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: 9052726
• 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 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9052726
• 关键词: Accounting; Affective; Anterior; Arousal; Behavior; Behavioral; Cerebrum; Chronic; Clinic; Data; Data Analyses; Development; Diffusion Magnetic Resonance 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; Structure; Substance abuse problem; Symptoms; Techniques; Testing; Therapeutic; Training; Trauma; Traumatic Brain Injury; Veterans; Visual; Work; affective neuroscience; anxiety symptoms; associated symptom; base; combat; disability; emotional behavior; emotional symptom; experience; injured; interest; mild traumatic brain injury; 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） 轻度的脑损伤（轻度TBI）经常发生在战斗人员中，并且与多达85％受伤的人的情绪症状的抱怨有关，PTSD症状，焦虑症，抑郁症和情绪波动率高。 TBI可能会导致脑白质损伤，即使与非常轻微的TB​​I，白质完整性的变化也与行为变化相关。轻度TBI的患者还具有较高的不可分散的军队排放率以及滥用毒品。这些行为变化中的许多与额叶网络的变化有关，这些变化在很大程度上取决于白质连接性。我们在此提出的CDA-2调查中的主要目标是开始了解可能是轻度TBI后情绪功能障碍的特定神经系统机制。轻度TBI中的白质损伤不是同质的，但是在情绪障碍发展中可能特别重要的两个白质结构是内部胶囊的筋膜和前肢（30-40％的轻度TBI患者受伤）。其他人群中这些结构的变化与可怕的情绪处理和对压力源的自主性反应改变有关。此外，基于表现出右半球情绪处理中右半球差异的文献，白质损伤可能会产生横向作用。因此，对这些途径的损害可能会增加一个人对异常情绪功能发展的脆弱性，包括与PTSD相关的症状。这项研究的目的是比较患有PTSD的患者，但没有TBI的TBI患者有或没有情绪症状。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这些机制，以解决情绪和情感行为的这些变化。找到在该人群中观察到的慢性情绪症状星座的神经系统和特定于损伤的基础，可能具有治疗意义，以便对患者的治疗与没有损伤引起的PTSD的患者的治疗可能具有不同的效率（例如，暴露疗法可能最适合与非伤口相关的患者患有与非伤口相关的患者的PTSD患者）。 为了检验这些假设，我们将招募来自OEF/OIF聚创伤诊所的轻度TBI受试者和40个对照（20个具有PTSD，但没有TBI）。我们将使用情感神经科学方法论测试情绪行为，并根据该人群中报告的症状特征选择的指标。具体而言，我们将评估内部胶囊的肠道上的白质损伤与情感反应的变化在生理学上的改变（例如，在观看高强度和负面的视觉场景时，震荡反应）和认知（识别6个主要情绪）。为了确定白质途径的完整性，我们将使用具有扩散张量成像（DTI）和相关分析技术的高分辨率扩散加权成像（DWI）。除了帮助更好地了解TBI诱发的情绪障碍的基础外，该项目还将为候选人提供在神经成像方法的技术方面的培训，包括预处理和后处理技术，感兴趣的识别区域识别，程序选择和用法，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融为一体。此外，候选人将获得对脑部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，这将有助于我们了解这些患者所面临的某些残疾和挑战。