Neurobiological Foundations of reading (dis)ability

描述（由申请人提供）：拟定的纵向研究旨在检查非受损（NI）和阅读障碍（RD）队列中阅读发展的关键点（从7.5-10.5岁）。我们以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方面的差异;拟议的纵向研究旨在更好地了解导致这种观察到的分歧的行为，神经生物学和遗传病因学因素。我们研究的假设，可能是神经发育和行为轨迹的变化背后的候选病原体是γ-氨基丁酸（GABA）：研究表明，GABA在学习和记忆中起着至关重要的作用。因此，拟议中的研究将允许相关的阅读性能和功能神经解剖学的阅读（用功能磁共振成像测量）的GABA表达，磁共振波谱（MRS）和遗传分析，GABA家族基因的多态性在大脑中的GABA表达。具体而言，该研究旨在：1）在阅读发展的2个重要时间点表征遗传学、神经化学、功能性神经解剖学和阅读行为之间的并发关系，2）调查这些测量中的每一个的NI和RD差异，3）检查NI和RD组群中的后续发展轨迹，4）更好地表征这些组群中的学习能力和学习风格，5）开发对遗传分析敏感的动态脑/行为表型，以及6）对比RD亚组中的多水平概况和发育轨迹。

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.