Neurocognitive bases of treatment resistance in developmental dyslexia

描述（由申请人提供）：发育性阅读障碍（DD）是一种神经发育障碍，被认为反映了特定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确定。沿着环境因素，这些异常共同导致某些复杂技能的发展，特别是那些涉及阅读的技能，困难，在最严重的情况下，极难治疗。神经计算）表征DD治疗抵抗者，其相对顽固的损伤可能主要是基于脑的。一个相关的目标是将DD治疗抵抗者的神经计算特征与DD治疗应答者和典型发育（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影像学的相似性和差异，以及对差异结局（特别是治疗结局）贡献最大的神经计算缺陷，将确定治疗结局。该项目通过比较年轻（3/4年级学生）和老年（7/8年级学生）DD儿童来解决重要的发展问题，并将使用多维框架类似地研究患有DD和显著语言和/或注意力障碍的共病年轻（3/4年级学生）儿童。在所有组中，该项目采用综合治疗前和治疗后的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，以检查产生噪音系统，速率限制，限制容量和巩固失败（因此作为DD中高阶阅读相关问题的近端原因）的认知缺陷之间的关系，以及大脑组织的潜在差异，以及它们对预测治疗抵抗的影响。

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.