The Functional Neuroanatomy of the Human Physiological Stress Response

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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.