Interacting noradrenergic and corticosteroid systems shift human brain activation patterns during encoding

Emotionally arousing experiences are usually well retained, an effect that depends on the release of adrenal stress hormones. Animal studies have shown that corticosterone and noradrenaline - representing the two main stress hormone systems - act in concert to enhance memory formation by actions involving the amygdala, hippocampus and prefrontal cortex (PFC). Here we test whether interactions between these two stress hormone systems also affect human memory formation as well as the associated pattern of brain activation. To this end, forty-eight male human subjects received hydrocortisone, yohimbine or both before presentation of emotional and neutral pictures. Activity in the amygdala, hippocampus and PFC was monitored with functional Magnetic Resonance Imaging (fMRI) during encoding of these stimuli, when hormonal levels were elevated. Memory performance was tested 1 week later. We investigated whether an increased level of one of the two hormone systems would lead to differential effects compared to the combined application of the drugs on brain activation and memory performance. We report that the application of cortisol led to an overall enhancing effect on recognition memory, with no significant additional effect of yohimbine. However, during encoding the brain switched from amygdala/hippocampus activation with either hormone alone, to a strong deactivation of prefrontal areas under the influence of the combination of both exogenous hormones. Although we did not find evidence that exogenous stimulation of the noradrenergic and corticosteroid systems led to significant interaction effects on memory performance in this experiment, we conclude that stress hormone levels during encoding did differentially determine the activation pattern of the brain circuits here involved.