MEG Studies of Auditory Processing in Minimally/Non-Verbal Children with ASD and Intellectual Disability

患有自闭症谱系障碍和智力障碍的最小/非语言儿童听觉处理的 MEG 研究

• 批准号: 9054636
• 负责人: Timothy P Roberts
• 金额: $ 24.55万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-11-01 至 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9054636
• 关键词: Address; Age; Animal Behavior; Animal Model; Area; Auditory; Autistic Disorder; Behavioral; Biological Markers; Brain; Cerebral Dominance; Child; Clinical; Cognitive; Control Groups; Data; Data Collection; Detection; Development; Developmental Disabilities; Diagnosis; Elements; Feedback; Financial compensation; Foundations; Frequencies; Goals; Head; Image; Impaired cognition; Impairment; Individual; Intellectual functioning disability; Intervention; Language; Language Delays; Left; Linguistics; Literature; Magnetic Resonance Imaging; Magnetoencephalography; Measures; Mental Retardation and Developmental Disabilities Research Centers; Motion; National Institute of Mental Health; Outcome Measure; Parents; Participant; Pathogenesis; Pharmaceutical Preparations; Pharmacologic Substance; Phenotype; Population; Process; Protocols documentation; Provider; Research; Research Project Grants; Scanning; Severities; Signal Transduction; Source; Stimulus; Therapeutic Intervention; Time; aged; autism spectrum disorder; base; cognitive ability; cognitive function; disability; improved outcome; insight; language impairment; lexical; neuroimaging; pre-clinical; relating to nervous system; response; study population; success

(RESEARCH PROJECT: MEG IN ASD)  PROJECT SUMMARY We have developed magnetoencephalography (MEG) measures that predict both a diagnosis of ASD and the degree of language impairment. Thus, (i) auditory encoding latency (M100) discriminates ASD versus non- ASD; (ii) auditory change detection latency (mismatch field, MMF) predicts severity of language impairment in ASD and in other groups with a developmental disability; and (iii) lexical distinction (word versus non-word low-frequency neural oscillatory activity) both predicts language impairment as well as atypical hemispheric specialization for language in ASD and, perhaps, in other neurodevelopmental groups. Prior imaging studies of ASD (including our own) have focused on an intellectually higher-functioning population (high-functioning autism, or HFA). One reason for this bias is that the majority of imaging studies entail magnetic resonance imaging (MRI), which presupposes a participant's ability to remain motionless during the study, thereby disqualifying from study the large ASD population with language delay and intellectual disability (possibly as high as 50%). We seek to investigate the neural basis of autism and associated language and cognitive impairment in an under-studied population of minimally verbal/non-verbal ASD children (MVNV-ASD, N = 40, aged 8 to 12 years). To this end, MVNV-ASD encoding, change detection, and lexical MEG measures will be compared with the same measures already available in age-matched HFA and typically developing (TD) children. Using the same tasks, MEG data will be obtained from a “positive control” group of children with intellectual disability (ID; N =40) but without ASD, matched for age and non-verbal IQ in order to isolate neural abnormalities specific to MVNV-ASD and not consequent to impairment of general cognitive function. Thus, our primary goals are: (a) A search for pathogenic mechanisms common to HFA and MVNV-ASD, thereby enabling a deeper understanding of the pathogenesis of disability across the ASD spectrum; and (b) A search for mechanisms of language impairment that are ASD-specific rather than a consequence of more general effects of low cognitive ability. To obtain high-quality MEG data, we will deploy a research strategy we designate “MEG-PLAN (MEG Protocol for Low-Language/Cognitive Functioning Ability Neuroimaging). The key elements of MEG-PLAN are: (1) Engage stakeholders (parents/providers) as “partners in research” to develop a MEG scanning protocol that maximizes data collection success; (2) Examine automatic brain responses elicited with passive auditory paradigms, thereby obviating the need for participants to attend to the task or provide feedback; (3) Remove the need for an individual MRI to localize the MEG signal source by using a MEG which is registered to an age-appropriate template MRI; (4) Achieve motion tolerance of up to 2 cm via real-time MEG head tracking/motion compensation. This study addresses focus area #2 in the RFA – “Outcome Measures for Interventions or Treatments”.

（研究项目：ASD中的MEG） 项目摘要 我们已经开发了磁脑摄影（MEG）措施，以预测ASD诊断和 语言障碍程度。 （i）编码延迟（M100）的听觉区分ASD与非 - ASD; （ii）听觉变化检测潜伏期（不匹配字段，MMF）语言障碍的严重程度 在ASD和其他具有发育障碍的群体中；和（iii）词汇区别（单词与非单词 低频神经振荡活动）既预测语言障碍，又是非典型半球 ASD中语言的专业化以及其他神经发育群体中的专业化。先前的成像研究 ASD（包括我们自己的）专注于直接功能更高的人群（高功能） 自闭症或HFA）。这种偏见的原因之一是大多数成像研究需要磁共振 成像（MRI），它以参与者在研究期间保持一动不动的能力为前提 从研究中取消语言延迟和智力残疾的大量ASD人群的资格（可能是 高达50％）。我们试图研究自闭症和相关语言和认知的神经基础 最低少数言语/非语言ASD儿童的人口损害（MVNV-ASD，n = 40， 8至12岁）。为此，MVNV-ASD编码，更改检测和词汇MEG测量将是 与已经在年龄匹配的HFA和通常开发的相同措施（TD）相比 孩子们。使用相同的任务，MEG数据将从“正面对照”组中获得 智力残疾（ID; n = 40），但没有ASD，与年龄和非语言智商相匹配，以隔离中立 MVNV-ASD特有的异常，而不是一般认知功能受损。那， 我们的主要目标是：（a）寻找HFA和MVNV-ASD常见的致病机制，从而 能够更深入地了解ASD频谱中残疾的发病机理； （b）搜索 对于ASD特异性的语言障碍机制，而不是更一般的结果 低认知能力的影响。为了获得高质量的MEG数据，我们将部署一种研究策略 指定“ MEG计划（低语言/认知功能能力神经影像学的MEG协议）。 MEG计划的关键要素是：（1）与利益相关者（父母/提供者）作为“研究合作伙伴”与 制定MEG扫描协议，以最大化数据收集成功； （2）检查自动大脑 通过被动听觉范式引起的响应，从而消除了参与者参加的需求 任务或提供反馈； （3）删除对单个MRI的需求，以通过 使用注册为适合年龄的模板MRI的MEG； （4）达到多达2的运动耐受性 CM通过实时MEG头部跟踪/运动补偿。这项研究介绍了RFA中的焦点区域＃2 “干预或治疗的结果措施”。