Neural Mechanisms of Attention in PTSD and Comorbid TBI

描述（由申请人提供）： 该项目将寻求使用创新的心理学和神经影像学方法来表征PTSD中的注意力和抑制功能障碍，并将重点关注一个尚未回答的核心问题：PTSD中注意力/抑制功能障碍的增加是由于无法持续参与大脑的任务积极认知控制网络，还是由于与分心相关的任务消极大脑网络的不适当参与？因此，这个项目将通过使用大脑活动的时空模式来预测真实的时间内的注意力缺失，以及识别负责PTSD中注意力中断的神经网络 以预测临床诊断和严重程度。该提案使用主要研究者开发的新型行为和功能磁共振成像方法，系统地探索了在恐惧刺激背景下以及更中性的日常背景下的持续注意力和抑制控制。PTSD中注意力和抑制控制的特征将有助于解释 这些人在日常生活中遇到的困难，并将转化为治疗增强和改善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，并允许申请人承担作为VA科学家的领导角色，并帮助培训下一代研究人员。申请人完全致力于扩大他的技能，以改善退伍军人的生活。他不打算无限期地在退伍军人事务部继续他的职业生涯。产品设计：首先，该项目包括一个基于任务的功能磁共振成像实验，研究PTSD患者持续注意力和抑制性控制缺陷的神经信号。参与者（n=96）将从VA波士顿的RR&D TBI卓越中心抽取-一个具有不同程度PTSD的OEF/OIF退伍军人的大型，行为特征非常良好的样本。第二，该项目包括静息功能磁共振成像数据的功能连接分析，包括多变量模式分析，在一组扩大的个人从TBI中心。方法：第一组实验使用了一种新的连续性能任务和并发功能磁共振成像，以评估持续的注意力和抑制控制，以及情感和非情感分心的影响。第二，扩大的参与者队列将接受MRI扫描，以检查大脑核心注意力和抑制控制网络的静息状态功能连接。功能连接的模式分类（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的PTSD。假设1A。创伤后应激障碍+与创伤后应激障碍-中的持续注意力缺陷将因注意力分散，特别是情绪分散（中性和恐惧的面孔）而加剧。假设1B。PTSD+与PTSD-中的持续注意力缺陷将以增加的分心（分心模型）为特征，如默认模式网络（走神）和与中性面部分心物（特别是恐惧面部分心物）相关的面部特异性脑区的不适当参与所反映的。假设1C。独立于分心，PTSD+与PTSD-中的持续注意力缺陷的特征在于未能持续地参与任务-积极的大脑网络，包括显著性和背侧注意力网络（耗尽模型）。目标二。使用多变量模式分析（MVPA）检查PTSD相关的内在功能性脑连接改变。 假设2.创伤后应激障碍将与1）显著性网络和2）背侧注意力网络中的异常连接相关，与注意力，抑制和情绪控制相关，以及3）默认模式网络，与走神和任务无关的想法相关。这些连接模式将可靠地预测PTSD的存在和严重程度。

DESCRIPTION (provided by applicant): 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 t 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.