Longitudinal Study of childhood dyslexia fMRI markers prior to reading onset

描述(申请人提供)：发育性阅读障碍(DD)是最突出的特殊学习障碍之一，影响5%-17%的儿童。来自分子遗传学研究和对患有DD的双胞胎和家庭的研究的强有力的证据支持了DD的遗传性。大量证据表明，儿童和成人DD的基础是神经系统的异常。多项功能神经成像研究将患有痴呆症的成人和儿童与典型对照组进行比较，观察到不同大脑区域的功能障碍。与没有阅读或语言障碍家族史的婴儿相比，有阅读或语言障碍家族史的婴儿在语言和听觉处理的神经关联方面也有差异。此外，有研究表明，在DD儿童中观察到的功能差异可能与大脑形态的差异有关。对脑容量的测量揭示了患有DD的儿童和成人的结构异常，这些区域与观察到的功能差异大体重叠。一些关键问题仍然没有得到回答。我们不知道观察到的与DD相关的大脑功能和结构差异是否在阅读开始之前出现在那些稍后将接受诊断的人中。我们不知道这些功能和结构上的差异是否可以被用来预测以后的阅读结果。发展迟缓儿童的关键技能(例如，语音处理和快速听觉处理)在儿童从读前阶段进入熟练阅读阶段时如何发展，目前还不清楚。此外，我们不知道这些受损的技能是如何影响后来阅读流利性的发展轨迹的。这些悬而未决的问题表明，尽管我们对患有DD的个体的大脑了解很多，但这些知识还没有导致对阅读前大脑的全面检查，以调查神经前标志物对DD的预测价值，并表征有和没有DD家族史的儿童的大脑功能和结构测量的发展轨迹。我们将通过对60名有DD家族史的预读读者和60名没有DD家族史的预读读者从读前阶段到三年级的纵向跟踪他们的阅读发展来寻找这些缺失的联系。具体地说，我们将确定：1.是否在阅读开始之前就已经观察到与DD相关的大脑功能差异(特定目标1)；2.是否在开始阅读之前就已经观察到与DD相关的大脑结构差异(特定目标2)；3.关键阅读技能(语音处理、快速听觉处理和阅读流畅性)是如何随着儿童从阅读前阶段发展到熟练阅读阶段而发展的(特定目标3)；从阅读前和/或初级读者那里获得的哪一项或哪一组预测因子最能预测儿童在三年阅读指导后的阅读结果。(具体目标4)总的来说，本研究的目的是在阅读开始前对有和没有DD家族史的儿童的大脑功能和形态进行全面的表征，并纵向跟踪这些儿童的大脑发育。使用大脑功能和结构指数以及心理测量学和心理物理测量来实现这一目标，将使我们能够确定哪些或哪些标记可以最好地预测以后的阅读结果。这项拟议的研究具有重要的临床、心理和社会影响。研究表明，有学习障碍的孩子比他们的同龄人更不可能获得高中文凭或进入高等教育项目。在学校挣扎的孩子也更容易进入少年司法系统。早期识别阅读障碍的预测因素对于发展和改进早期干预计划是至关重要的。更重要的是，识别这些早期预测因素可能会预防DD对临床、心理和社会的影响。

DESCRIPTION (provided by applicant): Developmental dyslexia (DD) is one of the most prominent specific learning disabilities, affecting 5-17% of children. Heritability of DD has been supported by strong evidence from molecular-genetic studies and from studies of twins and families with DD. Substantial evidence suggests that neurological abnormalities underlie DD in children and adults. Multiple functional neuroimaging studies comparing adults and children with DD to typical controls have observed dysfunctions within various brain regions. Differences in the neural correlates of language and auditory processing have also been observed in infants with a family history of reading or language impairments compared to those without. Additionally, it has been suggested that the functional differences observed in children with DD may be related to morphological brain differences. Measures of brain volume have revealed structural abnormalities in children and adults with a diagnosis of DD in regions that broadly overlap with observed functional differences. A number of key questions remain unanswered. We do not know whether observed functional and structural brain differences associated with DD are present prior to reading onset in those who will later receive a diagnosis. We do not know whether these functional and structural differences could be exploited to predict later reading outcome. It also remains unclear how key skills that are impaired in those with DD (e.g., phonological processing and rapid auditory processing) develop in children as they move from the pre-reading to the skilled reading stage. Additionally, we do not know how these impaired skills affect the later developmental trajectory of reading fluency. These open questions make it apparent that while we know much about the brain of individuals with DD, this knowledge has not yet led to a comprehensive examination of the pre-reading brain to investigate the predictive value of neural pre-markers for DD and to characterize the developmental trajectories of functional and structural brain measures in children with and without a family history of DD. We will make these missing connections by examining 60 pre-readers with and 60 pre-readers without a family history of DD by following their reading development longitudinally from the pre-reading stage until third grade. Specifically, we will determine: 1. If the functional brain differences that are associated with DD can already be observed prior to reading onset (Specific Aim 1); 2. If the structural brain differences that are associated with DD can already be observed prior to reading onset (Specific Aim 2); 3. How key reading skills (phonological processing, rapid auditory processing and reading fluency) develop as children move from being pre-readers to skilled readers (Specific Aim 3); and 4. Which single predictor, or set of predictors, obtained from pre-readers and/or beginning readers will best predict reading outcome in children after three years of reading instruction.(Specific Aim 4) Overall, the aim of the proposed study is to comprehensively characterize brain function and morphology in children with and without a family history of DD prior to the onset of reading and longitudinally follow these children's brain development. Achieving this aim using functional and structural brain indices, as well as psychometric and psychophysical measures, will allow us to identify which marker or markers can be used to best predict later reading outcome. The proposed research has crucial clinical, psychological and social implications. Studies show that children with learning disabilities are less likely than their peers to receive a high school diploma [8] or to enroll in programs of higher education. Children who struggle in school are also more apt to enter the juvenile justice system. The early identification of predictors for reading disability is essential for the development and improvement of early intervention programs. More importantly, identifying these early predictors may prevent the clinical, psychological and social impact of DD.