The functional neuroanatomy of the human physiological stress response

压力，包括生理压力，是现代生活中无处不在的一个方面，对健康不利 后果包括心血管发病率和死亡率。然而，很少有研究检查 生理应激源对神经和心血管系统的影响，以及 从压力中恢复这些系统。 在这个建议中，我们介绍了一种新的机制，综合方法来评估的反应， 以及从特定生理应激源-胰岛素诱导的低血糖中恢复。我们的总体假设是 低血糖应激会改变自主神经和感觉脑网络，并会影响临床相关的 生理结果（心血管自主神经功能和感觉处理）;以及 这些大脑网络的恢复程度将提供一个恢复能力的衡量标准 我们的具体目标是：1）使用功能磁共振成像（fMRI）来确定， 控制对大脑网络的低血糖应激，重点是自主神经和疼痛相关网络; 2)以确定低血糖诱导的脑网络变化与脑内神经元的关系。 心血管自主神经功能的生理结果;以及3）确定 低血糖引起的脑网络变化和感觉处理的生理结果 结合起来，这种方法将使我们第一次能够定义应力影响的大小 神经回路和临床相关应激相关生理结果（心血管 和感觉处理），并定义脑回路的恢复和这些相关的生理结果。 我们还将评估研究程序的心理影响，并在研究前和研究期间测量压力 研究。这种方法将提供一个集成的系统，适用于模拟生理弹性 应力 如果成功，我们的结果将不仅与糖尿病患者有关，他们经常暴露于 低血糖应激，但可推广到暴露于其他生理应激的个体。这 该提案还将为未来的研究奠定科学基础，以评估参与 对生理压力的恢复力，以及生理压力和心理压力之间的相互作用。

Stress, including physiological stress, is a ubiquitous aspect of modern life and has adverse health consequences including cardiovascular morbidity and mortality. However, few studies have examined the effects of physiological stressors on the nervous and cardiovascular systems, and the rate and extent of recovery of these systems from stress. In this proposal, we introduce a novel mechanistic, integrative approach to the assessment of the response to and recovery from a specific physiologic stressor – insulin-induced hypoglycemia. Our overall hypothesis is that a hypoglycemic stress will alter autonomic and sensory brain networks, and will affect clinically relevant physiological outcomes (cardiovascular autonomic function and sensory processing); and that the rate and extent of recovery of these brain networks will provide a measure of resilience Our Specific Aims are: 1) to identify, using function magnetic resonance imaging (fMRI), the effect of a controlled hypoglycemic stress on brain networks, with an emphasis on autonomic- and pain-related networks; 2) to determine the relationships between hypoglycemia-induced changes in brain networks and the physiological outcome of cardiovascular autonomic function; and 3) to determine the relationships between hypoglycemia-induced changes in brain networks and the physiological outcome of sensory processing In combination, this approach will allow us for the first time to define the magnitude of the effect of stress exposure on neural circuitry and on clinically relevant stress-related physiological outcomes (cardiovascular and sensory processing) and to define the recovery of brain circuitry and these related physiological outcomes. We will also assess the psychological impact of the study procedures and measure stress prior to and during the studies. This approach will provide an integrated system suitable for modeling resilience to physiological stress. If successful, our results will be relevant not only to patients with diabetes, who are frequently exposed to hypoglycemic stress, but may be generalizable to individuals exposed to other physiologic stresses. This proposal will also establish a scientific foundation for future studies to assess mechanisms involved in resilience to physiological stress, and the interactions between physiological and psychological stress.