Brain Development and Pre-Speech Function in Infants with Isolated Oral Clefts: Relationship to Anesthesia Exposure and Oxygenation

孤立性口裂婴儿的大脑发育和言语前功能：与麻醉暴露和氧合的关系

• 批准号: 10427075
• 负责人: Amy Lynn Conrad
• 金额: $ 51.05万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427075
• 关键词: Academic achievement; Accounting; Address; Adolescent; Adult; Age-Months; Anesthesia procedures; Anesthetics; Animals; Applications Grants; Audiology; Biological; Birth; Brain; Brain imaging; Cell Death; Cells; Child; Cleft lip with or without cleft palate; Clinical; Cognitive; Cognitive deficits; Cortical Dysplasia; Data; Development; Early treatment; Etiology; Evaluation; Exposure to; Functional disorder; Genetic; Goals; Growth; Hypoxia; Image; Incidence; Infant; Intervention; Label; Language; Language Development; Language Disorders; Learning Disabilities; Life; Lip structure; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Medical; Neuraxis; Neurological observations; Neurons; Neuropsychology; Operative Surgical Procedures; Orthopedics; Outcome; Outcome Measure; Oxygen; Palate; Participant; Performance; Persons; Pilot Projects; Population; Proxy; Pulse Oximetry; Reading; Reading Disorder; Reporting; Research; Research Design; Research Project Grants; Risk; Role; Sample Size; Sampling; Site; Sleep; Speech; Speech Development; Structure; Syndrome; Techniques; Time; Work; airway obstruction; base; brain cell; brain volume; cell motility; cerebral oxygenation; classical conditioning; college; comorbidity; disability; early life exposure; functional near infrared spectroscopy; infancy; innovation; interest; language outcome; male; migration; neural growth; neurodevelopment; neuroimaging; neuron development; oral cleft; reading difficulties; recruit; relating to nervous system; sex; theories; trend; white matter; young adult

Project Summary/Abstract The purpose of this research grant application is to expand a pilot project evaluating the earliest markers of brain and pre-speech development in infants with isolated cleft of the lip and/or palate (iCL/P) – before their first exposure to anesthesia. Research has documented a high incidence of specific learning disabilities (most notably language or reading deficits) among this population. These disabilities, while not in the range of Intellectual Dysfunction, do result in academic achievement problems and lower rates of college attendance. Recent work has also documented differences in brain structure and function among people with an isolated oral cleft that is correlated to measures of cognitive and academic functioning. These differences have been identified across child, adolescent, young adult, and adult samples. Current theories on the etiology of these structural and functional differences have proposed: 1) early exposure to anesthesia, 2) obstructed airway and resulting reduced oxygenation, and 3) abnormal neural migration as potential contributing factors. The PI conducted a pilot study, obtaining structural MRI scans and vocal recording in infants with (n = 4; 2 with successful MRI) and without (n = 4) isolated oral clefts at 2 months of age (prior to any exposure to anesthesia). Results demonstrated a trend of reduced volume of myelinated white matter and reduced vocal complexity (pre-speech marker of language development) in infants with iCL/P compared to unaffected controls. While preliminary, these findings suggest that differences in infants with iCL/P may be present shortly after birth and prior to exposure to anesthesia – supporting a stronger role of genetics and development in the progression of structural and functional differences identified later in life. The proposed study will expand the pilot by recruiting a larger sample from two sites, obtaining vocal and neuronal measures at three different time points (before and after surgery for those with iCL/P), utilizing both MRI and functional near-infrared spectroscopy (fNIRS) for neural measurement, and obtaining measures of oxygenation. Specific goals of the current project are to: 1) Assess the effects of cleft presence and sex (as well as their interaction) and oxygen level on brain structure/function and pre-speech/language measures at each time point; 2) Evaluate the relationship of early brain structure/function to later brain function and language outcomes; and 3) Assess the potential impact of exposure to anesthesia on developmental trajectories within groups (i.e., iCL, iCP, iCLP, and Unaffected). The results of this study will significantly contribute to the understanding of neuronal development in infants with iCL/P and the impact of exposure to anesthesia and reduced oxygenation have on this development.

项目摘要/摘要 本研究赠款申请的目的是扩展一个试点项目，以评估最早的标记 在嘴唇和/或pa裂（ICL/p）的孤立裂缝的婴儿中的大脑和前语音发育 - 首次暴露于麻醉。研究记录了一系列特定学习障碍的高事件（大多数 在该人群中，值得注意的语言或阅读定义）。这些疾病，虽然不在 智力功能障碍，确实会导致学术成就问题和较低的大学出勤率。 最近的工作还记录了一个孤立的人的大脑结构和功能差异 与认知和学术功能的测量相关的口腔裂缝。这些差异已经 在儿童，青少年，年轻和成人样本中确定。有关这些病因的当前理论 结构和功能差异提出：1）早期暴露于麻醉，2）障碍物和 导致氧合作用降低，3）神经迁移异常，作为潜在的因素。 PI进行了一项试验研究，在患有（n = 4; 2的婴儿）中获得结构性MRI扫描和声带记录 成功的MRI）和没有（n = 4）在2个月大的时候孤立的口腔裂口（在任何暴露之前 麻醉）。结果表明，骨髓白质和人声的减少趋势 ICL/P的婴儿的复杂性（语言发展前语言标记）与不受影响的婴儿相比 控件。虽然初步的结果表明，ICL/P的婴儿可能很快存在差异 出生后和暴露于麻醉之前 - 支持遗传学和发育在 生命后期确定的结构和功能差异的进展。 拟议的研究将通过从两个地点招募较大样本来扩大飞行员，从而获得声音和 在三个不同的时间点（手术前后ICL/p患者的神经元测量），都使用两者 用于神经测量的MRI和功能近红外光谱（FNIRS），并获得测量 氧合。当前项目的具体目标是：1）评估存在和性别的影响（如 以及它们的相互作用）和氧气水平在大脑结构/功能和语音/语言测量方面 每个时间点； 2）评估早期大脑结构/功能与晚期大脑功能的关系 语言结果； 3）评估暴露于麻醉对发育的潜在影响 组内的轨迹（即ICL，ICP，ICLP和不受影响）。这项研究的结果将显着 有助于理解ICL/P的婴儿的神经元发育以及暴露的影响 麻醉和氧合减少对此发育。