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

神经影像学揭示 DLD 中与治疗相关的变化：一项随机对照试验

• 批准号: 10641925
• 负责人: Karla N Washington
• 金额: $ 59.45万
• 依托单位: UNIVERSITY OF TORONTO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10641925
• 关键词: 5 year old; Address; Adult; Aftercare; Basal Ganglia; Behavioral; Brain region; Businesses; Cerebellum; Child; Childhood; Clinical; Data; Decision Making; Development; Diagnosis; Diffusion; Disease; Early Intervention; Eating; Education; Elements; Enrollment; Functional Magnetic Resonance Imaging; Goals; Hippocampus; Image; Impairment; Individual; Inferior; Intervention; Language; Language Development; Language Development Disorders; Learning; Maintenance; Mediating; Memory; Methods; Motor Cortex; Neurobiology; Neurodevelopmental Disorder; Nursery Schools; Occupational; Outcome; Paper; Performance; Population; Preschool Child; Prevalence; Process; Randomized, Controlled Trials; Recording of previous events; Research; Research Personnel; Role; Semantics; Social isolation; Social outcome; Structural defect; System; Temporal Lobe; Testing; Treatment outcome; Unemployment; Washington; Work; age group; behavior measurement; behavioral response; boys; computer assisted patient care; design; effective intervention; efficacious intervention; efficacious treatment; evidence base; experience; follow-up; frontal lobe; improved; insight; knowledge base; language impairment; learning network; neural; neuroimaging; neuromechanism; novel; peer; procedural memory; randomized controlled design; recruit; specific language impairment; support network; therapy design; tool

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.

项目概要/摘要 尽管发展性语言障碍（DLD）（一种流行的学前障碍）的影响可能是 通过基于证据的早期干预措施可以缓解，但人们对 DLD 的神经基础知之甚少， 尤其是对于幼儿，虽然许多证据对于设计有效的治疗方法很有用。 已由研究领域特定过程（语言网络）、通用领域的研究提供 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 推进当前的知识库。程序电路缺陷假设（PDH）定位语法。 缺陷可以通过程序记忆（规则学习，“知道如何”）受损来解释。 与额叶脑区和基底神经节之间连接的结构异常有关， 然而，陈述性记忆系统相应的激活不足和功能连接减少。 （语义上，“知道什么”），由颞叶的皮质和皮质下区域支持，包括 海马体则幸免于难，充当弥补语法缺陷的补偿机制。 这项拟议的研究将使用神经影像学（功能性 MRI 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） 我们将收集有关患有 DLD 的学龄前儿童语法学习之前、之后和之后的关键数据。 干预中断后（计算机辅助治疗：DLD 治疗；“一切如常”：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发展中（TD）同行。 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，并与语言功能的增强相关 改善的程度可能与基线语法的潜在神经生物学有关 赤字。 基于招募和治疗患有 DLD 的学龄前儿童的悠久历史，我们将招募 184 名 目标 1 将由 100 名患有 DLD 的学龄前儿童（n=50 名接受治疗；n=50 名无对照治疗）和 84 名 TD 儿童组成。 患有 DLD 的学龄前儿童与其 TD 同龄人的功能和结构连接之间的关系 在目标 2 中，我们将建立程序性学习和陈述性网络中的区域之间的关系。 我们仅检查 DLD 中治疗相关变化的神经生物学基础。 以及程序性学习和陈述性记忆网络区域之间的结构连接，以及 调查治疗相关的变化是否发生在典型范围内（DLD 和 TD）以满足我们的要求。 为了实现科学目标，我们将行为工具（传统语法工具）与神经影像相结合来描述同时发生的事件 这项研究将为学习和结果提供新的见解。 学习和障碍背后的机制，有助于推进 DLD 的循证管理。