Time-dependent effects of cortisol on selective attention and emotional interference: a functional MRI study

Abstract

Acute stress is known to induce a state of hypervigilance, allowing optimal detection of threats. Although one may benefit from sensitive sensory processing, it comes at the cost of unselective attention and increased distraction by irrelevant information. Corticosteroids, released in response to stress, have been shown to profoundly influence brain function in a time-dependent manner, causing rapid non-genomic and slow genomic effects. Here, we investigated how these time-dependent effects influence the neural mechanisms underlying selective attention and the inhibition of emotional distracters in humans. Implementing a randomized, double-blind, placebo-controlled design, 65 young healthy men received 10 mg hydrocortisone either 60 min (rapid effects) or 270 min (slow effects), or placebo prior to an emotional distraction task, consisting of color-naming of either neutral or aversive words. Overall, participants responded slower to aversive compared to neutral words, indicating emotional interference with selective attention. Importantly, the rapid effects of corticosteroids increased emotional interference, which was associated with reduced amygdala inhibition to aversive words. Moreover, they induced enhanced amygdala connectivity with frontoparietal brain regions, which may reflect increased influence of the amygdala on an executive network. The slow effects of corticosteroids acted on the neural correlates of sustained attention. They decreased overall activity in the cuneus, possibly indicating reduced bottom-up attentional processing, and disrupted amygdala connectivity to the insula, potentially reducing emotional interference. Altogether, these data suggest a time-specific corticosteroid modulation of attentive processing. Whereas high circulating corticosteroid levels acutely increase emotional interference, possibly facilitating the detection of threats, a history of elevation might promote sustained attention and thereby contribute to stress-recovery of cognitive function.

Keywords: amygdala; attention; corticosteroids; cuneus; emotional interference; functional MRI; insula; prefrontal cortex.

Figure 1

Salivary cortisol data and experimental design. (A) Participants received two capsules (drug1 and drug2) containing either 10 mg of hydrocortisone (CORT) or placebo at different time points before the emotional distraction task. Hydrocortisone intake significantly elevated salivary cortisol levels in both hydrocortisone administration groups to levels observed during moderate-to-severe stress (Morgan et al., 2000). (B) The emotional distraction task consisted of 30 s-blocks of neutral (N) or aversive (A) words or fixation (+). Participants were requested to button press as fast as possible for the color in which the presented words were displayed. Mood: POMS questionnaire (Reddon et al., ; Wald and Mellenbergh, ; de Groot, 1992). Error bars represent S.E.M. N.B. In reality Dutch words were used, the words in Figure 1B only serve an illustrative purpose.

Figure 2

Effects of corticosteroids on amygdala activity. (A) Hydrocortisone administration induced trend of a corticosteroid x emotion interaction in the amygdala (y = −4). For visualization purposes the statistical parametric map is thresholded at p < 0.05 uncorrected with a minimal cluster-size of 250 voxels. (B) This interaction appeared to be driven by a significant effect of emotion in the amygdala due to the rapid effects of corticosteroids, suggesting insufficient suppression of emotional interference in this group. The amygdala in the placebo and slow corticosteroid group did not distinguish between the processing of aversive vs. neutral words. For visualization purposes the statistical parametric maps are thresholded at p < 0.005 uncorrected with a minimal cluster-size of 25 voxels.

Figure 3

Effects of corticosteroids on amygdala connectivity. (A) The rapid effects of corticosteroids increased the functional connectivity of the amygdala to regions involved in task execution (middle frontal gyrus, precentral gyrus, and postcentral gyrus), potentiating its influence on task execution. (B) The slow effects of corticosteroids disrupted the negative connectivity between the amygdala and insula, attenuating the effects the amygdala can exert on task execution. For visualization purposes the statistical parametric maps are thresholded at p < 0.01 uncorrected with a minimal cluster-size of 250 voxels.