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The Functional Neuroanatomy of the Human Physiological Stress Response

人类生理应激反应的功能神经解剖学

基本信息

批准号：
10609821
负责人：
Gail Kurr Adler
金额：
$ 72.84万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-15 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10609821
关键词：
Acute Affect Affective Amygdaloid structure Baroreflex Blood Glucose Brain Brain region Cardiovascular Physiology Cardiovascular system Central Nervous System Closure by clamp Data Diabetes Mellitus Disease Emotional Emotional Stress Environment Equilibrium Esthesia Event Experimental Models Exposure to Foundations Functional Magnetic Resonance Imaging Future Health Hour Human Hyperalgesia Hypoglycemia Immune response Immune system Individual Inflammatory Insulin Life Magnetic Resonance Imaging Measures Medical Metabolic Methods Modeling Modernization Morbidity - disease rate Nervous System Neuroanatomy Neurosecretory Systems Norepinephrine Outcome Pain Patients Persons Physiological Predictive Value Procedures Psychological Impact Psychological Stress Psychosocial Stress Questionnaires Recovery Reporting Reproducibility Research Resolution Sensory Solid Stimulus Stress System Systems Integration Techniques Testing Time Woman biological adaptation to stress brain circuitry cardiovascular risk factor clinically relevant cytokine experience experimental study immune function men mortality neural circuit novel orthostatic stress pain perception physiologic model physiologic stressor psychologic psychosocial stressors resilience response restoration stressor

项目摘要

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.

压力，包括生理压力，是现代生活中普遍存在的一个方面，对健康不利后果包括心血管发病率和死亡率。然而，很少有研究考察生理应激源对神经和心血管系统的影响，以及影响的速度和程度这些系统从压力中恢复。在本提案中，我们引入了一种新颖的机械综合方法来评估对以及从特定的生理应激源——胰岛素引起的低血糖中恢复。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，并会影响临床相关生理结果（心血管自主功能和感觉处理）；并且比率和这些大脑网络的恢复程度将提供恢复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) 来识别控制大脑网络的低血糖压力，重点是自主神经和疼痛相关网络； 2）确定低血糖引起的大脑网络变化与心血管自主功能的生理结果； 3）确定之间的关系低血糖引起的大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压力影响的程度暴露于神经回路和临床相关的应激相关生理结果（心血管和感觉处理）并定义大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测量研究之前和期间的压力研究。这种方法将提供一个适合模拟生理恢复能力的集成系统压力。如果成功，我们的结果将不仅与糖尿病患者相关，因为他们经常接触低血糖应激，但可能适用于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，以评估涉及的机制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。