Neurodevelopmental Basis of Persistent Mathematical Learning Disabilities

描述（由申请人提供）：数学技能的坚实基础对于学术成功和日常生活中的定量推理至关重要。这些技能的缺陷会损害学术技能的发展，并限制成年后的未来就业机会。虽然计算能力差的后果是巨大的，但随着时间的推移，对数学技能发展中典型和非典型变化的神经生物学基础知之甚少。数学障碍（MD）可以定义为在多个时间点上稳定的低成就，并已被假设为伴有后顶叶皮层的结构和功能畸变。令人惊讶的是，许多孩子在一个时间点得分很低，只是在下一个时间点反弹。是什么导致了个体儿童数学成就轨迹的差异？我提出的工作的总体目标是研究从童年到青春期持续低数学技能的认知和神经概况。在斯坦福大学获得的MD儿童的独特纵向队列将与最先进的大脑结构和功能的大脑成像相结合。在数学技能获得的关键时间窗口（7 - 9岁）期间，数学技能的标准化行为测量将用于识别以下儿童的子集：（1）通常正在发展（TD），（2）开始为MD但随着时间的推移恢复其数学技能（MD Gainer）和（3）随着时间的推移持续存在数学障碍（Persistent MD）。我将在儿童时期和青春期（15 - 17岁）的两个时间点检查这些群体的行为，结构和功能大脑概况，表征数学技能纵向变化的个体差异，并确定与那些随着时间的推移而改善的儿童相比，表现出持续缺陷的儿童的长期结果。这些不同轨迹的结构和功能大脑基础将使用解剖学和功能MRI方法来表征，以确定为什么一些儿童随着时间的推移而改善，而另一些儿童则表现出持续性缺陷，并将利用预测算法来识别持续性MD的生物标志物。这项研究对改善数学学习障碍儿童的学习具有广泛的意义。建议的研究是高度相关的使命的NIH计划公告“发展数学认知和推理和预防数学学习障碍”（PA-12-248）。拟议的工作将提供重要的新见解：（1）MD儿童及其TD同龄人的大脑可塑性，（2）从童年到青春期持续MD的神经生物学基础，以及（3）预测MD儿童将在青春期表现出持续缺陷的方法。这项工作最终也将有助于早期识别可能受益于有针对性的干预措施的持续性MD儿童。

DESCRIPTION (provided by applicant): A strong foundation in mathematical skills is critical for both academic success and for quantitative reasoning in everyday life. Deficiencies in these skills can impair academic skill development and limit future job opportunities in adulthood. Although the consequences of poor numeracy are substantial, little is known about the neurobiological basis of typical and atypical changes in mathematical skill development over time. Mathematical disability (MD) can be defined by stable low achievement over multiple time points, and has been hypothesized to be accompanied by structural and functional aberrations in the posterior parietal cortex. Surprisingly, many children score poorly at one time point, only to rebound at the next. What underlies this variation in the trajectory of math achievement across individual children? The overarching goal of my proposed work is to examine the cognitive and neural profile of persistent low math skills from childhood to adolescence. A unique longitudinal cohort of children with MD acquired at Stanford will be combined with state-of-the-art brain imaging of brain structure and function. Standardized behavioral measures of math skills during a critical time window for math skill acquisition (ages 7 - 9) will be used to identify subsets of children who (1) are typically developing (TD), (2) start as MD but recover their math skills over time (MD Gainers) and (3) persist with math disability over time (Persistent MD). I will examine the behavior, structural and functional brain profile of these groups at two points during childhood and then again during adolescence (ages 15 - 17), characterizing individual differences in longitudinal change in math skills and determine the long-term outcome of children that show persistent deficits compared to those that improve over time. The structural and functional brain bases for these different trajectories will be characterized using anatomical and functional MRI methodologies to determine why some children improve over time while others show persistent deficits, and predictive algorithms will be utilized to identify biomarkers of Persistent MD. The proposed research has broad implications for improving learning in children with math learning disabilities. The proposed studies are highly relevant to the mission of the NIH Program Announcement "Development of Mathematical Cognition and Reasoning and the Prevention of Math Learning Disabilities" (PA-12-248). The proposed work will provide important new insights into (1) brain plasticity in children with MD and their TD peers, (2) the neurobiological basis of persistent MD from childhood to adolescence and (3) ways to predict which children with MD will show persistent deficits into adolescence. This work will also eventually aid in the early identification of children with persistent MD who might beneft from targeted interventions.