White Matter Changes and Mild TBI: Emotional and Autonomic Consequences

描述(由申请人提供) 轻度创伤性脑损伤(轻度脑损伤)经常发生在作战人员中，并与高达85%的伤者的情绪症状有关，创伤后应激障碍症状、焦虑、抑郁和情绪波动的发生率很高。脑外伤可能导致脑白质损伤，白质完整性的改变与行为改变相关，即使是非常轻微的脑损伤。轻度创伤性脑损伤的患者也有更高的不光彩退伍率和药物滥用。其中许多行为变化与额叶-皮质下网络的改变有关，而额叶-皮质下网络严重依赖于白质连接。在这项拟议的CDA-2研究中，我们的主要目标是开始了解轻微脑外伤后可能导致情绪障碍的特定神经机制。轻度颅脑损伤的白质损伤并不是同质的，但在情绪障碍的发展中可能特别重要的两个白质结构是钩状束和内囊前肢(在30%-40%的轻度脑损伤患者中受损)。在其他人群中，这些结构的变化与恐惧的情绪处理和对压力源的自主反应改变有关。此外，根据文献显示左右半球在情绪处理上的差异，白质损伤可能存在偏侧效应。因此，这些通路的破坏可能会增加一个人发展异常情绪功能的脆弱性，包括与创伤后应激障碍相关的症状。这项研究的目的是比较PTSD但没有脑外伤的患者与有和没有情绪症状的脑损伤患者。这可能是这些人群的基本情绪反应不同，这些差异可能有助于阐明导致情绪和情绪行为变化的机制。为在这一人群中观察到的一系列慢性情绪症状找到神经学和损伤特有的基础可能具有治疗意义，因此，对患有与非损伤相关的创伤后应激障碍的患者的治疗可能具有不同的疗效(例如，暴露疗法可能对与伤害无关的创伤后应激障碍患者效果最好)。为了验证这些假设，我们从我们的OEF/OIF多发创伤诊所招募了40名轻度脑外伤患者和40名对照组(20名患有创伤后应激障碍，但没有脑外伤)。我们将使用情感神经科学方法测试情绪行为，并根据该人群中报告的症状特征选择指标。具体地说，我们将评估内囊钩束和前肢白质损伤与生理上(例如，在观看高强度正面和负面配值的视觉场景时的惊吓反应)和认知(识别6种主要情绪，包括强度和唤醒等级)的变化之间的关系。为了确定白质通路的完整性，我们将使用高分辨率扩散加权成像(DWI)和扩散张量成像(DTI)及相关分析技术。除了帮助更好地了解脑外伤导致情绪障碍的基础外，该项目还将为应聘者提供神经成像方法的技术方面的培训，包括前后处理技术、感兴趣区域识别、用于准确识别白质的程序选择和使用以及数据分析。此外，这些技能将与应聘者的心理生理学和神经心理学背景相结合。此外，候选人将获得有关患有创伤性脑损伤的退伍军人的研究经验，同时提供有价值的数据，帮助我们了解这些患者面临的一些残疾和挑战。

DESCRIPTION (provided by applicant) Mild traumatic brain injury (mild TBI) occurs frequently in combat personnel and has been linked to complaints of emotional symptoms in up to 85% of those injured, with high rates of PTSD symptoms, anxiety, depression, and mood swings. TBI may cause cerebral white matter injury and changes in white matter integrity have been correlated with behavioral changes even with very mild TBI. Patients with mild TBI also have higher rates of dishonorable discharge from the military, as well as substance abuse. Many of these behavioral changes are associated with alterations in frontal-subcortical networks, which are heavily dependent on white matter connectivity. Our primary goal in this proposed CDA-2 investigation is to begin to understand the specific neurological mechanisms that may underlie emotional dysfunction following mild TBI. White matter injury in mild TBI is not homogenous, but two white matter structures that may be of particular importance in the development of emotional disorders are the uncinate fasciculus and the anterior limb of the internal capsule (injured in between 30-40% of patients with mild TBI). Changes in these structures in other populations have been linked to fearful emotional processing and altered autonomic responses to stressors. Further, based on the literature demonstrating right-left hemispheric differences in emotional processing, there may be laterality effects of white matter injury. Thus damage to these pathways may increase a person's vulnerability to the development of abnormal emotional functioning, including symptoms associated with PTSD. A goal of this study is to compare patients with PTSD but no TBI to patients with TBI with and without emotional symptoms. It may be that the basic emotional responses of these populations are different and that these differences may help elucidate the mechanism accounting for these changes in mood and emotional behaviors. Finding a neurological and injury-specific basis for the constellation of chronic emotional symptoms observed in this population could have treatment implications such that the treatment of patients with versus those without injury induced PTSD may have different efficacies (e.g., exposure therapy may work best for the patients with non-injury related PTSD). To test these hypotheses, we will recruit 40 subjects with mild TBI from our OEF/OIF poly-trauma clinic and 40 controls (20 with PTSD but no TBI). We will test emotional behaviors using an affective neuroscience methodology with indicators chosen based on the reported symptom profiles in this population. Specifically, we will assess the relationship between white matter injury in the uncinate fasciculus and anterior limb of the internal capsule and alteration of affective response physiologically (e.g., startle response while viewing high intensity positively and negatively valenced visual scenes) and cognitively (identification of the 6 primary emotions including ratings of intensity and arousal). To determine the integrity of white matter pathways, we will use high-resolution diffusion weighted imaging (DWI) with diffusion tensor imaging (DTI) and related analysis techniques. In addition to helping better understand the basis of TBI induced emotional disorders, this project will provide the candidate with training in the technical aspects of neuroimaging methods including pre and post-processing techniques, region of interest identification, program choice and usage to accurately identify white matter, and data analyses. Further, these skills will be integrated with the candidate's psychophysiology and neuropsychology backgrounds. In addition, the candidate will gain experience with research on veterans with traumatic brain injury, while providing valuable data that will help us understand some of the disabilities and challenges faced by these patients.