Neurophysiology and Neuroimaging of Mild Traumatic Brain Injury

描述（由申请人提供）： 随着在战斗中获得创伤性脑损伤（TBI）的返回士兵的数量持续上升，创伤性脑损伤（TBI）正在成为退伍军人管理局越来越关注的问题。然而，对于脑损伤的严重程度、所导致的神经病理学和随后的神经行为障碍之间的关系知之甚少。目前，我们仍然缺乏一个明确的TBI生物标志物，既对损伤的历史和/或存在敏感，又与损伤的严重程度成比例。因此，拟议研究的总体目标是通过验证用于TBI诊断的体内非侵入性生物标志物来满足这一需求。通过使用扩散张量成像（DTI），我们试图调查在丘脑和脑干特定的白色物质束的完整性，在确定一个潜在的一致的生物标志物TBI的希望。为了实现我们的目标，我们将招募72名因爆炸相关损伤而有轻度TBI病史的退伍军人，24名未受伤的对照组和24名颅外受伤的对照组。患者将根据创伤后应激障碍症状的严重程度、在战区的时间和战斗暴露进行匹配。患者还将完成丘脑和脑干的高分辨率DTI的3特斯拉MRI，以及量化萎缩和病变的结构成像。此外，为了评价脑干-丘脑-前额叶回路的功能完整性，将进行眼功能测试（注视、视觉引导扫视、反扫视）。认知、脑震荡后症状、情绪、焦虑和创伤后应激障碍症状将使用对轻度TBI敏感的一系列神经心理学测试进行评估。将分析数据以确定（a）丘脑投射纤维和（B）脑干纤维是否受到爆炸相关TBI的影响，并确定对这些纤维的损伤是否导致神经生理学和神经心理学损害。主要结果将确定该措施是否与返回的OIF/OEF退伍军人临床相关，以及这些方法是否有效评估和诊断继发性冲击伤所致轻度TBI。

DESCRIPTION (provided by applicant): PROJECT SUMMARY / ABSTRACT Traumatic brain injury (TBI) is becoming an increasing concern for the Veterans Administration, as the number of returning soldiers who have acquired a TBI in combat continues to rise. Still, little is known about the relationship between brain injury severity, resultant neuropathology, and subsequent neurobehavioral disability. At present, we still lack a clear biomarker of TBI that is both sensitive to the history and/or presence of injury, and one that scales with severity of injury. Therefore, the overall objective of the proposed research is to fill this need by validating an in vivo, non-invasive biomarker for TBI diagnosis. Through the use of diffusion tensor imaging (DTI), we seek to investigate the integrity of specific white matter tracts in the thalamus and brainstem, in the hopes of identifying a potential consistent biomarker of TBI. To accomplish our objectives, we will recruit a total of 72 veterans with a history of mild TBI due to blast-related injury, 24 non-injured controls and 24 extra-cranial injured controls. Patients will be matched for post traumatic stress disorder symptom severity, time in theater and combat exposure. Patients will also complete a 3 Tesla MRI with high resolution DTI of the thalamus and brain stem, and structural imaging to quantify atrophy and lesions. In addition, in order to evaluate the functional integrity of the brain stem-thalamic-prefrontal circuit, tests of oculomotor function (fixation, visually guided saccades, anti-saccades) will be administered. Cognition, post-concussive symptoms, mood, anxiety and post traumatic stress disorder symptoms will be evaluated using a battery of neuropsychological tests sensitive to mild TBI. The data will be analyzed to determine whether (a) thalamus projection fibers and (b) brain stem fibers are affected by blast-related TBI and determine whether damage to these fibers results in neurophysiologic and neuropsychological impairment. The primary outcome will determine whether this measure is clinically relevant in returning OIF/OEF veterans, and whether or not these methods are valid in assessing and diagnosing mild TBI due to secondary blast injury.