络，包括显着性和背侧注意力网络（耗尽模型）。目标 2. 检查 使用多变量模式分析 (MVPA) 发现与 PTSD 相关的内在功能性大脑连接的改变。 假设 2. PTSD 将与 1) 突显网络和 2) 背侧网络的异常连接相关 注意网络，与注意力、抑制和情绪控制相关，3）默认模式网络， 与走神和与任务无关的想法有关。这些连接模式将可靠地预测 PTSD 的存在和严重程度。