White Matter Changes and Mild TBI: Emotional and Autonomic Consequences

白质变化和轻度 TBI：情绪和自主神经后果

• 批准号: 8426005
• 负责人: John B Williamson
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8426005
• 关键词: Accounting; Affective; Anterior; Anxiety; Arousal; Behavior; Behavioral; Cerebrum; Chronic; Clinic; Data; Data Analyses; Development; Diffusion Magnetic Resonance Imaging; Diffusion weighted imaging; Disease; Emotional; Emotional disorder; Emotions; Functional disorder; Goals; Handedness; Human Resources; Injury; Internal Capsule; Investigation; Knowledge; Lead; Left; Limb structure; Link; Literature; Mental Depression; Methodology; Methods; Military Personnel; Moods; Nervous System Trauma; Neurologic; Neuropsychology; Pathway interactions; Patients; Persons; Population; Post-Traumatic Stress Disorders; Process; Psychophysiology; Recruitment Activity; Reporting; Research; Resolution; Solutions; Structure; Substance abuse problem; Symptoms; Techniques; Testing; Therapeutic; Training; Trauma; Traumatic Brain Injury; Veterans; Visual; Work; affective neuroscience; base; combat; disability; experience; injured; interest; neuroimaging; outcome forecast; programs; response; skills; stressor; white matter; white matter change; white matter injury

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.

描述（由申请人提供） 轻度创伤性脑损伤（轻度 TBI）经常发生在战斗人员中，高达 85% 的受伤人员与情绪症状有关，其中 PTSD 症状、焦虑、抑郁和情绪波动的发生率很高。 TBI 可能会导致脑白质损伤，即使是非常轻微的 TBI，白质完整性的变化也与行为变化相关。轻度创伤性脑损伤患者退伍和滥用药物的比例也较高。许多行为变化都与额叶皮质下网络的改变有关，而额叶皮质下网络在很大程度上依赖于白质连接。我们在这项拟议的 CDA-2 调查中的主要目标是开始了解轻度 TBI 后可能导致情绪功能障碍的特定神经机制。轻度 TBI 中的白质损伤不是同质的，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束和内囊前肢（30-40% 的轻度 TBI 患者受伤）。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的改变有关。此外，根据证明左右半球在情绪处理方面存在差异的文献，白质损伤可能存在偏侧效应。因此，这些通路的损害可能会增加一个人情绪功能异常的脆弱性，包括与创伤后应激障碍相关的症状。本研究的目的是将患有 PTSD 但没有 TBI 的患者与患有或不患有情绪症状的 TBI 患者进行比较。这些人群的基本情绪反应可能是不同的，这些差异可能有助于阐明解释情绪和情绪行为变化的机制。找到在该人群中观察到的一系列慢性情绪症状的神经学和损伤特异性基础可能会对治疗产生影响，例如，对患有与没有损伤引起的 PTSD 的患者进行治疗可能会产生不同的疗效（例如，暴露疗法可能对非损伤相关的 PTSD 患者最有效）。 为了检验这些假设，我们将从我们的 OEF/OIF 多发伤诊所招募 40 名患有轻度 TBI 的受试者和 40 名对照者（20 名患有 PTSD，但没有 TBI）。我们将使用情感神经科学方法来测试情绪行为，并根据该人群报告的症状特征选择指标。具体来说，我们将评估钩束和内囊前肢的白质损伤与生理上情​​感反应的改变（例如，观看高强度正价和负价视觉场景时的惊吓反应）和认知上（识别 6 种主要情绪，包括强度和唤醒等级）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）与扩散张量成像（DTI）和相关分析技术。除了帮助更好地了解 TBI 引起的情绪障碍的基础之外，该项目还将为候选人提供神经影像方法技术方面的培训，包括预处理和后处理技术、感兴趣区域识别、程序选择和使用以准确识别白质以及数据分析。此外，这些技能将与候选人的心理生理学和神经心理学背景相结合。此外，候选人还将获得对患有创伤性脑损伤的退伍军人进行研究的经验，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。