Cerebral metabolism, EEG, and sleep cycling in critically ill neonates

危重新生儿的脑代谢、脑电图和睡眠周期

• 批准号: 8639589
• 负责人: Renee A. Shellhaas
• 金额: $ 13.31万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-03 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8639589
• 关键词: Address; Adult; Affect; Award; Behavioral; Biological Markers; Brain; Brain Injuries; Cerebral Palsy; Cerebrum; Certification; Cessation of life; Child; Clinical; Clinical Research; Collaborations; Commit; Complex; Consultations; Critical Illness; Data; Development; Development Plans; Developmental Disabilities; Diagnostic; Early identification; Educational process of instructing; Electroencephalography; Encephalopathies; Engineering; Environment; Etiology; Evaluation; Faculty; Foundations; Functional disorder; Funding; Goals; Grant; Health; Impact Seizures; Individual; Infant; Influentials; Lead; Learning; Logistic Regressions; Master' s Degree; Measures; Medicine; Mental Retardation; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Metabolic; Metabolism; Methods; Michigan; Near-Infrared Spectroscopy; Neonatal; Neonatology; Neurodevelopmental Disability; Neurologist; Neurology; Neuronal Injury; Neurosciences; Newborn Infant; Outcome; Outcome Assessment; Oxygen; Pattern; Perfusion; Physiological; Physiology; Polysomnography; Population; Positioning Attribute; Predictive Value; Predisposition; Principal Investigator; Protocols documentation; Public Health Schools; Recording of previous events; Research; Research Design; Research Personnel; Risk; Scientist; Secure; Seizures; Series; Signal Transduction; Sleep; Sleep Disorders; Sleep Wake Cycle; Spectrum Analysis; Stratification; Survivors; Teaching principal; Techniques; Technology; Therapeutic; Time; Tissues; Training; Translational Research; Universities; Wakefulness; Work; adverse outcome; age group; behavior influence; biobehavior; brain metabolism; career; career development; clinical care; clinical risk; design; high risk; improved; innovation; insight; interdisciplinary approach; medical schools; neonatal hypoxic-ischemic brain injury; neonate; neurophysiology; neuroprotection; novel; novel diagnostics; novel therapeutic intervention; patient population; pediatric department; pediatrician; predictive modeling; programs; prospective; protocol development; signal processing; skills; statistical center; statistics; success; theories; treatment strategy

DESCRIPTION (provided by applicant): Candidate: The PI is a board-certified child neurologist and pediatrician, with additional certification in clinical neurophysiology and a master's degree in clinical research design and statistics. She plans a clinical research career focused on neonatal seizures and encephalopathy. The PI secured initial funding from foundation and intramural grants to begin studies that combine near-infrared spectroscopy (NIRS), conventional electroencephalography (EEG), and amplitude-integrated EEG as biomarkers of brain function and integrity in neonates with seizures and with hypoxic ischemic encephalopathy. Exciting preliminary results led to the new hypotheses and research strategies now proposed. Key short-term goals include expansion of the PI's research to incorporate neonatal sleep physiology and complex signal analysis techniques, which will require additional mentorship and training. The PI's long-term goal is to develop rigorous multidisciplinary approaches that could substantially improve the evaluation and treatment of neonatal seizures and encephalopathy. This award will transition the PI to independence as a clinical researcher, broaden her research to incorporate sleep physiology, and assemble new collaborations to innovate state-of-the art analytic methods. With the expertise obtained through this K23 award, the PI will position herself as a clinical scientist uniquely able to pursue critical questions at the interface of neonatology, clinical neurophysiology, neurology, and sleep medicine. Environment: The PI will draw on major institutional strengths in sleep medicine and neonatal neurology, in addition to her mentor's long-standing research collaborations with colleagues in statistics and engineering, to create a unique mentoring team solidly committed to her success. The University of Michigan Medical School, Department of Pediatrics, and Sleep Disorders Center provide an exceptional environment for career development. Each has a long history of influential clinical and translational research, along with a well demonstrated and productive track record in junior faculty career development. Career Development Plan: The PI will benefit from an outstanding mentorship team, including experts in sleep medicine, neonatology, engineering, and statistics, to develop her research career in a novel direction. Dr. Chervin, primary mentor, is director of the Sleep Disorders Center and will oversee the PI's training in the theory, practice, and interpretation of polysomnography, and provide assistance with protocol development and implementation, along with guidance on transition to research independence. Dr. Barks, co-mentor, is director of Neonatology and serves as the PI's mentor for her currently funded studies. He will be instrumental in protocol design and implementation, and provide mentorship in aspects of neonatal neurology and neuroprotection. Consultants will offer additional expertise in neonatal neuromonitoring and in statistics and signal analysis. Through rigorous graduate-level course work at the University of Michigan's renowned School of Public Health, Neuroscience Program, and Center for Statistical Consultation and Research, as well as seminars and one-on-one teaching, the PI will gain expertise in sleep physiology, neonatal polysomnography, and the advanced signal processing and repeated measures statistics necessary to address complex time series data on multiple physiological functions. Research Plan: Background: Survivors of neonatal seizures are at high risk for neurodevelopmental disability. The pathophysiology underlying adverse outcomes is poorly understood, but data from adults suggest that behavioral (sleep) state influences susceptibility to seizures, alters cerebral metabolism, and could modify vulnerability to seizure-related neuronal injury. We propose to analyze the complex relationships between neonatal seizures and sleep physiology using state-of-the-art technology, including electroencephalography (EEG) to assess seizure burden, polysomnography (PSG) to characterize biobehavioral state, and near- infrared spectroscopy (NIRS) to evaluate cerebral metabolism. Hypotheses: 1) Neonatal sleep-wake cycling is associated with reproducible changes in cerebral metabolism. 2) Neonatal seizures are associated with increased metabolic demand, which is magnified during behavioral states with inherently increased cerebral metabolism. 3) Among neonates with seizures, biobehavioral state assessment, cerebral metabolism, and seizure burden can accurately predict neurodevelopmental outcome. Aims: 1) Perform cross-channel analyses of NIRS and EEG in 50 critically ill neonates during wakefulness, active and quiet sleep. 2) Employ measures of coherence, causality, and directed transfer functions to assess for altered cerebral metabolism associated with seizures arising from wakefulness, active and quiet sleep. 3) Perform 18-month neurodevelopmental assessments on survivors of neonatal seizures and determine the predictive value of PSG, NIRS, and EEG for identification of infants at highest risk for adverse outcomes. Significance: Quantification of the complex interplay between neonatal seizures, behavioral state, and cerebral metabolism will generate novel insight into the pathophysiology of adverse outcomes in high-risk individuals, and could lead to new diagnostic and therapeutic approaches. The PI will gain a unique combination of skills - in sleep, neonatal neurology, and signal processing - that will enable her to launch a successful independent research career with great promise to improve the health of a highly vulnerable patient population.

描述（由申请人提供）：候选人：PI是委员会认证的儿童神经学家和儿科医生，具有临床神经生理学的额外认证以及临床研究设计和统计学硕士学位。她计划从事新生儿癫痫和脑病的临床研究。PI从基金会和校内赠款中获得了初始资金，开始研究，将联合收割机近红外光谱（NIRS）、常规脑电图（EEG）和振幅积分EEG结合起来，作为癫痫发作和缺氧缺血性脑病新生儿脑功能和完整性的生物标志物。令人兴奋的初步结果导致了现在提出的新假设和研究策略。关键的短期目标包括扩大PI的研究，将新生儿睡眠生理学和复杂的信号分析技术，这将需要额外的指导和培训。PI的长期目标是开发严格的多学科方法，可以大大改善新生儿癫痫发作和脑病的评估和治疗。该奖项将使PI转变为独立的临床研究人员，扩大她的研究，将睡眠生理学纳入其中，并建立新的合作，以创新最先进的分析方法。凭借通过K23奖项获得的专业知识，PI将把自己定位为一名临床科学家，能够在神经病学，临床神经生理学，神经病学和睡眠医学的界面上寻求关键问题。工作环境：PI将利用睡眠医学和新生儿神经病学的主要机构优势，以及她的导师与统计和工程领域同事的长期研究合作，创建一个独特的指导团队，坚定地致力于她的成功。密歇根大学医学院，儿科系和睡眠障碍中心为职业发展提供了一个特殊的环境。每个有影响力的临床和转化研究的悠久历史，沿着在初级教师职业发展的良好证明和富有成效的跟踪记录。职业发展计划：PI将受益于一个优秀的导师团队，包括睡眠医学，神经病学，工程学和统计学专家，在一个新的方向发展她的研究生涯。主要导师Chervin博士是睡眠障碍中心的主任，他将监督PI在多导睡眠图的理论、实践和解释方面的培训，并提供方案制定和实施方面的帮助，沿着向研究独立性过渡的指导。Barks博士，共同导师，是新生儿科主任，并担任PI的导师，为她目前资助的研究。他将在协议的设计和实施，并在新生儿神经学和神经保护方面提供指导。顾问将提供新生儿神经监测以及统计和信号分析方面的额外专业知识。通过在密歇根大学著名的公共卫生学院，神经科学项目和统计咨询与研究中心严格的研究生课程工作，以及研讨会和一对一教学，PI将获得睡眠生理学，新生儿多导睡眠图，以及高级信号处理和重复测量统计学方面的专业知识，以解决多种生理功能的复杂时间序列数据。研究计划：背景：新生儿癫痫发作的幸存者是神经发育障碍的高危人群。不良结局的病理生理学基础尚不清楚，但成人数据表明，行为（睡眠）状态影响癫痫发作的易感性，改变脑代谢，并可能改变癫痫相关神经元损伤的脆弱性。我们建议使用最先进的技术分析新生儿癫痫发作和睡眠生理之间的复杂关系，包括脑电图（EEG）评估癫痫发作负荷，多导睡眠图（PSG）表征生物行为状态，近红外光谱（NIRS）评估脑代谢。假设：1）新生儿睡眠-觉醒周期与脑代谢的可重复变化有关。2)新生儿癫痫发作与代谢需求增加有关，在大脑代谢固有增加的行为状态下，代谢需求被放大。3)在癫痫发作的新生儿中，生物行为状态评估、脑代谢和癫痫负荷可以准确预测神经发育结果。目的：1）对50例危重新生儿在清醒、主动睡眠和安静睡眠状态下的近红外光谱（NIRS）和脑电图（EEG）进行跨通道分析。2)采用连贯性，因果关系和定向传递函数的措施，以评估与觉醒，主动和安静睡眠引起的癫痫发作相关的脑代谢改变。3)对新生儿癫痫发作的幸存者进行18个月的神经发育评估，并确定PSG、NIRS和EEG的预测价值，以识别不良结局风险最高的婴儿。重要性：新生儿癫痫发作，行为状态和脑代谢之间的复杂相互作用的量化将产生新的见解不良后果的病理生理学在高危人群，并可能导致新的诊断和治疗方法。PI将获得独特的技能组合-在睡眠，新生儿神经学和信号处理-这将使她能够启动一个成功的独立研究生涯，具有很大的希望，以改善高度脆弱的患者群体的健康。

项目成果

Phenobarbital and neonatal seizures affect cerebral oxygen metabolism: a near-infrared spectroscopy study.

• DOI: 10.1038/pr.2015.64
• 发表时间: 2015-07
• 期刊: PEDIATRIC RESEARCH
• 影响因子: 3.6
• 作者: Sokoloff, Max D.;Plegue, Melissa A.;Chervin, Ronald D.;Barks, John D. E.;Shellhaas, Renee A.
• 通讯作者: Shellhaas, Renee A.

Quantitative sleep stage analyses as a window to neonatal neurologic function.

定量睡眠阶段分析是新生儿神经功能的窗口。

• DOI: 10.1212/wnl.0000000000000085
• 发表时间: 2014
• 期刊: Neurology
• 影响因子: 9.9
• 作者: Shellhaas,RenéeA;Burns,JosephW;Barks,JohnDE;Chervin,RonaldD
• 通讯作者: Chervin,RonaldD

Impact of hands-on care on infant sleep in the neonatal intensive care unit.

• DOI: 10.1002/ppul.23513
• 发表时间: 2017-01
• 期刊: Pediatric pulmonology
• 影响因子: 3.1
• 作者: Levy J;Hassan F;Plegue MA;Sokoloff MD;Kushwaha JS;Chervin RD;Barks JD;Shellhaas RA
• 通讯作者: Shellhaas RA

Sleep-wake cycling and cerebral oxygen metabolism among critically ill neonates.

危重新生儿的睡眠-觉醒循环和脑氧代谢。

• DOI: 10.1177/0883073812470972
• 发表时间: 2014
• 期刊: Journal of child neurology
• 影响因子: 1.9
• 作者: Shellhaas,RenéeA;Burns,JosephW;Wiggins,StephanieA;Christensen,MaryK;Barks,JohnDE;Chervin,RonaldD
• 通讯作者: Chervin,RonaldD

Impact of NICU design on environmental noise.

NICU 设计对环境噪声的影响。

• DOI: 10.1016/j.jnn.2013.07.003
• 发表时间: 2014
• 期刊: Journal of neonatal nursing : JNN
• 作者: Szymczak,StacyE;Shellhaas,RenéeA
• 通讯作者: Shellhaas,RenéeA