Longitudinal Study of childhood dyslexia fMRI markers prior to reading onset

阅读开始前儿童阅读障碍功能磁共振成像标记的纵向研究

• 批准号: 8432049
• 负责人: Nadine Gaab
• 金额: $ 61.05万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-15 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8432049
• 关键词: 6 year old; Acoustics; Adult; Affect; Area; Auditory; Behavioral; Brain; Brain region; Child; Clinical; Development; Developmental reading disorder; Diagnosis; Early Intervention; Early identification; Education; Enrollment; Family; Family history of; Functional Magnetic Resonance Imaging; Functional disorder; Genetic; Health; Heritability; Impairment; Individual; Infant; Instruction; Knowledge; Language; Learning Disabilities; Left; Link; Longitudinal Studies; Measures; Molecular Genetics; Morphology; Neuroanatomy; Neurologic; Outcome; Predictive Value; Process; Psychological Impact; Psychometrics; Psychophysics; Reader; Reading; Reading Disabilities; Research; School-Age Population; Schools; Social Impacts; Speech Sound; Staging; Stimulus; Twin Studies; base; brain morphology; brain volume; childhood dyslexia; disability; gray matter; high school; indexing; intervention program; juvenile justice system; longitudinal design; neurodevelopment; neuroimaging; peer; phonology; prevent; programs; psychologic; relating to nervous system; remediation; response; skills; social; social implication; third grade; white matter

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.

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 的遗传性得到了分子遗传学研究以及对患有 DD 的双胞胎和家庭的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。多项功能神经影像研究将 DD 成人和儿童与典型对照进行比较，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，在语言和听觉处理的神经相关性方面也观察到了差异。此外，有人提出，在 DD 儿童中观察到的功能差异可能与大脑形态差异有关。脑容量测量显示，诊断为 DD 的儿童和成人的大脑区域存在结构异常，这些区域与观察到的功能差异大致重叠。许多关键问题仍未得到解答。我们不知道在阅读开始之前，观察到的与 DD 相关的大脑功能和结构差异是否存在于随后接受诊断的人身上。我们不知道这些功能和结构差异是否可以用来预测以后的阅读结果。目前还不清楚，DD 儿童从预阅读阶段进入熟练阅读阶段时，受损的关键技能（例如语音处理和快速听觉处理）是如何发展的。此外，我们不知道这些受损的技能如何影响后来阅读流畅性的发展轨迹。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，但这些知识尚未对预阅读大脑进行全面检查，以研究 DD 神经预标记的预测价值并表征有或没有 DD 家族史的儿童的功能性和结构性大脑测量的发育轨迹。我们将通过检查 60 名有 DD 家族史的学前阅读者和 60 名没有 DD 家族史的学前阅读者，从学前阅读阶段到三年级纵向跟踪他们的阅读发展，来弥补这些缺失的联系。具体来说，我们将确定： 1. 与 DD 相关的大脑功能差异是否可以在阅读开始之前观察到（具体目标 1）； 2. 如果在阅读开始之前就已经观察到与 DD 相关的大脑结构差异（具体目标 2）； 3. 随着儿童从预阅读者转变为熟练阅读者，关键的阅读技能（语音处理、快速听觉处理和阅读流畅性）如何发展（具体目标3）； 4. 从预读者和/或初学者那里获得的哪个单一预测变量或一组预测变量最能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，拟议研究的目标是在开始阅读之前，全面表征有或无 DD 家族史的儿童的大脑功能和形态，并纵向跟踪这些儿童的大脑发育。使用功能性和结构性大脑指数以及心理测量和心理物理学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用于最好地预测以后的阅读结果。拟议的研究具有重要的临床、心理和社会影响。研究表明，有学习障碍的儿童比同龄人获得高中文凭 [8] 或就读高等教育课程的可能性较小。在学校表现不佳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素对于早期干预计划的制定和改进至关重要。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。