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

描述（由申请人提供）：关于产前可卡因暴露（PCE）对人类大脑发育、行为和认知的影响的知识远远落后于其他滥用药物。来自动物研究的证据表明，PCE会导致灰质和白质发育的显著改变，并对行为功能产生长期影响。迄今为止，在患有PCE的儿童和青少年中进行的人类神经影像学研究未发现明显的脑结构异常；然而，皮层下结构体积的减少和额叶白质束完整性的差异已被报道。对PCE患儿神经心理功能的研究得出了不同的结果。一般来说，患有PCE的儿童在智商测试中没有表现出整体认知能力的显著下降，但在与注意力控制、反应抑制和其他执行功能相关的特定技能方面确实表现出一些问题。我们的研究小组先前已经证明，在患有PCE的儿童样本中，与没有PCE的儿童相比，额叶白质发育和执行功能之间存在显著的关系。与PCE相比，有关产后可卡因暴露对大脑发育影响的知识仅来自动物模型。这些研究揭示了与冲动和攻击行为相关的神经递质功能的改变。为了响应RA-DA-09-020药物滥用研究的二级数据分析（R21/R33），我们建议使用nida资助的PCE纵向研究的两个数据集，包括前瞻性参与者的招募，药物暴露的定量测量，良好的保留，以及反复收集儿童头发样本来检测青少年的可卡因使用情况。这两个数据集分别收集于101/2至121/2和14至16岁，包括高分辨率t1加权和弥散张量神经成像数据、神经心理学评估和标准化行为报告。这个多学科项目汇集了来自三所大学的研究人员，他们在神经心理学、影像学、神经解剖学、产前药物滥用研究和统计学方面具有专业知识。使用先进的，最先进的图像分析技术，包括皮质模式匹配，基于张量的形态测量和基于束的空间统计，该项目有望产生关于PCE影响的重要科学信息，以及产前和产后可卡因暴露对发育中的人类大脑结构和功能的综合影响。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Although subtle effects of prenatal cocaine exposure on behavior and thinking abilities have been demonstrated, the literature considerably lags behind our understanding of the effects of alcohol and other drugs on brain development and behavior. This study will provide vital information regarding the long-term effects of prenatal cocaine exposure, as well as postnatal use, on brain development, cognition, and behavior in children and adolescents. Emphasis is placed on the use of novel, cutting edge, state-of-the-art structural image analysis tools in conjunction with sophisticated neuropsychological tests to better understand the effects of cocaine on the structure and function of the developing human brain.