Spina Bifida: Cognitive and Neurobiological Variability

描述（由申请人提供）：本项目的目的是确定遗传、中枢神经系统和环境的变异性来源，这些变异性解释了与脊柱裂脑膜脊髓膨出（SB）相关的神经行为结果的变异，SB是北美最常见的严重致残性出生缺陷。 在过去的五年中，研究小组确定了几个与临床标志物相关的潜在候选基因（例如，病变水平）和种族。 这些临床标志物解释了遗传和神经变异性，并与结果相关。 他们确定了跨认知和运动功能领域的过程（例如，定时），并将其与脑畸形。 在本延续申请中，研究人员建议在两个主要数据收集地点（德克萨斯大学休斯顿分校和多伦多儿童医院）的四个项目和三个核心中评估450名SB儿童和成人、20名导水管狭窄儿童和277名对照儿童。 项目一（遗传学; Northrup，PI）在超过2,000名西班牙裔和高加索参与者的样本中评估了与SB和相关神经管缺陷相关的遗传因素。 将使用不同的统计模型来测试候选基因的遗传连锁/协会，并评估与SB的遗传性相关的环境因素。项目II（早期学习;兰德里，PI）继续对85名SB婴儿和73名出生时确定的对照组进行纵向研究，随访至7.5岁，8.5岁和9.5岁。 本研究探讨了SB核心神经认知缺陷的早期发展与产生学龄期结果的环境因素（SES，父母教养）的关系。 项目III（神经认知; Dennis，PI）评估了与SB儿童和成人脑畸形相关的核心神经认知过程，将研究扩展到整个生命周期。 项目IV（磁源成像; Papanicolaou，PI）利用磁源成像评估SB和AS儿童的运动、躯体感觉、语言和认知技能的重组，代表了先天性脑损伤儿童的首批功能性神经成像研究之一。 这四个项目由行政服务核心（A;弗莱彻，PI）、受试者招募和评估核心（B;弗莱彻，PI）以及数据库和统计核心（C;弗朗西斯，PI）提供支持。 这个综合性的计划项目将促进SB的综合，多学科的理解，并为其他具有遗传异质性，脑畸形和可变神经行为结果的神经发育障碍提供模型。

DESCRIPTION (provided by applicant): The objective of this program project is to identify genetic, CNS, and environmental sources of variability that explain the variations in neurobehavioral outcomes associated with spina bifida meningomyelocele (SB), the most common severely disabling birth defect in North America. In the previous five years, the investigative team identified several potential candidate genes that were associated with clinical markers (e.g., lesion level) and ethnicity. These clinical markers accounted for genetic and neurological variability and were linked to outcomes. They identified processes that cross domains of cognitive and motor function (e.g., timing) and related them to brain dysmorphology. In this continuation application, the investigators propose to evaluate 450 children and adults with SB, 20 with aqueductal stenosis, and 277 controls in four projects and three cores at two primary data collection sites: the University of Texas-Houston, and The Hospital for Sick Children, Toronto. Project I (Genetics; Northrup, PI) evaluates genetic factors associated with SB and related neural tube defects in a sample of over 2,000 Hispanic and Caucasian participants. Different statistical models will be used to test candidate genes for genetic linkage/associations and to evaluate environmental factors related to the heritability of SB. Project II (Early Learning; Landry, PI) continues a longitudinal study of 85 infants with SB and 73 controls identified at birth, following them to 7.5, 8.5, and 9.5 years of age. This study addresses the early development of core neurocognitive deficits in SB in relation to environmental factors (SES, parenting) that produce school age outcomes. Project III (Neurocognitive; Dennis, PI) evaluates core neurocognitive processes in relation to brain dysmorphology in children and adults with SB, extending the study across the life span. Project IV (Magnetic Source Imaging; Papanicolaou, PI) utilizes magnetic source imaging to evaluate the reorganization of motor, somatosensory, language, and cognitive skills in children with SB and AS, representing one of the first functional neuroimaging studies of children with congenital brain injury. These four projects are supported by an Administrative Services Core (A; Fletcher, PI), Subject Recruitment and Evaluation Core (B; Fletcher, PI), and Database and Statistics Core (C; Francis, P.I.). This comprehensive program project will facilitate an integrated, multidisciplinary understanding of SB and provides a model for other neurodevelopmental disorders with genetic heterogeneity, brain dysmorphologies, and variable neurobehavioral outcomes.