The Development of Inhibitory Networks Regulating Sustained Attention

项目摘要/摘要 持续性注意力缺陷在普通人群中很常见，在患有 潜在的神经精神疾病。由于缺乏客观的生物标记物，诊断变得复杂。 最有效的治疗方法是兴奋剂，它是可能被滥用或被滥用的受控物质。 转移视线。这项建议的重点是探索脑振荡在脑电中的应用 (EEG)作为一种转换工具来评估作为基础的快慢频率之间的关系 注意力的机制。这种独特的脑电信号，称为相位-幅度耦合(PAC)，具有潜在的 整合将注意力集中在一项任务上的大脑过程。这一点的中心假设是 有观点认为，小鼠大脑后顶区的PAC协调正常注意力 在注意力缺陷的小鼠身上，这种PAC受到损害。两种遗传性癫痫小鼠模型 PAC异常，一种遗传模型具有相同类型的癫痫但PAC正常，第四种遗传模型具有相同类型的癫痫 模型无癫痫，但PAC异常。对这些模型同时进行脑电和行为测试 然而，之前还没有进行过测试。此外，这些模型还提供了对 在细胞和网络层面上的疾病。使用同时视频-脑电的行为实验 在小鼠的监测中，本项目的具体目的是：(1)论证PAC和PAC的关系 正常小鼠的注意力；(2)在整个发育过程中评估正常和异常的PAC；以及(3)确定 遗传和环境对PAC发育的影响及其持续性的关系 请注意。该建议通过合并EEG的计算分析来独特地接近这些目标， 神经发育过程中的行为研究和药物/遗传操作。在 短期内，这项建议的工作将阐明持续的发展机制 在网络层面上的关注。从长远来看，这项工作可能会验证PAC作为翻译的使用 啮齿动物药物发现的生物标记物以及对患者的诊断、预后和治疗的帮助 注意力不集中。最终，这项研究的完成将为两国关系提供新的线索 大脑振荡、行为和治疗之间的关系，并可以直接导致药物开发的改进， 神经反馈和病人护理。

Project Summary/Abstract Deficits in sustained attention are common in the general population, and even more common in patients with underlying neuropsychiatric diseases. The diagnosis is complicated by the lack of an objective biomarker, and the most effective treatments are stimulants, which are controlled substances with the potential for abuse or diversion. The focus of this proposal is to explore the use of brain oscillations in the electroencephalogram (EEG) as a translational tool to evaluate the relationship between fast and slow frequencies as an underlying mechanism for attention. This unique EEG signal, known as phase-amplitude coupling (PAC), has the potential to integrate the brain processes involved with focusing attention on a task. The central hypothesis of this proposal is that PAC in the posterior parietal region of the brain in mice coordinates normal attention processes, and this PAC is impaired in mice with attention deficits. Two genetic mouse models of epilepsy have abnormal PAC, one genetic model has the same type of epilepsy but normal PAC, and a fourth genetic model has no epilepsy but abnormal PAC. Testing of these models with simultaneous EEG and behavioral testing, however, has not previously been done. In addition, these models provide mechanistic insight to the disease on a cellular and network level. Using behavioral experiments with simultaneous video-EEG monitoring in mice, the specific aims of this project are to: (1) Demonstrate the relationship between PAC and attention in normal mice; (2) evaluate normal and aberrant PAC throughout development; and (3) determine the relationship between genetic and environmental influences on the development of PAC and sustained attention. This proposal uniquely approaches these aims by merging computational analysis of EEG, behavioral studies, and pharmacological/genetic manipulations over the course of neurodevelopment. In the short term, the work from this proposal will elucidate the developmental mechanisms underlying sustained attention on a network level. In the long term, this work may validate the use of PAC as a translational biomarker for drug discovery in rodents as well as aid in the diagnosis, prognosis, and treatment of patients with deficits in attention. Ultimately, the completion of this research will shed new light on the relationship between brain oscillations, behavior and therapy, and can directly lead to improvements in drug development, neurofeedback, and patient care.