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: 10697380
• 负责人: James Christopher EDGAR
• 金额: $ 80.51万
• 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 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10697380
• 关键词: 8 year old; Acceleration; 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 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; autism spectrum disorder; autistic children; brain abnormalities; clinically significant; cognitive ability; cognitive process; comorbidity; density; design; diagnostic biomarker; early adolescence; early childhood; infancy; neural; neural circuit; rate of change; 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.

项目摘要/摘要 尽管经常在听觉编码和静止状态（RS）神经活动中的差异在 患有典型发育（TD）与自闭症谱系障碍（ASD）的儿童，发现的模式 整个研究都是不一致的。 PI感觉通过研究以上的成熟来理解上述 在这些过程中，这项工作得到了他当前R01的支持（当地称为“大脑变化” 学习）。一致的发现是大脑发育的模式，表明遵循 ASD中的大脑成熟太慢。延续R01将证明这种大脑的模式 ASD的成熟至少继续通过早期青少年作为发展的基础 疾病阶段特异性评估和治疗方法。除了继续绘制 RS神经元活性的成熟，两个听觉皮层神经元过程在儿童后期出现 是针对性的。首先是听觉M100响应，当前R01的发现已经暗示 反映高阶听觉编码的M100在ASD中出现了太早。第二，新的40 Hz 听觉稳态反应检查将评估皮质抑制的出现和发展 中神经元和锥体细胞兴奋和抑制过程。成熟发现，期望 证明早期加速，然后在ASD中进行平坦的开发，将显示一个重复的过程 在整个童年时期本身，因此导致了新兴神经过程的图案出轨 ASD远远超出了婴儿期和幼儿。与上述相关的是两个其他目标。 首先，鉴于脑部成熟率的群体差异，研究了一个年龄段的平均发现 范围将错过效果，将编译横截面比较。 PI的研究确定 年龄特异性的大脑标志物为开发疾病特异性评估的基础 和治疗目标。其次，并在PIS成人研究基础上，简单地分析 收集的MEG和EEG有望证明获得特定于区域的优势 评估群体差异时采取的措施以及识别仅EEG评估的措施 在诊所通常可行的方法。我们的意图是大脑改变发现将 通过示范的群体模式来改变ASD研究的方式 跨时间的差异变化（即使在3年的时间内），并通过确定非常具体的 与年龄，大脑位置和大脑过程有关的ASD的大脑异常。电流 项目评估6至8岁儿童的大脑功能，结构和临床指标，然后是18岁 36个月后。对于续签R01，每个孩子都会再遵循3年（3个脑成像 考试之间有18个月的考试）。允许在时间3的时间3 样品（n = 35/组）将增加65+/组，以100 ASD和100 TD开始延续。

项目成果

A MEG Study of Acute Arbaclofen (STX-209) Administration.

急性阿巴氯芬 (STX-209) 给药的 MEG 研究。

• DOI: 10.3389/fnint.2019.00069
• 发表时间: 2019
• 期刊: Frontiers in integrative neuroscience
• 影响因子: 3.5
• 作者: Roberts,TimothyPL;Bloy,Luke;Blaskey,Lisa;Kuschner,Emily;Gaetz,Leah;Anwar,Ayesha;Ku,Matt;Dipiero,Marissa;Bennett,Amanda;Edgar,JChristopher
• 通讯作者: Edgar,JChristopher

A comparison of resting-state eyes-closed and dark-room alpha-band activity in children.

儿童静息状态闭眼和暗室 α 波段活动的比较。

• DOI: 10.1111/psyp.14285
• 发表时间: 2023
• 期刊: Psychophysiology
• 影响因子: 3.7
• 作者: Edgar,JChristopher;Franzen,RoseE;McNamee,Marybeth;Green,HeatherL;Shen,Guannan;DiPiero,Marissa;Liu,Song;Airey,Megan;Goldin,Sophia;Blaskey,Lisa;Kuschner,EmilyS;Kim,Mina;Konka,Kimberly;Roberts,TimothyPL;Chen,Yuhan
• 通讯作者: Chen,Yuhan