Maternal Brain and Behavioral Responses to Infant Cues in Cocaine Exposed Mothers

说明（由申请人提供）：产妇滥用可卡因是一个重大的公共卫生问题，尤其影响到儿童，据报滥用、忽视和寄养的比例很高。然而，人们对可卡因暴露如何影响与母性行为有关的大脑回路知之甚少，尤其是人类。功能性核磁共振研究表明，在母亲身上，婴儿的线索激活了与可卡因相似的大脑奖励回路，表明了共同的多巴胺能途径。母性行为强烈影响催产素，这是一种重要的神经调节剂和激素，也可能受到母体可卡因滥用的调节。因此，与婴儿有关的自然奖励刺激和人工兴奋剂（如可卡因）可能不同地影响神经发育，影响多巴胺能和催产素系统。在这个项目中，我们使用1)功能性核磁共振成像和2)母婴互动录像来测试暴露于可卡因的新妈妈对婴儿线索的反应是否受损。我们假设，与对照组相比，接触可卡因的母亲在观看自己孩子的脸部照片和哭泣线索时，前额叶皮层和与奖励相关的大脑区域的激活程度明显低于对照组。我们感兴趣的特定区域包括中皮质边缘多巴胺回路（腹侧被盖区、腹侧纹状体和内侧前额叶皮层）和黑质纹状体区域（黑质、背侧纹状体和背外侧前额叶皮层）。来自两个研究地点（贝勒医学院和耶鲁儿童研究中心）的400名母亲将被招募（200名可卡因暴露母亲和200名对照母亲），以及她们6至7个月大的婴儿，在三个月的时间里参加三次研究访问。在访问1期间，母亲将完成成人依恋访谈，以探索自己的童年经历和依恋模式。在第二次访问中，母亲将与婴儿进行“自由游戏”互动，这将被录像和编码。在最后的研究访问中，将使用功能性磁共振成像来比较母亲对婴儿面部和哭泣线索的大脑反应，比较“自己的”婴儿和“自己的”婴儿。“未知的”婴儿暗示。最终，这项研究可能会让我们更好地理解不良的早期生活经历如何影响成人的照顾模式，以及成瘾的易感性，这可能会进一步损害育儿能力。了解可卡因暴露如何与其他环境因素相互作用，从而影响母亲的行为，可能有助于我们更好地应对成瘾，并防止儿童的长期后果——这本身可能包括对成瘾的脆弱性增加。

DESCRIPTION (provided by applicant): Maternal cocaine abuse is a significant public health issue particularly affecting children, with high rates of reported abuse, neglect and foster care placement. However, little is known about how cocaine exposure affects brain circuits involved in maternal behavior, especially in humans. Functional MRI studies have shown that in mothers, infant cues activate similar brain reward circuits to cocaine, suggesting common dopaminergic pathways. Maternal behavior is strongly influenced my oxytocin, an important neuromodulator and hormone, which may also be modulated by maternal cocaine abuse. Thus, natural infant-related reward stimuli and artificial stimulants such as cocaine may differentially affect neural development, affecting both dopaminergic and oxytocin systems. In this project we test whether maternal responses to infant cues are impaired in cocaine exposed new mothers, using 1) functional MRI and 2) videotaped mother-infant interaction. We hypothesize that cocaine exposed mothers will show significantly less activation of the prefrontal cortex and reward-associated brain regions, on viewing pictures of their own baby's face and cry cues vs. an unknown baby, compared to controls. Specific regions of interest will include the mesocorticolimbic dopamine circuits (ventral tegmental area, ventral striatum and medial prefrontal cortex) and the nigrostriatal regions (substantia nigra, dorsal striatum and dorsolateral prefrontal cortex). 400 mothers from 2 study sites (Baylor College of Medicine and Yale Child Study Center) will be enrolled (200 cocaine exposed and 200 control mothers), along with their 6 to 7 month old infants, to participate in three study visits over a three month period. During Visit 1, mothers will complete the Adult Attachment Interview to explore their own childhood experience and attachment patterns. At Visit 2, mothers will participate in a "free play" interaction with their infant, which will be videotaped and coded. At the final study visit, functional MRI will be used to compare maternal brain responses to infant facial and cry cues, comparing "own" infant vs. "unknown" infant cues. Ultimately, this research may lead to a better understanding of how adverse early life experiences may contribute to adult patterns of caregiving, as well as susceptibilities to addiction, which may further impair parenting capacities. Understanding how cocaine exposure interacts with other environmental factors to influence maternal behavior may help us both to better respond to addiction, and prevent long-term consequences in children-which may itself include an increased vulnerability to addiction.