Effect of Hydrocortisone on the Brain
Condition: Healthy
Study type: Observational

Summary: 
      The purpose of this study is to use brain imaging technology to examine the effect of the
      hormone hydrocortisone on the brain's response to various facial expressions.

      Glucocorticoids can influence emotional behavior and cognition; when given long-term, the
      hormones may lead to mania or depression. One way glucocorticoids may influence emotional
      behavior is by affecting the activity of certain parts of the brain that participate in
      emotional processing. Brain imaging studies indicate that the amygdala, ventral medial
      prefrontal, and other prefrontal cortical areas of the brain are activated during tasks that
      require processing of emotional stimuli. These brain structures contain dense concentrations
      of glucocorticoid receptors. This study will use functional magnetic resonance imaging (fMRI)
      to study the brain activity of participants as they view faces that express different
      emotions. Participants will perform this task under a dose of either the glucocorticoid
      hydrocortisone or placebo (an inactive solution).

      Participants in this study will be screened with a medical history, physical examination,
      blood tests, and an interview about their mood, degree of nervousness, and behavior. On Visit
      1, participants will undergo screening and neuropsychological testing. For 3 days prior to
      Visit 2, participants will collect their saliva. During Visit 2, participants will undergo
      MRI scans of the brain after infusion with either a high or low dose of hydrocortisone or
      placebo. Participants will also undergo functional MRI (fMRI). Blood samples will be
      collected every 15 minutes during the scan. Following the MRI, participants will take
      attention and memory tests.

      ...
    

Detailed description: 
      Glucocorticoids influence performance on declarative memory tasks and tasks of memory for
      emotional information. The cognitive effects of exogenous glucocorticoids depend on dose, the
      time period between administration and testing, and the time of testing within the diurnal
      pattern of cortisol secretion. Additionally, glucocorticoid administration can influence
      mood, and with chronic administration glucocorticoids may lead to development of mania or
      depression.

      A potential mechanism by which glucocorticoids may influence emotional behavior is via their
      effects on the neurophysiological activity of the amygdala and prefrontal cortical structures
      known to participate in emotional processing. Human imaging studies indicate that amygdala,
      ventral medial prefrontal, and other prefrontal cortical areas are activated during tasks
      requiring processing of affective stimuli. These data converge with lesion analysis and
      electrophysiological studies performed in humans or experimental animals to indicate that
      these structures participate in brain circuits that process emotional information. These
      brain structures contain dense concentrations of glucocorticoid and mineralocorticoid
      receptor mRNA, glucocorticoid receptors and mineralocorticoid receptors. Increased
      glucocorticoids appear to potentiate activation of the amygdala and affect processing of
      emotionally laden stimuli based on both experimental animal studies and correlational human
      studies.

      The present study investigates the influence of glucocorticoids on the hemodynamic response
      that occurs while processing emotionally-valenced visual stimuli known to activate the
      amygdala and anatomically-related areas of the prefrontal cortex (PFC) in healthy humans.
      Functional magnetic resonance images will be acquired during the performance of tasks that
      involve viewing emotionally expressive faces both before and following either hydrocortisone
      (synthetic cortisol) (0.15 mg/kg or 0.45 mg/kg bolus) or placebo administration. The change
      in the BOLD signal in structures of interest will be compared across high dose cortisol, low
      dose cortisol and placebo conditions. In addition, the effects of hydrocortisone on relative
      blood flow in the amygdala and PFC will be assessed using an arterial spin labeling (ASL)
      technique to measure perfusion. The findings of this study will guide future research into
      the effects of glucocorticoids on emotional perception in subjects with mood disorders.
    

Keywords: Amygdala; Medial Prefrontal Cortex; Orbitofrontal Cortex; Cortisol; Memory; Glucocorticoid; Hydrocortisone; Stress; Perception; Affect; Healthy Volunteer; HV