Detection and Amelioration of Gamma Oscillation Abnormalities in Blast-Related Brain Injury_523_Spencer

最近冲突的退伍军人经历了严重的认知和情感问题， 暴露在爆炸中。最近的研究表明，爆炸暴露后遗症的一个关键因素是距离 而不是有没有脑震荡症状暴露在爆炸中， <10米的距离与认知和神经障碍显著相关， 暴露于>10 m的爆炸。爆炸相关脑损伤的神经相关性知之甚少， 迄今为止，这种类型的脑损伤很少受到研究关注。 我们建议使用脑电图（EEG）的伽马波段（30-100 Hz）中的振荡， 检测和修复与退伍军人爆炸伤相关的神经回路功能障碍。伽玛带振荡 已经被证明与几种大脑功能有关，包括视觉感知，选择性注意， 工作记忆、长期记忆和运动控制。最近的动物模型研究表明， 创伤性脑损伤对表达小白蛋白（PV+）的抑制性中间神经元的影响，这是一个关键的 皮层回路中产生伽马振荡的元素。PV+中间神经元功能障碍与 诱发伽马振荡的缺陷和宽带伽马“噪声”的功率增加，以及 认知缺陷最近还表明，通过模式化刺激刺激PV+中间神经元， γ带可以改善动物中这些中间神经元的功能以及认知功能 神经精神疾病的模型。因此，我们认为伽马振荡和刺激提供了 有希望的目标，为调查退伍军人谁遭受爆炸有关的脑损伤。我们将调查 将从VA参与者库中招募的50名退伍军人的伽马波段活动和刺激 创伤性脑损伤和应激障碍转化研究中心（TRACTS）在VA波士顿医疗保健系统。 目的1：评估是否诱发伽马缺陷和增加的伽马噪声存在于 暴露于近距离（<10米）和远距离（>10米）爆炸的个人。我们预测，诱发伽马将减少， 功率和相位同步，而伽马噪声的功率将增加，在近距离爆炸相比， 组 目的2：确定γ振荡异常是否与近距离爆炸暴露有关 可以通过伽马波段的非侵入性模式化感觉刺激来补救。我们将管理6分钟 40赫兹的听觉稳态刺激。我们预测伽马条件反射会增加诱发伽马 振荡引起的音调在条件与非条件的频率，而伽马噪声将 降低与远爆炸组相比，近爆炸组中的这些影响更大。 本项目还有两个探索性目的：1）研究静息状态下δ频段（1-4 Hz） EEG功率在近距离爆炸暴露组中相对于远距离爆炸暴露组增加，因为Δ功率在近距离爆炸暴露组中增加。 与健康对照组相比，患有轻度创伤性脑损伤的个体。2)如blast 暴露与白色物质缺陷有关，PV+中间神经元轴突有髓鞘，我们将检查 通过扩散张量成像评估伽马异常是否与白色物质缺陷相关 (DTI)听觉皮层的测量，可从TRACTS数据库中获得。 总之，这个项目旨在促进我们对爆炸对大脑功能影响的理解， 通过探测爆炸暴露对产生伽马振荡的神经回路的影响， 通过测试一种新型的非侵入性脑刺激是否可以改善退伍军人的脑功能， 爆炸如果成功，该项目可能会导致新的方法来检测和补救爆炸的影响 接触退伍军人和帮助他们的功能恢复。

Veterans of recent conflicts have experienced serious cognitive and emotional problems resulting from exposure to blasts. Recent work suggests that a critical factor in the sequelae of blast exposure is distance from the blast, rather than the presence or absence of concussion symptoms. Exposure to blasts from a distance of <10 m has been associated with significantly greater cognitive and neural disturbances than exposure to blasts from >10 m. The neural correlates of blast-related brain injury are poorly understood, as to date this type of brain injury has received little research focus. We propose to use oscillations in the gamma band (30-100 Hz) of the electroencephalogram (EEG) to detect and remediate neural circuit dysfunction related to blast injury in veterans. Gamma band oscillations have been shown to be involved in several brain functions, including visual perception, selective attention, working memory, long term memory, and motor control. Recent studies in animal models have linked the effects of traumatic brain injury to parvalbumin-expressing (PV+) inhibitory interneurons, which are a critical element of the cortical circuitry that generates gamma oscillations. PV+ interneuron dysfunction is associated with deficits in evoked gamma oscillations and increased power of broadband gamma “noise”, as well as cognitive deficits. It has also recently been shown that stimulation of PV+ interneurons by patterned stimuli in the gamma band can improve the function of these interneurons, as well as cognitive function, in animal models of neuropsychiatric disorders. Hence, we believe that gamma oscillations and stimulation provide promising targets for investigation in veterans who suffer from blast-related brain injury. We will investigate gamma band activity and stimulation in 50 veterans who will be recruited from the participant pool of the VA Translational Research Center for TBI and Stress Disorders (TRACTS) at the VA Boston Healthcare System. Aim 1: To assess whether evoked gamma deficits and increased gamma noise are present in individuals exposed to Close (<10 m) vs. Far (>10 m) blasts. We predict that evoked gamma will be reduced in power and phase synchrony, while gamma noise will be increased in power, in Close compared to Far blast groups. Aim 2: To determine whether gamma oscillation abnormalities associated with close blast exposure can be remediated by non-invasive patterned sensory stimulation in the gamma band. We will administer 6 min of auditory steady-state stimulation at 40 Hz. We predict that gamma conditioning will increase evoked gamma oscillations elicited by tones at the conditioned vs. unconditioned frequency, while gamma noise will be decreased. These effects will be greater in the Close compared to the Far blast groups. This project also has 2 exploratory aims: 1) To investigate whether resting state delta-band (1-4 Hz) EEG power is increased in Close relative to Far blast exposure groups, as delta power is increased in individuals who have experienced mild traumatic brain injury compared to healthy controls. 2) As blast exposure is associated with white matter deficits, and PV+ interneuron axons are myelinated, we will examine whether gamma abnormalities are correlated with white matter deficits as assessed by diffusion tensor imaging (DTI) measures in the auditory cortex, available from the TRACTS database. In sum, this project seeks to advance our understanding of the effects of blasts on brain function in veterans by probing the effects of blast exposure on the neural circuits that generate gamma oscillations, and by testing whether a new type of non-invasive brain stimulation can improve brain function in veterans exposed to blasts. If successful, this project could lead to new approaches to detect and remediate the effects of blast exposure on veterans and aid in their functional recovery.