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：MEG在ASD） 项目摘要 我们已经开发出脑磁图（MEG）的措施，预测ASD的诊断和 语言障碍的程度。因此，（i）听觉编码潜伏期（M100）区分ASD与非ASD。 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ASD和其他发育障碍的群体中;以及（iii）词汇区分（词与非词 低频神经振荡活动）既预测语言障碍，也预测非典型半球 自闭症谱系障碍的语言专业化，也许在其他神经发育组。既往影像学研究 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，大多数成像研究需要磁共振 成像（MRI），其前提是参与者在研究期间保持不动的能力，从而 丧失研究具有语言延迟和智力残疾的大量ASD人群的资格（可能作为 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功能， 在研究中的最小语言/非语言ASD儿童群体（MVNV-ASD，N = 40， 8至12岁）。为此，MVNV-ASD编码，变化检测和词汇MEG测量将被 与年龄匹配的HFA和典型发展中国家（TD）中已有的相同措施相比， 孩子使用相同的任务，MEG数据将从“阳性对照”儿童组获得， 智力残疾（ID; N =40），但没有ASD，年龄和非语言智商匹配，以分离神经 MVNV-ASD特异性异常，而不是一般认知功能受损的结果。因此，在本发明中， 我们的主要目标是：（a）寻找HFA和MVNV-ASD共同的致病机制，从而 使得能够更深入地理解ASD谱系中的残疾发病机制;以及（B）搜索 语言障碍的机制是ASD特异性的，而不是更普遍的结果， 低认知能力的影响。为了获得高质量的MEG数据，我们将部署一项研究策略， 命名为“MEG-MEG（用于低语言/认知功能能力神经成像的MEG方案）。的 MEG-ESTA的关键要素是：（1）让利益相关者（父母/供应商）作为“研究伙伴”参与， 制定一个MEG扫描协议，最大限度地提高数据收集的成功率;（2）检查自动大脑 被动听觉范式引起的反应，从而避免了参与者需要注意的问题。 任务或提供反馈;（3）通过以下方式消除对单个MRI定位MEG信号源的需要： 使用与年龄相适应的模板MRI配准的MEG;（4）实现高达2 cm通过实时MEG头部跟踪/运动补偿。本研究涉及RFA中的重点领域#2- “干预或治疗的结果指标”。