Brain Bases of Language Deficits in SLI and ASD

SLI 和 ASD 语言缺陷的大脑基础

• 批准号: 8313906
• 负责人: JOHN GABRIELI
• 金额: $ 61.42万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-08 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8313906
• 关键词: 12 year old; Adolescence; Age; Area; Base of the Brain; Behavioral; Bilateral; Biological Markers; Brain; Brain region; Child; Childhood; Clinical; Clinical Markers; Communication; Complex; Development; Diffusion Magnetic Resonance Imaging; Discrimination; Disease; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Gene Mutation; Genetic; Goals; Image; Impairment; Inferior frontal gyrus; Intervention; Judgment; Knowledge; Language; Language Development; Language Development Disorders; Language Disorders; Lead; Left; Length; Magnetic Resonance Imaging; Matched Group; Measures; Morphology; Neurobiology; Nursery Schools; Pattern; Performance; Phenotype; Population; Process; Recruitment Activity; Research; School-Age Population; Severities; Short-Term Memory; Structure; Subgroup; Superior temporal gyrus; Thick; Time; Variant; Work; age effect; age related; aged; autism spectrum disorder; base; behavior measurement; clinical practice; design; gray matter; language processing; morphometry; neuroimaging; novel strategies; phonology; programs; relating to nervous system; research study; response; social communication; specific language impairment; white matter

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.

描述（由申请人提供）：特定的语言障碍（SLI）和自闭症谱系障碍（ASD）是复杂的高度遗传性疾病，涉及语言和交流中的主要障碍。 ASD的子类型包括在SLI中发现的语言障碍，其中包括SLI的两个核心临床标记：语音工作记忆中的缺陷，如非单词重复任务衡量，以及语法形态的缺陷，尤其是在动词上标记时态。该项目的目的是研究SLI，ASD和这些核心语言能力的典型发展中这两个核心缺陷的大脑基础。 AIM 1将研究语音工作记忆（非单词歧视）和语法判断的神经基础，通常是96岁，通常是5至12岁的儿童。对于非单词歧视任务，我们预测，非单词长度的增加将导致双侧上级颞回（STG）和左下额叶（LIFG）的募集更大，并且主要的发育变化主要是LIFG。在语法判断任务中，我们预测，与正确的句子相比，涉及涉及省略时态的错误（例如，过去时-ED）将导致LIFG和左STG的激活更大。 AIM 2将在48名患有SLI的儿童和96名ASD儿童（48例，没有合并语言障碍的儿童）中实施相同的实验范例，年龄在8-12岁之间，他们将与年龄和语言匹配的典型对照进行比较。我们预测，在具有SLI的儿童中，IFG和STG之间的功能连接程度将降低，并且在两个实验中，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行为性能相关。我们还预测，具有语言障碍的ASD儿童将显示出与SLI组相似的非典型激活模式，并且随着时间的流逝，这两个组将显示出与典型儿童更相似的激活模式。这是关于SLI和ASD语言核心障碍神经生物学基础的首次发展研究。这些发现将为识别这些疾病的潜在生物标志物铺平道路，并将为针对单独针对生物标志物概况量身定制的学龄儿童提供密集的干预措施。