Brain Bases of Language Deficits in SLI and ASD

描述（由申请人提供）：特殊语言障碍（SLI）和自闭症谱系障碍（ASD）是复杂的高度遗传性疾病，涉及语言和沟通方面的原发性障碍。ASD的一个亚型包括与特殊语言障碍相似的语言障碍，包括特殊语言障碍的两个核心临床标志：语音工作记忆缺陷，通过非单词重复任务来衡量，以及语法形态缺陷，特别是在动词时态标记上。本项目的目标是研究特殊语言障碍、泛自闭症障碍这两种核心缺陷的大脑基础，以及这些核心语言能力的典型发展。目的1研究96名5-12岁正常发育儿童语音工作记忆（非词辨别）和语法判断的神经基础。在非词识别任务中，我们预测非词长度的增加会导致双侧颞上回（STG）和左侧额下回（LIFG）的增加，其中发育变化主要发生在额下回。在语法判断任务中，我们预测，与正确的句子相比，遗漏义务时态（如过去式-ed）的错误会导致左后脑区和左后脑区更大的激活。目标2将在48名8-12岁的特殊语言障碍儿童和96名ASD儿童（48名有共病语言障碍，48名无共病语言障碍）中实施相同的实验范式，并将他们与年龄和语言匹配的典型对照进行比较。我们预测，在患有特殊语言障碍的儿童中，IFG和STG之间的功能连接程度将会降低，并且STG和/或LIFG的功能激活以及这些区域之间的功能连接将与两个实验中的行为表现相关。我们还预测，患有语言障碍的ASD儿童将表现出与特殊语言障碍儿童相似的非典型激活模式，随着时间的推移，两组儿童的激活模式将更接近于典型儿童。这是第一个关于特殊语言障碍和泛自闭症障碍核心语言障碍的神经生物学基础的发展研究。这一发现将为识别这些疾病的潜在生物标志物铺平道路，并将为针对生物标志物特征量身定制的学龄儿童提供强化干预措施开辟可能性。

DESCRIPTION (provided by applicant): Specific language impairment (SLI) and autism spectrum disorders (ASD) are complex highly heritable disorders that involve primary impairments in language and communication. A subtype of ASD includes impairments in language that parallel those found in SLI, including two core clinical markers for SLI: deficits in phonological working memory, as measured on nonword repetition tasks, and deficits in grammatical morphology, particularly in marking tense on verbs. The goal of this project is to investigate the brain bases of these two core deficits in SLI, ASD, and typical development of these core language abilities. Aim 1 will investigate the neural basis of phonological working memory (nonword discrimination) and grammaticality judgments in 96 typically developing children aged 5-12. For the nonword discrimination task, we predict that increases in nonword length will result in greater recruitment of bilateral superior temporal gyrus (STG) and left inferior frontal gyrus (LIFG), with developmental changes primarily in LIFG. In the grammaticality judgment task we predict that errors involving omission of obligatory tense (e.g., past tense -ed) will lead to greater activation in LIFG and left STG, compared to correct sentences. Aim 2 will implement the same experimental paradigms in 48 children with SLI and 96 children with ASD (48 with and 48 without co-morbid language impairment) aged 8-12 years old, who will be compared to age- and language-matched typical controls. We predict that in children with SLI the degree of functional connectivity between IFG and STG will be reduced and that functional activation in STG and/or LIFG and functional connectivity between these regions will correlate with behavioral performance in both experiments. We also predict that the ASD children with language impairment will show similar atypical activation patterns as in the SLI group and that over time, both groups will show activation patterns that more closely resemble the typical children. This is the first developmental study on the neurobiological bases of core impairments in language in SLI and ASD. The findings will pave the way to identifying potential biomarkers for these disorders and will open up the possibility of providing intensive interventions for school-aged children that are individually tailored to biomarker profiles.