Human Sleep Neuroscience

描述(申请人提供)：这个研究项目的目的是使用功能神经成像来研究睡眠，以增加我们对抑郁症等精神障碍的神经生物学的了解。该项目之前的研究表明，有一个层次化的神经网络来调节唤醒，它可能会在各种神经精神障碍中发挥异常作用，如抑郁和失眠。在抑郁症患者中，REM睡眠时腹侧边缘和边缘旁系统异常过度活跃，NREM睡眠时包括前额叶皮质在内的背侧执行系统异常。我们假设，在REM睡眠中，抑郁对增强腹侧神经系统功能的影响部分是通过腹侧神经系统(杏仁核/前扣带回)fMRI对情绪刺激反应的增加而实现的。其次，考虑到大量文献支持NREM睡眠在恢复前额叶皮质功能中的作用，我们假设抑郁对前额叶皮质功能降低的影响，如fMRI认知探针所测量的，部分是通过抑郁症患者在NREM睡眠期间前额叶皮质缺乏恢复所介导的。在这项K24应用的研究计划(EA Nofzinger，Pi，MH61566)中，我们将使用[18F]-FDG PET评估清醒、REM和NREM睡眠探头的大脑代谢反应，以及使用fMRI评估35名抑郁症患者和35名年龄和性别匹配的健康受试者的脑血流反应。此外，失眠症患者在NREM睡眠期间大脑高代谢的发现，以及抑郁症和失眠症患者未能将前额叶皮质从清醒状态停用到NREM睡眠，增加了在这些人群中，对前额叶皮质区域进行低温刺激可能会降低新陈代谢，促进睡眠的可能性。促进这一研究方向的职业发展活动集中在两个领域：1)磁共振形态测量、功能磁共振和复杂多模式成像数据分析方面的培训；2)可能适用于睡眠障碍患者的脑低温的使用和机制方面的培训。指导活动的目标是每年至少从医学生、住院医生或博士后研究员队伍中招募和指导一名新的实习生。指导的成功将通过学员在同行评议的出版物中的生产率、在科学会议上的研究报告以及对独立职业发展奖和资金提案的追求来衡量。首席研究员将指导学员进行以患者为中心的研究，包括开发IRB批准的方案，实施研究计划，以及解释和提交数据。指导年轻研究人员的内容领域包括睡眠期间使用的功能神经成像方法，行为状态调节的神经科学，以及研究的伦理行为。

DESCRIPTION (provided by applicant): The aim of this research program is to study sleep using functional neuroimaging in order to increase our understanding of the neurobiology of mental disorders such as depression. Prior studies from this program showed that there is a hierarchical neural network that regulates arousal and that may function abnormally across a variety of neuropsychiatric disorders such as depression and insomnia. In depression, a ventral limbic and paralimbic system is abnormally overactive in REM sleep and a dorsal executive system including the prefrontal cortex is abnormal in NREM sleep. We hypothesize that the effects of depression on increasing ventral neural system function in REM sleep is partially mediated by an increase in ventral neural system (amygdale/sugenual anterior cingulated cortex) fMRI responses to emotional stimuli. Second, given a substantive literature supporting a role for NREM sleep in restoring prefrontal cortex function, we hypothesize that the effects of depression on decreased prefrontal cortex function, as measured by fMRI cognitive probes, is in part mediated by the lack of restoration of the prefrontal cortex during NREM sleep in depressed patients. In the research plan of this K24 application (EA Nofzinger, PI, MH61566), we will assess cerebral metabolic responses to waking, REM and NREM sleep probes using [18F]-FDG PET and cerebral blood flow responses to affective and cognitive challenges using fMRI in 35 depressed and 35 age- and gender-matched healthy subjects. Additionally, findings of cerebral hypermetabolism during NREM sleep in insomnia, and a failure to deactivate the prefrontal cortex from waking to NREM sleep in depressed and insomnia patients raise the possibility that a hypothermic stimuli to the scalp over the area of the prefrontal cortex may decrease metabolism and facilitate sleep in these populations. Career development activities to further this line of investigation focus on two areas: 1) training in MR morphometry, fMRI and the analysis of complex multimodal imaging data; and 2) training in the use and mechanisms of cerebral hypothermia that may have applicability to sleep disordered patients. The goals of mentoring activities are to recruit and mentor at least one new trainee per year from the ranks of medical students, residents, or post-doctoral fellows. Success in mentoring will be measured by trainee's productivity in peer-reviewed publications, presentations of research at scientific meetings, and pursuit of independent career development awards and funding proposals. The principal investigator will mentor trainees in conducting patient oriented research, including the development of IRB approved protocols, implementing a research plan, and interpreting and presenting data. Content areas for mentoring young investigators include functional neuroimaging methods for use during sleep, the neuroscience of behavioral state regulation and in the ethical conduct of research.