Neural Development of Lexical Processing

描述（由申请人提供）：我们基于横断面功能磁共振成像（fMRI）数据制定了正常读者词汇加工的发育神经认知模型，并收集了这些儿童最初评估后2年的第一批纵向数据。拟议的拨款将纵向跟踪正常儿童（7至17岁）和阅读障碍儿童（11至15岁），当他们执行各种任务时。这些任务包括在视觉和听觉模式下的正字法（拼写）、音韵（押韵）和语义（意义）判断。这一建议不仅具有创新性，因为我们使用了各种各样的任务，而且我们也有多种知觉控制和难度的多种参数操纵，因此我们可以更有效地研究词汇加工方面的发展和群体效应。此外，我们的范式允许检查启动和词汇效应（例如词频、语音一致性和正字法一致性），因此观察到的发展和群体差异不太可能是由于任务的特定特征造成的。本研究的总体目的是确定不同的群体是否有不同的发展轨迹。纵向设计对于排除队列效应和从早期阅读技能和大脑激活模式中检验个体后续大脑发育的可预测性至关重要。除了研究高技能和低技能的正常读者是否有不同的发展轨迹外，我们还将研究在解码正字法刺激方面有特殊缺陷的阅读困难读者与在解码正字法刺激方面有缺陷的语言障碍读者是否有不同的发展轨迹。我们还将比较年龄匹配的儿童与阅读匹配的正常读者，以解决发育迟缓与偏差的问题。我们的一般假设是，读者之间大脑活动的个体差异会随着年龄的增长而增加。这将使用层次线性模型来测试变化速率（例如斜率）和变化形状（例如加速度）的增长曲线。我们将使用这种技术来观察我们感兴趣的关键区域信号强度的发展变化，以及使用动态因果模型（DCM）来观察有效连接的变化。这一建议将为我们提供关于典型儿童的大脑在整个童年和青春期在阅读和语言处理过程中如何变化的基本信息，以及阅读和语言障碍儿童的大脑在发育过程中如何不同的信息。这项拨款与生物医学问题的相关性在于，它对患有阅读和语言障碍的儿童的诊断和干预具有影响。

DESCRIPTION (provided by applicant): We have formulated a developmental neuro-cognitive model of lexical processing in normal readers based on cross-sectional functional magnetic resonance imaging (fMRI) data and we have collected our first longitudinal data on these children 2 years after their initial assessment. The proposed grant will longitudinally follow normal children (7- to 17- year-olds) and children with reading disorders (11- to 15-year-olds) when they perform a variety of tasks. These tasks include orthographic (spelling), phonological (rhyming) and semantic (meaning) judgments in the visual and auditory modalities. Not only is this proposal innovative because we use a variety of tasks, but we also have multiple perceptual controls and multiple parametric manipulations of difficulty, so we can more effectively examine developmental and group effects specific to aspects of lexical processing. Furthermore, our paradigms allow an examination of priming and lexical effects (e.g. word frequency, phonological consistency and orthographic consistency) so observed developmental and group differences are not likely to be due to specific characteristics of the tasks. The overall aim of this study is to determine whether different groups have different developmental trajectories. A longitudinal design is crucial to rule out cohort effects and to examine the predictability of the individual's subsequent brain development from their earlier reading skill and brain activation patterns. In addition to examining whether higher and lower skill normal readers have different developmental trajectories, we will examine whether dyslexic readers with specific deficits in decoding orthographic stimuli have different developmental trajectories from language-impaired readers with deficits in decoding orthographic stimuli in addition to general language processing deficits. We will also compare children with disorders to age-match versus reading-match normal readers to address the question of developmental delay versus deviance. Our general hypothesis is that individual differences in brain activation between readers will increase with age. This will be tested using hierarchical linear modeling to examine growth curves in the rate of change (e.g. slope) and in the shape of change (e.g. acceleration). We will use this technique to look at developmental changes in signal intensity in our critical regions of interest, but also for changes in effective connectivity using Dynamic Causal Modeling (DCM). PUBLIC HEALTH RELEVANCE This proposal will give us basic information about how the brains of typical children change throughout childhood and adolescence during reading and language processing, but also how the brains of children with reading and language disorders differ in their development. The relevance of this grant to biomedical issues is that it has implications for diagnosis and intervention in children with reading and language disorders.