Brain Development, Behavior and Cognition in Pre- and Postnatal Cocaine Exposure

项目总结/摘要 了解产前可卡因暴露（PCE）对大脑发育的影响， 人类的行为和认知远远落后于其他滥用药物。证据 动物研究表明，PCE导致灰质和白色物质的显著改变 对行为功能具有长期影响的发展。人类神经影像学 迄今为止，对患有PCE的儿童和青少年的研究显示， 异常;然而，皮质下结构体积减少， 额叶中白色物质束的完整性已经被报道。研究 神经心理功能与PCE的儿童产生了混合的结果。一般而言， PCE儿童的总体认知能力没有显著下降， 但在注意力控制、反应能力等特定技能方面确实存在一些问题， 抑制和执行功能的其他方面。我们的团队之前已经证明了 额叶白色发育与执行功能之间的重要关系 一个样本的儿童与PCE相对那些没有。与PCE相比， 出生后可卡因暴露对大脑发育的影响仅来自动物 模型这些研究揭示了神经递质功能的改变， 冲动和攻击性行为。响应RA-DA-09-020次要数据分析， 物质滥用研究（R21/R33），我们建议使用来自NIDA资助的 PCE的纵向研究，包括参与者的前瞻性入组，定量 药物暴露的措施，良好的保留，并重复收集儿童头发样本 来检测青少年中可卡因的使用情况这两个数据集收集于101/2至121/2岁， 年龄14至16岁，包括高分辨率T1加权和扩散张量神经成像数据， 神经心理学评估和标准化行为报告。这种多学科 该项目汇集了来自三所大学的神经心理学专家， 影像学、神经解剖学、产前药物滥用研究和统计学。使用先进的，国家- 最先进的图像分析技术，包括皮层模式匹配、基于张量的 形态测量学和基于轨迹的空间统计学，该项目有望产生重要的科学成果。 关于PCE的影响以及产前和产后可卡因的综合影响的信息 对发育中的人脑的结构和功能的影响。

PROJECT SUMMARY/ABSTRACT Knowledge about the effects of prenatal cocaine exposure (PCE) on brain development, behavior and cognition in humans lags far behind that of other drugs of abuse. Evidence from animal studies suggests that PCE causes significant alterations in gray matter and white matter development with long-lasting implications for behavioral functioning. Human neuroimaging studies in children and adolescents with PCE to date have revealed no gross structural brain abnormalities; however, decreases in subcortical structure volumes and differences in the integrity of white matter tracts in the frontal lobe have been reported. Studies of neuropsychological functioning in children with PCE have yielded mixed results. Generally, children with PCE do not show significant decrements in overall cognitive abilities as measured by IQ tests but do show some problems with specific skills related to attention control, response inhibition, and other aspects of executive functioning. Our group has previously demonstrated significant relationships between frontal white matter development and executive functioning in a sample of children with PCE relative to those without. Compared to PCE, knowledge about the effects of postnatal cocaine exposure on brain development comes solely from animal models. These studies reveal alterations in neurotransmitter functioning that correlate with impulsive and aggressive behavior. In response to RA-DA-09-020 Secondary Data Analyses for Substance Abuse Research (R21/R33), we propose to use two datasets from a NIDA-funded longitudinal study of PCE that included prospective enrollment of participants, quantitative measures of drug exposures, excellent retention, and repeated collection of child hair samples to detect cocaine use among the youth. The two datasets, collected at ages 101/2 to 121/2 and ages 14 to 16, include high-resolution T1-weighted and diffusion tensor neuroimaging data, neuropsychological assessments, and standardized behavior reports. This multidisciplinary project brings together investigators from three universities with expertise in neuropsychology, imaging, neuroanatomy, prenatal drug abuse research, and statistics. Using advanced, state-of- the-art image analysis techniques including cortical pattern matching, tensor based morphometry and tract-based spatial statistics, this project promises to yield important scientific information about the effects of PCE and the combined effects of pre- and postnatal cocaine exposure on the structure and function of the developing human brain.