fMRI VIsualization Of The Human Brain During Sleep Onset

描述（由申请人提供）：睡眠开始是人类大脑通常经历的最强大和最戏剧性的变化之一。然而，无法启动睡眠（失眠）或适当抑制睡眠（白天过度嗜睡，嗜睡症）每年对数百万人产生不利影响，导致巨大的个人和社会成本。过去10年的动物研究在我们对调节睡眠开始的局部细胞和神经化学机制的认识方面取得了显着进展。离散的下丘脑核团通过选择性抑制脑干中的关键行为状态控制中心参与睡眠的主动产生。 人类睡眠的生理学研究在很大程度上局限于EEG技术，其具有较差的空间分辨率。使用SPECT和最近的PET的工作揭示了与NREM和REM睡眠阶段相关的功能性神经解剖学的复杂分离模式，过去的电生理学研究只能暗示这些发现。尽管有这些发现，但在整个系统水平上，关于负责人类大脑中睡眠开始过渡的神经机制存在明显的知识差距。 利用功能性磁共振成像（fMRI）的上级空间和时间分辨率，结合同步脑电图（EEG），我们最近已经证明了记录人类睡眠开始时皮质下和皮质区域血氧水平变化的能力。这些数据提供了证据，证明激活水平的解离变化与脑干、丘脑和下丘脑核团的睡眠开始时间以及皮质激活的变化密切相关。 这里提出的研究旨在提供足够的试点数据，以建立这种研究范式的价值，更大的目标是从这些试点研究中开发出具体的假设，这些假设可以使用功能磁共振成像结合睡眠多导睡眠图（PSG）进行测试，并通过合作企业，在动物模型中进行测试。

DESCRIPTION (provided by applicant): Sleep onset is one of the most robust and dramatic changes that the human brain normally undergoes. However, the inability to initiate sleep (insomnia) or appropriately restrain it (excessive daytime sleepiness, narcolepsy) adversely affects millions of people each year, resulting in large personal as well as societal costs. Animal research from the last 10 years has produced remarkable advances in our knowledge of the local cellular and neurochemical mechanisms that regulate sleep onset. Discrete hypothalamic nuclei have been implicated in the active production of sleep through the selective inhibition of key behavioral state control centers in the brainstem. The physiological study of human sleep has largely been limited to EEG techniques, which suffers from poor spatial resolution. Work using SPECT and, more recently, PET has revealed complex dissociated patterns of functional neuroanatomy associated with the sleep stages of NREM and REM, findings that past electrophysiological studies could only hint at. Despite these findings, there exists a clear knowledge gap regarding the neural mechanisms responsible for the sleep onset transition in the human brain, at a whole systems level. Using the superior spatial and temporal resolution of functional magnetic resonance imaging (fMRI), combined with simultaneous electroencephalography (EEG), we have recently demonstrated the ability to record changes in regional blood oxygenation levels in both subcortical and cortical regions across sleep onset in humans. The data provide evidence for dissociated shifts in activation levels that are tightly linked to the time of sleep onset in brainstem, thalamic, and hypothalamic nuclei, as well as shifts in cortical activation. The studies proposed here are designed to provide sufficient pilot data to establish the value of this research paradigm, with the larger goal of developing specific hypotheses from these pilot studies that can be tested using fMRI combined with sleep polysomnography (PSG) and, through collaborative ventures, in animal models as well.