Neuroimaging Reveals Treatment-Related Changes in DLD: A Randomized Controlled Trial

项目总结/文摘

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.