Neural basis for differential vulnerability to sleep deprivation

描述（由申请人提供）：睡眠不足增加睡眠倾向，使清醒状态不稳定，损害精神运动和认知表现，并造成相当大的社会、经济和健康相关成本。虽然睡眠不足是肥胖、心血管疾病、糖尿病、抑郁症和预期死亡率的一个危险因素，但约有20%至40%的美国成年人睡眠时间少于防止认知能力累积恶化的最低睡眠时间（每晚7-8小时）。我们之前的研究和其他研究小组的神经行为证据表明，在睡眠不足的情况下，困倦程度和认知表现的个体差异是强大的、高度可复制的（类似特征的）。虽然一些健康的成年人在睡眠不足时表现出严重的认知缺陷，但其他人在睡眠不足时几乎没有表现出认知变化。然而，对于为什么一些睡眠不足的人更容易出现认知缺陷，从而导致代价高昂的错误和事故，人们知之甚少。为了回答这个问题，我们建议结合我们在神经影像学和睡眠剥夺的神经行为影响方面的跨学科专业知识来阐明这种差异认知脆弱性的神经基础。我们将使用一种新的动脉自旋标记（ASL）灌注功能磁共振成像（fMRI）技术来量化N=60名健康受试者在正常睡眠和睡眠剥夺后进行精神运动警觉性测试（PVT）时无任务和强直激活的静息脑活动。PVT是一种简单、可靠和高度敏感的任务，用于测量由于睡眠剥夺引起的注意力和表现缺陷。我们还将使用传统的BOLD fMRI来测量快速和慢速PVT反应中的相激活，并使用功能连通性分析来研究正常睡眠和睡眠剥夺后的大脑连通性。该项目的研究结果将阐明睡眠剥夺影响行为表现的神经机制，以及睡眠剥夺对不同易感性个体的影响是如何变化的。从这项研究中获得的新知识将有助于理解和管理由许多常见睡眠障碍（如睡眠呼吸暂停和其他睡眠障碍；情感性障碍；轮班工作睡眠障碍）引起的过度嗜睡。该项目也有可能产生基于大脑的生物标志物，可用于预测个体对睡眠剥夺及其治疗的反应。

DESCRIPTION (provided by applicant): Sleep loss increases sleep propensity, destabilizes the wake state, impairs psychomotor and cognitive performance, and causes considerable social, financial and health-related costs. Although insufficient sleep is a risk factor for obesity, cardiovascular disease and diabetes, depression, and prospective mortality, about 20% to 40% of the US adults sleep less than the minimum sleep duration (7-8 hours per night) to prevent cumulative deterioration in cognitive performance. Neurobehavioral evidence from our previous studies and other groups has indicated robust and highly replicable (trait-like) individual differences in the magnitude of sleepiness and cognitive performance vulnerability to sleep deprivation. While some healthy adults show substantial cognitive deficits during sleep loss, others show few cognitive changes when sleep is deprived. However, little is known about why some sleep-deprived people are more prone to cognitive deficits that can result in costly errors and accidents. To answer this question, we propose to combine our interdisciplinary expertise in neuroimaging and neurobehavioral effects of sleep deprivation to elucidate the neural basis underlying this differential cognitive vulnerability. We will use a new technique of arterial spin labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) for quantification of resting brain activity without task and tonic activation during performance of the psychomotor vigilance test (PVT) in a large sample of N=60 healthy subjects after normal sleep and following sleep deprivation. PVT is a simple, reliable and highly sensitive task for measuring attentional and performance deficits due to sleep deprivation. We will also use traditional BOLD fMRI for measuring phasic activation during fast and slow PVT responses and functional connectivity analysis for studying brain connectivity after normal sleep and following sleep deprivation. The findings from this project will elucidate the neural mechanisms by which sleep deprivation affects behavioral performance and how the effects of sleep deprivation vary across individuals of differential vulnerability. The new knowledge gained from this study will have relevance for understanding and managing excessive sleepiness due to a number of common sleep disorders (e.g., sleep apnea and other sleep disorders; affective disorders; shift work sleep disorder). The project also has the potential to yield brain-based biomarkers that can be used to predict individual responses to sleep deprivation and its treatment. PUBLIC HEALTH RELEVANCE: Although insufficient sleep is a risk factor for obesity, cardiovascular disease and diabetes, depression, and prospective mortality, about 20% to 40% of the adult US population sleep less than the minimum sleep duration (7-8 hours per night) to prevent cumulative deterioration in performance on a range of cognitive tasks. There are robust and highly replicable individual differences in the magnitude of sleepiness and cognitive performance vulnerability to sleep deprivation. This project will use multimodal brain imaging techniques to evaluate neural predictors of response to sleep deprivation and identify why some sleep-deprived people are more prone to cognitive deficits that can result in costly errors and accidents.