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.

项目概要/摘要 说话晚是 3 岁以下儿童被转诊的最常见原因之一 言语评估，也影响了该年龄段约 10%-20% 的说话晚者 (LT)。 与 4 – 5 岁时被诊断患有发展性语言障碍 (DLD) 的儿童有相似之处， 支持这两个临床组之间可能存在共同的神经生物学基础的观点。 然而，人们对晚说话的神经基础知之甚少，但仍需要更好地为晚说话的设计提供信息。 有效的疗法可以解决 DLD 人群的语法和词汇延迟问题。 与记忆和语言相关的一般过程正在家长资助中进行研究，提供了有价值的信息 也是推进有关 LT 的当前知识库的试验场。 假设（PDH）认为程序性（受损）和程序性（受损）之间存在相对优势和劣势。 额叶脑之间连接的陈述性（受损程度较低）记忆系统的结构异常。 然而，皮质和基底神经节的活性不足和连通性降低也很明显。 颞叶皮质下区域（包括海马体）可能受到较小程度的损害。 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） 我们将通过 PDH 收集有关 LT 之前、之后的数据。 中断了著名的家长主导疗法（Target WordTM-The Hanen Program® forParents of 接受 LT 的儿童：LT 治疗；“照常”：LT 不治疗）作为高度可行的 RCT 的一部分 利用现有的管道，我们还将包括典型的开发（TD）同行，以告知开发与后期的情况。 我们的中心假设是，旨在改善语法和词汇的治疗将会改变。 程序性和陈述性网络与语言功能和程度的增加相关 改善可能与基线语法和词汇缺陷的潜在神经生物学有关。 以 The Hanen Center® 招募和治疗幼儿的悠久历史为基础，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 Aim 1 同行。 在程序学习和区域之间建立 LT 及其 TD 对等体的结构连接 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。 我们仅研究程序学习区域之间结构连通性的潜在变化。 陈述性记忆网络，并研究治疗相关的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）与神经影像学结合起来。 描述学习和结果背后同时发生的行为表现，同时还收集父母的意见 以及有关治疗结果的临床医生定性数据。这项研究将为我们提供新的见解。 学习和损伤背后的机制为我们对 LT 的理解提供了突破性的转变。