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: 10374327
• 负责人: Karla N Washington
• 金额: $ 68.9万
• 依托单位: UNIVERSITY OF CINCINNATI
• 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/10374327
• 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; Elements; Enrollment; Foundations; Functional Magnetic Resonance Imaging; Goals; Hippocampus (Brain); Image; Impairment; Individual; Inferior; Intervention; Language; Language Development; Language Development Disorders; Learning; Life; 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; Structure; System; Temporal Lobe; Testing; Treatment outcome; Unemployment; Washington; Work; age group; base; 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; learning outcome; neuroimaging; neuromechanism; novel; peer; procedural memory; randomized controlled design; recruit; relating to nervous system; 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.

项目摘要/摘要 尽管发展语言障碍（DLD）的影响是一种普遍的学龄前疾病，可以是 减轻基于证据和早期干预措施，对DLD的神经基础知之甚少 尤其是在幼儿中，但在设计有效治疗方面很有用。虽然大部分证据 研究了研究特定领域的过程（语言网络），域，域将来提供的研究 与记忆和语言有关的过程还提供了有价值的测试地面，并提供了机会 推进当前的知识库。程序电路赤字假设（PDH）认为语法 缺陷是通过损害程序记忆（规则学习，“知道”）来解释的。这种障碍 与额脑区域与基本神经节之间的联系中的结构异常有关， 相应的基础和降低功能连接性。但是，声明的内存系统 （语义，“知道什么”），在临时爱中的皮质和皮层区域的支持下，包括 海马被幸免，充当抵消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 语法学习和与治疗相关的变化的神经基础（功能和结构连接性） PDH。我们将在以前，之后，之后和 干预中断之后（计算机辅助处理：DLD治疗；“照常业务”：DLD否 治疗）作为随机对照试验的一部分。我们还将包括通常开发（TD）的同行 告知发展与障碍。我们的中心假设是旨在改善语法的治疗 学习将使程序学习网络正常于语言功能的增加和 改善程度可能与基线语法的潜在神经生物学有关 缺陷。 基于DLD招募和治疗学龄前儿童的稳健历史，我们将注册184 学龄前儿童，100例DLD（n = 50治疗； n = 50无治疗对照）和84 TD。 AIM 1将确定 DLD及其TD同行的学龄前儿童功能和结构连通性之间的关系 程序学习和声明性网络中的区域之间。在AIM 2中，我们将确定 DLD中与治疗相关的变化的神经生物学基础。我们检查功能的潜在变化 程序学习和声明性记忆网络的区域之间的结构连通性，以及 研究与治疗相关的变化是否发生到典型范围（DLD和TD）中。见我们 科学目标，我们将行为工具（传统的语法工具）与神经影像配对，以描述共同存在 学习和结果的行为表现。这项研究将促进新颖的见解 学习和损害的基础机制，以帮助推进基于证据的DLD管理。