Imaging neural dynamics at high temporal resolution in sleep and sleep deprivation

项目摘要 许多精神疾病，包括精神分裂症、抑郁症和自闭症，都与 打乱了睡眠。睡眠障碍可能会导致消极的认知症状，因为睡眠对 维持和恢复健康的大脑功能。特别是，慢(0.1-1赫兹)振荡特性 深度睡眠被认为在睡眠的恢复功能中起着至关重要的作用，而这些振荡 复杂的空间属性，可能对它们对认知的影响很重要。然而，确定速度有多慢 由于我们目前无法测量迟缓，振荡对大脑功能的影响一直是一个挑战 在整个大脑中以空间精确度振荡。 该项目利用加速多层成像方法的最新发展来测量 快速(&gt；0.2赫兹)fMRI信号。这项工作的中心是创新地使用加速功能磁共振成像， 同时脑电直接测量整个人脑的缓慢振荡动力学，同时， 并使用这些信息来创建第一个慢速振荡的全脑地图。我们将首先优化成像 以及定位慢振荡的分析方法。然后我们将测试一个假设，看看振荡的速度有多慢 影响认知功能：即，大脑皮质和丘脑的空间局部性慢振荡导致 通过大脑皮层网络重新组织信息传输，从而影响认知功能。 应聘者在唤醒调节系统神经科学、麻醉药理学、 电生理学和信号处理，为进行这种先进的成像提供了坚实的基础 对睡眠状态的研究。K99将在1)功能和解剖核磁共振方面提供必要的培训；2) 睡眠时同步脑电-功能磁共振成像；3)人类睡眠神经生理学。这项研究将在 阿蒂努拉·A·马蒂诺斯中心，这是一个高度协作的环境，配备了最先进的设施 神经成像。首席导师布鲁斯·罗森教授将提供神经成像和 过渡到一个独立的职位。此外，联合导师罗伯特·斯蒂克戈尔德教授将提供以下培训 睡眠神经生理学，以及暴露于临床背景下的睡眠是如何影响精神病患者的 睡眠障碍，以及睡眠障碍如何导致认知缺陷。乔纳森博士的补充建议 Polimeni和Jeff Duyn博士在成像和分析技术方面将确保在这些方面进行高水平的培训 方法论方法。这种方法和科学的培训将使应聘者能够 成功完成这些目标，并制定一个以系统为重点的独立研究计划 睡眠和觉醒调节的神经科学，睡眠回路和睡眠调节药物 影响大脑皮层功能，以及睡眠不足如何导致认知障碍。这项研究的结果将 有助于改进人脑动态成像的方法，并阐明睡眠的影响 剥夺，这对一般人群，特别是对病人都有重大的负面影响 患有精神障碍。

Project Abstract Many psychiatric disorders including schizophrenia, depression, and autism, are associated with disrupted sleep. Disrupted sleep may contribute to negative cognitive symptoms, as sleep is crucial for maintaining and restoring healthy brain function. In particular, the slow (0.1-1 Hz) oscillations characteristic of deep sleep are thought to play essential roles in the restorative functions of sleep, and these oscillations have complex spatial properties that may be important for their effects on cognition. However, determining how slow oscillations influence brain function has been challenging due to our current inability to measure slow oscillations with spatial precision throughout the whole brain. This project exploits the recent development of accelerated multi-slice imaging methods to measure fast (>0.2 Hz) fMRI signals. This work is centered around an innovative use of accelerated fMRI with simultaneous EEG to directly measure slow oscillation dynamics throughout the human brain simultaneously, and use this information to create the first whole-brain maps of slow oscillations. We will first optimize imaging and analysis methods for localizing slow oscillations. We will then test a hypothesis for how slow oscillations affect cognitive function: namely, that spatially localized slow oscillations in cortex and thalamus lead to reorganized information transfer across cortical networks, and thereby influence cognitive function. The candidate has expertise in systems neuroscience of arousal regulation, anesthesia pharmacology, electrophysiology, and signal processing, providing a strong foundation for conducting this advanced imaging study of sleep states. The K99 will provide necessary training in 1) functional and anatomical MRI; 2) simultaneous EEG-fMRI during sleep; and 3) human sleep neurophysiology. The research will take place at the Athinoula A. Martinos Center, a highly collaborative environment equipped with state-of-the-art facilities for neuroimaging. The primary mentor Prof. Bruce Rosen will provide mentorship in neuroimaging and in transitioning to an independent position. In addition, the co-mentor Prof. Robert Stickgold will provide training in sleep neurophysiology, as well as exposure to clinical contexts of how sleep is affected in psychiatric disorders, and how disrupted sleep can contribute to cognitive deficits. Additional advice from Dr. Jonathan Polimeni and Dr. Jeff Duyn on imaging and analysis techniques will ensure high-level training in these methodological approaches. This methodological and scientific training will enable the candidate both to successfully complete these aims and to develop an independent research program focused on the systems neuroscience of sleep and arousal regulation, how sleep circuits and sleep-modulating pharmaceutical agents influence cortical function, and how sleep deficits lead to disrupted cognition. The results of this research will contribute to improved methods for imaging dynamics in the human brain, and shed light on the effects of sleep deprivation, which have significant negative effects both on the general population and particularly in patients with psychiatric disorders.