Electrocortical and hormonal responses to threat across development

成功地适应不断变化的环境取决于迅速发现、注意和应对威胁刺激的能力。这种反应依赖于引导和维持对威胁的注意力的神经网络，以及下丘脑-垂体-肾上腺轴（HPA）及其激素终产物皮质醇。这些系统以关键的互惠方式相互作用，随着时间的推移，形成后续的高阶认知和情感发展。然而，尽管有大量的动物研究，很少有人类研究检查了这些神经网络和HPA轴在发育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，本研究项目的主要目的是在神经发育的两个敏感时期（青春期和从妊娠期到婴儿期）建立下丘脑轴功能与威胁注意神经标志物之间的因果关系。

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.