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

描述（由申请人提供）：母亲滥用可卡因是一个重大的公共卫生问题，特别是影响儿童，报告的虐待，忽视和寄养安置率很高。然而，关于可卡因暴露如何影响涉及母性行为的大脑回路，尤其是人类，我们知之甚少。功能性磁共振成像研究表明，在母亲身上，婴儿的暗示激活了与可卡因类似的大脑奖励回路，这表明了共同的多巴胺能通路。母亲的行为受到催产素的强烈影响，催产素是一种重要的神经调节剂和激素，也可能受到母亲滥用可卡因的影响。因此，天然的婴儿相关的奖励刺激和人工兴奋剂，如可卡因可能会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，我们测试是否母亲对婴儿线索的反应在可卡因暴露的新母亲受损，使用1）功能性磁共振成像和2）录像母婴互动。我们假设，与对照组相比，可卡因暴露的母亲在观看自己婴儿的面部和哭泣线索的照片时，前额叶皮层和奖励相关的大脑区域的激活明显减少。感兴趣的特定区域将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质）和黑质纹状体区域（黑质、背侧纹状体和背外侧前额叶皮质）。将招募来自2个研究中心（贝勒医学院和耶鲁儿童研究中心）的400名母亲（200名可卡因暴露母亲和200名对照母亲）沿着6至7个月大的婴儿，在3个月内参加3次研究访视。在第1次访视期间，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2次访视时，母亲将参与与婴儿的“自由游戏”互动，并进行录像和编码。在最后一次研究访视时，将使用功能性MRI比较母体大脑对婴儿面部和哭泣线索的反应，比较“自己的”婴儿与“未知的”婴儿线索。最终，这项研究可能会导致更好地了解不良的早期生活经历如何有助于成年人的成瘾模式，以及成瘾的可能性，这可能会进一步损害养育能力。了解可卡因暴露如何与其他环境因素相互作用，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，这本身可能包括增加成瘾的脆弱性。

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.