Neurobiology of Suicide Risk in Traumatic Brain Injury and Substance Abuse

项目摘要 努力了解创伤性脑损伤（TBI）、前额叶功能和 自杀意念迄今为止没有得出结论。原发性冲击波相关的TBI在返回时很常见。 退伍军人，似乎产生类似于弥漫性轴索损伤（DAI）的神经生理学变化。 支持TBI患者认知过程的脑神经回路中断可能导致 执行功能缺陷，包括解决问题和决策能力下降。此外，委员会认为， 患有TBI的退伍军人通常患有药物滥用的并发症，并且已经表明使用酒精和非法药物 药物可能进一步损害已知依赖于额叶皮层的执行介导功能。已经 提出这些功能缺陷可能导致认知僵化和心理困扰，因此可能 作为自杀风险的标志。这项研究建立在现有的额叶神经生物学模型的基础上。 功能，并将扩大我们的理解TBI相关的脑变化，通过应用功能磁 磁共振成像（fMRI）和扩散张量成像（DTI）技术。因此，我们将检查血液 扣带回和背外侧前额叶皮质内的氧水平依赖（BOLD）信号变化以及 作为TBI受试者的杏仁核，有和没有药物滥用史，以表征 这些信号模式相对于健康对照受试者改变（更高/更低）。我们将决定 通过DTI方法测量的白色物质微结构的测量在TBI受试者中是异常的， 与健康对照组相比，没有药物滥用史。我们亦会研究 BOLD信号变化与FA值降低和自杀意念之间的关系。最后，我们将测试 这一假设，减少FA和减少激活额区在物质滥用和非- 物质滥用TBI退伍军人组与自杀意念显著相关， 在创伤性脑损伤加药物滥用人群中会更强。我们认为，拟议的研究将影响退伍军人的 通过提供对自杀和TBI的神经生物学相关性的重要见解， 识别和治疗TBI行为后果的新方法。

Project Summary Efforts at understanding the neurobiological correlates of traumatic brain injury (TBI), prefrontal function and suicidal ideation have thus far provided inconclusive results. Primary blast-related TBI is common in returning veterans and appears to produce neurophysiological changes that resemble diffuse axonal injury (DAI). Disruptions in brain neural circuits that support cognitive processing in individuals with TBI may result in deficits in executive function including reduced problem solving and decision-making capacity. Moreover, veterans with TBI are often co-morbid for substance abuse and it has been shown that use of alcohol and illicit drugs can further compromise executive mediated functions known to depend on the frontal cortex. It has been proposed that these functional deficits may lead to cognitive rigidity and psychological distress and thus may serve as markers for suicidal risk. The proposed research builds on existing neurobiologic models of frontal function and will extend our understanding of TBI related brain changes by applying functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) techniques. Accordingly, we will examine blood oxygen level dependent (BOLD) signal changes within the cingulate and dorsolateral prefrontal cortices as well as the amygdala in TBI subjects, with and without a history of substance abuse, to characterize the nature of these patterns of signal change (higher/lower) in relation to healthy control subjects. We will determine whether measures of white matter microstructure, as measured by DTI methods, are abnormal in TBI subjects, with and without a history of substance abuse compared with healthy control subjects. We will also examine the relationship between BOLD signal changes and reduced FA values and suicidal ideation. Lastly, we will test the hypothesis that reduced FA and reduced activation in frontal regions in both substance abusing and non- substance abusing TBI veteran groups is significantly correlated with suicidal ideation, and that the correlation will be stronger for the TBI plus substance abuse cohort. We believe the proposed studies will impact veteran's health by providing important insights into the neurobiological correlates of suicide and TBI that may lead to new approaches for identification and treatment of behavioral consequences of TBI.