Neuroimaging Reveals Treatment-Related Changes in DLD: A Randomized Controlled Trial

项目摘要/摘要 尽管发育性语言障碍(DLD)--一种普遍的学龄前障碍--的影响可能 通过循证和早期干预缓解，对DLD的神经基础知之甚少， 尤其是在幼儿中，但在设计有效的治疗方法时是有用的。虽然有很多证据 已经通过研究领域特定的过程(语言网络)、领域一般提供了 与记忆和语言相关的过程也提供了宝贵的试验场，并提供了机会 推进现有的知识库。程序性回路缺陷假说(PDH)假定语法 缺陷的原因是程序性记忆受损(规则学习，“知道怎么做”)。这一损害 与额叶脑区和基底节之间连接的结构异常有关， 相应的激活不足和功能连接性降低。然而，声明性记忆系统 (语义，“知道什么”)，由颞叶皮质和皮质下区域支持，包括 海马体则幸免于难，它是一种补偿机制，可以弥补语法缺陷。 这项拟议的研究将使用神经成像(功能磁共振成像和扩散成像)来描述 语法学习和治疗相关变化的神经基础(功能和结构连接) 是PDH的。我们将收集有关学习困难的学龄前儿童语法学习前、后和 在干预中断后(计算机辅助治疗：DLD治疗；“一切照常”：DLD否 治疗)作为随机对照试验的一部分。我们还将包括典型的开发(TD)对等项 告知发展与无序。我们的中心假设是，旨在改善语法的治疗 学习将使程序性学习网络正常化，同时增加语言功能和 改善的程度可能与基线语法的潜在神经生物学有关 赤字。 在招募和治疗患有DLD的学龄前儿童方面，我们将招收184名 学龄前儿童，DLD组100人(治疗组50人，对照组n=50人)，TD组84人。目标1将建立 学龄前学习障碍儿童与TD同龄人功能和结构连接性的关系 在程序性学习和陈述性网络中的区域之间。在目标2中，我们将建立 治疗相关改变的神经生物学基础仅限于DLD。我们检查了功能上的潜在变化 以及程序性学习和陈述性记忆网络的区域之间的结构连接性，以及 调查与治疗相关的变化是否发生在典型范围内(DLD和TD)。为了满足我们的 科学目标，我们将行为工具(传统语法工具)与神经成像相结合来描述共生现象 学习和结果背后的行为表现。这项研究将对以下问题提供新的见解 学习和损害的基础机制，以帮助推进DLD的循证管理。

Project Summary/Abstract Although the impact of developmental language disorder (DLD), a prevalent preschool disorder, can be mitigated through evidence-based and early interventions, little is known about the neural basis of DLD, especially in young children, yet is useful in the design of efficacious treatments. While much of the evidence has been furnished by studies examining domain-specific processes (language network), domain-general processes relating memory and language also offer valuable testing ground and present the opportunity to advance the current knowledge base. The Procedural circuit Deficit Hypothesis (PDH) posits that grammar deficits are explained by an impairment of procedural memory (rule learning, “knowing how”). This impairment is associated with structural abnormalities in connections between frontal brain regions and basal ganglia, with corresponding underactivation and reduced functional connectivity. However, the declarative memory system (semantic, “knowing what”), supported by cortical and subcortical regions in the temporal lobes, including hippocampus, is spared, acting as a compensatory mechanism to offset grammar deficits. This proposed research will use neuroimaging (functional MRI and diffusion imaging) to describe the neural basis (functional and structural connectivity) of grammar learning and treatment-related change by way of the PDH. We will gather critical data regarding grammar learning in preschoolers with DLD before, after, and following a break in intervention (computer-assisted treatment: DLD treatment; “business as usual”: DLD no treatment) as part of a randomized controlled trial. We will also include typically developing (TD) peers to inform development vs disorder. Our central hypothesis is that treatment designed to improve grammar learning will normalize the procedural learning network in association with increases in language function and that the degree of improvement may be associated with the underlying neurobiology of baseline grammar deficits. Building on a robust history of recruitment and treatment of preschoolers with DLD, we will enroll 184 preschoolers, 100 with DLD (n=50 treatment; n=50 no treatment controls) and 84 TD. Aim 1 will establish the relationship between functional and structural connectivity for preschoolers with DLD and their TD peers between regions in the procedural learning and declarative networks. In Aim 2, we will establish the neurobiological basis of treatment-related changes in DLD only. We examine potential changes in functional and structural connectivity between regions of the procedural learning and declarative memory networks, and investigate whether treatment-related changes occur into the typical range (DLD and TD). To meet our scientific goals, we pair behavioral tools (traditional grammar tools) with neuroimaging to describe co-occurring behavioral performance underlying learning and outcome. This research will contribute novel insights into mechanisms underlying learning and impairment to help advance the evidence-based management of DLD.