Sleep-related behavior and cortical activity in premature human infants as predictors of developmental outcomes.

项目摘要 睡眠渗透在我们的早期生活中：一个典型的人类新生儿每天平均睡16个小时， 睡眠与睡眠之间的关系。新生儿活跃睡眠的比例相对较高， 这是几十年来关于积极睡眠对婴儿大脑发育很重要的假设的基础。在 考虑到这一假设，重要的是要记住，积极睡眠是一个复杂的状态， 在发育过程中出现和融合的各种行为和生理成分。因此， 这些成分中的一种或多种在促进大脑发育方面发挥着巨大的作用。一个这样 候选成分是包括肢体、面部和眼睛的抽搐的阶段性活动。过去 15年来，对幼鼠的研究表明，肢体抽搐的感觉反馈会触发离散和 整个感觉运动系统的丰富活动，从脊髓级联到脑干， 小脑、丘脑、感觉运动皮层和海马。近年来，在盖茨基金会的资助下， 基金会和NICHD的R21，调查扩展到足月人类婴儿的前七个月， 产后数月使用行为测量和高密度脑电图（EEG）记录， 研究揭示了婴儿睡眠的时空组织的未知特征， 抽搐，并引入了新的发展里程碑和假设。在这里，我们建议扩展这些 努力早产儿有两个原因：早产儿表现出更高比例的积极睡眠， 新生儿足月婴儿，他们在运动技能，脑瘫，自闭症， 其他神经发育障碍。因此，我们将确定抽搐是否可以增强我们的理解 研究非典型发展轨迹的起源和时间进程，并指导未来的干预措施。极早产 人类婴儿（月经后<32周龄）和轻度早产婴儿（月经后32-36周龄）， 爱荷华州大学Stead家庭儿童医院的新生儿重症监护室（NICU）将 招募参与一项跨越出院前（I期）和出院后（II期）的纵向研究 从新生儿重症监护室在第一阶段，每两周记录一次睡眠行为和脑电图活动， 呼吸频率在第二阶段，在相同的早产儿以及足月年龄匹配的对照组中， 行为、EEG活动和呼吸频率将在一周到六个月之间记录三次 纠正年龄神经行为和运动技能评估将在一个月和六个月大时进行 并在两岁时进行临床随访评估。因为这项研究是纵向的， 在第一阶段和第二阶段，将比较相同婴儿的行为和生理睡眠数据， 发展成果。最终，这个项目将提供一个前所未有的机会， 睡眠和睡眠相关行为如何促进早期生命的典型和非典型发育。

PROJECT SUMMARY Sleep permeates our early existence: A typical human newborn sleeps 16 hours each day, evenly divided between active (REM) sleep and quiet sleep. The relatively high proportion of active sleep in newborns is the foundation for the decades-old hypothesis that active sleep is important for infant brain development. In considering this hypothesis, it is important to remember that active sleep is a complex state composed of a variety of behavioral and physiological components that emerge and coalesce over development. Thus, it may be that one or more of these components play outsized roles in promoting brain development. One such candidate component is the phasic activity that comprises twitches of the limbs, face, and eyes. Over the past 15 years, research in infant rats has revealed that sensory feedback from twitching limbs triggers discrete and abundant activity throughout the sensorimotor system, cascading from the spinal cord to the brainstem, cerebellum, thalamus, sensorimotor cortex, and hippocampus. In recent years, with funding from the Gates Foundation and an R21 from NICHD, investigations were extended to full-term human infants over the first seven postnatal months. Using behavioral measures and high-density electroencephalographic (EEG) recordings, this research revealed heretofore unknown features about the spatiotemporal organization of infant sleep and twitching and introduced new developmental milestones and hypotheses. Here, we propose to extend these efforts to preterm infants for two reasons: Preterm infants exhibit an even higher proportion of active sleep than newborn full-term infants, and they are at increased risk for deficits in motor skill, cerebral palsy, autism, and other neurodevelopmental disorders. Thus, we will determine whether twitching can enhance our understanding of the origins and time course of atypical developmental trajectories and guide future interventions. Very preterm human infants (<32 weeks postmenstrual age) and mildly preterm infants (32-36 weeks postmenstrual age) in the neonatal intensive care unit (NICU) in the Stead Family Children’s Hospital at the University of Iowa will be recruited to participate in a longitudinal study spanning the period before (Phase I) and after (Phase II) discharge from the NICU. Every two weeks during Phase I, sleep behavior will be recorded along with EEG activity, and respiratory rate. During Phase II, in the same preterm infants as well as full-term age-matched controls, sleep behavior, EEG activity, and respiratory rate will be recorded three times between one week and six months corrected age. Neurobehavioral and motor skill assessments will be performed at one and six months of age and clinical follow-up assessments will be performed at two years of age. Because this study is longitudinal, behavioral and physiological sleep data will be compared in the same infants across Phases I and II and related to developmental outcomes. Ultimately, this project will provide an unprecedented opportunity to understand how sleep and sleep-related behavior contribute to typical and atypical development in early life.