An fMRI Study of Deployment-Related TBI in Veterans and Service Members

描述(由申请人提供)： 项目背景：据估计，10%至23%的持久自由行动/伊拉克自由行动/新黎明行动(OEF/OIF/OND)战斗人员发生了创伤性脑损伤(TBI)，导致认知、神经行为和情感后遗症和残疾。慢性期的诊断很困难，因为常规的脑成像不敏感，急性损伤记录可能不可用，而且创伤后应激障碍(PTSD)的症状经常与脑外伤的症状重叠。先进的脑功能成像技术有可能识别弥散张量成像(DTI)上白质(WM)束的破坏、在功能磁共振成像(FMRI)中执行认知任务时大脑激活的变化，以及从静息状态fMRI测量的功能连接性(FC)的变化。基本原理：我们报告了DTI指标的脑损伤与退伍军人在执行空间冲突解决(SPCR)任务时大脑激活的增加有关，我们和其他人将这一发现归因于WM损伤对神经资源的需求增加。创伤后应激障碍症状的严重程度对减少任务相关的大脑活动有相反的作用。这项研究的局限性包括对急性颅脑损伤的限制，缺乏对创伤后应激障碍的明确诊断工具，以及我们的发现可能是针对SPCR任务的。我们也没有评估静息状态FC。目的：研究轻度颅脑损伤的BLAST和非BLAST机制，增加一项可能对弥漫性WM损伤更敏感的复杂注意的fMRI任务，测量默认模式网络(DMN)的FC，探索无mTBI病史的退伍军人冲击波暴露的影响，并进行综合分析，以检查多模式脑成像与结果指标的关系。该项目将确定mTBI组和非TBI组的WM束损伤(DTI)、SPCR和注意任务期间的功能磁共振脑激活、静息状态下的连接性和功能、情绪和认知状态之间的关系。方法：对60例颅脑损伤(伤后3个月)和60例无冲击波暴露的非颅脑损伤以及20例有冲击波暴露史但无冲击波暴露的退伍军人和现役军人进行SPCR和复杂注意相关脑激活的研究。DTI将测量WM的完整性，而静息状态的fMRI将提供FC的测量。我们将评估认知、情绪和功能结果以达到目标，临床医生辅助的创伤后应激障碍量表将用于识别患有创伤后应激障碍的受试者。统计分析将整合多模式脑成像，以评估mTBI和PTSD在SPCR和注意任务以及FC中对大脑激活的贡献。大脑成像变量的阵列将被分析与认知、情绪和功能结果的关系。与退伍军人医疗保健的相关性：改善对慢性脑外伤的诊断，包括无脑外伤病史的冲击波暴露的影响，将有助于治疗计划并导致更早的转诊。有关机制的信息也可能建议对创伤性脑损伤和创伤后应激障碍的干预方法，并提供评估治疗反应的方法。

DESCRIPTION (provided by applicant): Project Background: Traumatic brain injury (TBI) is estimated to have occurred in 10 to 23% of Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) combatants, resulting in cognitive, neurobehavioral, and emotional sequelae and disability. Diagnosis in the chronic phase is difficult because conventional brain imaging is insensitive, acute injury records may be unavailable, and symptoms of posttraumatic stress disorder (PTSD) often overlap with those of TBI. Advanced brain imaging of TBI could potentially identify disruption of white matter (WM) tracts on diffusion tensor imaging (DTI), alterations in brain activation while performing cognitive tasks during functional magnetic resonance imaging (fMRI), and changes in functional connectivity (FC) measured from resting state fMRI. Rationale: We reported that TBI indexed by DTI was related to increases in brain activation in Veterans while they performed a spatial conflict resolution (SPCR) task, a finding that we and others have attributed to increased demand upon neural resources due to WM injury. PTSD symptom severity had the opposite effect of reducing task-related brain activation. Limitations of this study included restriction to blast TBI, lack of a definitive diagnostic instrument for PTSD, and the possibility that our findings were specific to the SPCR task. We also did not evaluate resting state FC. Objectives: Study blast and non-blast mechanisms of mild TBI (mTBI), add an fMRI task of complex attention that is likely to be more sensitive to diffuse WM injury, measure FC of the default mode network (DMN), explore the effects of blast exposure in Veterans without a history of mTBI, and perform a comprehensive analysis to examine multi-modality brain imaging in relation to outcome measures. This project will determine relationships between WM tract injury (DTI), fMRI brain activation during SPCR and attention tasks, connectivity during resting state fMRI, and functional, emotional, and cognitive status in mTBI and non-TBI groups. Methods: Study SPCR and complex attention-related brain activation in 60 mTBI (e 3 months post-injury) and 60 non-TBI without blast exposure, as well as 20 Veterans and Service Members with a history of blast exposure but not TBI. DTI will measure WM integrity and resting state fMRI will provide a measure of FC. We will assess cognitive, emotional, and functional outcome to address the Aims and the Clinician Assisted PTSD Scale will be used to identify subjects with PTSD. Statistical analyses will integrate the multimodality brain imaging to evaluate the contributions of mTBI and PTSD to brain activation on the SPCR and attention tasks, as well as FC. The array of brain imaging variables will be analyzed in relation to cognitive, emotional, and functional outcome. Relevance to Veterans' Healthcare: Improved diagnosis of chronic mTBI, including effects of blast exposure without a history of TBI, would facilitate treatment planning and lead to earlier referral. Information about mechanisms may also suggest intervention approaches for TBI and PTSD and provide methods for assessing treatment response.