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成像方法来表征PTSD的注意力和抑制功能障碍，并将重点放在一个中心未回答的问题上：PTSD中注意力/抑制失败的增加是由于无法始终如一地参与大脑的任务积极认知控制网络，或者更确切地说，它们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实时预测注意力缺失，从而识别导致创伤后应激障碍注意力障碍的神经网络。 以预测临床诊断和严重程度。该提案使用首席研究者开发的新的行为和功能磁共振成像方法，系统地探索了在可怕刺激的背景下以及在更中性的日常背景下的持续注意和抑制控制。创伤后应激障碍患者注意控制和抑制控制的这种特征将有助于解释 这些人在日常生活中遇到的困难，将转化为治疗增强和改进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，并允许申请者承担退伍军人科学家的领导角色，并帮助培训下一代研究人员。申请者完全致力于扩展自己的技能，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，该项目包括一个基于任务的功能磁共振实验，研究创伤后应激障碍患者持续注意和抑制性控制缺陷的神经特征。参与者(n=96)将从退伍军人事务部波士顿RR&D TBI卓越中心-一个行为特征极其良好的大型OEF/OIF退伍军人样本中挑选出来，这些退伍军人患有不同程度的创伤后应激障碍。其次，该项目包括对来自TBI中心的一组扩大的个体进行的静息fMRI数据的功能连通性分析，包括多变量模式分析。方法：第一组实验采用一种新的持续操作任务和并行功能磁共振成像，以评估持续注意和抑制控制，以及情感和非情感分心的影响。其次，一组扩大的参与者将接受核磁共振扫描，以检查大脑核心注意和抑制控制网络中休息状态的功能连接。功能连接的模式分类(解码)模型可能揭示创伤后应激障碍的神经生物学标记物。目的：目的1.创伤后应激障碍持续注意和抑制缺陷的神经学和行为学特征。假设1A。创伤后应激障碍+与创伤后应激障碍相比，持续的注意力缺陷会因分心，特别是情绪分心(中性和恐惧的面孔)而加剧。假设1B。创伤后应激障碍+与创伤后应激障碍--持续的注意力缺陷的特征将是更多的分心(分心模式)，这反映在默认模式网络(走神)的不适当参与以及与中性面孔干扰相关的特定脸部区域，特别是恐惧的面孔分心。假设1C。与分心无关，PTSD+与PTSD-的持续性注意力缺陷的特征是无法持续地参与任务积极的大脑网络，包括突出和背部注意网络(耗竭模型)。目的2.使用多变量模式分析(MVPA)检查与创伤后应激障碍相关的脑内在功能连接的改变。 假设2.创伤后应激障碍与1)显著网络和2)背侧注意网络中的异常连接有关，与注意、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创伤后应激障碍的存在和严重程度。

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.