A longitudinal study of brain development in children with autism

自闭症儿童大脑发育的纵向研究

• 批准号: 9052396
• 负责人: James Christopher EDGAR
• 金额: $ 73.51万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9052396
• 关键词: Activities of Daily Living; Age; Alpha Rhythm; Animal Experimentation; Animal Model; Animals; Auditory; Auditory area; Autistic Disorder; Back; Biological Neural Networks; Brain; Child; Clinical; Cognitive; Complex; Coupling; Deep Brain Stimulation; Development; Developmental Process; Enrollment; Eye; Failure; Frequencies; Functional disorder; Future; Genes; Human; Impaired cognition; Impairment; Laboratories; Language; Longitudinal Studies; Measures; Multimodal Imaging; Neuronal Dysfunction; Parietal; Participant; Pathology; Pathway interactions; Pattern; Pharmacologic Substance; Phase; Plant Roots; Process; Radiation; Recruitment Activity; Rest; Role; Severities; Structural defect; Structure; Superior temporal gyrus; Symptoms; Thalamic structure; Therapeutic Studies; Time; Translating; Work; aged; autism spectrum disorder; base; brain dysfunction; functional disability; image guided therapy; improved; innovation; interest; language impairment; longitudinal design; nerve stem cell; neuroregulation; prognostic; public health relevance; rate of change; relating to nervous system; repetitive behavior; response; sensory input; signal processing; social; social skills; stem cell therapy; targeted treatment; theories; white matter

 DESCRIPTION (provided by applicant): Our laboratory has observed abnormalities in resting-state (RS) and auditory neural activity in children with autism spectrum disorder (ASD). There is a clinical component to these findings, with RS and auditory brain rhythms predicting symptom severity. There is a developmental/maturational component, with age cross-sectional findings indicating greater clinical impairment in the children with ASD with the most delayed maturation of RS and auditory processes. Finally, there is a structural component, with our analyses demonstrating thalamic involvement in RS and auditory neural abnormalities. Given the central role of the thalamus in modulating and coordinating neural activity, understanding the contribution of thalamic structure and thalamocortical connectivity to cortical oscillatory abnormalities in ASD is of high priority. This proposed R01 will demonstrate that neural dysfunction and clinical symptoms in ASD arise, in part, from abnormal thalamic and thalamocortical structure. A primary tenet of this proposal is that understanding brain dysfunction in children with ASD requires assessing developmental processes rather than a single time-point (snapshot) measure. To this end, a three time-point longitudinal study is proposed, with brain and clinical measures obtained in typically developing control (TDC) and ASD participants aged 6- to 8-years and then both 18 and 36 months later (N=70 per group at enrollment). It is hypothesized that children with ASD will show slower development of brain rhythms/patterns, with rate of change (i.e. slope) rather than single time-point measures better separating TDC and ASD. It is also hypothesized that rate of change rather than single time-point measures will better predict functional capacity, with baseline measures demonstrating pathology (e.g., auditory processing abnormalities) but with rate-of-change indicating the degree of successful brain maturation and thus offering greater prognostic utility. It is expected that R0 findings will offer conceptual innovation by motivating the need to develop 'thalamic therapies', with R01 human neural and associated thalamocortical white-matter abnormalities back-translated to animal models, and with animal research identifying potential pharmaceutical treatments. Animal work will likely build on current gene and neural stem cell therapy research. Pro-myelinating therapies and image-guided deep brain stimulation or other target-based neuro-modulation treatments may also be of future interest.

 描述（由应用程序提供）：我们的实验室观察到自闭症谱系障碍儿童（ASD）的静息状态（RS）和听觉中性活性异常。这些发现有一个临床成分，RS和听觉脑节律预测了符号的严重性。有一个发育/成熟的成分，年龄横截面的发现表明ASD儿童的临床障碍更大，RS和听觉过程的成熟度最长。最后，有一个结构成分，我们的分析表明了丘脑在RS和听觉神经元异常中的参与。鉴于丘脑在调节和协调神经元活性中的核心作用，了解丘脑结构和丘脑皮质连通性对ASD中皮质振荡异常的贡献是高优先级。该提出的R01将证明ASD的神经元功能障碍和临床症状部分来自异常的丘脑和丘脑皮质结构。该提案的主要宗旨是了解ASD儿童的脑功能障碍需要评估发展过程，而不是单个时间点（快照）测量。为此，提出了三个时间点纵向研究，在典型发展的对照（TDC）和6至8岁的ASD参与者中获得了大脑和临床措施，然后在18和36个月后（招收时n = 70）。假设ASD患有ASD的儿童会显示出脑部节律/模式的发展较慢，并具有变化率（即斜率），而不是单个时间点测量，可以更好地分离TDC和ASD。还可以假设，变化速率而不是单个时间点测量将更好地预测功能能力，基线测量结果表明病理学（例如听觉处理异常），但变化速度表明成功的脑成熟程度，从而提供了更大的预后效用。预计R0的发现将通过激励开发“丘脑疗法”的需求来提供概念创新，R01人类神经元和相关的丘脑皮层白血病异常反向转换为动物模型，并通过动物研究识别潜在的药物治疗。动物工作可能会基于当前基因和神经元干细胞疗法研究。促膜疗法和图像引导的深脑刺激或其他基于目标的神经调节疗法也可能引起未来的兴趣。