Longitudinal Study of childhood dyslexia fMRI markers prior to reading onset

描述（由申请人提供）：发展性阅读障碍（DD）是最突出的特殊学习障碍之一，影响了5-17%的儿童。分子遗传学研究以及对双胞胎和DD家庭的研究有力地支持了DD的遗传性。大量证据表明，儿童和成人的DD背后是神经异常。多项功能性神经影像学研究将成人和儿童的DD与典型对照进行了比较，发现在大脑的各个区域都存在功能障碍。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相关方面也存在差异。此外，有研究表明，DD患儿的功能差异可能与脑形态差异有关。脑容量测量显示，在诊断为DD的儿童和成人中，结构异常的区域与观察到的功能差异广泛重叠。许多关键问题仍未得到解答。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发病之前就存在于那些后来被诊断为DD的人身上。我们不知道这些功能和结构上的差异是否可以用来预测以后的阅读结果。当儿童从阅读前阶段过渡到熟练阅读阶段时，DD患者受损的关键技能（如语音处理和快速听觉处理）是如何发展的，目前还不清楚。此外，我们不知道这些受损的技能如何影响阅读流畅性的后期发展轨迹。这些悬而未决的问题表明，虽然我们对DD患者的大脑了解很多，这些知识还没有导致对阅读前大脑的全面检查，以调查神经预标记物对DD的预测价值，并表征有和没有DD家族史的儿童的功能和结构脑测量的发展轨迹。我们将通过对60名有和60名没有DD家族史的阅读前读者进行调查，从阅读前开始纵向跟踪他们的阅读发展，从而找到这些缺失的联系直到三年级。具体来说，我们将确定：1。如果与DD相关的功能性脑差异在阅读开始之前就已经可以观察到（具体目标1）；2. 如果在阅读开始之前就可以观察到与DD相关的大脑结构差异（具体目标2）；3. 当孩子从预阅读到熟练阅读时，关键的阅读技能（语音处理、快速听觉处理和阅读流畅性）是如何发展的（具体目标3）；和4。哪一个单一的预测因子，或一组预测因子，从pre-readers和/或初级读者中获得，将最好地预测三年后儿童阅读指导的结果？（具体目标4）总的来说，本研究的目的是全面表征有或没有DD家族史的儿童在开始阅读之前的脑功能和形态学，并纵向跟踪这些儿童的大脑发育。通过使用大脑功能和结构指数，以及心理测量和心理物理测量来实现这一目标，将使我们能够确定哪些标记或哪些标记可以用来最好地预测以后的阅读结果。这项提议的研究具有重要的临床、心理和社会意义。研究表明，与同龄人相比，有学习障碍的孩子获得高中文凭或接受高等教育的可能性更小。在学校表现不佳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早期干预计划的发展和改进至关重要。更重要的是，识别这些早期预测因素可以预防DD的临床、心理和社会影响。

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.