Effects of Music Based Intervention (MBI) on Neurodevelopment and Pain Response in Preterm Infants

项目摘要 2018年，世界卫生组织报告了1500万（>十分之一）早产， rates. 50%的早产儿患有神经发育障碍，所有早产儿都经历过 作为医疗护理的一部分的大量痛苦的程序。早产儿音乐干预显示， 心率和氧饱和度的生理改善，以及对 痛苦目前尚不清楚的是音乐如何影响早产儿的大脑成熟、神经发育和疼痛 早产儿的反应。我们提出了一个R61项目，以探索音乐的生物学机制， 利用脑电图（EEG）对早产儿脑成熟和神经发育进行MBI干预 事件相关电位（ERP）EEG捕获大脑的电位振荡， 关于大脑功能的重要信息连续脑电图可以跟踪早产儿的大脑成熟。ERPs 量化脑电电位变化与刺激的时间锁定。1个月校正年龄试验时的ERP 识别记忆功能和认知加工，并提供了另一个客观的措施，以研究早期 MBI对神经发育的影响。R61还将探索潜在的行为过程 使用EEG和早产儿疼痛特征（PIPP）研究MBI对疼痛的影响。在早产儿中，中枢脑电图 当时间锁定到疼痛刺激时，振幅发生变化，PIPP评分用疼痛刺激来衡量疼痛反应。 程序.特别录制的摇篮曲和简单的琶音伴奏将在一个为期6周的 在50例医学稳定的30周早产儿中开展的小型随机、设盲、对照研究。探索性R61结果 将通过特定的Go/NoGo里程碑进行评估，这些里程碑可深入了解MBI对生物学的影响。 神经发育的潜在机制和疼痛的行为过程。通过实现其中一个 Go/NoGo里程碑，该提案进展到R33概念验证试点临床试验， 100名随机受试者将评估两个主要结局指标：1）MBI对晚期 在6个月矫正年龄时使用Bayley's III神经发育测试的神经发育，以及2） 使用基线PIPP评分和基线PIPP评分的纵向比较， MBI 4周后的最终PIPP评分。次要措施将探讨更微妙的方面， 神经发育：1）MBI对脑成熟的影响与EEG睡眠成分的扩展分析; 2） 在6个月矫正年龄时重复ERP分析，并进行扩展记忆和认知测试（附加 不匹配负性范例）;和疼痛反应：3）MBI对疼痛相关EEG反应的影响， 比较分析额叶、顶叶、颞叶和枕叶的中枢脑电图振幅变化。

Project Summary In 2018, the World Health Organization reported 15 million (>1 in 10) preterm births with rising annual rates. 50% of preterm infants suffer from neurodevelopmental impairments, and all preterm infants experience high volumes of painful procedures as part of medical care. Preterm music intervention shows immediate physiologic improvements in heart rate and oxygen saturation, as well as improved physiologic responses to pain. What remains unknown is how music impacts preterm brain maturation, neurodevelopment, and pain responses in preterm infants. We propose a R61 project to explore biological mechanisms of music based intervention (MBI) on preterm brain maturation and neurodevelopment using electroencephalography (EEG) and event related potentials (ERPs). EEG captures electrical potential oscillations of the brain which yields valuable information about brain function. Serial EEGs can track brain maturation in preterm infants. ERPs quantify electrical brain potentials changes time-locked with a stimulus. ERPs at 1 month corrected age test recognition memory function and cognitive processing and offers another objective measure to study the early effects of the MBI’s on neurodevelopment. The R61 will also explore the behavioral processes underlying effects of MBI on pain using EEG and the premature infant pain profile (PIPP). In preterm infants, central EEG amplitudes change when time-locked to a painful stimulus and PIPP scores scale pain responses with painful procedures. Specific recorded lullabies with simple arpeggiated accompaniment will be played for 6 weeks in a small randomized, blinded, controlled study of 50 medically stable 30 week preterms. Exploratory R61 findings will be assessed by specific Go/NoGo milestones that provide insight into the effects of MBI on biological mechanisms underlying neurodevelopment and behavioral processes underlying pain. By achieving one of the Go/NoGo milestones, the proposal progresses to the R33 proof of concept pilot clinical trial with an additional 100 randomized subjects that will assess two primary outcomes measures: 1) MBI effects on Late Neurodevelopment using Bayley’s III neurodevelopmental testing at 6 month corrected age, and 2) Cumulative effects of MBI on Pain Response using longitudinal comparisons of baseline PIPP scores and final PIPP scores after 4 weeks of MBI. Secondary measures would explore more nuanced aspects of neurodevelopment: 1) MBI effects on brain maturation with expanded analyses of EEG-sleep components; 2) repeat ERP analysis at 6 months corrected age with expanded memory and cognitive testing (additional mismatch negativity paradigms); and pain response: 3) MBI effects on pain related EEG responses with comparative analyses of central EEG amplitude changes to the frontal, parietal, temporal, and occipital lobes.