Brain Bases of Language Deficits in SLI and ASD

描述(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，涉及原发语言和沟通障碍。ASD的一个亚型包括与SLI相似的语言障碍，包括SLI的两个核心临床标记：通过非单词重复任务测量的语音工作记忆缺陷，以及语法形态缺陷，特别是在标记动词时态方面。这个项目的目标是调查SLI和ASD这两个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对96名5-12岁典型发育儿童的语音工作记忆(非单词辨别)和语法判断的神经基础进行研究。对于非单词辨别任务，我们预测非单词长度的增加将导致双侧颞上回(STG)和左额下回(LIFG)更多的招募，主要是LIFG的发育变化。在语法判断任务中，我们预测，与正确的句子相比，省略强制性时态(例如，过去时ed)的错误会导致LIFG和Left STG中更大的激活。目的2将在8-12岁的48名SLI儿童和96名ASD儿童(48名伴有语言障碍和48名不伴有语言障碍)儿童中实施相同的实验范式，并将其与年龄和语言匹配的典型对照组进行比较。我们预测，在SLI儿童中，IFG和STG之间的功能连接程度将会降低，STG和/或LIFG中的功能激活以及这些区域之间的功能连接将与这两个实验中的行为表现相关。我们还预测，有语言障碍的ASD儿童将表现出与SLI组相似的非典型激活模式，随着时间的推移，两组儿童都将表现出更接近于典型儿童的激活模式。这是第一个关于SLI和ASD语言核心损害的神经生物学基础的发展研究。这些发现将为确定这些疾病的潜在生物标记物铺平道路，并将为学龄儿童提供针对生物标记物特征量身定做的强化干预措施的可能性。

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.