GABA-mediated connectivity in the preterm brain

描述（由申请人提供）：根据2007年医学研究所报告，早产（PT）是当今美国最重要的儿科公共卫生问题之一。每年在美国出生的超过60，000名婴儿体重为1500克或更轻，据报道，这些婴儿的围产期护理费用每年超过180亿美元。早产儿残疾的风险很高; 30 - 40%的早产儿被诊断为轻微残疾，近五分之一的学龄早产儿被发现患有严重残疾，导致每年在长期教育和服务需求方面的新成本达到40亿美元。 围产期重症监护的一个主要重点是制定预防早产儿不良结局的策略，但对早产儿脑发育中导致神经发育障碍的根本改变仍知之甚少。先进的MRI策略允许调查早产对大脑发育的影响，最近的功能成像研究表明，早产儿的语言，记忆和执行功能的替代神经系统的参与。γ-氨基丁酸（GABA）中间神经元是这些网络发育的核心，临床前数据表明，这些细胞容易受到早产的伤害。 该建议的首要假设是，与足月对照组相比，PT受试者在足月等效年龄时的静息状态连接发生了变化。采用高度创新的功能性MRI策略来创建基于静息状态体素的对比度，即内在连接对比度（ICC），我们将在极低出生体重儿（500 - 1500 g）中识别受早产影响的神经回路，并与性别和年龄匹配的足月对照组在足月年龄进行比较。早产儿和足月对照婴儿的GABA编辑磁共振波谱检查将评估经水分校正的静息GABA浓度的区域差异;使用一般线性模型分析，将分析GABA、性别和胎龄对ICC变化的贡献。这些数据将提供有关早产对大脑发育影响的关键信息，并为预防早产儿残疾提供基本见解。

DESCRIPTION (provided by applicant): According to the 2007 Institute of Medicine report, preterm (PT) birth represents one the most important pediatric public health problems in the United States today. More than 60,000 infants born in the US each year weigh 1500 grams or less, and the perinatal care costs for these infants are reported to exceed 18 billion dollars each year. Preterm infants are at high risk for handicap; minor impairment is diagnosed in 30 - 40% and major disabilities are found in almost one-fifth of preterm children at school age, resulting in annual new costs of 4 billion dollars in long term educational and service needs. A major focus of perinatal intensive care is the development of strategies to prevent adverse outcome in the prematurely-born, but the fundamental alterations in brain development responsible for neuro- developmental disability in the prematurely-born remain poorly understood. Sophisticated MRI strategies permit investigation of the impact of preterm birth on developing brain, and recent functional imaging studies suggest the engagement of alternative neural systems for language, memory and executive function in the prematurely-born. Gamma aminobutyric acid (GABA) interneurons are central to the development of these networks, and preclinical data suggest that these cells are vulnerable to the injuries of preterm birth. The overarching hypothesis of this proposal is that there are alterations in resting state connectivity in PT subjects compared to term controls at term equivalent age. Employing a highly innovative functional MRI strategy to create a resting state voxel-based contrast, the intrinsic connectivity contrast (ICC), we will identify those neural circuits influenced by preterm birth in very low birth weight neonates (500 - 1500 g) compared to gender- and age-matched term controls at term equivalent age. GABA-edited magnetic resonance spectro- scopy of preterm and term control infants will assess regional differences in resting GABA concentrations corrected for water; using general linear model analyses, the contribution of GABA, gender and gestational age to ICC changes will be analyzed. These data will provide critical information about the impact of preterm birth on the developing brain and offer fundamental insights into prevention of handicap in the prematurely born.