Human Sleep Neuroscience

描述（由申请人提供）：本研究项目的目的是利用功能性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理解。这个项目之前的研究表明，有一个层次神经网络可以调节觉醒，它可能在各种神经精神疾病（如抑郁症和失眠）中发挥异常作用。在抑郁症患者中，腹侧边缘和副边缘系统在快速眼动睡眠中异常过度活跃，而包括前额叶皮质在内的背侧执行系统在非快速眼动睡眠中异常。我们假设，抑郁对快速眼动睡眠中腹侧神经系统功能增加的影响部分是由腹侧神经系统（杏仁核/前扣带皮层）对情绪刺激的fMRI反应增加介导的。其次，鉴于大量文献支持非快速眼动睡眠在恢复前额叶皮质功能中的作用，我们假设抑郁症对前额叶皮质功能下降的影响，正如fMRI认知探针所测量的那样，部分是由于抑郁症患者在非快速眼动睡眠期间前额叶皮质缺乏恢复。在这项K24申请（EA Nofzinger， PI, MH61566）的研究计划中，我们将使用[18F]- fdg PET评估35名抑郁症和35名年龄和性别匹配的健康受试者对清醒、快速眼动和非快速眼动睡眠探针的脑代谢反应，并使用fMRI评估35名抑郁症和35名健康受试者对情感和认知挑战的脑血流反应。此外，失眠患者在非快速眼动睡眠期间的大脑高代谢，以及抑郁症和失眠患者在醒来进入非快速眼动睡眠时前额叶皮质未能失活，这些发现提出了一种可能性，即对前额叶皮质区域的头皮进行低温刺激可能会降低这些人群的新陈代谢并促进睡眠。进一步研究的职业发展活动集中在两个方面：1)磁共振形态测量学、功能磁共振成像和复杂多模态成像数据分析的培训；2)对可能适用于睡眠障碍患者的脑低温的使用和机制进行培训。指导活动的目标是每年从医学生、住院医生或博士后中招募和指导至少一名新的培训生。指导的成功将通过学员在同行评审的出版物中的生产力、在科学会议上的研究报告、对独立职业发展奖励和资助提案的追求来衡量。首席研究员将指导受训者进行以患者为导向的研究，包括制定IRB批准的方案，实施研究计划，以及解释和展示数据。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和研究的道德行为。

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.