Pathogenic insight into ASD from the study of neonatal brain-behavior transitions

从新生儿大脑行为转变的研究中了解自闭症谱系障碍的致病原因

• 批准号: 9321382
• 负责人: Sarah Shultz
• 金额: $ 17.18万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-22 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9321382
• 关键词: Age; Age-Months; Amygdaloid structure; Area; Attention; Autistic Disorder; Behavior; Behavioral; Benchmarking; Birth; Brain; Childhood; Clinical Sciences; Congenital Disorders; Data; Data Analyses; Data Collection; Development; Diagnosis; Early Intervention; Environment; Exhibits; Eye; Face; Functional Magnetic Resonance Imaging; Fusiform gyrus; Future; Goals; Imaging technology; Individual; Infant; Infant Behavior; Infant Development; Intervention; Knowledge; Life; Magnetic Resonance Imaging; Maps; Measures; Mediating; Mentored Research Scientist Development Award; Mentors; Modeling; Nature; Neonatal; Newborn Infant; Parents; Pathogenesis; Pathogenicity; Phenotype; Predisposition; Prefrontal Cortex; Pulvinar structure; Reciprocal Social Interaction; Reflex action; Reflex eye movement; Reporting; Research; Rest; Smiling; Social Behavior; Statistical Methods; Structure; Structure of superior temporal sulcus; System; Technology; Testing; Time; Training; United States National Institutes of Health; Work; autism spectrum disorder; awake; base; bioimaging; brain behavior; career; clinical care; data acquisition; disability; experience; high risk; improved; infancy; innovation; insight; multidisciplinary; neonatal brain; neonate; neuroimaging; prospective; reflex disorder; relating to nervous system; social

Project Summary/Abstract The goal of this Mentored Research Scientist Development Award (K01) is to promote an independent research career by bridging the candidate's training in infant development and pediatric neuroimaging with innovations in biomedical imaging, advances in statistical methods for longitudinal data analysis, and cutting- edge clinical science.  The candidate's short-term goal is to identify changes in the brain that accompany transitions in social behavior in typical infancy and disruptions thereof in ASD. This work is motivated by a recent finding that preferential attention to the eyes of others—a basic mechanism of social adaptive action in typical infants—was not immediately diminished in infants later diagnosed with ASD. Instead, infants later diagnosed with ASD exhibited a slight but significant increase in eye-looking at 2 months, which then declined; in contrast, typical infants exhibited a relative low point in eye-looking at 2 months, which then increased. The timing of this difference coincides with a developmental transition, around month 2, in which typical infants are thought to move from experience-expectant mechanisms of social adaptive action (that is: subcortically- mediated, `reflex-like' behaviors) to experience-dependent ones (i.e., cortically-mediated voluntary actions that build iteratively on new experiences). This theoretical account suggests a specific hypothesis in ASD: reflex- like adaptive action may initially be present, while the emergence of experience-dependent voluntary social adaptive action subsequently fails. This study will test this hypothesis by measuring, from birth to 6 months in infants at low and high-risk for ASD,: 1) the decline of reflex-like predispositions and the emergence of voluntary behaviors (eye-looking and social smiling, measured by eye-tracking and parent-infant interaction); and 2) developmental change in subcortical and cortical networks (measured by fMRI and DTI) and their relationship to unfolding behavior. To achieve these aims, the candidate will receive training in 5 areas: 1) phenotypic assessment of infants at low and high-risk for ASD; 2) advances in eye-tracking technology that optimize data acquisition in neonates; 3) innovations in biomedical imaging for improving acquisition and pre- processing of infant neuroimaging data; 4) analysis of infant resting-state fMRI and DTI data; and 5) breakthroughs in statistical methods for the analysis of infant longitudinal data. The training plan is supported by a multidisciplinary team of mentors—including Drs. Ami Klin, Warren Jones, John Pruett, Gordon Ramsay, and Xiaoping Hu—and the strengths of two centers within Emory: the Marcus Autism Center, one of only three NIH Autism Centers of Excellence, providing groundbreaking research and clinical care for individuals with ASD, and the Biomedical Imaging Technology Center, a center for cutting-edge biomedical imaging research. The intersection of these strengths provides an ideal training environment for promoting the candidate's long- term goal of understanding the pathogenesis of ASD and informing intervention.

项目摘要/摘要 这个导师研究科学家发展奖(K01)的目标是促进一个独立的 通过将应聘者在婴儿发育和儿科神经成像方面的培训与 生物医学成像方面的创新，纵向数据分析统计方法的进步，以及切割- 边缘临床科学。候选人的短期目标是识别伴随着 典型婴儿期社会行为的转变及其在ASD中的破坏。这项工作的动机是 最近发现，优先关注他人的眼睛--这是中国社会适应行动的基本机制 典型的婴儿--在后来被诊断为ASD的婴儿中没有立即减少。相反，后来的婴儿 被诊断为ASD的患者在2个月后视力略有增加，但显著增加，然后下降； 相比之下，典型的婴儿在2个月时的视力相对较低，然后有所增加。这个 这种差异的时间恰好与2个月左右的发育转变相吻合，在这一转变中，典型的婴儿 认为从经验-期待的社会适应行动机制(即：亚皮质- 依赖经验的行为(即，皮层调节的自愿行为， 在新体验的基础上迭代构建)。这一理论解释提出了ASD的一个特定假说：反射- 类似适应性的行动最初可能会出现，而依赖经验的自愿社会的出现 适应性行动随后失败。这项研究将通过测量从出生到6个月的婴儿来检验这一假设 ASD的低风险和高风险婴儿：1)反射样倾向的下降和 自愿行为(眼神和社交微笑，通过眼神跟踪和亲子互动来衡量)； 2)皮质下和皮质网络的发育变化(通过fMRI和DTI测量)及其 与展开行为的关系。为了实现这些目标，应聘者将接受5个方面的培训：1) 对ASD低风险和高风险婴儿的表型评估；2)眼球跟踪技术的进步， 优化新生儿的数据采集；3)生物医学成像方面的创新，以改善采集和预 婴儿神经影像数据的处理；4)婴儿静息状态fMRI和DTI数据的分析；5) 在分析婴儿纵向数据的统计方法方面取得突破。培训计划得到支持 由阿米·克林博士、沃伦·琼斯博士、约翰·普鲁特博士、戈登·拉姆齐博士、 胡小平和埃默里两个中心的优势：马库斯自闭症中心，仅有的三个中心之一 NIH自闭症卓越中心，为患有自闭症的患者提供开创性的研究和临床护理 ASD和生物医学成像技术中心，这是一个尖端生物医学成像研究中心。 这些优势的交汇点为促进候选人的长期发展提供了理想的培训环境 目的：了解ASD的发病机制及告知干预措施。