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

总结： 发展性阅读障碍（DD）是一种遗传性很强的神经生物学起源的学习障碍， 但 潜在的神经机制在很大程度上是未知的。虽然DD是不诊断，直到一个孩子已经失败， 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 如果负担明显，干预措施对幼儿最有效。因此，到目前为止，DD通常 在最有效的干预时间过去后才被诊断出来。一种尝试性的途径， 影响，早期大脑发育和行为的DD已提出，但只有少数研究已经检查 有DD风险的婴儿的纵向大脑发育，没有人研究过大脑的发育 结构或代谢功能。此外，虽然行为研究已经证明了一个强大的 父母与孩子的阅读能力之间的关系、结构性的代际传递 DD的脑功能改变尚不清楚。基于我们之前的工作， 婴儿、学龄前儿童和有阅读障碍风险的成年人的大脑功能和结构发育， 这个项目的目标是描述婴儿早期大脑发育的轨迹， (FHD+）和无（FHD-）DD的家族风险，从婴儿早期到小学，并进一步 研究与儿童-父母二人组中DD相关的大脑改变的代际传递。我们将 采用纵向方法， 将在新的婴儿队列和现有儿童中获得MR测量结果 已收集婴儿数据的队列。此外，所有儿童的父母将 考察利用功能和结构磁共振成像以及磁共振成像 光谱学和行为测量，目标1（横截面）将表征非典型的结构，功能 FHD+与FHD-婴儿和儿童在5个时间点的代谢性脑发育。目的2 （纵向）利用生长曲线和轨迹分析来表征和比较发展 FHD+和FHD-婴儿从婴儿期到小学的轨迹。目标3将审查 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 在亲子二人组中。目前的做法是在阅读失败数年后才进行DD诊断，这是有害的 多年来经历DD心理社会影响的儿童及其家庭的福祉 在诊断之前。确定婴儿期DD的潜在神经机制是高度创新的， 为早期识别风险儿童和制定早期预防和 在大脑可塑性增强的时期采取干预策略。它也可能吸引更多的研究 注意这个年龄组（婴儿期）的DD，并有可能提供一个模型的纵向研究， 其他发展障碍。它可以进一步突出检查大脑发育的重要性 从婴儿期开始的轨迹，以照亮整个发展过程中新兴的大脑行为关联， 时间轴。

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.