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: 10689397
• 负责人: Karla N Washington
• 金额: $ 61.67万
• 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/10689397
• 关键词: 5 year old; Achievement; Address; Adult; Aftercare; Assessment tool; Basal Ganglia; Behavioral; Brain; Brain region; Businesses; Cerebellum; Child; Clinical; Combined Modality Therapy; Decision Making; Development; Diagnosis; Diffusion; Disease; Enrollment; Foundations; Functional Magnetic Resonance Imaging; Future; Generations; Goals; Image; Impairment; Individual; Inferior; Intervention; Knowledge; Language; Language Development Disorders; Learning; Life; Maintenance; Mediating; Memory; Methods; Motor Cortex; Neurobiology; Nursery Schools; Outcome Measure; Paper; Performance; Population; Randomized Controlled Trials; Recording of previous events; Research; Research Personnel; Semantics; Social isolation; Social outcome; Structural defect; System; Testing; Treatment Efficacy; Treatment outcome; Unemployment; Washington; Work; age group; base; behavioral phenotyping; career; comparison group; computer assisted patient care; design; developmental disease; effective intervention; efficacious intervention; efficacious treatment; efficacy evaluation; evidence base; experience; experimental study; follow-up; frontal lobe; improved; individualized medicine; insight; intervention program; learning network; lexical; neuroimaging; neuromechanism; novel; peer; procedural memory; recruit; relating to nervous system; specific language impairment; support network; therapy design; tool; treatment group; treatment responders; treatment response; trial comparing

Project Summary/Abstract Developmental language disorders (DLD), a prevalent preschool disorder, can result in life-long impacts on academic and career achievement. Although the impact of DLD can be mitigated through evidence-based and efficacious interventions, not all children with DLD respond to these treatments, creating a challenge in the management of this developmental disorder. To date no studies have tested the hypothesis that grammar learning is mediated by baseline neurobiological function (underactivation and reduced connectivity between regions in the network supporting procedural learning including inferior frontal cortex, motor cortex, basal ganglia, and cerebellum). However, identifying the neurobiological foundations of DLD could reveal the neural basis of grammatical learning deficits; as well as of treatment-related change. Assessment tools based on behavioral methods richly characterize behavioral phenotypes, but may not provide insights into the neural mechanisms underlying treatment-related change and therefore are insufficient in the management of DLD. This proposed research will examine the contributions of neuroimaging in describing the neural basis of grammar learning in treatment response. A randomized controlled trial (RCT) comparing a PI-designed efficacious treatment to no treatment is the essential next step needed to guide evidence-based decision making for this prevalent population. We will gather critical information regarding grammar learning in preschoolers with DLD before, after, and following a break in intervention (i.e., computer-assisted treatment for the DLD treatment group, “business as usual” for DLD no treatment controls). We will also include a comparison group – typically developing (TD) preschoolers – to inform development versus disorder. The overall objective is to provide novel insights into the neurobiological basis of grammar deficits while also describing response to treatment. Our central hypothesis is that treatment designed to improve procedural learning will improve structural and functional connectivity in related networks (assessed using structural and functional MRI) and that the underlying neurobiology of grammar deficits is related to response to treatment. 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 network. In Aim 2, we will evaluate the efficacy of treatment in significantly changing functional and structural connectivity in the procedural learning network (DLD only) and that treatment-related changes might occur into the typical range (DLD and TD). To meet our scientific goals, we pair behavioral tools (traditional grammar tools) with neuroimaging to describe mechanisms underlying grammar learning and treatment-change. This research will establish the first estimates of how baseline neurobiological function impacts response to treatment, critically needed for the management of DLD.

项目总结/摘要 发育性语言障碍（DLD）是一种流行的学龄前疾病，可导致终身影响， 学术和职业成就。虽然DLD的影响可以通过循证医学和 有效的干预措施，但并非所有DLD儿童都对这些治疗有反应，这给DLD的治疗带来了挑战。 管理这种发展障碍。到目前为止，还没有研究证实语法 学习是由基线神经生物学功能介导的（激活不足和 网络中支持程序性学习的区域包括下额叶皮层、运动皮层、基底皮层、 神经节和小脑）。然而，识别DLD的神经生物学基础可以揭示神经系统的 语法学习缺陷的基础;以及治疗相关的变化。评估工具基于 行为方法丰富地表征了行为表型，但可能无法提供对神经系统的深入了解。 治疗相关变化的潜在机制，因此不足以管理DLD。 这项拟议的研究将探讨神经影像学在描述神经基础的贡献， 治疗反应中的语法学习。一项比较PI设计的 有效治疗或不治疗是指导循证决策所需的重要下一步 为这个流行的人群。我们将收集有关语法学习的重要信息， 在干预中断之前、之后和之后患有DLD的学龄前儿童（即，计算机辅助治疗 DLD治疗组，DLD无治疗对照组“照常工作”）。我们还将包括一个 对照组-通常是发展中（TD）学龄前儿童-以告知发展与障碍。 总体目标是提供新的见解，语法缺陷的神经生物学基础， 也描述了对治疗的反应。我们的中心假设是，旨在改善程序性的治疗 学习将改善相关网络的结构和功能连接（使用结构和功能评估）。 功能性MRI），并且语法缺陷的潜在神经生物学与对治疗的反应有关。 基于招募和治疗学龄前DLD儿童的强大历史，我们将招募184名 学龄前儿童，100例DLD（n=50例治疗; n=50例未治疗对照）和84例TD。目标1将建立 学龄前DLD儿童与TD同龄人的功能和结构连接关系 在程序学习网络中的区域之间。在目标2中，我们将评估治疗的有效性， 显著改变程序学习网络中的功能和结构连接（仅DLD）， 治疗相关变化可能发生在典型范围内（DLD和TD）。为了实现我们的科学目标， 我们将行为工具（传统的语法工具）与神经成像结合起来， 语法学习和治疗改变。这项研究将建立第一个估计如何基线 神经生物学功能影响对治疗的反应，这对于DLD的管理至关重要。