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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

基本信息

批准号：
10674799
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
项目类别：
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/10674799
关键词：
11 year old 6 year old Accounting Age Area Behavioral Biological Markers Birth Birth Records Brain Brain Injuries Brain imaging Bypass Child Clinical 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 Mentored Clinical Scientist Development Program 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 School-Age Population Science Social Environment Statistical Methods Training Work brain based cohort experimental study extreme prematurity flexibility imaging biomarker improved multimodal neuroimaging neural network neuroimaging neuroprotection outcome prediction predictive marker premature prognostic tool promote resilience recruit resilience social adversity socioenvironmental factor statistics theories therapy development tool white matter injury

项目摘要

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.

早产是一种公共卫生危机，影响所有出生人口的10%。存在神经认知功能障碍的显著风险包括语言障碍。这可能会对生活质量产生不利影响。目前的预测工具后期语言成绩的显著差异比例无法解释，重点是风险因素，而这些因素往往不是可修改，并且无法识别弹性，或尽管存在风险但仍有积极成果。迫切需要先进的学龄期表现良好的极早产儿（EPT，<28周妊娠）的神经影像学研究以及其他方面，以确定基于大脑的弹性标记，同时明确考虑社会环境因素，因素拟议的实验将通过利用现有的45名EPT儿童的队列来解决这一需求无明显脑损伤的儿童和45名足月对照儿童。这些EPT儿童被发现增加了功能和结构连接--包括胼胝体外半球间通路--与足月儿相比， 4~6岁EPT儿童的语言能力与语言能力呈显著正相关。中央一个假设是，EPT儿童在正常范围内完成语言任务是通过适应性神经网络--胼胝体外和旁路区域易受早产儿白色物质损伤--和 EPT儿童发展的环境驱动了这种适应性超连接。的目的拟议的研究是确定这种超连接是否仍然是8 - 10岁时恢复力的大脑生物标志物。 11年，并分析孩子的社会环境对超连接的影响。第一个目标是确定我们在4 - 6岁时观察到的胼胝体外超连接（与足月儿童相比）是否存在于 EPT组持续到8 - 11岁。第二个目的是确定语言成绩在多大程度上与EPT儿童的超连通性有关。第三个目标是评估环境因素驱动大脑连接。将对儿童进行纵向评估，脑磁图、功能性磁共振成像（MRI）和弥散MRI，以验证独特的神经影像学特征。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岁和8 - 11岁，以评估它们对早产儿大脑的影响程度连通性。候选人的长期目标是减少神经发育障碍的负担，通过揭示适应性神经保护机制和开发成像标记物，可以随后用于在语言可以被可靠地评估之前改进结果的预测。通过正式的课程，研讨会，并在拟议的研究与她的跨学科实践培训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，评估几代人之间的社会环境风险以及逆境和复原力科学。这是一关键的下一步是建立科学的独立性，作为一个研究者和领导者，早产儿大脑的社会环境弹性、语言发育和神经保护机制。