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

早产是一种公共卫生危机，影响10%的新生儿。对神经认知有很大的风险 语言障碍，包括语言障碍。这可能会对生活质量产生不利影响。当前的预测工具会留下一个 在后来的语言成绩中有很大比例的差异无法解释，关注的是通常不会解释的风险因素 可修改的，尽管有风险，但未能确定恢复能力或积极结果。迫切需要先进的 表现良好的极早产(EPT)学龄儿童的神经影像研究 在明确考虑社会环境因素的同时，确定基于大脑的弹性标记 各种因素。拟议的实验将通过利用现有的45名EPT儿童来满足这一需求 没有明显的脑损伤和45个学期比较的儿童。这些EPT儿童被发现增加了 功能和结构的连通性--包括大脑半球外通路--与足月儿 仅在4~6岁时，EPT儿童的语言能力与语言能力呈正相关。中环 假设EPT儿童在语言任务上的表现在正常范围内是通过适应性神经实现的 网络--这是容易受到早产儿脑白质损伤的皮质外和旁路区域--以及 EPT儿童发育的环境推动了这种适应性的超连通性。该计划的目标是 拟议的研究是要确定这种超连通性是否在8岁时仍然是基于大脑的弹性生物标记物- 11岁，分析儿童的社会环境对超连通性的影响。第一个目标是 确定我们在4-6岁时观察到的骨外过度连接(与足月儿童相比)是否 EPT组坚持到8~11岁。第二个目标是确定语言得分的程度 8-11岁与EPT儿童的过度连接有关。第三个目标是评估 环境因素推动着大脑的连通性。将对儿童进行纵向评估， 脑磁图、功能磁共振成像(MRI)和弥散成像以验证独特 先前识别出的神经影像特征。基于环境的因素将在出生时评估(通过 与出生记录的联系)、4-6年和8-11年，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轻神经发育障碍的负担 儿童通过揭示适应、神经保护机制和开发成像标记物来出生EPT 随后可以用来改进对结果的预测，然后才能可靠地评估语言。穿过 在拟议的跨学科研究期间，进行正式的课程作业、研讨会和实践培训 专家顾问和导师委员会，候选人将获得流行病学方法方面的专业知识 在逆境和复原力的科学中，评估世代之间的社会环境风险。这是一个 关键的下一步是建立作为研究人员和研究领导者的科学独立性 早产儿大脑中的社会环境弹性、语言发展和神经保护机制。

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.