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

(研究项目：Meg IN AASD) 项目总结 我们已经开发出脑磁图(MEG)测量方法，可以预测ASD的诊断和 语言障碍程度。因此，(I)听觉编码潜伏期(M100)区分ASD和非ASD (Ii)听觉变化检测潜伏期(失配场，MMF)预测语言障碍的严重程度 在自闭症和其他发育障碍人群中；以及(Iii)词汇区分(单词与非单词 低频神经振荡活动)既可以预测语言障碍，也可以预测非典型半球 在自闭症和其他神经发育群体中，语言的专门化。先前的影像研究 ASD(包括我们自己的)专注于智力更高功能的人群(高功能 自闭症，或HFA)。这种偏见的一个原因是，大多数成像研究都需要磁共振 磁共振成像(MRI)，前提是参与者在研究过程中保持不动的能力，从而 有语言迟缓和智力残疾的大量ASD人群丧失研究资格(可能是 高达50%)。我们试图研究自闭症的神经基础以及相关的语言和认知。 轻度语言/非语言ASD儿童(MVNV-ASD，N=40， 8至12岁)。为此，MVNV-ASD编码、变化检测和词法MEG措施将 与年龄匹配的HFA和典型发展中(TD)中已有的相同措施进行比较 孩子们。使用同样的任务，脑磁图数据将从一组患有 智力残疾(ID；N=40)，但没有ASD，年龄和非语言智商匹配，以隔离神经 MVNV-ASD特有的异常，不是一般认知功能损害的结果。因此， 我们的主要目标是：(A)寻找HFA和MVNV-ASD共同的致病机制，从而 能够更深入地了解ASD谱系中残疾的发病机制；以及(B)搜索 对于ASD特有的语言障碍机制，而不是更普遍的结果 认知能力低下的影响。为了获得高质量的脑磁图数据，我们将部署一项研究战略，我们 指定“MEG-PLAN(MEG低语言/认知功能神经成像方案)”。这个 MEG计划的关键要素是：(1)让利益攸关方(家长/提供者)作为“研究合作伙伴”参与研究 开发最大限度提高数据收集成功率的脑磁图扫描方案；(2)检查自动大脑 用被动听觉范例引起的反应，从而消除了参与者关注 任务或提供反馈；(3)通过以下方式消除单独MRI定位脑磁图信号源的需要 使用注册到适合年龄的模板MRI的脑磁图；(4)实现高达2的运动容差 Cm通过实时脑磁头跟踪/运动补偿。这项研究涉及RFA中的重点领域#2- “干预或治疗的结果衡量标准”。

(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”.