Neurobiological Foundations of reading (dis)ability

描述(由申请人提供)：这项拟议的纵向研究旨在考察阅读发展的关键点(从7.5岁到10.5岁)在非受损(NL)和阅读障碍(RD)队列中。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学和行为轨迹上的差异；拟议的纵向研究旨在更好地了解导致这种差异的行为、神经生物学和遗传病因。我们检验了这样一种假设，即可能导致神经发育和行为轨迹变化的候选病原体是伽马氨基丁酸(GABA)：研究表明，GABA在学习和记忆中发挥着关键作用。因此，拟议的研究将允许将阅读能力和阅读功能神经解剖学的发育变化(通过功能磁共振成像测量)与通过磁共振波谱(MRS)测量的GABA表达和遗传分析联系起来，将GABA家族基因的多态与大脑中的GABA表达联系起来。具体地说，本研究的目的是：1)表征阅读发展中两个重要时间点的遗传学、神经化学、功能神经解剖学和阅读行为之间的并行关系；2)考察这些测量中每一项的NL和RD差异；3)考察NL和RD队列中随后的发展轨迹；4)更好地表征这些队列中的学习能力和学习风格；5)发展对遗传分析敏感的动态大脑/行为表型；以及6)对比RD亚组中的多水平概况和发展轨迹。

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.