Importance of cortisol dynamics for brain activity and cognition with focus on emotional face processing and resting state connectivity using functional magnetic resonance imaging

Abstract

Background and Aims: Cortisol is the primary human stress hormone and is a glucocorticoid (GCC) produced by the hypothalamic-pituitary-adrenocortical (HPA) axis, an important neuroendocrine system which follows both circadian (≈daily) and ultradian (≈hourly) rhythms. It is this rhythmicity, referred to as cortisol pulsatility, that is believed to be essential for healthy neurological and physiological function. Our aim was to use Functional Magnetic Resonance Imaging (fMRI) to investigate the importance of cortisol rhythmicity on emotional processing and resting state connectivity.
Methods: Two studies were conducted. (i) The Pulses Study explored the functional neuropsychology of patients with Addison's Disease (AD) (a condition of cortisol/adrenal insufficiency; n=13) receiving two different patterns of hydrocortisone replacement therapy (HCRT), using fMRI. This included an emotional faces task, the implicit face expression processing task (IFEPT) and a resting scan on the rising phase of a single physiological cortisol pulse (4mg) of a pulsatile HCRT schedule and during the equivalent time on their typical oral HCRT. (ii) The Cortisol Effects on Brain Activity and Cognition (CEBAC) Study was designed to discern the importance of the different phases of cortisol pulsatility on the functional neuropsychology of healthy volunteers whose natural cortisol rhythm was suppressed and replenished with a controlled pulsatile infusion (n=16). These participants completed an fMRI emotional processing task named the facial expression ambiguity resolution task (FEART) and two resting scans, on three occasions: (i) during the rising phase of an elevated cortisol pulse (15mg), (ii) during the falling phase and (iii) on a following visit ≈15 hours of cortisol suppression without replenishment.
Results: In AD patients with long-term GCC treatment, we found that different patterns of HCRT result in differential emotional processing to the IFEPT. The healthy participants' data showed that the brain is sensitive to acute changes in GCC dynamics with the responsivity to emotional stimuli in the FEART being phase-dependent. In both studies, corticolimbic areas emerged as regions of differential activation, suggesting this system is particularly sensitive to changes in GCC dynamics.
Conclusions: These findings suggest an important role for cortisol pulsatility in emotional processing. Our work corroborates animal studies of GCC dynamics and offers scope for subsequent translational work. We anticipate this area of psychoneuroendocrinology will open up a breadth of therapeutic potential.

Date of Award	6 Dec 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Stafford L Lightman (Supervisor), Susanne Quadflieg (Supervisor) & Rosalyn J Moran (Supervisor)