fMRI VIsualization Of The Human Brain During Sleep Onset

描述(由申请人提供)：入睡是人脑通常经历的最强劲和最戏剧性的变化之一。然而，无法启动睡眠(失眠)或适当控制睡眠(日间过度困倦、嗜睡)每年对数百万人造成不利影响，导致巨大的个人和社会代价。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了解方面取得了显着的进展。通过选择性地抑制脑干中的关键行为状态控制中心，下丘脑的离散核团参与了积极的睡眠产生。 人类睡眠的生理学研究在很大程度上局限于脑电技术，存在空间分辨率低的问题。使用SPECT和最近的PET的工作揭示了与NREM和REM睡眠阶段相关的复杂的功能神经解剖学分离模式，过去的电生理学研究只能暗示这一发现。尽管有这些发现，但在整个系统水平上，关于人类大脑中导致睡眠开始转变的神经机制存在明显的知识差距。 利用功能磁共振成像(FMRI)优越的空间和时间分辨率，结合同步脑电(EEG)，我们最近展示了记录人类睡眠开始时皮质下和皮质区域局部血氧水平变化的能力。这些数据为脑干、丘脑和下丘脑核团中与睡眠开始时间密切相关的激活水平的分离变化以及皮质激活的变化提供了证据。这里提出的研究旨在提供足够的先导数据来确定这一研究范式的价值，更大的目标是从这些先导研究中开发具体的假说，这些假说可以使用功能磁共振结合睡眠多导图(PSG)进行测试，也可以通过合作项目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.