Brain changes underlying emotional and executive alterations in TBI

TBI 中情绪和执行能力改变背后的大脑变化

• 批准号: 10454825
• 负责人: Damon G Lamb
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10454825
• 关键词: Affect; Amygdaloid structure; Animal Model; Back; Behavioral; Brain; Brain region; Characteristics; Chronic; Cognitive; Communities; Conflict (Psychology); Data; Development; Disease; Disease remission; Disinhibition; Emotional; Emotional disorder; Emotions; Employment; Evaluation; Family; Functional Magnetic Resonance Imaging; GABA Receptor; Goals; Happiness; Health; Health Services Administration; High Prevalence; Individual; Injury; Insula of Reil; Intervention; Investigation; Knowledge; Limbic System; Literature; Magnetic Resonance; Magnetic Resonance Spectroscopy; Measurement; Measures; Mediating; Memory; Neurotransmitters; Norepinephrine; Outcome; Participant; Pathology; Patient Self-Report; Patients; Pattern; Performance; Pharmacotherapy; Physiological; Population; Post-Traumatic Stress Disorders; Predisposition; Prefrontal Cortex; Prevalence; Quality of life; Recovery; Rehabilitation therapy; Reporting; Research; Research Training; Resources; Role; Selective Serotonin Reuptake Inhibitor; Serotonin; Short-Term Memory; Signal Transduction; Signs and Symptoms; Social outcome; Symptoms; System; Testing; Theoretical model; Translational Research; Treatment Efficacy; Veterans; Veterans Health Administration; Visual; Work; base; blood oxygen level dependent; career; cognitive task; combat veteran; common symptom; comorbidity; design; diagnostic biomarker; effective therapy; emotion dysregulation; emotional experience; emotional symptom; executive function; experience; frontal lobe; functional decline; gamma-Aminobutyric Acid; improved; in vivo; inhibitor; innovation; interest; mild traumatic brain injury; military veteran; negative affect; personalized medicine; post-traumatic symptoms; receptor; reuptake; service member; social relationships; therapy development; visual stimulus

The primary goal of this proposal is to elucidate the possible mechanistic basis of emotional disorders, particularly posttraumatic stress disorder, after mild traumatic brain injury. Problem: Posttraumatic stress disorder (PTSD) is common in military Veterans and often causes chronic suffering including damaging social relationships, employment prospects, health, and overall happiness of those who experience it. Mild traumatic brain injury (mTBI) is a frequent preceding injury and the relationship between injury characteristics associated with mTBI and emotional dysregulation disorders such as PTSD remains unclear, with mixed findings reported in the literature. mTBI can damage important connections between brain regions, especially brain regions critical for emotional experience. Veterans who have suffered one or more mTBIs also are more likely to have other psychiatric conditions, and they also have worse health and social outcomes. Many of these poor outcomes are due to emotional dysregulation. Individuals who have suffered a mTBI or who have PTSD often show changes in brain function in emotional and executive brain regions. Even when their performance on executive tasks is still normal, the underlying brain regions show altered functional relationships including increased activity. Interpretation of these functional changes presents challenges, however. In other populations, these sorts of findings are often associated with pathology or are leading indicators of functional decline. Further, such activity may reflect differences in the capacity to adaptively manage cognitive and emotional resources. When performing emotional tasks, individuals with PTSD show increased activity in emotional brain regions. This may be due in part to reduced executive capacity or to increased demands placed on executive capacity by an overactive emotional system, possibly mediated by dysfunctional neurotransmitter systems. Notably, PTSD is associated with a reduction in the receptors of and the levels of the brain's primary inhibitory neurotransmitter, GABA. Similarly, GABA is reduced after a TBI and this change is associated with a reduced ability to forget fearful memories and to regulate emotions. This overlap in brain changes may suggest a linkage between injury characteristics associated with mTBI and the development of PTSD. Preliminary Work: Consistent with our theoretical model, our pilot data demonstrate damage in limbic and prefrontal connectivity is related to symptoms of PTSD in patients with mTBI. Further, we showed that injury characteristics of mTBI affect performance on emotional tasks. Finally, we demonstrated feasibility for each of the magnetic resonance measures and tasks that we will use in the proposed research. Plan: The proposed investigation will examine the relationship between two key brain networks, limbic (emotional) and prefrontal, which are dysfunctional in individuals with emotional dysregulation and the function of which may be altered after a mTBI. The proposed investigation is also designed to evaluate how GABA mediates these alterations. To test these relationships and changes, we will use functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy (MRS) to measure regional task-dependent brain activity and regional GABA levels in combat Veterans. We will measure these factors during emotion and cognitive tasks previously reported to be altered in patients with PTSD. We predict that the pattern of activity in executive and emotional brain regions will show changes in activity that relate to PTSD symptoms and to GABA levels. These relationships have not been reported in the literature. If there is a linkage between functional connectivity after mTBI, PTSD and regional GABA levels, there may be potential personalized treatment options that could be harnessed to enact positive changes in these systems and alleviate suffering.

这个提议的主要目标是阐明情绪的可能的机械基础 精神障碍，特别是创伤后应激障碍，在轻度创伤性脑损伤后。 问题：创伤后应激障碍（PTSD）在退伍军人中很常见， 痛苦，包括破坏社会关系，就业前景，健康和整体幸福感， 轻度创伤性脑损伤（mTBI）是一种常见的先行损伤， 与mTBI相关的损伤特征和情绪失调障碍（如PTSD）之间的关系 目前尚不清楚，文献中报告的结果不一。mTBI可能会损坏重要的连接 尤其是对情绪体验至关重要的大脑区域。经历过苦难的老兵们 一个或多个mTBI也更有可能患有其他精神疾病，他们的健康状况也更差 和社会成果。许多这些不良结果是由于情绪失调。 患有mTBI或PTSD的人通常会在情绪方面表现出大脑功能的变化。 和执行大脑区域。即使他们在执行任务上的表现仍然正常， 大脑区域显示出改变的功能关系，包括增加的活动。解释这些 然而，职能变化带来了挑战。在其他人群中，这类发现通常 与病理学相关，或者是功能衰退的主要指标。此外，这种活动可能反映了 适应性管理认知和情感资源能力的差异。当执行 在情感任务中，PTSD患者的大脑情感区域活动增加。这可能是由于在 部分原因是执行能力降低或过度活跃的人对执行能力的要求增加 情绪系统，可能由功能失调的神经递质系统介导。值得注意的是，PTSD与 大脑中主要的抑制性神经递质GABA的受体和水平都有所下降。 同样，GABA在TBI后减少，这种变化与忘记恐惧的能力降低有关。 记忆和调节情绪。大脑变化的这种重叠可能暗示了损伤与 与mTBI和PTSD的发展相关的特征。 初步工作：与我们的理论模型一致，我们的试点数据表明边缘系统和 前额叶连接与mTBI患者的PTSD症状有关。此外，我们发现， mTBI的特征影响情绪任务的表现。最后，我们证明了每种方法的可行性。 我们将在拟议的研究中使用的磁共振措施和任务。 计划：拟议的调查将研究两个关键的大脑网络之间的关系，边缘系统， （情绪）和前额叶，这是功能失调的个人情绪失调和功能， 在mTBI后可能会发生变化。拟议的调查还旨在评估GABA 调节这些变化。为了测试这些关系和变化，我们将使用功能磁 磁共振成像（fMRI）和磁共振波谱（MRS）来测量区域任务依赖性 退伍军人的大脑活动和局部GABA水平。我们将在情绪和 先前报道PTSD患者的认知任务发生改变。我们预测， 执行和情绪大脑区域将显示与PTSD症状相关的活动变化， 伽马氨基丁酸水平。这些关系尚未在文献中报道。如果两者之间存在联系， 功能连接后mTBI，PTSD和区域GABA水平，可能有潜在的个性化 可以利用的治疗方案，在这些系统中产生积极的变化，减轻痛苦。