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

产前和产后接触可卡因时的大脑发育、行为和认知

• 批准号: 8319738
• 负责人: TAMARA Duckworth WARNER
• 金额: $ 29.7万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8319738
• 关键词: 2 year old; Administrative Supplement; Adolescent; Adult; Age; Aggressive behavior; Allegra; Animal Model; Animals; Attention; Aventyl; Behavior; Behavioral; Birth; Brain; Brain imaging; California; Child; Childhood; Clinical; Cocaine; Cocaine Abuse; Cognition; Cognitive; Collection; Computer software; Computers; Data; Data Analyses; Data Collection; Data Set; Databases; Development; Dictionary; Diffusion; Diffusion Magnetic Resonance Imaging; Doctor of Medicine; Doctor of Philosophy; Drug Exposure; Drug abuse; Drug usage; Enrollment; Environment; Enzyme-Linked Immunosorbent Assay; Evaluation; Faculty; Fetal Alcohol Exposure; Fetal Cocaine Exposure; Florida; Funding; Goals; Grant; Hair; Hand; Housing; Human; Image; Image Analysis; Impulsive Behavior; Interview; Knowledge; Label; Libraries; Literature; Long-Term Effects; Longitudinal Studies; Los Angeles; Magnetic Resonance Imaging; Maps; Mass Fragmentography; Measures; Methods; Modality; Morphology; Names; National Institute of Drug Abuse; Neuroanatomy; Neurology; Neuropsychological Tests; Neuropsychology; Neurosciences; Neurotransmitters; Output; Paper; Participant; Patient Self-Report; Pattern; Pediatrics; Phase; Probability; Procedures; Psychologist; Psychology; Recording of previous events; Relative (related person); Reporting; Research; Research Personnel; Resolution; Risk Factors; Running; Rural; Sampling; Scanning; Screening procedure; Self-Administered; Specific qualifier value; Specimen; Structure; Structure-Activity Relationship; Substance abuse problem; Surveys; System; Techniques; Technology; Testing; Thick; Thinking; Time; Universities; Urine; Weight; Work; Writing; Youth; alcohol and other drug; base; behavior measurement; benzoylecgonine; brain shape; brain volume; child battery; cocaethylene; cocaine exposure; cocaine use; cohort; comparison group; computerized; data integrity; database design; design; drug of abuse; executive function; expectation; experience; frontal lobe; gray matter; member; methamphetamine exposure; morphometry; multidisciplinary; neuroimaging; neuropsychological; novel; postnatal; prenatal; professor; programs; prospective; response; skills; statistics; tool; white matter

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.

描述(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变化，并对行为功能产生长期影响。到目前为止，对患有PCE的儿童和青少年进行的人类神经成像研究显示，大脑没有大体结构异常；然而，据报道，皮质下结构体积减少，额叶白质束完整性存在差异。对PCE儿童神经心理功能的研究结果喜忧参半。一般来说，患有PCE的儿童在智商测试中总体认知能力没有明显下降，但确实在注意力控制、反应抑制和执行功能的其他方面表现出一些特殊技能方面的问题。我们小组之前在PCE儿童样本中证明了额叶白质发育和执行功能之间的显著关系，而不是那些没有PCE儿童。与PCE相比，关于出生后接触可卡因对大脑发育影响的知识完全来自动物模型。这些研究揭示了与冲动和攻击性行为相关的神经递质功能的变化。针对药物滥用研究的RA-DA-09-020次级数据分析(R21/R33)，我们建议使用NIDA资助的PCE纵向研究中的两个数据集，其中包括参与者的预期登记、药物暴露的定量测量、出色的保留率以及重复收集儿童头发样本来检测青少年中的可卡因使用情况。这两个数据集分别在101/2岁到121/2岁和14岁到16岁之间收集，包括高分辨率T1加权和扩散张量神经成像数据、神经心理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，他们拥有神经心理学、成像、神经解剖学、产前药物滥用研究和统计学方面的专业知识。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区域的空间统计，该项目有望获得关于PCE的影响以及出生前和出生后接触可卡因对发育中的人脑结构和功能的综合影响的重要科学信息。 与公共健康相关：尽管产前接触可卡因对行为和思维能力的微妙影响已经被证明，但文献远远落后于我们对酒精和其他药物对大脑发育和行为影响的理解。这项研究将提供有关出生前接触可卡因以及出生后使用可卡因对儿童和青少年大脑发育、认知和行为的长期影响的重要信息。重点是使用新颖、尖端、最先进的结构图像分析工具，结合复杂的神经心理测试，更好地了解可卡因对发育中的人脑结构和功能的影响。