Fluctuations of endogenous estrogen modulates fear extinction, but the influence of exogenous estradiol is less studied. Moreover, little focus has been placed on the impact of estradiol on broad network connectivity beyond the fear extinction circuit. Here, we examined the effect of acute exogenous estradiol administration on fear extinction-induced brain activation, whole-brain functional connectivity (FC) during the fear extinction task and post-extinction resting-state. Ninety healthy women (57 using oral contraceptives [OC], 33 naturally cycling [NC]) were fear conditioned on day 1. They ingested an estradiol or placebo pill prior to extinction learning on day 2 (double-blind design). Extinction memory was assessed on day 3. Task-based functional MRI data were ascertained on days 2 and 3 and resting-state data were collected post-extinction on day 2 and pre-recall on day 3. Estradiol administration significantly modulated the neural signature associated with fear extinction learning and memory, consistent with prior studies. Importantly, estradiol administration induced significant changes in FC within multiple networks, including the default mode and somatomotor networks during extinction learning, post-extinction, and during extinction memory recall. Exploratory analyses revealed that estradiol impacted ventromedial prefrontal cortex (vmPFC) activation and FC differently in the NC and OC women. The data implicate a more diffused and significant effect of acute estradiol administration on multiple networks. Such an effect might be beneficial to modulating attention and conscious processes in addition to engaging neural processes associated with emotional learning and memory consolidation.

内源性雌激素的波动调节恐惧消退，但外源性雌二醇的影响研究较少。此外，很少有人关注雌二醇对恐惧消退回路之外的广泛网络连接的影响。在这里，我们检查了急性外源性雌二醇给药对恐惧消退诱导的大脑激活、恐惧消退任务期间的全脑功能连接（FC）和消退后静息状态的影响。 90 名健康女性（57 名使用口服避孕药 [OC]，33 名自然循环 [NC]）在第一天表现出恐惧条件。她们在第二天的消除学习之前服用雌二醇或安慰剂药丸（双盲设计）。第 3 天评估消退记忆。第 2 天和第 3 天确定基于任务的功能 MRI 数据，并在第 2 天收集消退后和第 3 天预回忆的静息态数据。雌二醇给药显着调节相关的神经特征。与恐惧消退相关的学习和记忆，与之前的研究一致。重要的是，雌二醇给药引起多个网络内 FC 的显着变化，包括消退学习期间、消退后和消退记忆回忆期间的默认模式和躯体运动网络。探索性分析显示，雌二醇对 NC 和 OC 女性腹内侧前额皮质 (vmPFC) 激活和 FC 的影响不同。这些数据表明急性雌二醇给药对多个网络的影响更加分散和显着。除了参与与情绪学习和记忆巩固相关的神经过程之外，这种效应可能还有利于调节注意力和意识过程。