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: 10840617
• 负责人: Karla N Washington
• 金额: $ 44.95万
• 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/10840617
• 关键词: 3 year old; 5 year old; Address; Adult; Aftercare; Award; Basal Ganglia; Behavioral; Brain region; Businesses; Canada; Child; Child Language; Clinical; Cross-Sectional Studies; Data; Decision Making; Development; Diagnosis; Diffusion; Early Intervention; Enrollment; Environment Design; Evaluation; Future; Geography; Goals; High Prevalence; Hippocampus; Image; Impairment; Infant; Intervention; Investigation; Knowledge; Language; Language Delays; Language Development; Language Development Disorders; Language Disorders; Learning; Maintenance; Memory; Methods; Neurobiology; Ontario; Outcome; Parents; Participant; Performance; Population; Population Heterogeneity; Process; Randomized, Controlled Trials; Recording of previous events; Rehabilitation therapy; Reporting; Research; Scanning; Site; Sleep; Speech; Structural defect; System; Temporal Lobe; Testing; Time; Toddler; Treatment outcome; Vocabulary; age group; base; behavior measurement; behavioral response; design; effective intervention; efficacious treatment; epidemiology study; evidence base; experience; follow up assessment; follow-up; improved; insight; knowledge base; neural; neuroimaging; neuromechanism; novel; parent grant; peer; programs; recruit; success; syntax; therapy design; tool

Project Summary/Abstract Late talking represents one of the most common reasons children under 3-years of age are referred for speech-language evaluations, impacting about 10%-20% of children in this age-group. Late talkers (LT) also share similarities with children diagnosed with developmental language disorder (DLD) at 4 – 5 years of age, endorsing the notion that shared neurobiological underpinnings might exist between these two clinical groups. However, little is known about the neural basis of late talking, yet is needed to better inform the design of efficacious therapies that address hallmark delays in syntax and vocabulary. For the DLD population, domain- general processes relating memory and language are being investigated in the parent grant, offering valuable testing ground for also advancing the current knowledge base regarding LT. The Procedural circuit Deficit Hypothesis (PDH) posits that relative strengths and weaknesses exist between procedural (impaired) and declarative (less impaired) memory systems. Structural abnormalities in connections between frontal brain regions and basal ganglia, with underactivation and reduced connectivity also evident. However, cortical and subcortical regions in the temporal lobes, including hippocampus, might be impaired to a lesser degree. This proposed research will use diffusion imaging to describe the neural basis (structural connectivity) of late talking and treatment-related change by way of the PDH. We will gather data regarding LT before, after, and following a break in a well-known parent-led therapy (Target WordTM-The Hanen Program® for Parents of Children who are LT: LT treatment; “business as usual”: LT no treatment) as part of a highly feasible RCT that leverages existing pipelines. We will also include typically developing (TD) peers to inform development vs late talking. Our central hypothesis is that treatment designed to improve syntax and vocabulary will change procedural and declarative networks in association with increases in language function and the degree of improvement may be associated with the underlying neurobiology of baseline syntax and vocabulary deficits. Building on a robust history of recruitment and treatment of toddlers by The Hanen Centre®, and our successful imaging partner, we will enroll 30 LT (n=15 treatment; n=15 controls) and 15 TD peers. Aim 1 will establish the structural connectivity in LT 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 LT only. We examine potential changes in structural connectivity between regions of the procedural learning and declarative memory networks, and investigate whether treatment-related changes occur into the typical range (LT, TD). To meet our scientific goals, we pair behavioral tools (syntax and vocabulary) with neuroimaging to describe co-occurring behavioral performance underlying learning and outcome, while also gathering parental and clinican qualitative data regarding treatment outcomes. This research will contribute novel insights into mechanisms underlying learning and impairment to offer a groundbreaking shift in our understanding of LT.

项目总结/摘要 晚说话是3岁以下儿童被转诊的最常见原因之一。 言语语言评估，影响了这个年龄组约10%-20%的儿童。Late Talkers（LT） 与4 - 5岁时被诊断患有发育性语言障碍（DLD）的儿童有相似之处， 支持这两个临床群体之间可能存在共同的神经生物学基础的概念。 然而，人们对晚说话的神经基础知之甚少，但需要更好地为设计提供信息。 有效的治疗方法来解决语法和词汇方面的标志性延迟。对于DLD人群，域- 一般的记忆和语言相关的过程正在研究中的父母补助金，提供宝贵的 测试地面也推进目前的知识基础，关于LT。程序电路缺陷 假设（PDH）假定程序（受损）和 陈述性（受损较少）记忆系统。额叶脑与大脑皮层之间的连接结构异常 区域和基底神经节，也明显存在激活不足和连接性降低。然而，皮质和 颞叶中的皮质下区域，包括海马，可能受损程度较轻。 这项拟议的研究将使用扩散成像来描述神经基础（结构连接） 迟发性谈话和治疗相关的变化。我们将收集LT之前，之后， 在一个著名的父母主导的治疗（目标WordTM-哈南计划®的父母， LT儿童：LT治疗;“照常”：LT不治疗）作为高度可行的RCT的一部分， 利用现有管道。我们还将包括典型的开发（TD）同行，以告知开发与后期 说话了我们的中心假设是，旨在改善句法和词汇的治疗方法将会改变 程序性和陈述性网络与语言功能的增加和 改善可能与基线句法和词汇缺陷的潜在神经生物学有关。 建立在哈宁中心®招募和治疗幼儿的强大历史基础上，我们的 成功的成像合作伙伴，我们将招募30名LT（n=15名治疗组; n=15名对照组）和15名TD同行。目标1将 在程序学习中的区域之间建立LT及其TD对等体的结构连接， 宣告性网络在目标2中，我们将建立LT治疗相关变化的神经生物学基础 只.我们研究了程序性学习区域之间结构连接的潜在变化， 陈述性记忆网络，并调查治疗相关变化是否发生在典型范围内 (LT，TD）。为了实现我们的科学目标，我们将行为工具（语法和词汇）与神经成像结合起来， 描述共同发生的行为表现的基础学习和结果，同时也收集父母 和关于治疗结果的临床定性数据。这项研究将有助于新的见解， 潜在的学习和损伤机制，为我们对LT的理解提供了突破性的转变。