PTSD and the Default Network: Developing Imaging Phenotypes

描述（由申请人提供）： 这个职业发展建议的目的是探索默认网络（DN）上创伤后应激障碍（PTSD）的神经影像学相关性，作为培训PTSD神经影像学研究职业候选人的工具。候选人将使用三种独立和互补的方法来检查PTSD对DN的影响，通过评估一组患有该疾病的受试者的静息状态功能连接、任务诱导的失活和白色完整性的变化，与适当的对照组进行比较。候选人是由以前的研究在这些领域的平民创伤后应激障碍的指导;鉴于这项研究的潜力，这是至关重要的调查这些发现在退伍军人群体。 候选人的长期职业目标是研究DN作为PTSD的潜在预后工具：预测创伤暴露后发生PTSD的风险，并制定衡量或预测治疗反应的指标。候选人的直接职业目标是使用此提案来学习在退伍军人临床神经影像学方面追求独立职业所需的研究技能。这个职业奖的中心假设是，PTSD对内侧前额叶皮层（MPFC）产生不利影响，这是DN的一个节点，进而导致网络水平的影响，导致PTSD的临床症状。 候选人将使用三个特定目标来评估该假设;与没有PTSD的退伍军人相比，患有战斗相关PTSD的退伍军人具有1）降低的静息状态功能性DN连接，2）增加的任务相关DN失活的幅度，和3）降低的连接DN区域的白色物质束的完整性。 为了实现这些目标，候选人将在一个跨学科指导小组的专家指导下进行精心的培训计划。这种方法是创新的，因为它探索了不同但互补的方法来评估DN，并且是重要的，因为它可能导致鉴定PTSD的可能生物标志物，具有许多潜在的应用，以改善我们的退伍军人的健康。这项提案的重点影响是，它追求研究，在候选人的培训服务，使一个年轻的调查员到VA的职业生涯中独立资助的创伤后应激障碍神经影像学研究。

DESCRIPTION (provided by applicant): The aim of this career development proposal is to explore neuroimaging correlates of Post-Traumatic Stress Disorder (PTSD) on the Default Network (DN), as a vehicle to train the candidate for a career in PTSD neuroimaging research. The candidate will use three separate and complementary means to examine the effects of PTSD on the DN, by evaluating changes in resting state functional connectivity, task-induced deactivations, and white matter integrity utilizing diffusion tensor imaging (DTI) in a group of subjects with the disorder for comparison with an appropriate control group. The candidate is guided by previous research in these areas in civilian PTSD; given the potential of this research it is critical to investigate these findingsin Veteran populations. The candidate's long-term career goal is to investigate the DN as a potential prognostic tool for PTSD: to predict those at risk for developing PTSD after trauma exposure and develop metrics to measure, or predict, treatment response. The candidate's immediate career goals are to use this proposal to learn the research skills needed to pursue an independent career in clinically informed neuroimaging in Veterans. The central hypothesis of this career award is that PTSD adversely affects the medial prefrontal cortex (MPFC), a node of the DN, which in turn leads to network-level effects that contribute to the clinical symptoms of PTSD. The candidate will evaluate this hypothesis using three Specific Aims; that Veterans with combat associated PTSD have 1) decreased resting state functional DN connectivity, 2) increased magnitude of task-associated DN deactivations, and 3) decreased integrity of white matter tracts connecting DN regions, compared to Veterans without PTSD. To accomplish these aims, the candidate will pursue a careful training plan under the expert tutelage of a transdisciplinary mentoring team. This approach is innovative, as it explores different yet complementary means to evaluate the DN, and is significant because it may lead to identification of possible biomarkers of PTSD with many potential applications to improve our Veterans' health. The focused impact of this proposal is that it pursues research in the service of the candidate's training, to bring a young investigator to the VA for a career in independently funded PTSD neuroimaging research.