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

摘要： 发育性阅读障碍(Development Dyslexia，DD)是一种源于神经生物学的高度遗传性的特殊学习障碍， 但是 潜在的神经机制在很大程度上是未知的。虽然直到儿童未能诊断出DD才能诊断出 在阅读障碍和相关心理障碍后，通常在小学后期学习阅读 负担明显，干预措施对年龄较小的儿童最有效。因此，到目前为止，DD通常是 在经过最有效的干预时间后确诊。基因之间的一条试探性途径 DD的影响、早期脑发育和行为已被提出，但只有几项研究进行了检验 有DD风险的婴儿的纵向脑发育，没有人研究过脑的发育 结构或代谢功能。此外，尽管行为研究表明， 亲子阅读技能的代际传递结构 而痴呆症患者的功能性脑改变尚不清楚。在我们之前工作的基础上，它显示了非典型的 有阅读障碍风险的婴儿、学龄前儿童和幼儿园儿童的大脑功能和结构发育， 这项提议的项目的目标是描述婴儿早期脑发育的轨迹。 (FHD+)和不(FHD-)是从婴儿期到小学以及以后的DD的家族风险 研究与双亲发育迟缓相关的脑部改变的代际传递。我们会 利用纵向方法和 MR措施将在新的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是 检查过了。使用功能和结构磁共振成像以及磁共振 光谱和行为测量，目标1(横截面)将表征非典型的结构、功能 在5个时间点，与FHD-婴儿和儿童相比，FHD+组的代谢性脑发育情况。目标2 (纵向)利用增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将研究 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-父母二人组中。目前只有在多年阅读失败后才进行DD诊断的做法是有害的 对于多年来经历了DD的心理社会影响的儿童及其家人的福祉 在诊断之前。在婴儿期确定DD的潜在神经机制是非常有创新性的，并具有 为早期识别处于危险中的儿童提供信息的可能性以及早期预防和发展 在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 注意这一年龄组(婴儿期)的DD，并有可能为纵向研究提供一个模型 其他发育障碍。它可以进一步强调检查大脑发育的重要性 从婴儿期开始的轨迹图，阐明了整个发育阶段的新出现的大脑行为关联 时间线。

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.