Electrocortical and hormonal responses to threat across development

对不断变化的环境的成功适应依赖于快速检测、关注和响应威胁刺激的能力。这种反应依赖于神经网络来引导和维持对威胁和下丘脑-垂体-肾上腺(HPA)轴及其荷尔蒙最终产物皮质醇的关注。随着时间的推移，这些系统以关键的相互作用的方式相互作用，塑造了随后的更高层次的认知和情感发展。然而，尽管有大量的动物研究，但很少有人体研究考察这些神经网络和HPA轴在发育过程中或纵向上的相互作用，这对于确定这些系统如何随着时间的推移相互编程至关重要。因此，该研究项目的主要目的是在神经发育的两个敏感期：青春期和从妊娠到婴儿早期，建立HPA轴功能与注意威胁的神经标志物之间的因果联系。*在这个项目的第一阶段，我和我的研究生将记录200名早期青少年的事件相关电位(ERP)，以确定反应性皮质醇反应以及HPA轴的慢性激活如何预测神经对威胁的反应。在第二阶段之后，对同一样品进行纵向分析。在接下来的24个月里，我们将收集三次清醒的皮质醇，然后进行第二次访问，以评估神经对基线威胁的反应的变化，使我们能够评估HPA轴的活动随着时间的推移可能会改变参与威胁定向和评估的神经结构的功能的方式。*在第三阶段，我们将招募200名怀孕前三个月的女性来评估神经对威胁的反应，以及清醒状态和头发皮质醇。然后，我们将收集他们怀孕期间清醒的皮质醇，以检查基线上的神经对威胁的反应是否预测成人皮质醇的增加。在第四阶段，我们将邀请这些妇女的婴儿回来，检查妊娠皮质醇暴露是否随后与慢性和/或反应性皮质醇分泌增加有关，以及妊娠皮质醇暴露的变化是否直接预测神经对威胁和新奇事物的反应。*这项研究计划将为我的研究生提供宝贵的培训机会，以及关于神经和荷尔蒙对发育威胁的反应之间相互作用的关键新见解。通过在神经发育的敏感期对这些相互作用进行横向和纵向评估，拟议的研究计划将为期待体验的大脑发育模型提供重要信息，识别将生活经历的多样性与功能多样性联系起来的生物机制，并最终为寻求了解人类认知和情感发展的研究做出贡献。

Successful adaptation to a changing environment depends upon the ability to rapidly detect, attend to, and respond to threatening stimuli. This response relies on neural networks that direct and sustain attention to threat and the Hypothalamic-Pituitary-Adrenal (HPA) axis and its hormonal end-product, cortisol. These systems interact with one another in critical reciprocal ways, over time shaping subsequent higher-order cognitive and affective development. Yet, despite a wealth of animal research, very few studies in humans have examined the interactions of these neural networks and the HPA axis across development or longitudinally, which is critical for identifying how these systems program one another over time. Thus, the primary aim of this program of research is to establish causal links between HPA axis functioning and neural markers of attention to threat in two sensitive periods of neural development: adolescence and the period spanning gestation through early infancy. ***In the first phase of this program, my graduate students and I will record event-related potentials (ERPs) from 200 early adolescents to identify how reactive cortisol response, as well as chronic activation of the HPA axis, predict neural response to threat. This is followed in phase two by longitudinal analyses on the same sample. We will collect waking cortisol three times over the next 24 months, followed by a second visit to assess changes in neural response to threat from baseline, allowing us to evaluate the ways in which activity of the HPA axis over time may alter the function of neural structures involved in threat orienting and appraisal. ***In phase three, we will recruit 200 women in their first trimester of pregnancy to assess neural response to threat, along with waking and hair cortisol. We will then collect waking cortisol across their pregnancies to examine whether neural response to threat at baseline predicts cortisol increases in adults. In phase four, we will invite the infants of these women back, to examine whether gestational cortisol exposure is subsequently associated with heightened chronic and/or reactive cortisol secretion, and whether variation in gestational cortisol exposure directly predicts neural responses to threat and novelty. ***This research program will provide invaluable training opportunities to my graduate students, as well as critical new insights regarding interactions between neural and hormonal responses to threat across development. By assessing these interactions cross-sectionally and longitudinally in sensitive periods of neural development, the proposed program of research will significantly inform models of experience-expectant brain development, identifying biological mechanisms that link diversity of life experiences to diversity in functioning, and ultimately contributing to research that seeks to understand human cognitive and affective development.