Human Sleep Neuroscience

描述（由申请人提供）：本研究计划的目的是使用功能性神经成像研究睡眠，以增加我们对抑郁症等精神障碍的神经生物学的理解。该项目之前的研究表明，有一个层次神经网络可以调节唤醒，并且可能在各种神经精神疾病（如抑郁症和失眠症）中发挥异常作用。在抑郁症中，腹侧边缘系统和脑边缘系统在REM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NREM睡眠中异常。我们假设，在REM睡眠中增加腹侧神经系统功能的抑郁症的影响是部分介导的腹侧神经系统（杏仁核/sugenual前扣带皮层）fMRI对情绪刺激的反应增加。第二，鉴于大量文献支持NREM睡眠在恢复前额叶皮层功能中的作用，我们假设抑郁症对前额叶皮层功能下降的影响，通过fMRI认知探针测量，部分是由抑郁症患者NREM睡眠期间前额叶皮层缺乏恢复介导的。在这项K24应用的研究计划中（EA Nofzinger，PI，MH 61566），我们将在35名抑郁症患者和35名年龄和性别匹配的健康受试者中，使用[18 F]-FDG PET评估清醒、REM和NREM睡眠探针的脑代谢反应，并使用fMRI评估情感和认知挑战的脑血流反应。此外，失眠症患者NREM睡眠期间大脑代谢亢进的发现，以及抑郁症和失眠症患者从清醒到NREM睡眠期间前额叶皮层失活的失败，提高了对前额叶皮层区域头皮的低温刺激可能会降低代谢并促进这些人群的睡眠的可能性。职业发展活动，以进一步这条线的调查集中在两个领域：1）在MR形态测量学，功能磁共振成像和复杂的多模态成像数据的分析培训;和2）培训的使用和脑低温的机制，可能有适用于睡眠障碍患者。指导活动的目标是每年从医学生、住院医生或博士后研究员中招募和指导至少一名新的实习生。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，以及追求独立的职业发展奖项和资助建议来衡量。主要研究者将指导学员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性神经成像方法，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.