Neurobiological Foundations of reading (dis)ability

描述（由申请人提供）：拟议的纵向研究旨在检查非受损（Nl）和阅读障碍（RD）队列在其建立的关键点（从7.5-10.5岁）的阅读发展。我们之前的横断面研究已经确定了阅读组在功能神经解剖和行为轨迹上的差异；提出的纵向研究旨在更好地了解导致这种观察到的差异的行为、神经生物学和遗传病因学因素。我们研究了可能导致神经发育和行为轨迹变化的候选致病因子是γ -氨基丁酸（GABA）的假设：研究表明，GABA在学习和记忆中起着至关重要的作用。因此，拟议的研究将允许将阅读表现的发育变化和阅读功能神经解剖学（用fMRI测量）与GABA表达（用磁共振波谱（MRS）和遗传分析测量）联系起来，将GABA家族基因的多态性与GABA在大脑中的表达联系起来。具体而言，本研究旨在：1)在阅读发展的2个重要时间点上，研究遗传学、神经化学、功能神经解剖学和阅读行为之间的同步关系；2)研究这些指标的Nl和RD差异；3)检查Nl和RD队列的后续发展轨迹；4)更好地表征这些队列的学习能力和学习风格；5)开发对遗传分析敏感的动态大脑/行为表型。6)比较RD亚群的多层次特征和发展轨迹。

DESCRIPTION (provided by applicant): The proposed longitudinal study is designed to examine reading development at critical points in its establishment (from ages 7.5-10.5) in nonimpaired (Nl) and reading disabled (RD) cohorts. Our previous cross sectional research has identified reading group differences in both functional neuroanatomical and behavioral trajectories; the proposed longitudinal study is aimed at gaining a better understanding of behavioral, neurobiological, and genetic etiological factors responsible for this observed divergence. We examine the hypothesis that the candidate etiological agent that might underlie variation in neurodevelopmental and behavioral trajectories is gamma-aminobutyric acid (GABA): research has shown that GABA plays a critical role in learning and memory. Accordingly, the proposed research will permit relating developmental changes in reading performance and functional neuroanatomy for reading (measured with fMRI) to GABA expression, measured with magnetic resonance spectroscopy (MRS) and genetic analyses, linking polymorphisms in the GABA family genes to GABA expression in the brain. Specifically, the research aims to: 1) Characterize concurrent relations among genetics, neurochemistry, functional neuroanatomy, and reading behavior at 2 important timepoints in reading development, 2) Investigate Nl and RD differences for each of these measures, 3) Examine subsequent developmental trajectories in Nl and RD cohorts, 4) Better characterize learning capacities and learning styles in these cohorts, 5) Develop dynamic brain/behavior phenotypes sensitive to genetic analyses, and 6) Contrast multi-level profiles and developmental trajectories in subgroups of RD.