Simultaneous glucocorticoid and noradrenergic activity disrupts the neural basis of goal-directed action in the human brain.

Stress promotes a shift from goal-directed action-outcome learning toward habitual stimulus-response learning. This shift is mediated by an interaction of noradrenergic activity and glucocorticoid stress hormones. In the present experiment, we examined the neural correlates of the stress (hormone)-induced shift from goal-directed to habit learning in the human brain. Healthy participants were administered hydrocortisone, the α2-adrenoceptor antagonist yohimbine, or both before they were trained in two instrumental actions leading to two distinct food rewards. After training, one of the rewards was devalued by feeding participants to satiety on that food. Finally, participants were presented the two instrumental actions in extinction. We collected functional magnetic resonance images both during instrumental training and during extinction testing. Our behavioral data confirmed that the simultaneous administration of hydrocortisone and yohimbine renders instrumental behavior insensitive to the outcome devaluation (and thus habitual), whereas hydrocortisone or yohimbine alone have no such effect. At the neural level, the combined administration of hydrocortisone and yohimbine reduced the sensitivity of the orbitofrontal and medial prefrontal cortex to changes in outcome value. Brain areas that have been previously implicated in habit learning were not modulated by hydrocortisone and yohimbine. These findings suggest that concurrent glucocorticoid and noradrenergic activity disrupts the neural bases of goal-directed action and thus renders behavior habitual.