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，涉及语言和交流的原发性障碍。 ASD 的一个亚型包括与 SLI 中发现的语言障碍类似的语言障碍，包括 SLI 的两个核心临床标志：语音工作记忆缺陷（在非单词重复任务中测量）和语法形态缺陷，特别是在标记动词时态方面。该项目的目标是研究 SLI、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。目标 1 将调查 96 名 5-12 岁正常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。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）的更多募集，发育变化主要发生在 LIFG 中。在语法判断任务中，我们预测与正确句子相比，涉及省略强制时态（例如过去时 -ed）的错误将导致 LIFG 和左 STG 更大的激活。目标 2 将在 48 名年龄为 8-12 岁的 SLI 儿童和 96 名 ASD 儿童（48 名患有共病语言障碍，48 名没有共病语言障碍）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 SLI 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，有语言障碍的自闭症谱系障碍儿童将表现出与 SLI 组相似的非典型激活模式，并且随着时间的推移，两组将表现出更接近典型儿童的激活模式。这是第一个针对 SLI 和 ASD 语言核心障碍的神经生物学基础的发展研究。这些发现将为识别这些疾病的潜在生物标志物铺平道路，并将开辟为学龄儿童提供针对生物标志物情况单独定制的强化干预措施的可能性。