Essential Features of Neural Damage in Mild Traumatic Brain Injury

描述（由申请人提供）： 尽管防护装甲和紧急医疗干预使士兵能够在爆炸中幸存下来，但越来越多的退伍军人将因爆炸相关的脑损伤而致残。士兵们从战斗中返回时也会因创伤性战争事件造成心理残疾。与爆炸有关的脑损伤和创伤后精神病理学的个人的临床表现明显重叠，因此，爆炸性爆炸的直接后果的明确描述是复杂的心理创伤的情感和认知后遗症。无法清楚地证明提出脑损伤学的基础阻碍了创伤性脑损伤（TBI）有效治疗的发展和实施。因此，需要客观的测试，在爆炸相关的脑损伤神经损伤的基本特征，以推进临床护理。 到目前为止，很少有研究专门研究爆炸引起的神经损伤。在伊拉克自由行动和持久自由行动（OIF/OEF）部队的试点调查中，我们发现患有爆炸相关TBI（bTBI）的个体在两个大脑半球的侧额头皮部位之间表现出减少的脑电图（EEG）相位同步（Sponheim等人，Neuroimage，2011）。部署后精神病理学未解释同步性降低，并且与bTBI受试者额叶中白色物质束的结构完整性相关。我们还即将完成国防部资助的一项研究，该研究调查了使用EEG和弥散张量成像（DTI）测量来评估国民警卫队OIF/OEF样本中bTBI的功能和结构神经后果。到目前为止，我们已经研究了超过150名被分为bTBI、bTBI+PTSD、PTSD和对照组的个体，并发现了与bTBI相关的弥漫性白色物质异常的证据。 当前提案解决的问题是神经结构的测量（例如，DTI）和功能（EEG）在区分bTBI与创伤后精神病理学在退伍军人中的影响方面具有临床实用性，这些退伍军人被转诊到区域VA多发性创伤中心。因此，拟议项目的目标是验证神经功能和结构的措施，将bTBI的影响与在VA多发伤中心接受评估的退伍军人的创伤后精神病理学分开。具体目标1。我们将确定EEG和DTI指数是否区分bTBI和创伤后精神病理学的退伍军人谁筛选阳性TBI和被转介到地区VA多发伤中心。分析将包括测试bTBI和冲击TBI（iTBI）对神经指标的不同影响。我们假设，与仅患有创伤后精神病理学的个体相比，患有bTBI的个体将表现出大脑区域之间的EEG相位同步减少，并且具有低分数各向异性（FA）的白色体素的百分比更大（如DTI所测量的）。具体目标2。鉴于受轻度TBI（冲击波或撞击）影响的个体结局的可变性，我们将确定慢性EEG和白色物质异常如何预测TBI筛查阳性并被转诊至区域VA多发伤中心的退伍军人的长期功能。我们推测，在轻度TBI患者中，EEG和DTI指标的异常程度越大，功能障碍越严重。具体目标3。由于大脑对损伤的适应因个体而异，我们将进行分析，以确定神经损伤的风险基因是否介导TBI的数量和类型（爆炸，冲击）与慢性EEG和DTI异常之间的关联。我们假设ApoE 4等位基因与轻度脑外伤患者的神经指标异常程度更高有关。

DESCRIPTION (provided by applicant): Although protective armor and acute medical intervention allow soldiers to survive explosions, a growing number of veterans will have disability stemming from blast-related brain damage. Soldiers also return from combat with psychological disabilities caused by traumatic war events. The clinical presentations of individuals with blast-related brain damage and post-traumatic psychopathology markedly overlap and thus a clear description of the direct consequences of explosive blast is complicated by the emotional and cognitive sequelae of psychological trauma. The inability to clearly demonstrate the basis of presenting symptomatology impedes the development and implementation of effective treatments for traumatic brain injury (TBI). Objective tests that characterize the essential features of neural damage in blast-related brain injury are therefore required to advance clinical care. To date, very few studies have specificall investigated neural injury from blast. In a pilot investigation of Operation Iraqi Freedom and Operation Enduring Freedom (OIF/OEF) troops we found individuals with blast-related TBI (bTBI) exhibited diminished electroencephalography (EEG) phase synchronization between lateral frontal scalp sites of the two cerebral hemispheres (Sponheim et al., Neuroimage, 2011). Diminished synchrony was not accounted for by post-deployment psychopathology and was associated with the structural integrity of white matter tracts in the frontal lobes of bTBI subjecs. We are also near completion of a Department of Defense funded study investigating the use of EEG and Diffusion Tensor Imaging (DTI) measures to assess the functional and structural neural consequences of bTBI in a National Guard OIF/OEF sample. To date we have studied over 150 individuals divided into bTBI, bTBI+PTSD, PTSD, and control groups and found evidence of diffuse white matter abnormalities associated with bTBI. The question that the current proposal addresses is whether measures of neural structure (e.g., DTI) and function (EEG) have clinical utility in differentiating the effects of bTBI from post-traumatic psychopathology in veterans referred to a Regional VA Polytrauma Center. Hence, the goal of the proposed project is to validate measures of neural function and structure as means of separating the effects of bTBI from post-traumatic psychopathology in veterans being seen at a VA Polytrauma Center for evaluation. Specific Aim 1. We will determine whether EEG and DTI indices differentiate between bTBI and post- traumatic psychopathology in veterans who have screened positive for TBI and were referred to a Regional VA Polytrauma Center. Analyses will include testing for differential effects of bTBI and impact TBI (iTBI) on neural indices. We hypothesize that compared to individuals with only post-traumatic psychopathology, individuals with a bTBI will exhibit diminished EEG phase synchronization between brain regions and a greater percentage of white matter voxels with low fractional anisotropy (FA) as measured by DTI. Specific Aim 2. Given variability in the outcome of individuals affected by mild TBI (either blast or impact) we will determine how chronic EEG and white matter abnormalities predict long-term functioning in veterans who screened positive for TBI and were referred to a Regional VA Polytrauma Center. We hypothesize that greater abnormalities on EEG and DTI indices will be associated with functional impairment in subjects with mild TBI. Specific Aim 3. Because the adaptation of the brain to damage varies across individuals, we will carry out analyses to determine whether risk genes for neural injury mediate the association between the number and type (blast, impact) of TBI with the presence of chronic EEG and DTI abnormalities. We hypothesize that the ApoE ¿4 allele will be associated with greater abnormalities on neural indices in individuals who have sustained a mild TBI.