The neuroanatomical basis for the human stress response

描述（由申请人提供）：此小额资助奖（R03）申请是为Tony Buchanan博士收集人类应激反应的神经控制的初步数据所需的研究活动提供资金支持，目的是发展一个正在进行的研究项目。心理社会压力在许多疾病状态的发展中起着重要作用。动物研究表明，杏仁核、海马体和前额皮质控制应激反应。人类应激反应的神经控制尚不清楚；这些项目将在扁桃体、海马体和前额皮质受损的人类中研究这一问题。我们将测量皮质醇和自主神经指数（血压、心率、心率变异性和呼吸），以响应Trier社会压力测试，这是一种广泛使用的标准化实验室压力源。我们将在一个单独的无压力的日子里，通过评估皮质醇的昼夜周期来控制激素功能的潜在基线差异。测量对直立性挑战的反应将控制自主神经系统活动的潜在基线组差异。我们预测，杏仁核、海马体或前额皮质受损的受试者对社会心理压力的反应会比这些目标区域以外的大脑受损的受试者更弱。将收集对压力源的认知评估和主观压力评级的措施，以检查对压力源感知的潜在组差异。我们预测应激反应的群体差异不是由于基线生理功能，而是由于对心理社会应激的不同主观和/或生理反应。精神疾病如抑郁症和创伤后应激障碍的特点是杏仁核、海马体和前额皮质紊乱。这些疾病也与应激生理的改变有关。更好地了解这些神经结构在应激反应中的作用，可以增加我们对压力在精神疾病发展中的作用的理解，并有可能开发出治疗这些疾病的方法。这项工作是脑损伤研究的新延伸，结合了神经内科患者登记的优势，提供了无与伦比的局灶性脑损伤患者登记和首席研究员在压力研究方面的专业知识。

DESCRIPTION (provided by applicant): This Small Grant Award (R03) Application is a request for funding to support the research activities necessary for Tony Buchanan, Ph.D. to collect preliminary data on the neural control of the human stress response, with the goal of developing an ongoing research program on this topic. Psychosocial stress plays a role in the development of many disease states. Animal research has implicated the amygdala, hippocampus, and prefrontal cortex in the control of the stress response. The neural control of the human stress response is not well understood; these projects will examine this issue in humans with damage to the amygdala, hippocampus, and prefrontal cortex. We will measure cortisol and autonomic indices (blood pressure, heart rate, heart rate variability, and respiration) of stress in these subjects in response to the Trier Social Stress Test, a widely used and standardized laboratory stressor. We will control for potential baseline differences in hormonal function by assessing the diurnal cycle of cortisol on a separate, stress free day. Measurement of responses to an orthostatic challenge will control for potential baseline group differences in autonomic nervous system activity. We predict that subjects with damage to the amygdala, hippocampus, or prefrontal cortex will show a diminished response to psychosocial stress compared to subjects with brain damage outside these target areas. Measures of cognitive appraisal of the stressor and subjective stress ratings will be collected to examine potential group differences in the perception of the stressor. We predict that group differences in stress responses are not due to baseline physiological functioning, but to differential subjective and/or physiological responses to psychosocial stress. Psychiatric disorders such as depression and posttraumatic stress disorder are characterized by disturbance in the amygdala, hippocampus, and prefrontal cortex. These diseases are also associated with alterations in stress physiology. A better understanding of the role of these neural structures in the stress response could increase our understanding of the role of stress in the development of mental illness with the potential for developing treatments for these diseases. This work is a novel extension of research with brain damaged subjects, incorporating the strengths of the Department of Neurology's Patient Registry, which provides an unequalled registry of patients with focal brain damage and the expertise in stress research of the principal investigator.