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（由申请人提供）：我们的实验室观察到自闭症谱系障碍（ASD）儿童的静息态（RS）和听觉神经活动异常。这些发现具有临床成分，RS 和听觉脑节律可以预测症状的严重程度。存在发育/成熟的成分，年龄横断面研究结果表明患有 ASD 的儿童具有更大的临床障碍，RS 和听觉过程的成熟最延迟。最后，还有一个结构部分，我们的分析表明丘脑参与 RS 和听觉神经异常。鉴于丘脑在调节和协调神经活动中的核心作用，了解丘脑结构和丘脑皮质连接对 ASD 皮质振荡异常的贡献是当务之急。拟议的 R01 将证明 ASD 中的神经功能障碍和临床症状部分是由异常的丘脑和丘脑皮质结构引起的。该提案的主要原则是，了解自闭症谱系障碍儿童的大脑功能障碍需要评估发育过程，而不是单个时间点（快照）测量。为此，提出了一项三时间点纵向研究，在 6 至 8 岁以及 18 个月和 36 个月后的典型发育对照 (TDC) 和 ASD 参与者中获得大脑和临床测量（入组时每组 N = 70）。据推测，患有自闭症谱系障碍 (ASD) 的儿童的大脑节律/模式发展较慢，变化率（即斜率）而不是单一时间点测量可以更好地区分 TDC 和自闭症谱系障碍 (ASD)。还假设变化率而不是单个时间点测量将更好地预测功能能力，基线测量显示病理学（例如听觉处理异常），但变化率表明大脑成功成熟的程度，从而提供更大的预后效用。预计 R0 的研究结果将通过激发开发“丘脑疗法”的需求来提供概念创新，其中 R01 人类神经和相关丘脑皮质白质异常可反向翻译到动物模型，并通过动物研究确定潜在的药物治疗。动物工作可能会建立在当前的基因和神经干细胞治疗研究的基础上。促髓鞘形成疗法和图像引导的深部脑刺激或其他基于目标的神经调节治疗也可能在未来引起人们的兴趣。