Neural Mechanisms of Attention in PTSD and Comorbid TBI

该项目将寻求使用创新的方法来描述PTSD中的注意力和抑制功能障碍。 心理学和神经影像学方法，并将重点关注一个尚未解答的核心问题：增加 PTSD中的注意力/抑制失败是由于无法持续地参与任务积极的认知 控制网络的大脑，或者更确切地说，他们是由于不适当的参与任务消极的大脑 与分心有关的网络因此，该项目将确定负责 PTSD的注意力中断，通过使用大脑活动的时空模式来预测 真实的时间，以及预测临床诊断和严重程度。该提案系统地探讨了持续的 注意力和抑制控制在恐惧刺激的背景下，以及在更中性的日常环境中， 使用由首席研究员开发的新型行为和功能磁共振成像方法。这一特点， 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， 生活，并将转化为治疗增强和改善神经认知为基础的干预措施。 该项目还将提供创伤后应激障碍的神经心理学、精神病学和神经影像学方面的培训。 这将有助于申请人的职业目标，成为一个全职的，完全资助的独立调查员 研究退伍军人面临的神经认知损伤，并允许申请人担任领导角色， 一位退伍军人事务部的科学家，并帮助培养下一代的研究人员。申请人完全致力于 扩展他的技能来改善退伍军人的生活。他打算无限期地在VA继续他的职业生涯。 设计：首先，以任务为基础的功能磁共振成像实验，研究神经信号 持续的注意力和抑制性控制缺陷。参与者（n=96）将 来自VA波士顿的RR&D TBI卓越中心-一个大型的，非常良好的行为特征 OEF/OIF退伍军人样本，患有不同程度的PTSD。第二，项目功能包括 静息功能磁共振成像数据的连接分析，包括多变量模式分析，在一个扩展的 TBI中心的人。 方法：第一组实验使用了一种新的连续执行任务和并发fMRI， 为了评估持续的注意力和抑制控制，以及情感和非情感的影响， 分心第二，扩大的参与者队列将接受MRI扫描，以检查静息状态 大脑核心注意力和抑制控制网络的功能连接。模式分类 功能连接的（解码）模型将潜在地揭示PTSD的神经生物学标志物。 目标：目标1。神经和行为特征持续的注意力和抑制缺陷， 创伤后应激障碍假设1A。PTSD+与PTSD-的持续注意力缺陷将因分心而加剧， 特别是情绪分散（中性和恐惧的面孔）。假设1B。持续的注意力缺陷， PTSD+ vs. PTSD-的特征是注意力分散增加（注意力分散模型），如不适当的 默认模式网络（走神）和面部特定大脑区域的参与 中性面孔干扰物，特别是恐惧面孔干扰物。假设1C。不受干扰， PTSD+与PTSD的持续注意力缺陷-将以未能持续参与任务为特征- 积极的大脑网络，包括显著性和背侧注意网络（耗尽模型）。目标2.审查 PTSD相关的内在功能性脑连接的改变，使用多变量模式分析（MVPA）。 假设2.创伤后应激障碍与1）突出网络和2）背侧网络的异常连接有关。 注意力网络，与注意力、抑制和情绪控制有关; 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。

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.