Prenatal Cocaine Exposure: Studies of Brain Function

产前可卡因暴露：脑功能研究

• 批准号: 7361861
• 负责人: LESLIE K JACOBSEN
• 金额: $ 21.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7361861
• 关键词: Adolescence; Adolescent; Age; Animals; Anisotropy; Anterior; Attention; Birth; Brain; Brain region; Child; Cocaine; Cognitive; Cognitive deficits; Collaborations; Corpus striatum structure; Data; Development; Diffusion Magnetic Resonance Imaging; Dopamine D1 Receptor; Event-Related Potentials; Exhibits; Exposure to; Fetal Cocaine Exposure; Foundations; Functional Magnetic Resonance Imaging; Future; GTP-Binding Proteins; Human; Image; Impairment; Inferior; Link; Magnetic Resonance Imaging; Measures; Mediating; Memory; Methods; Middle frontal gyrus structure; Morphology; Neurons; Outcome; Parietal; Pathway interactions; Performance; Process; Public Health; Range; Relative (related person); Resolution; Retrieval; Role; Sampling; Signal Transduction; Speed; Stimulus; Structure; Structure of genu of corpus callosum; Task Performances; Visuospatial; Work; age related; blood oxygen level dependent; caudate nucleus; cingulate cortex; cognitive function; executive function; frontal lobe; human study; maternal cocaine use; myelination; neurodevelopment; piriform cortex; pre-clinical; prenatal; prenatal exposure; psychosocial; receptor coupling; response; size; white matter; white matter change

DESCRIPTION (provided by applicant): Evidence suggests that prenatal exposure to cocaine produces a permanent uncoupling of the dopamine D1 receptor from its G-protein in frontal and cingulate cortices and in caudate nucleus. Activation of D1 receptors during brain development exerts modulatory effects on neuronal development, and prenatal cocaine exposure has been shown to alter neuronal cytoarchitecture in brain regions receiving dopaminergic inputs, including frontal, entorhinal, and piriform cortices. D1 receptors are abundant in frontal cortex and appear to modulate neurocircuits that support the performance of tasks that tap executive functions. Prenatal cocaine exposure has been linked with deficits in executive cognitive capacities, such as allocation of attention, memory, and the ability to suppress processing of and responses to competing stimuli that, in humans, undergo important developmental changes during adolescence. Functional magnetic resonance imaging (fMRI) has demonstrated that performance of executive function tasks is associated with increased activation of fronto-striatal and fronto-parietal networks with increasing age during the adolescent developmental epoch. Event related potential (ERP) studies, have demonstrated consistent maturational changes in ERP morphology, amplitude and latency during performance of attention and executive function tasks. Diffusion tensor imaging (DTI), which provides quantitative measures of white matter microstructure, has demonstrated age related increases in fractional anisotropy, reflecting increases in myelination, in cortical and subcortical white matter pathways that correlate with age related changes in cognitive abilities. This proposal aims to develop and refine fMRI, DTI, and ERP methods for assessing the functional and structural integrity of neurocircuitry supporting selective and divided attention and verbal and visuospatial memory in adolescents with and without prenatal exposure to maternal cocaine use. This work will be performed in collaboration with Linda Mayes, MD, and will form the foundation for future planned projects that will examine the relationship between the integrity of these circuits and cognitive, academic, and psychosocial outcome in a sample of adolescents with and without prenatal exposure to maternal cocaine use that have been followed longitudinally from birth at the Yale Child Study Center (R01 DA-06025, PI: L.C. Mayes). PUBLIC HEALTH RELEVANCE: Children and adolescents with prenatal cocaine exposure have deficits in executive cognitive abilities, including allocation of attention, memory, and the ability to suppress processing of and responses to competing stimuli. This proposal will develop and refine fMRI, DTI, and ERP methods for assessing the function and structure of neurocircuitry supporting selective and divided attention and verbal and visuospatial memory in adolescents with and without prenatal exposure to maternal cocaine use. This work will form the foundation for future planned projects that will examine the relationship between the integrity of these circuits and cognitive, academic, and psychosocial outcome in a sample of adolescents with and without prenatal exposure to maternal cocaine use that have been followed longitudinally from birth at the Yale Child Study Center (R01 DA-06025, PI: L.C. Mayes).

描述（由申请人提供）：证据表明，产前暴露于可卡因会在其额叶和扣带回皮质和尾状核中与多巴胺D1受体的永久解偶联。大脑发育过程中D1受体的激活对神经元发育发挥了调节作用，并且已经显示出产前可卡因暴露会改变接受多巴胺能输入的脑区域的神经元细胞结构，包括额叶，内膜和梨状肌皮质。 D1受体在额叶皮层中很丰富，并且似乎调节了支持执行功能的任务执行的神经信号。产前可卡因暴露与执行认知能力的缺陷有关，例如分配注意力，记忆以及抑制竞争刺激的处理和对竞争刺激的反应的能力，在人类中，在青春期会经历重要的发展变化。功能磁共振成像（fMRI）表明，执行功能任务的性能与青少年发育时期期间年龄增加的额叶和额叶网络的激活增加有关。事件相关的潜力（ERP）研究表明，在注意力和执行功能任务执行过程中，ERP形态，振幅和潜伏期的成熟变化一致。扩散张量成像（DTI）提供了白质微观结构的定量测量，它表明了分数各向异性的年龄相关增加，反映了皮质和皮层白质途径的髓鞘形成增加，这些途径与年龄相关的认知能力相关。该提案旨在开发和完善fMRI，DTI和ERP方法，以评估神经通律的功能和结构完整性，从而支持选择性和分裂的注意力，并在未经产前暴露于母体可卡因使用的青少年中的选择性和口头和视觉空间记忆。这项工作将与医学博士Linda Mayes合作进行，并将为未来的计划项目构成基础，这些项目将研究这些回路的完整性与认知，学术和心理社会的完整性之间的关系，并在具有产前可卡因使用的青少年和不接受母体可卡因使用的青少年样本中，从Yale Child condern the Yale condern condern the yale pi y0 1 a y01 a y01 a y01 a。 L.C. Mayes）。公共卫生相关性：具有产前可卡因暴露的儿童和青少年在执行认知能力方面存在缺陷，包括分配注意力，记忆以及抑制加工的能力和对竞争刺激的反应。该建议将开发和完善fMRI，DTI和ERP方法，以评估神经记录的功能和结构，从而在有或没有产前暴露于产妇可卡因的青少年中支持选择性和分裂的注意力和口头和视觉空间记忆。这项工作将为未来的计划项目奠定基础，这些项目将研究这些电路的完整性与认知，学术和心理社会成果之间的关系，并在有或没有产前暴露于产妇可卡因使用的青少年样本中，从耶鲁大学的出生开始，Yale Child Center在Yale Child Center上纵向遵循（R01 DA-DA-DA-DA-DA-0606025，PI。