Auditory precursors of language delay in toddlers with autism spectrum disorders

摘要 语言延迟和障碍在自闭症谱系障碍（ASD）中很常见，感觉（包括 听觉）异常。由于口语的习得依赖于听觉系统的完整性， 语言延迟和障碍可能与声音处理异常有关， 在ASD儿童中观察到（尽管外周听力正常）。然而，人们不明白， 早期听觉脑异常可能在发育上导致语言发育受损。 这个项目将研究早期大脑中听觉和语言系统的成熟 童年是语言习得的关键时期。我们将采用纵向设计， 多模式神经成像，包括高分辨率解剖、弥散和功能磁共振 影像学检查（MRI），增加频繁和广泛的行为和神经心理学评估。我们 核心假设是，大脑皮层声音处理的早期中断先于并预测语言 自闭症障碍，因此可能被认为是因果贡献者-一个假设，已被频繁 在文献中考虑过，但从未在神经水平上进行过测试。 我们的目标是彻底表征的结构完整性和功能分化的 皮质听觉和语言系统（目标1）和他们的成熟轨迹（目标2）在幼儿与 ASD和年龄匹配的典型发育中的同龄人。这将使我们能够确定神经异常是否 在幼儿复杂声音的皮层处理中， 学龄前行为（目标3）。该项目的基本原理和翻译意义在于， 确定与儿童最初几年语言延迟和障碍有关的大脑发育变化， 生活将允许在听觉领域进行更有针对性的干预，而这些干预是最有效的。

Abstract Language delay and impairments are common in autism spectrum disorders (ASDs), as are sensory (including auditory) anomalies. Since acquisition of spoken language relies on the integrity of the auditory system, language delay and impairments may be related to sound processing abnormalities that are frequently observed in children with ASDs (despite normal peripheral hearing). However, it is not understood if and how early auditory brain anomalies may developmentally contribute to impaired language development. This project will examine the maturation of auditory and language systems in the brain across early childhood, during the critical period for language acquisition. We will employ a longitudinal design and multimodal neuroimaging, including high-resolution anatomical, diffusion, and functional magnetic resonance imaging (MRI), with added frequent and extensive behavioral and neuropsychological assessments. Our central hypothesis is that early disruptions to cortical sound processing precede and predict language impairments in ASDs and may thus be considered causal contributors – a hypothesis that has been frequently considered in the literature, but never tested at the neural level. Our aims are to thoroughly characterize the structural integrity and functional differentiation of the cortical auditory and language systems (Aim 1) and their maturational trajectories (Aim 2) in toddlers with ASDs and age-matched typically developing peers. This will allow us to establish whether neural abnormalities in cortical processing of complex sounds in toddlers are predictive of language development and social behavior at the pre-school age (Aim 3). The rationale and translational significance of this project are that identification of alterations in brain development linked to language delay and impairment in the first years of life will allow for more targeted interventions in the auditory domain at a time when they are most effective.