Towards biomarkers of resiliency in the extremely preterm child: a multimodal neuroimaging study of brain and environment

极早产儿弹性的生物标志物：大脑和环境的多模式神经影像研究

• 批准号: 10299819
• 负责人: MARIA E BARNES-DAVIS
• 金额: $ 19.31万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10299819
• 关键词: 11 year old; 6 year old; Accounting; Address; Age; Area; Base of the Brain; Behavioral; Biological Markers; Birth; Birth Records; Brain; Brain Injuries; Brain imaging; Bypass; Child; Clinical Research; Cognition; Cohort Studies; Data; Development; Developmental Disabilities; Diffusion Magnetic Resonance Imaging; Educational workshop; Environment; Environmental Risk Factor; Epidemiologic Methods; Epidemiology; Evaluation; Exhibits; Fostering; Functional Magnetic Resonance Imaging; Funding; Generations; Goals; Knowledge; Language; Language Development; Magnetoencephalography; Mentors; Multimodal Imaging; Neurocognitive Deficit; Neurodevelopmental Impairment; Neuronal Plasticity; Outcome; Pathway interactions; Phenotype; Pregnancy; Public Health; Quality of life; Reporting; Research; Research Personnel; Risk; Risk Factors; SECTM1 gene; School-Age Population; Science; Social Environment; Statistical Methods; Structure; Training; Work; base; cohort; experimental study; flexibility; imaging biomarker; improved; multimodality; neural network; neuroimaging; neuroprotection; outcome prediction; predictive marker; premature; prognostic tool; recruit; resilience; social; socioenvironmental factor; statistics; therapy development; tool; white matter injury

Prematurity is a public health crisis impacting 10% of all births. There is significant risk for neurocognitive impairment, including language. This can adversely impact quality of life. Current prognostic tools leave a significant proportion of variance in later language scores unexplained, focus on risk factors which are often not modifiable, and fail to identify resiliency, or positive outcome despite risk. There is a critical need for advanced neuroimaging studies of well-performing extremely preterm (EPT, <28 weeks gestation) children at school-age and beyond to identify brain-based markers of resiliency while explicitly accounting for socioenvironmental factors. The proposed experiments will address this need by leveraging an existing cohort of 45 EPT children with no overt brain injury and 45 term comparison children. These EPT children were found to have increased functional and structural connectivity--including an extracallosal interhemispheric pathway--versus term children, which positively correlated with language at 4 to 6 years of age for EPT children exclusively. The central hypothesis is that EPT children performing within normal limits on language tasks do so via adaptive neural networks--which are extracallosal and bypass areas vulnerable to white matter injury of prematurity--and the environment in which EPT children are developing drives this adaptive hyperconnectivity. The objective of the proposed research is to determine if this hyperconnectivity remains a brain-based biomarker of resiliency at 8- 11 years and analyze the influence of the child’s social environment on hyperconnectivity. The first aim is to determine if the extracallosal hyperconnectivity (versus term children) we observed at 4-6 years of age in the EPT group persists to 8-11 years of age. The second aim is to determine the extent to which language scores at 8-11 years relate to hyperconnectivity for EPT children. The third aim is to evaluate the extent to which environmental factors drive brain connectivity. Children will be assessed longitudinally with magnetoencephalography, functional magnetic resonance imaging (MRI), and diffusion MRI to validate unique neuroimaging signatures previously identified. Environment-based factors will be assessed at birth (through linkage with birth records), 4-6 years, and 8-11 years to evaluate the extent to which they influence preterm brain connectivity. The candidate’s long-term goal is to reduce the burden of neurodevelopmental impairment for children born EPT by uncovering adaptive, neuroprotective mechanisms and developing imaging markers that can subsequently be used to improve prediction of outcomes before language can be reliably assessed. Through formal coursework, workshops, and hands-on training during the proposed research with her interdisciplinary committee of expert advisors and mentors, the candidate will gain expertise in epidemiological methods to evaluate socioenvironmental risk across generations and in the science of adversity and resiliency. This is a critical next step to establish scientific independence as an investigator and a leader in the study of socioenvironmental resiliency, language development, and neuroprotective mechanisms in the preterm brain.

早产是影响所有出生的10％的公共卫生危机。神经认知的风险很大 损害，包括语言。这可能会对生活质量产生不利影响。当前的预后工具留下 以后语言分数的显着差异意外，专注于通常不是的风险因素 可修改，无法识别弹性或积极的结果目的地风险。高级需要 对良好表现非常早产（EPT，<28周妊娠）儿童的神经影像学研究 除了确定基于大脑的弹性标记，同时明确考虑社会环境 因素。拟议的实验将通过利用现有的45个EPT儿童的队列来满足这种需求 没有明显的脑损伤和45个学期比较儿童。发现这些EPT儿童增加了 功能性和结构连通性 - 包括外膜外途径的途径 - 术语儿童， EPT儿童仅与4至6岁的语言正相关。中央 假设是，EPT儿童在正常限制语言任务内进行的EPT儿童通过适应性神经元进行 网络 - 外部和旁路区域容易受到早产损伤的影响 - EPT儿童正在发展的环境驱动着这种自适应超连接性。目的 拟议的研究是确定这种超连续性是否仍然是8--的基于大脑的弹性生物标志物 11年并分析孩子社会环境对超连接性的影响。第一个目的是 确定我们在4-6岁时观察到的外卵外超连接性（与期限儿童相对于年龄儿童）是否 EPT组持续到8-11岁。第二个目的是确定语言得分的程度 与EPT儿童的超连续性有关的8 - 11年。第三个目的是评估 环境因素推动大脑连通性。儿童将通过纵向评估 磁脑摄影，功能磁共振成像（MRI）和扩散MRI以验证独特 先前鉴定出的神经影像学特征。基于环境的因素将在出生时进行评估（通过 与出生记录的联系），4 - 6年和8 - 11年，以评估它们影响早产大脑的程度 连接性。候选人的长期目标是减少神经发育障碍的燃烧 通过发现适应性，神经保护机制和开发成像标记的儿童 随后，可以使用在可靠评估语言之前，用于改善结果的预测。通过 在拟议的研究期间，正式的课程，讲习班和动手培训与她的跨学科 专家顾问和导师委员会，候选人将获得流行病学方法的专业知识 在世代和广告和弹性科学中评估社会环境风险。这是一个 建立科学独立的下一步的关键步骤，作为研究者和研究领导者 早产大脑中的社会环境弹性，语言发展和神经保护机制。