Neurocognitive bases of treatment resistance in developmental dyslexia

描述(申请人提供)：发育性阅读障碍(DD)是一种神经发育障碍，被认为反映了局限性的神经生物学异常和病因，尽管涉及的确切大脑机制尚未明确。与环境因素一起，这些反常现象会使某些复杂技能的发展变得困难，尤其是那些涉及阅读的技能，在最严重的情况下，甚至极难治疗。该项目的首要目标是提供DD治疗抵抗者的第一个详细和综合的神经生物学和认知(即神经计算)特征，其相对棘手的损害可能主要是基于大脑的。一个相关的目标是将DD治疗抵抗者的这种神经计算特征与DD治疗应答者和典型的发育中(TD)儿童的神经计算特征进行对比。通过系统地研究这些组中认知和神经成像的相似和差异，以及对不同结果，特别是治疗结果影响最大的神经计算缺陷，将被确定。该项目通过比较年龄较小的(3/4年级)和较大的(7/8年级)DD儿童来解决重要的发展问题，并将类似地使用多维框架研究患有DD和严重语言和/或注意力障碍的共病幼儿(3/4年级)。在所有小组中，该项目采用综合治疗前后功能和结构神经成像、认知测试、在线语言和非语言学习实验以及计算建模。有了这些工具，一个关键的目标是开发和测试神经计算理论，以检查产生噪声系统、速率限制、限制容量和巩固失败的认知缺陷(因此是与DD的高阶阅读相关问题的近端原因)与大脑组织的潜在差异之间的关系，以及它们对预测治疗耐药性的影响。

DESCRIPTION (provided by applicant): Developmental Dyslexia (DD) is a neurodevelopmental disorder thought to reflect circumscribed neurobiological anomalies and etiologies, although the exact brain mechanisms involved have not been clearly identified. Along with environmental factors, these anomalies conspire to make the development of a certain complex sets of skills, particularly those involved in reading, difficult, and in the most severe cases, extremely difficult to treat. This project's overarching goal is to provide the first detaild and integrated neurobiological and cognitive (i.e., neurocomputational) characterization of DD treatment resisters, whose relatively intractable impairments are likely to be primarily brain-based. A related goal is to contrast this neurocomputational characterization of the DD treatment resisters with those of DD treatment responders and typically developing (TD) children. By systematically investigating the cognitive and neuroimaging similarities and differences in these groups, and the neurocomputational deficits that contribute most strongly to differential outcomes, particularly treatment outcomes will be identified. The project addresses important developmental questions by comparing younger (3rd/4th graders) and older (7th/8th graders) DD children, and will similarly study comorbid young (3rd/4th graders) children, using a multidimensional framework, that have DD and significant language and/or attentional impairments. In all groups, the project employs integrated pre- and post-treatment functional and structural neuroimaging, cognitive testing, online linguistic and non-linguistic learning experiments, and computational modeling. With these tools, a key goal is to develop and test neurocomputational theories in order to examine the relationship between cognitive deficits that generate noisy systems, rate limitations, limit capacity and consolidation failure (and therefore function as proximal causes of higher order reading-related problems in DD), and underlying differences in brain organization, and their impact on predicting treatment resistance.