Ovarian Effects on Intrinsic Connectivity and the Affective Enhancement of Memory

众所周知，女性比男性表现出更高的情感障碍发生率。这种差异在创伤后应激障碍中尤其明显，女性经历创伤后应激障碍的可能性是男性的两倍多。最近的证据表明，女性对创伤后应激障碍的易感性随着她们卵巢激素水平的不同而不同。在黄体期，当孕酮升高时，女性在创伤后出现创伤后应激障碍症状的可能性是前者的三倍以上。同样，女性被诊断为抑郁症的可能性是男性的两倍 症状也因月经不同而不同。这两种疾病都涉及记忆、应激反应和大脑内部网络中静止连接的改变。在创伤后应激障碍中，个体经历创伤的侵入性记忆 抑郁个体表现出显著的负性提取偏向。压力引起的应激激素皮质醇的释放也在这两种疾病中升高。同样，在患有这两种障碍的个体中，默认模式网络(在记忆提取过程中参与的一组结构)和突显网络(一组涉及处理情绪的结构)之间的静止连接性也会升高。最近的研究表明，情感记忆、压力反应和静息连接都会受到卵巢激素水平变化的影响。与其他月经期相比，黄体期获得的负面记忆被更好地保留了下来。黄体酮的增加也与压力引起的皮质醇分泌增加有关。同样，服用黄体酮药丸会增加默认网络和显著网络关键节点之间的连通性。然而，到目前为止，还没有研究评估卵巢激素变化对月经周期内网络连通性的影响。我们假设，月经周期中激素水平的变化会产生自然的 对创伤性生活事件的脆弱性，在此期间，大脑连接性的变化促进了压力反应，并增强了对负面经历的记忆。为了验证这一假设，我们将测量静息连接性、应激激素水平、生理反应以及对在月经周期不同荷尔蒙阶段学习的阴性物质的记忆。我们预测休眠模式和默认模式网络之间的连接性将处于最高水平 在黄体期，在负面情绪状态下学习的物质在黄体期将被最好地保留。此外，我们预测，这两个网络之间的连接量将显著预测负面情绪对记忆的增强，以及对负面情绪诱导的生理反应。这项研究的结果可能有助于确定创伤最脆弱的时期，从而促进预防，并指出新的、更有针对性的药物治疗。

It is well established that women exhibit a significantly higher rate of affective disorders than men do. This difference is particularly strong in post-traumatic stress disorder, where women are more than twice as likely to experience PTSD than men. Recent evidence suggests that women’s susceptibility to PTSD varies with their levels of ovarian hormones. During the luteal phase, when progesterone is elevated, women are more than three times as likely to develop PTSD symptoms after trauma. Similarly, women are twice as likely as men to be diagnosed with depression, and depressive symptoms also vary by menstrual phase. Both of these disorders involve alterations of memory, stress responses, and resting connectivity in the brain’s intrinsic networks. In PTSD, individuals experience intrusive memories of traumatic events, while individuals with depression show a marked negative retrieval bias. Stress-evoked release of the stress hormone cortisol is also elevated in both disorders. Similarly, resting connectivity between the default mode network, a group of structures engaged during the retrieval of memories, and the salience network, a group of structures involved in processing emotion, is elevated in individuals suffering from both disorders. Recent research indicates that affective memory, stress responsiveness, and resting connectivity are all influenced by changes in ovarian hormone levels. Negative memories acquired during the progesterone-rich luteal phase are better retained than during other menstrual phases. Increased progesterone is also associated with increased stress-evoked cortisol secretion. Similarly, ingestion of progesterone pills increases the connectivity between key nodes of default and salience networks. No study to date, however, has assessed the influence of changes in ovarian hormones on inter-network connectivity over the menstrual cycle. We hypothesize that changes in hormone levels over the menstrual cycle produce natural windows of vulnerability to traumatic life events, during which changes in the connectivity of the brain facilitate stress responses and enhance memory for negative experiences. To test this hypothesis, we will measure resting connectivity, stress hormone levels, physiological responses, and memory for negative material learned at hormonally distinct phases of the menstrual cycle. We predict that connectivity between resting and default mode networks will be at highest levels during the luteal phase, and that material learned in a negative emotional state will be best retained during the luteal phase. Additionally, we predict that the amount of connectivity between these two networks will significantly predict the enhancement of memory by negative affect, as well as the physiological response to negative mood induction. The results of this study could help to identify periods of maximum vulnerability trauma, thus facilitating prevention, as well as point to new and more targeted drug treatments.