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）是最突出的特定学习障碍之一，影响5 - 17%的儿童。DD的遗传性得到了来自分子遗传学研究以及双胞胎和DD家族研究的有力证据的支持。大量证据表明，神经系统异常是儿童和成人DD的基础。多功能神经影像学研究比较成人和儿童与典型的控制DD观察功能障碍的各种大脑区域。在有阅读或语言障碍家族史的婴儿中，与没有家族史的婴儿相比，语言和听觉处理的神经相关性也存在差异。此外，有人认为，在DD儿童中观察到的功能差异可能与大脑形态学差异有关。脑容量的测量结果显示，在儿童和成人中，诊断为DD的区域与观察到的功能差异广泛重叠，存在结构异常。一些关键问题仍然没有答案。我们不知道在阅读发作之前，在那些后来接受诊断的人中，是否存在与DD相关的功能和结构性大脑差异。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。目前还不清楚DD患者受损的关键技能（例如，语音处理和快速听觉处理）在儿童从阅读前阶段进入熟练阅读阶段时发展。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。这些开放性问题表明，虽然我们对DD患者的大脑有很多了解，但这些知识尚未导致对预读大脑进行全面检查，以调查DD神经前标记物的预测价值，并表征有和没有DD家族史的儿童的功能和结构性大脑措施的发展轨迹。我们将通过检查60名有DD家族史的预读者和60名没有DD家族史的预读者，从预读阅读阶段到三年级纵向跟踪他们的阅读发展，来建立这些缺失的联系。具体来说，我们将确定：1。如果在阅读发作之前已经可以观察到与DD相关的功能性脑差异（具体目标1）; 2.是否在阅读发作之前已经观察到与DD相关的脑结构差异（具体目标2）; 3.关键的阅读技能（语音处理，快速听觉处理和阅读流畅性）是如何发展的儿童从阅读前到熟练的读者（具体目标3）;和4。哪一个单一的预测因子，或一组预测因子，从预阅读者和/或开始阅读者那里获得的，将最好地预测三年阅读指导后儿童的阅读结果。（具体目标4）总体而言，所提出的研究的目的是全面表征在阅读开始之前有和没有DD家族史的儿童的脑功能和形态，并纵向跟踪这些儿童的脑发育。使用功能和结构脑指数以及心理测量和心理物理测量来实现这一目标，将使我们能够识别哪些标记或标记可以用于最好地预测以后的阅读结果。这项研究具有重要的临床、心理和社会意义。研究表明，有学习障碍的儿童比同龄人更不可能获得高中文凭[8]或参加高等教育课程。在学校挣扎的儿童也更容易进入少年司法系统。早期识别阅读障碍的预测因子对于发展和改善早期干预方案至关重要。更重要的是，识别这些早期预测因子可以预防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.