Frontal Lobe Injury and Executive Control of Cognition and Emotion

描述(由申请人提供)： 这项建议将解决神经心理学文献中的一些空白，这些文献提供了诊断和治疗持续性脑震荡后症状和心理健康损害的最佳做法。创伤性脑损伤(TBI)通常被认为是持久自由行动(OEF)和伊拉克自由行动(OIF)的“标志性损伤”。根据一些估计，先前部署的军事人员中有20%在OEF和OIF服役期间遭受了脑外伤，主要是由于爆炸伤。这些损伤中的大多数可以被归类为轻度脑外伤或脑震荡。此外，据估计，从阿富汗和伊拉克返回的退伍军人中有14%患有创伤后应激障碍(PTSD)，相当大比例的退伍军人同时患有这两种疾病。虽然大多数患有轻度脑外伤的患者恢复良好，但其他人可能会在记忆力、注意力、决策和情绪方面出现挥之不去的缺陷。大脑的额叶特别容易受到脑外伤的损害，额叶的损伤可能会导致一些严重的症状，这些症状可能会使患者及其家人致残。注意力、注意力、决策、个性和情绪调节方面的改变会影响社会功能和就业。然而，对于轻微的TBI对部署后问题的确切贡献，仍然存在实质性的分歧。与创伤后应激障碍症状的重叠是广泛的，要理清每一种症状的影响是具有挑战性的。此外，严重的抑郁症与创伤后应激障碍症状的严重程度高度相关，有问题的饮酒频率大大增加。最后，患有创伤后应激障碍的退伍军人有自杀意念的风险增加，尤其是在 有两种或两种以上共病障碍的患者。缺乏考虑所有这些变量如何相互作用从而在大脑中产生微妙变化的基础研究。因此，这个项目 打算通过一系列实验来填补这些空白，这些实验将识别抑制控制中的特定缺陷，即抑制不适当或考虑不周的反应的能力。调节抑制控制功能的大脑系统的损伤最终会导致冲动行为。然而，冲动并不是一个单一的结构，分成不同的领域将有助于识别和优先处理那些对患有mTBI/PTSD的OEF/OIF退伍军人来说最麻烦的问题。这项研究将使用非侵入性的大脑电生理记录来检查神经活动的时间进程，这些神经活动具有三种特定的抑制控制功能：(1)运动反应抑制，或抑制预先潜在的运动反应的能力；(2)冲动 在奖励背景下的选择，或不考虑未来后果的决策；(3)情绪调节，或控制情绪反应的能力。该项目将使用新颖、精心设计的任务，这些任务对细微的缺陷敏感，并与现实世界的功能相关，并将重点放在可能导致负面心理社会结果的冲动的不同维度。识别与mTBI/PTSD相关的神经异常-脑功能的非侵入性记录生物标记物-将加深我们的理解，并为开发改进的认知康复和其他治疗干预措施提供信息。更多地了解抑制控制功能的特定解剖学和功能基础将有助于为受认知和情绪调节障碍影响的退伍军人制定改进的诊断、治疗和康复策略。由于这些情况可能导致生产力的巨大损失，对大脑健康进行更敏感的评估可以帮助根据个别患者的需求进行康复工作。

DESCRIPTION (provided by applicant): This proposal will address a number of gaps in the neuropsychological literature that informs best practices for diagnosis and treatment of persistent post-concussive symptoms coupled with impairments in psychological health. Traumatic brain injury (TBI) is often considered the "signature injury" of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF). By some estimates, 20% of previously deployed military personnel have sustained TBIs during their service in OEF and OIF, primarily due to blast injuries. The majority of these injuries can be classified as mild TBI or concussion. Furthermore, it is estimated that 14% of Veterans returning from Afghanistan and Iraq have post-traumatic stress disorder (PTSD), and a substantial percentage of Veterans have both conditions. Although most individuals with mild TBI show good recoveries, others can experience lingering deficits in memory, concentration, decision-making, and mood. The frontal lobes of the brain are particularly vulnerable to damage from TBI, and frontal lobe injuries can lead to a number of serious symptoms that can be disabling to the patients and their families. Alterations in attention, concentration, decision-making, personality, and emotion regulation can affect social functioning and employment. However, there is still substantial disagreement about the precise contribution of mild TBI to post- deployment problems. The overlap with PTSD symptoms is extensive, and disentangling the effects of each has been challenging. Furthermore, major depression is highly correlated with the severity of PTSD symptoms, and the frequency of problematic drinking is substantially elevated. Finally, the risk for suicidal ideation is increased in Veterans with PTSD, especially in those with two or more co-morbid disorders. Basic research that considers how all of these variables might interact to produce subtle changes in the brain is lacking. Therefore, this project intends to fill these gaps with a series of experiments that will identify specific deficits in inhibitory control, the ability to withhold inappropriate or ill-conceived responses. Impairments i the brain systems that mediate inhibitory control functions can ultimately lead to impulsive behaviors. Impulsivity is not a unitary construct, however, and separation into different domains will help identify and prioritize those that are the most troublesome for OEF/OIF veterans with mTBI/PTSD. The study will use non-invasive electrophysiological recording of the brain to examine the time course of neural activity underlying three specific inhibitory control functions: (1) motor response inhibition, or the ability to withhold pre-potent motor responses; (2) impulsive choice in the context of reward, or decision making without regard to future consequences; (3) emotion regulation, or the ability to control affective responses. The project will use novel, carefully designed tasks that are sensitive to subtle deficits and relevant to real world functioning, and will focus on different dimensions of impulsivity that can lead to negative psychosocial outcomes. Identifying neurological abnormalities associated with mTBI/PTSD - noninvasively recorded biomarkers of brain function - will further our understanding and inform efforts to develop improved cognitive rehabilitation and other therapeutic interventions. Learning more about the specific anatomical and functional substrates of inhibitory control functions will help in the development of improved diagnosis, treatment, and rehabilitation strategies for Veterans affected by cognitive and emotional dysregulation. Since these conditions can result in tremendous losses of productivity, the development of more sensitive assessments of brain health can assist in tailoring rehabilitation efforts to the needs of individual patients.