Examining neural mechanisms of developmental dyslexia from infancy to school-age

检查从婴儿期到学龄期发育性阅读障碍的神经机制

• 批准号: 9349558
• 负责人: Nadine Gaab
• 金额: $ 66.11万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-15 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9349558
• 关键词: Adult; Affect; Age-Months; Animals; Area; Attention; Auditory; Behavior; Behavioral; Behavioral Research; Birth; Brain; Brain region; Child; Choline; Data; Development; Developmental Disabilities; Developmental reading disorder; Diagnosis; Dyslexia; Early identification; Electroencephalography; Equation; Failure; Family; Fathers; First Degree Relative; Functional disorder; Genes; Genetic; Glutamates; Goals; Growth; Heritability; Human; Impairment; Infant; Intercept; Intervention; Language; Learning; Learning Disabilities; Left; Link; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Metabolic; Modeling; Mothers; Neurobiology; Parents; Pathway interactions; Pattern; Play; Populations at Risk; Prevention strategy; Protocols documentation; Reader; Reading; Reporting; Research; Residual state; Risk; Role; School-Age Population; Single Nucleotide Polymorphism; Speech; Speech Sound; Structure; Susceptibility Gene; Testing; Thick; Time; TimeLine; Variant; Work; age group; behavior measurement; brain behavior; cognitive process; cohort; elementary school; endophenotype; experience; gray matter; in utero; infancy; innovation; intergenerational; kindergarten; longitudinal design; malformation; migration; neuroimaging; neuromechanism; phonology; psychologic; psychosocial; relating to nervous system; response; second grade; skills; transmission process; white matter

SUMMARY: Developmental Dyslexia (DD) is a strongly heritable specific learning disability of neurobiological origin, but the underlying neural mechanisms are largely unknown. Although DD is not diagnosed until a child has failed to learn to read, usually in late elementary school, after reading impairments and associated psychological burdens manifest, interventions are most effective in younger children. Thus, to date, DD is generally diagnosed after the most effective time for intervention has passed. A tentative pathway between genetic effects, early brain development, and behavior in DD has been proposed but only a few studies have examined longitudinal brain development in infants at risk for DD and none have investigated the development of brain structure or metabolic function. Furthermore, although behavioral research has demonstrated a strong relationship between reading skills in parents and their children, the intergenerational transmission of structural and functional brain alterations in DD is unknown. Building on our previous work, which showed atypical functional and structural brain development in infants, preschoolers, and kindergarteners at-risk for dyslexia, the goal of this proposed project is to characterize trajectories of early brain development in infants with (FHD+) and without (FHD-) a familial risk for DD from early infancy through elementary school and to further examine intergenerational transmission of brain alterations associated with DD in child-parent dyads. We will utilize a longitudinal approach and MR measures will be obtained in a new infant cohort, and an existing child cohort for which infant data have already been collected. Furthermore, the parents of all children will be examined. Using functional and structural magnetic resonance imaging as well as magnetic resonance spectroscopy and behavioral measures, Aim 1 (cross-sectional) will characterize atypical structural, functional and metabolic brain development in FHD+ compared to FHD- infants and children at 5 time points. Aim 2 (longitudinal) utilizes growth curve and trajectory analyses to characterize and compare developmental trajectories of FHD+ and FHD- infants from infancy through elementary school. Aim 3 will examine the intergenerational transmission of brain structure/function critical for reading as well as behavioral reading skills in children-parent dyads. The current practice of DD diagnosis only after years of reading failure is detrimental to the well-being of children and their families who experience the psychosocial implications of DD for years prior to diagnosis. Identifying the underlying neural mechanisms of DD in infancy is highly innovative and has the potential to inform early identification of children at risk and the development of early preventive and intervention strategies during a period of heightened brain plasticity. It may also draw increased research attention to this age group (infancy) in DD and has the potential to provide a model for longitudinal studies of other developmental disabilities. It can further highlight the importance of examining brain development trajectories starting in infancy to illuminate emerging brain-behavior associations across the developmental timeline.

概括： 发育性阅读障碍（DD）是一种具有强烈遗传性的神经生物学起源的特定学习障碍， 但是 潜在的神经机制很大程度上是未知的。虽然 DD 是在孩子无法诊断之前才被诊断出来的 在阅读障碍和相关的心理障碍之后，通常在小学后期学习阅读 由于负担明显，干预措施对年幼的儿童最为有效。因此，迄今为止，DD 通常是 过了最有效的干预时间后才确诊。遗传之间的尝试性途径 DD 的影响、早期大脑发育和行为已经被提出，但只有少数研究进行了检验 有 DD 风险的婴儿的纵向大脑发育，但没有人研究过大脑的发育 结构或代谢功能。此外，尽管行为研究已经证明了强有力的 父母与子女阅读技能的关系、结构性的代际传承 DD 中大脑功能的改变尚不清楚。以我们之前的工作为基础，该工作显示出非典型的 有阅读障碍风险的婴儿、学龄前儿童和幼儿园儿童的功能和结构性大脑发育， 该项目的目标是描绘患有以下疾病的婴儿的早期大脑发育轨迹： (FHD+) 和没有 (FHD-) 从婴儿早期到小学直至进一步发展的 DD 家族风险 检查与亲子二人中的 DD 相关的大脑改变的代际传递。我们将 利用纵向方法 MR 测量将在新婴儿队列和现有儿童中获得 已经收集了婴儿数据的队列。此外，所有孩子的父母都将 检查了。使用功能和结构磁共振成像以及磁共振 光谱学和行为测量，目标 1（横截面）将表征非典型结构、功能 与 FHD- 婴儿和儿童相比，FHD+ 在 5 个时间点的大脑代谢发育情况。目标2 （纵向）利用生长曲线和轨迹分析来表征和比较发育 FHD+ 和 FHD- 婴儿从婴儿期到小学的轨迹。目标 3 将检查 对阅读和行为阅读技能至关重要的大脑结构/功能的代际传递 在孩子与父母的二元关系中。当前仅在多年阅读失败后才进行 DD 诊断的做法是有害的 对多年来经历 DD 社会心理影响的儿童及其家庭的福祉 在诊断之前。识别婴儿期 DD 的潜在神经机制具有高度创新性，并且具有 为及早识别处于危险中的儿童以及制定早期预防和预防措施提供信息的潜力 大脑可塑性增强时期的干预策略。它还可能吸引更多的研究 关注 DD 中的这个年龄组（婴儿期），并有可能为 DD 的纵向研究提供模型 其他发育障碍。可以进一步凸显检查大脑发育的重要性 从婴儿期开始的轨迹阐明了整个发育过程中新兴的大脑行为关联 时间线。