Developmental Effects of Prenatal Cocaine Exposure

描述（由申请人提供）： 自20世纪80年代开始流行使用以来，产前可卡因暴露（CE）一直是一个主要的公共卫生问题。一些研究已经检查了父母滥用可卡因和产前可卡因暴露对婴儿和幼儿的身体、神经发育和心理社会影响，但对神经生物学基础和神经发育影响的理解有限。神经影像学方法的最新进展使得直接和非侵入性地检查功能性神经解剖学和连接性成为可能，使其非常适合用于研究产前CE的神经生物学和发育影响。本项目的总体目标是应用基于MRI的神经影像学方法，结合神经行为测试，研究产前CE对青春期神经发育的影响，并阐明产前CE影响的神经生物学基础。拟议的成像研究将重点关注唤醒和注意力调节，在大多数产前CE研究中最可靠地涉及的神经心理学功能，参与这些功能的脑回路，以及青春期对这些脑回路的发育影响，作为快速重组的时期，对于评估产前CE导致的发育延迟或差异是理想的。我们假设：（1）使用MRI，在12 - 18岁的6年期间，通过测量大脑活动、神经解剖连接和功能连接，在结构和功能上的发育变化将在青少年中明显;（2）与SES匹配的对照组相比，产前接触可卡因的青少年将表现出唤醒和注意力调节的缺陷，并且这些缺陷在涉及压力的情况下比在“基线”时更明显，并且可以使用MRI技术以及功能的行为评估来测量;以及（3）MRI和行为测量之间存在相关性。为了验证这些假设，具体的目的是：（1）比较CE受试者和SES和年龄匹配的对照者在12岁、15岁和18岁三个年龄水平上的功能解剖，以确定各组的发育特征模式;（二）为了评估这些群体中用于唤醒和注意力调节功能的区域内和区域之间的神经解剖学连接的可能改变，扩散张量成像;（3）评估这些组中神经回路的功能连接;（4）评估这些组中的行为和适应功能，并将这些结果与MRI结果相关联。我们相信，该项目中提出的研究，首次将神经影像学方法应用于这一人群，将使我们能够确定产前CE导致的大脑可能的变化，并测量青春期对大脑的任何发育影响。

DESCRIPTION (provided by applicant): Prenatal cocaine exposure (CE) has been a major public health concern since the epidemic of use that began in the 1980s. A number of studies have examined the physical, neurodevelopmental, and psychosocial effects of parental cocaine abuse and prenatal cocaine exposure in infants and young children but provided limited understanding of the neurobiological basis and neurodevelopmental effects. Recent advances in neuroimaging methods have made it possible to examine directly and noninvasively the functional neuroanatomy and connectivity, making them ideally suited for investigating the neurobiology and developmental effects of prenatal CE. The overall goal of this project is to apply MRI based neuroimaging methods, in conjunction with neurobehavioral testing, to study the neurodevelopmental effects of prenatal CE during adolescence and to elucidate neurobiological basis of the effect of prenatal CE. The proposed imaging study will focus on arousal and attention regulation, the neuropsycological functions which have been implicated most reliably in most studies of prenatal CE, the brain circuitry involved in these functions, and developmental effects on these brain circuitry during puberty, which, as a period of rapid reorganization, is ideal for the assessment of delays or divergences in development as a result of prenatal CE. We hypothesize that (1) using MRI, developmental change in structure and function will be evident in youth assessed over a 6 year period from 12 to 18 with measures of brain activity, neuroanatomic connectivity, and functional connectivity; (2) adolescents with prenatal cocaine exposure will exhibit deficit in arousal and attention regulation when compared to SES-matched controls, and these deficits will be more evident in situations involving stress than at "baseline" and will be measurable using MRI techniques as well as behavioral assessment of functioning; and (3)There will be correlations between MRI and behavioral measures. To test these hypotheses, the specific aims are (1) to compare functional anatomy of CE subjects and SES- and age matched controls at 3 age levels, 12, 15 and 18-years, to identify the patterns of developmental characteristic of each group; (2) to assess possible alterations in the neuroanatomic connectivity in and between areas serving the function of arousal and attention regulation in these groups using diffusion tensor imaging; (3) to assess functional connectivity in neural circuits in these groups; and (4) to assess behavior and adaptive functioning in these groups and correlate these outcomes with MRI findings. We believe the studies proposed in this project, the first to apply neuroimaging methods to this population, will allow us to ascertain possible alterations in the brain as a result of prenatal CE and measure any developmental effects on the brain during puberty.