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.

项目总结/摘要 这项研究资助申请的目的是扩大一个试点项目，评估最早的标志物， 患有孤立性唇腭裂（iCL/P）的婴儿的大脑和言语前发育-在他们 第一次接触麻醉剂。研究表明，特定学习障碍的发生率很高（大多数 特别是语言或阅读缺陷）。这些残疾，虽然不属于 智力障碍确实会导致学业成绩问题和大学入学率降低。 最近的研究还记录了患有孤立性脑血管病的人在大脑结构和功能上的差异。 唇裂与认知和学习功能相关。这些差异已经 在儿童、青少年、年轻人和成人样本中鉴定。目前关于这些病因的理论 结构和功能差异已经提出：1）早期暴露于麻醉，2）阻塞的气道， 导致氧合减少，和3）异常神经迁移作为潜在的促成因素。 PI进行了一项初步研究，获得了患有（n = 4; 2例 成功的MRI）和无（n = 4）孤立的口裂（在任何暴露于 麻醉）。结果显示有髓白色物质体积减少和发声减少的趋势 iCL/P婴儿与未受影响婴儿的复杂性（语言发育的言语前标记） 对照虽然是初步的，但这些发现表明iCL/P婴儿的差异可能很快就会出现 出生后和暴露于麻醉之前-支持遗传和发育在 在以后的生活中发现的结构和功能差异的进展。 拟议的研究将扩大试点，从两个地点招募更大的样本，获得声音和 在三个不同时间点（iCL/P患者手术前和手术后）进行神经元测量， MRI和功能性近红外光谱（fNIRS）用于神经测量，并获得 氧合本项目的具体目标是：1）评估唇腭裂的存在和性别的影响（如 以及它们之间的相互作用）和氧气水平对大脑结构/功能和言语前/语言测量的影响， 2）评估早期脑结构/功能与后期脑功能的关系， 语言结果;和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和未受影响）。这项研究的结果将显着 有助于了解iCL/P婴儿的神经元发育以及暴露于 麻醉和减少氧合对这种发展的影响。