Essential Features of Neural Damage in Mild Traumatic Brain Injury

描述(由申请人提供)： 尽管防护甲和紧急医疗干预使士兵们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残疾。士兵们从战斗中归来时，也会因战争创伤事件而导致心理残疾。与爆炸相关的脑损伤患者的临床表现与创伤后精神病理学明显重叠，因此，对爆炸的直接后果的清楚描述因心理创伤的情感和认知后遗症而变得复杂。无法清楚地展示症状学的基础阻碍了创伤性脑损伤(TBI)有效治疗的开发和实施。因此，为了推进临床护理，需要进行客观的测试，以表征爆炸相关脑损伤的神经损伤的基本特征。到目前为止，很少有研究专门研究爆炸造成的神经损伤。在对伊拉克自由行动和持久自由行动(OIF/OEF)部队的试点调查中，我们发现与爆炸相关的脑外伤(BTBI)患者在两个大脑半球的外侧额部头皮部位之间的脑电(EEG)相位同步减弱(Sponheim等人，NeuroImage，2011年)。同步性减弱没有被部署后的精神病理学所解释，而与bTBI受试者额叶白质束结构的完整性有关。我们还即将完成国防部资助的一项研究，该研究使用脑电和扩散张量成像(DTI)方法在国民警卫队OIF/OEF样本中评估bTBI的功能和结构神经后果。到目前为止，我们已经研究了150多名被分为bTBI、bTBI+PTSD、PTSD和对照组的个体，发现了与bTBI相关的弥漫性白质异常的证据。目前的建议解决的问题是，神经结构(例如，DTI)和功能(EEG)的测量在区分退伍军人中bTBI和创伤后精神病理学的影响方面是否具有临床实用价值，这些退伍军人转诊到地区退伍军人多处创伤中心。因此，拟议项目的目标是验证神经功能和结构的测量，以此作为将退伍军人中bTBI的影响与创伤后精神病理学分开的手段，以便在退伍军人多发创伤中心进行评估。具体目标1。我们将确定脑电波和DTI指标在脑损伤筛查呈阳性并被转诊至地区退伍军人多发创伤中心的退伍军人中，是否能区分bTBI和创伤后精神病理学。分析将包括测试bTBI和冲击性TBI(ITBI)对神经指标的不同影响。我们假设，与只有创伤后精神病理的个体相比，患有bTBI的个体将表现出大脑区域之间的脑电相位同步性减弱，以及DTI测量的具有低分数各向异性(FA)的更大比例的白质体素。具体目标2.考虑到受轻度脑外伤(冲击波或冲击波)影响的个体结局的差异性，我们将确定慢性脑电和脑白质异常如何预测脑损伤筛查呈阳性并被转诊至地区退伍军人管理局多发创伤中心的退伍军人的长期功能。我们假设，轻度脑外伤患者的脑电和DTI指数异常程度较大，与功能损害有关。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中介了脑损伤的数量和类型(冲击波、冲击波)与慢性EEG和DTI异常之间的关联。我们假设ApoE？4等位基因与持续轻度脑损伤的个体的神经指标的更大异常有关。

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.