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，尤其影响到儿童，报告的虐待、忽视和寄养安置的比率很高。然而，关于可卡因暴露如何影响涉及母亲行为的大脑回路，特别是在人类中，人们知之甚少。功能核磁共振研究表明，在母亲中，婴儿线索激活了与可卡因类似的大脑奖励电路，这表明了常见的多巴胺能通路。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，与婴儿有关的自然奖赏刺激和可卡因等人工刺激可能会不同地影响神经发育，影响多巴胺和催产素系统。在这个项目中，我们使用1)功能磁共振成像和2)录像的母婴互动来测试接触可卡因的新妈妈的母体对婴儿暗示的反应是否受损。我们假设，与对照组相比，与对照组相比，接触可卡因的母亲在观看自己婴儿的面部和哭泣线索的照片时，前额叶皮质和与奖励相关的大脑区域的激活程度会显著减少。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、腹侧纹状体和前额叶内侧皮质)和黑质纹状体区域(黑质、背侧纹状体和背外侧前额叶皮质)。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(200名接触可卡因的母亲和200名对照母亲)将与她们6至7个月大的婴儿一起参加为期三个月的三次研究访问。在访问1期间，母亲们将完成成人依恋访谈，以探索她们自己的童年经历和依恋模式。在第二次探访中，母亲们将参与与她们的婴儿的“自由玩耍”互动，这将被录像和编码。在最后的研究访问中，功能磁共振将被用来比较母亲的大脑对婴儿面部和哭泣暗示的反应，比较“自己”的婴儿和“未知”的婴儿的暗示。最终，这项研究可能会更好地理解不良的早期生活经历如何有助于成人的照料模式，以及对成瘾的易感性，这可能会进一步损害父母的养育能力。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，并防止儿童产生长期后果--这本身可能包括更容易上瘾。

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.