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.

项目概要/摘要 发展性语言障碍 (DLD) 是一种常见的学前障碍，可能对孩子造成终生影响 尽管 DLD 的影响可以通过基于证据的和 尽管采取了有效的干预措施，但并非所有 DLD 儿童都对这些治疗有反应，这给 迄今为止，还没有研究检验语法的假设。 学习是由基线神经生物学功能（激活不足和之间的连接减少）介导的 网络中支持程序学习的区域，包括额下皮层、运动皮层、基底皮层 然而，确定 DLD 的神经生物学基础可以揭示神经元的机制。 语法学习缺陷的基础；以及基于治疗的评估工具的改变。 行为方法丰富地描述了行为表型，但可能无法提供对神经网络的见解 治疗相关变化背后的机制，因此不足以管理 DLD。 这项拟议的研究将检验神经影像学在描述神经基础方面的贡献 一项比较 PI 设计的随机对照试验 (RCT) 的语法学习。 有效治疗或不治疗是指导循证决策所需的重要下一步 我们将收集有关语法学习的重要信息。 在干预（即计算机辅助治疗）中断之前、之后和之后患有 DLD 的学龄前儿童 DLD 治疗组，“一切照旧”，DLD 无治疗对照）。 对照组——通常是发育中（TD）学龄前儿童——以了解发育与障碍的情况。 总体目标是为语法缺陷的神经生物学基础提供新颖的见解，同时 还描述了对治疗的反应。我们的中心假设是治疗旨在改善程序。 学习将改善相关网络的结构和功能连接（使用结构和功能进行评估） 功能性 MRI），并且语法缺陷的潜在神经生物学与治疗反应有关。 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，我们将评估程序学习网络中区域之间的治疗效果。 显着改变程序学习网络中的功能和结构连接（仅限 DLD） 与治疗相关的变化可能会发生在典型范围内（DLD 和 TD） 为了实现我们的科学目标， 我们将行为工具（传统语法工具）与神经影像相结合来描述潜在的机制 这项研究将首次估计语法学习和治疗改变的基线。 神经生物学功能影响对治疗的反应，这对于 DLD 的治疗至关重要。