Brain changes underlying emotional and executive alterations in TBI

这一建议的主要目的是阐明情绪的可能机制基础。 轻度创伤性脑损伤后的精神障碍，尤其是创伤后应激障碍。 问题：创伤后应激障碍(PTSD)在退伍军人中很常见，通常会导致慢性 痛苦，包括破坏社会关系、就业前景、健康和总体幸福感 那些经历过它的人。轻型创伤性脑损伤(MTBI)是一种常见的先天损伤及其关系 与创伤性脑损伤相关的损伤特征与创伤后应激障碍等情绪失调 目前仍不清楚，文献中报道的结果褒贬不一。MTBI可能会破坏重要的连接 在大脑区域之间，尤其是对情绪体验至关重要的大脑区域之间。饱受磨难的退伍军人 一个或多个MTBI也更有可能有其他精神疾病，而且他们的健康状况也更差 和社会结果。这些糟糕的结果很多都是由于情绪失调造成的。 患有mTBI或患有创伤后应激障碍的人通常在情绪上表现出大脑功能的变化 和执行脑区。即使他们在执行任务上的表现仍然正常，潜在的 大脑区域显示出功能关系的改变，包括活动增加。对这些内容的解释 然而，职能变化带来了挑战。在其他人群中，这类发现通常是 与病理相关或是功能衰退的主要指标。此外，此类活动可能反映出 自适应管理认知和情绪资源的能力差异。在表演时 在情绪任务中，患有创伤后应激障碍的人表现出情绪脑区活动增加。这可能是在 部分原因是执行能力降低或过度活跃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调节。值得注意的是，创伤后应激障碍与 随着大脑主要抑制性神经递质GABA的受体和水平的减少。 类似地，脑损伤后GABA减少，这种变化与恐惧遗忘能力降低有关 记忆和调节情绪。这种脑部变化的重叠可能表明损伤之间的联系 与创伤性脑损伤相关的特征和创伤后应激障碍的发展。 前期工作：与我们的理论模型一致，我们的试点数据显示边缘和 前额叶连接与mTBI患者的创伤后应激障碍症状有关。此外，我们还展示了伤势 MTBI的特点会影响情绪任务的表现。最后，我们论证了每一种方法的可行性 我们将在拟议的研究中使用的磁共振测量和任务。 计划：拟议的调查将检查两个关键的大脑网络之间的关系，边缘 (情绪)和前额叶，在情绪调节障碍和功能障碍的个体中是功能障碍的 其在mTBI之后可以被改变。这项拟议的调查还旨在评估GABA如何 调解这些变化。为了测试这些关系和变化，我们将使用函数磁 磁共振成像(FMRI)和磁共振波谱(MRS)测量区域任务依赖性 退伍军人的脑活动和局部GABA水平。我们将在情绪和情绪变化过程中测量这些因素 此前有报道称，创伤后应激障碍患者的认知任务会发生改变。我们预测，中国的活动模式 执行和情绪脑区将显示与创伤后应激障碍症状和 GABA水平。这些关系在文献中还没有报道。如果两者之间存在联系 功能连接后的mTBI、PTSD和区域GABA水平，可能存在潜在的个性化 可利用的治疗选择，以使这些系统发生积极变化并减轻痛苦。

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.