Neurobiological predictors of spoken and written language learning

描述（由申请人提供）：越来越多的证据支持将阅读障碍（RD）描述为在获得流利阅读技能方面基于大脑的困难，通常与语音处理缺陷有关（Lyon et al., 2003）。在认知层面上，这些缺陷被认为阻碍了正字法(O)、音系(P)和语义(S)特征的充分结合，而这些特征构成了支持有效阅读所必需的词汇表征的基础（参见Harm & Seidenberg, 1999; Perfetti & Hart, 2001）。在脑系统水平上，神经影像学研究一致表明，相对于正常发育的（TD）阅读器，RD阅读器在组成O、P和S处理分布式电路的左半球（LH）区域显示出结构和功能上的差异。然而，目前我们还不知道这些结构和功能异常的发现中，哪些与阅读领域的特定学习问题有因果关系，哪些没有。关键的下一步是在受控实验条件下，生成和测试O、P和S学习的个体差异预测模型。为此，我们将在新的口头和书面单词学习任务中采用综合的神经生物学和行为测量，以确定大脑结构和功能的差异在一般情况下预测单词学习困难，以及最强的大脑预测因素是否随着对O， P或S编码的相对需求的操纵而变化。此外，尽管普遍认为RD的主要缺陷出现在解码和语音处理技能水平上，但临床、行为和神经影像学的发现表明，RD在将新学到的信息巩固为永久记忆方面存在其他问题。为了探索这一假设，我们将采用综合脑/行为分析来检查新学到的O、P和S形式的在线学习和离线巩固。为了更精确地研究巩固缺陷背后的神经机制，我们还将使用有针对性的语言和非语言学习任务，系统地调节程序性和陈述性记忆系统的需求。对于所有这些学习和巩固的语言和非语言测量，我们测试了特定的基于大脑的TD/RD差异模型。

DESCRIPTION (provided by applicant): A growing body of evidence supports a characterization of reading disability (RD) as a brain-based difficulty in acquiring fluent reading skills, usually associated with phonological processing deficits (Lyon et al., 2003). At a cognitive level, these deficits are thought to impede adequate binding of those orthographic (O), phonological (P), and semantic (S) features that form the basis of lexical representations necessary to support efficient reading (cf. Harm & Seidenberg, 1999; Perfetti & Hart, 2001). At the level of brain systems, neuroimaging studies have consistently shown that, relative to typically developing (TD) readers, RD readers show both structural and functional differences at those left hemisphere (LH) regions that comprise the distributed circuitry for O, P, and S processing. At present though, we do not know which of these findings of structural and functional anomalies are causally related to specific learning problems in the domain of reading and which are not. A crucial next step is to generate and test predictive models of individual differences in O, P and S learning under controlled experimental conditions. To that end, we will employ integrated neurobiological and behavioral measures during novel spoken and written word learning tasks to determine which structural and functional brain differences predict word learning difficulties in general, and whether the strongest brain predictors vary as the relative demands on O, P or S coding are manipulated. Also, despite the general consensus that the primary deficit in RD arises at the level of decoding and phonological processing skills, there are clinical, behavioral, and neuroimaging findings which suggest additional problems in consolidation of newly learned information into permanent memory in RD. To explore this hypothesis, we will employ integrated brain/behavior analyses to examine both online learning and offline consolidation of newly learned O, P and S forms. To examine neural mechanisms underlying consolidation deficits more precisely we will also use targeted linguistic and non-linguistic learning tasks that systematically modulate demands on procedural vs. declarative memory systems. For all of these language and non-linguistic measures of learning and consolidation we test specific brain-based models of TD/RD differences. PUBLIC HEALTH RELEVANCE: The proposed study will to use multiple neuroimaging methods to test predictive models of individual differences in learning consolidation for: 1) novel spoken and written word learning tasks that vary in demands on component processes relevant to reading, and 2) language and nonlinguistic tasks that systematically examine contributions from those cortical and subcortical neural systems associated with procedural and declarative memory as a window on basic learning and consolidation deficits in reading disability (RD). The overarching goal is to develop causal models of the ways in which any one, or some combination of, these functional and structural factors might act to impede language and reading-related skill acquisition in RD.