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: 10584837
• 负责人: James Christopher EDGAR
• 金额: $ 81.57万
• 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 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584837
• 关键词: 8 year old; Adolescent; Adult; Age; Alpha Rhythm; Anxiety; Attention; Attention deficit hyperactivity disorder; Auditory; Auditory area; Brain; Brain Diseases; Brain imaging; Child; Child Development; Childhood; Clinic; Clinical; Clinical Research; Clinical Treatment; Clinical assessments; Communication; Development; Developmental Process; Diagnosis; Disease; Electroencephalography; Foundations; Future; Gene Expression Regulation; Goals; Hearing problem; Intention; Interneurons; Intervention; Language; Left; Location; Longitudinal Studies; Magnetoencephalography; Maps; Measures; Methods; Pattern; Preventive; Process; Pyramidal Cells; Reporting; Research; Rest; Sampling; Scalp structure; Sensory; Series; Source; Specificity; Structure; Symptoms; Time; Translating; Work; aging brain; autism spectrum disorder; autistic children; base; brain abnormalities; clinically significant; cognitive ability; cognitive process; comorbidity; density; design; diagnostic biomarker; early adolescence; early childhood; infancy; neural circuit; process repeatability; rate of change; relating to nervous system; response

Project Summary/Abstract Although differences in auditory encoding and resting-state (RS) neural activity are often reported in children with typical development (TD) versus autism spectrum disorder (ASD), the pattern of findings across studies is inconsistent. The PI has sought to understand the above via studying the maturation of these processes, this work supported by his current R01 (locally referred to as the ‘Brains Change’ study). A consistent finding has been a pattern of brain development that indicates overly rapid followed by too slow brain maturation in ASD. The continuation R01 will demonstrate that this pattern of brain maturation in ASD continues through at least early adolescence as a basis for developing disease-stage-specific assessment and treatment methods. In addition to continuing to map the maturation of RS neural activity, two auditory cortex neural processes that emerge during late childhood are targeted. First is the auditory M100 response, with findings from the current R01 already suggesting that M100, reflecting higher-order auditory encoding, emerges too early in ASD. Second, a new 40 Hz auditory steady-state response exam will assess the emergence and development of cortical inhibitory interneuron and pyramidal cell excitation and inhibition processes. Maturation findings, expected to demonstrate early accelerated then later flat development in ASD, will show a process that repeats itself across childhood and thus leads to a patterned derailment of emerging neural processes in ASD that extends far beyond infancy and early childhood. Tied to the above are two additional goals. First, given group differences in brain maturation rates, studies that average findings across a large age range will miss effects, and cross-sectional comparisons will be complicated. The PI’s research identifies age-specific brain markers in order to provide a basis for developing disease-stage-specific assessment and treatment targets. Second, and building upon the PIs adult studies, analysis of simultaneously collected MEG and EEG is expected to demonstrate the advantage of obtaining regionally specific measures when assessing group differences as well as enable identification of EEG-only assessment methods that are routinely feasible in the clinic. Our intention is that Brains Change findings will change the way ASD research is conducted via demonstrations that the pattern of group differences changes across time (even across a 3-year period), and via identifying very specific brain abnormalities in ASD with respect to age, brain location, and brain process. The current project assesses brain function, structure, and clinical measures in children 6 to 8 years old, and then 18 and 36 months later. For the renewal R01, each child will be followed another 3 years (3 brain imaging exams with 18 months between exams). Allowing attrition of the current sample across time, the Time 3 sample (N = 35/group) will be increased by 65+/group to start the continuation with 100 ASD and 100 TD.

项目总结/摘要 虽然听觉编码和静息态（RS）神经活动的差异经常被报道， 典型发育（TD）与自闭症谱系障碍（ASD）的儿童， 研究结果是不一致的。PI试图通过研究 这些过程，这项工作得到了他目前的R 01（当地称为“大脑变化”）的支持。 研究）。一个一致的发现是，大脑发育的模式表明， 自闭症患者大脑发育过慢R 01将证明这种大脑模式 ASD的成熟至少持续到青春期早期，作为发展的基础。 疾病阶段的具体评估和治疗方法。除了继续绘制 RS神经活动的成熟，这两个听觉皮层神经过程出现在儿童后期 是有针对性的。首先是听觉M100反应，目前R 01的研究结果已经表明， 反映高阶听觉编码的M100在ASD中过早出现。第二，新的40 Hz 听觉稳态反应检查将评估皮层抑制性的出现和发展 中间神经元和锥体细胞兴奋和抑制过程。成熟结果，预计 在ASD中显示早期加速然后后期平坦发展，将显示重复的过程 它本身在童年时期，因此导致了一个模式化的脱轨新兴神经过程， ASD远远超出婴儿期和幼儿期。与上述目标相关的还有两个额外目标。 首先，考虑到大脑成熟率的群体差异， 范围将错过效果，横截面比较将变得复杂。PI的研究发现， 年龄特异性脑标志物，以便为开发疾病阶段特异性评估提供基础 治疗目标。第二，建立在成人研究的基础上，同时分析 收集的MEG和EEG有望证明获得区域特异性的优势， 评估组间差异时的测量，以及仅识别EEG评估 在临床上常规可行的方法。我们的意图是，大脑改变的发现将 改变ASD研究的方式，通过证明小组的模式 差异随着时间的推移而变化（甚至在3年的时间内），并通过识别非常具体的 ASD的大脑异常与年龄、大脑位置和大脑过程有关。当前 该项目评估了6至8岁儿童的大脑功能，结构和临床测量，然后是18岁， 36个月后。对于更新R 01，每名儿童将再随访3年（3次脑成像 考试间隔18个月）。允许当前样本随时间的损耗，时间3 样本（N = 35/组）将增加65+/组，以100 ASD和100 TD开始继续。