The Functional Neuroanatomy of the Human Physiological Stress Response

Stress is common in daily life and is associated with adverse health outcomes. This proposal will study how a physiological stress (low blood sugar), a stress often experienced by people with diabetes, affects connections in the brain. The investigators will focus on brain connections that are involved in autonomic control of cardiovascular function, and determine both how these brain connections are altered by low blood sugar and how these alterations associate with changes in pain perception and cardiovascular control.

In this study, the investigators introduce a novel mechanistic, integrative approach to the assessment of the response to and recovery from a specific physiologic stressor - insulin-induced hypoglycemia. The overall hypothesis is that a hypoglycemic stress will alter autonomic brain networks, and will affect clinically relevant physiological outcomes (cardiovascular autonomic function); and that the rate and extent of recovery of these brain networks will provide a measure of resilience.

In combination, this approach will allow the investigators 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 autonomic function) and to define the recovery of brain circuitry and these related physiological outcomes.

Inclusion criteria

• Healthy volunteers
• Males and Females age 18 to 45 years
• BMI 18-35 kg/m2

Exclusion criteria

• Pregnancy
• Lactation
• Menopause
• Any medical condition
• Current or prior alcohol or drug abuse
• Active tobacco use
• Abnormal ECG
• In all subjects, any individuals on oral, injected, inhaled or topical corticosteroids within the last year or oral contraceptives within the past 3 months will be excluded.
• Use of medications other than thyroid hormone or hormonal birth control
• Serum potassium >5.0 mmol/L
• Estimated GFR <60 mL/min/1.73 m2
• Hemoglobin A1c ≥6.5%
• Patient Health Questionnaire (PHQ9) for depression score ≥15
• GAD-7 Questionnaire for anxiety score ≥10
• PTSD Checklist for DSM-5 (PCL-5) score ≥31
• Perceived Stress Scale (PSS-14) score >28
• Blood pressure systolic ≥140 or <100 mmHg; Blood pressure diastolic >90 mmHg
• Metal in the body including: cardiac pacemakers, stents, artificial heart valves, artificial limbs or hands, brain stimulator devices, implanted drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to shrapnel or metal filings (wounded in military combat, sheet metal workers, welders, and others), other metallic surgical hardware in vital areas, certain tattoos with metallic ink, certain transdermal medication patches, and metal-containing IUDs