Neural Mechanisms of Attention in PTSD and Comorbid TBI

该项目将寻求用创新的方法来表征创伤后应激障碍患者的注意和抑制功能障碍。 心理学和神经成像方法，并将集中在一个中心悬而未决的问题：增加 无法始终如一地参与任务积极认知导致的创伤后应激障碍患者的注意/抑制失败 大脑的控制网络，或者更确切地说，它们是由于任务负性大脑的不适当参与 与分心有关的社交网络？因此，该项目将确定负责以下任务的神经网络 创伤后应激障碍中的注意力障碍：通过使用脑活动的时空模式来预测创伤后应激障碍患者的注意力缺失 实时，以及预测临床诊断和严重程度。该提案系统地探索了可持续的 在恐惧刺激的背景下，以及在更中性的日常背景下，注意和抑制控制， 使用首席研究人员开发的新的行为和功能磁共振方法。这一特征 创伤后应激障碍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 生活，并将转化为治疗增强和改进的神经认知为基础的干预。 该项目还将提供创伤后应激障碍的神经心理学、精神病学和神经成像方面的培训。 这将有助于申请人的职业目标，成为一名全职、全额资助的独立调查员 研究退伍军人面临的神经认知损伤，并允许申请者担任领导角色 一名退伍军人事务部科学家，并帮助培训下一代研究人员。申请者完全致力于 扩展他的技能以改善退伍军人的生活。他打算无限期地在退伍军人管理局继续他的职业生涯。 设计：首先，该项目由一个基于任务的功能磁共振实验组成，该实验研究神经信号 创伤后应激障碍患者的持续注意力和抑制控制缺陷。参与者(n=96)将是 来自弗吉尼亚州波士顿的RR&D TBI卓越中心-一家行为特征极其良好的大型企业 患有不同程度创伤后应激障碍的OEF/OIF退伍军人样本。第二，该项目包括功能 静态fMRI数据的连通性分析，包括多变量模式分析，在扩展的集合中 来自TBI中心的个人。 方法：第一组实验使用了一种新的持续操作任务和并发fMRI，在 以评估持续注意和抑制性控制，以及情感和非情感的影响 让人分心。其次，扩大的参与者队列将接受核磁共振扫描，以检查休息状态 大脑的核心注意和抑制控制网络中的功能连接。模式分类 (解码)功能连接的模型可能会揭示创伤后应激障碍的神经生物学标志。 目标：目标1.持续注意和抑制缺陷的神经学和行为学特征 创伤后应激障碍。假设1A。与PTSD-相比，PTSD+的持续注意力缺陷会因分心而加剧，而且 尤其是情绪分散(中性和恐惧的脸)。假设1B。持续的注意力缺陷 创伤后应激障碍+与创伤后应激障碍--表现为分心增加(分心模式)，表现为不适当 默认模式网络(走神)和面孔相关脑区的参与 中性的脸会让人分心，尤其是恐惧的脸会让人分心。假设1C。不受干扰， 创伤后应激障碍+与创伤后应激障碍的持续注意力缺陷的特征是无法始终如一地从事任务- 积极的大脑网络，包括突出和背侧注意网络(耗竭模型)。目标2.检查 使用多变量模式分析(MVPA)研究与创伤后应激障碍相关的脑内在功能连通性的改变。 假设2.创伤后应激障碍与1)突起网络和2)背部的异常连接有关 与注意、抑制和情绪控制相关的注意网络和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 创伤后应激障碍的存在和严重程度。

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.