Cocaine and Maternal Behavior: Effects on Trajectory of Infant Brain Development

可卡因和母亲行为：对婴儿大脑发育轨迹的影响

• 批准号: 9922883
• 负责人: Karen M Grewen
• 金额: $ 60.9万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9922883
• 关键词: Adolescence; Alcohols; Amygdaloid structure; Anterior; Attention; Behavior; Behavioral; Biological Markers; Birth; Brain; Brain imaging; Brain region; Childhood; Cocaine; Cognition; Cognitive; Data; Development; Early Intervention; Environment; Environmental Risk Factor; Exposure to; Fetal Cocaine Exposure; Fiber; Foundations; Gestational Age; Glean; Goals; Growth; Growth and Development function; Head circumference; Human; Impairment; Infant; Inferior; Informal Social Control; Knowledge; Learning; Link; Longitudinal Studies; Magnetic Resonance Imaging; Marijuana; Maternal Behavior; Measurement; Medial; Mediating; Mission; National Institute of Drug Abuse; Nicotine; Opioid; Outcome; Parietal; Pattern; Pharmaceutical Preparations; Physiological; Play; Prefrontal Cortex; Pregnancy; Psyche structure; Public Health; Reporting; Research; Risk; Role; Short-Term Memory; Structure; Testing; Time; Toddler; Vulnerable Populations; auditory comprehension; base; behavioral impairment; brain behavior; cocaine exposure; cocaine-exposed infant; cognitive ability; cognitive development; cognitive disability; cognitive function; cognitive skill; disability; drug of abuse; fetal; frontal lobe; gray matter; in utero; indexing; infancy; innovation; neonatal brain; postnatal; prenatal; prenatal exposure; prevent; public health relevance; relating to nervous system; remediation; resilience; response; social; success; thalamocortical tract; tractography; white matter

 DESCRIPTION (provided by applicant): Prenatal cocaine exposure (PCE) is related to cognitive and behavioral deficits in infancy, childhood and adolescence, however findings are diverse and inconsistent across studies, and the postnatal environment plays a powerful role in such developmental outcomes. MRI studies in childhood and adolescence report similarly inconsistent effects of PCE on brain structure, activation and links to behavior. Although gestational exposure occurs during a time of extraordinary brain growth and organization, and the months following birth are marked by massive expansion of brain structure and connectivity, little is known about the effects of PCE on early human brain development that may contribute to reported deficits in cognitive function. The long term goal is to understand prenatal effects of cocaine exposure on early development of brain structure and function, and to discern how postnatal factors may protect or further harm growth and connectivity of structures underlying nascent cognitive abilities. The objectives of this proposal are to quantify the effects of PCE on the developmental trajectory of infant brain structure in postnatal months 1-9, to determine the extent to which gray and white matter (GM, WM) growth trajectories contribute to the effects of PCE on early cognitive function, and to identify maternal factors that moderate these effects. The central hypothesis is that fetal brain development is impaired by PCE; deficits in GM and WM growth and connectivity mediate the effect of PCE on simultaneously developing early cognitive skills; and postnatal maternal behaviors interact with PCE to influence growth of brain structure and function. This hypothesis is based on the applicant's strong preliminary data showing reduced cortical prefrontal and frontal GM volume and connectivity in cocaine-exposed neonates compared with drug-free infants and infants exposed to other drugs (nicotine, marijuana, alcohol, opiates), and inverse association between prefrontal GM volume and duration of gestational cocaine exposure. The rationale for this research is that longitudinal study will determine whether the postnatal trajectory of brain growth is merely delayed or permanently altered by PCE, ascertain postnatal factors that contribute to greater risk or resilience in developing brain, and suggest new mechanisms and targets for earlier intervention. The hypothesis will be tested with three Specific Aims: 1) Determine effects of PCE on developmental trajectories of infant brain structure; 2) Determine the extent to which the effects of PCE on early cognitive functions are predicted by GM and WM developmental trajectories; 3) Determine the moderating effects of maternal behavior on brain development. The approach is innovative because it will integrate maternal behavioral and physiological responses to infant with neonatal brain imaging proximal to in utero exposure, in order to quantify the direct and interactive effects of initial neural deficit and postnatal environment on subsequent patterns of brain and cognitive development. The proposed research is significant because knowledge gleaned has potential to inform earlier interventions to prevent or reduce cognitive disabilities i this vulnerable population.

 描述（由申请人提供）：产前可卡因暴露 (PCE) 与婴儿期、儿童期和青春期的认知和行为缺陷有关，但不同研究的结果各不相同且不一致，而产后环境在此类发育结果中发挥着重要作用。儿童期和青春期的研究报告显示，四氯乙烯对大脑结构、激活和行为联系的影响也不一致，尽管妊娠期暴露发生在大脑异常生长和组织的时期，并且出生后的几个月以大脑结构的大规模扩张为标志。人们对 PCE 对人类早期大脑发育的影响知之甚少，而 PCE 可能会导致认知功能缺陷。长期目标是了解 PCE 的产前影响。 接触可卡因对大脑结构和功能早期发育的影响，并了解出生后因素如何保护或进一步损害新生认知能力结构的生长和连接性。该提案的目的是量化 PCE 对婴儿发育轨迹的影响。出生后 1-9 个月的大脑结构，以确定灰质和白质（GM、WM）生长轨迹对 PCE 对早期认知功能的影响的程度，并确定调节这些影响的母体因素。胎儿大脑发育是PCE 损害；GM 和 WM 生长和连接的缺陷介导 PCE 对同时发展的早期认知技能的影响；以及产后母亲行为与 PCE 相互作用，影响大脑结构和功能的生长。显示与未吸毒婴儿和接触其他药物（尼古丁、大麻、酒精、阿片类药物）的婴儿相比，接触可卡因的新生儿的皮质前额叶和额叶 GM 体积和连接性减少，并且前额叶 GM 之间呈负相关这项研究的基本原理是，纵向研究将确定产后大脑生长轨迹是否仅仅被 PCE 延迟或永久改变，确定导致大脑发育风险更大或恢复能力更大的产后因素。提出早期干预的新机制和目标。该假设将通过三个具体目标进行检验：1）确定 PCE 对婴儿大脑结构发育轨迹的影响；2）确定 PCE 对早期认知的影响程度。通过 GM 和 WM 发育轨迹预测功能；3）确定母亲行为对大脑发育的调节作用，该方法具有创新性，因为它将母亲对婴儿的行为和生理反应与接近子宫内暴露的新生儿大脑成像结合起来。量化初始神经缺陷和产后环境对随后的大脑和认知发展模式的直接和交互影响这项研究具有重要意义，因为收集的知识有可能为早期干预措施提供信息，以预防或减少这一弱势群体的认知障碍。