What a difference timing makes: Cortisol effects on neural underpinnings of emotion regulation.

The ability of emotion regulation under stress is of crucial importance to psychosocial health. Yet, the dynamic function of stress hormones for the cognitive control of emotions over time via non-genomic and genomic cortisol effects remains to be elucidated. In this randomized, double-blind, placebo-controlled neuroimaging experiment, 105 participants (54 men, 51 women) received 20 mg hydrocortisone (cortisol) or a placebo either 30min (rapid, non-genomic cortisol effects) or 90min (slow, genomic cortisol effects) prior to a cognitive reappraisal task including different regulatory goals (i.e., downregulate vs. upregulate negative emotions). On the behavioral level, cortisol rapidly reduced and slowly enhanced emotional responsivity to negative pictures. However, only slow cortisol effects improved downregulation of negative emotions. On the neural level, cortisol rapidly enhanced, but slowly reduced amygdala and dorsolateral prefrontal activation as well as functional connectivity between both structures in the down- minus upregulate contrast. This interaction speaks for an effortful but ineffective regulation of negative emotions during rapid cortisol effects and improved emotion regulation capacities during slow cortisol effects. Taken together, these results indicate a functional shift of cortisol effects on emotion regulation processes over time which may foster successful adaptation to and recovery from stressful life events.

Cortisol before extinction generalization alters its neural correlates during retrieval.

While generalization of fear seems to be naturally acquired as frequently observed in fear-related disorders, extinction learning appears to be stimulus-specific. Thus, treatments aiming to generalize extinction learning comprise the chance to overcome stimulus-specificity and consequently reduce relapse. One suggested candidate is the timing-dependent administration of the stress hormone cortisol. In the present pre-registered, three-day fear conditioning study, we aimed to create a generalized extinction memory trace in 60 healthy men and women using multiple sizes of one conditioned stimulus (CS+G; generalized) during extinction training, whereas the other CS (CS+N; non-generalized) and the CS- were solely presented in their original sizes. Extinction training took place either after pharmacological administration of 20 mg cortisol or placebo. Following successful fear acquisition on day one, generalization effects during extinction training and retrieval were investigated in the comparison of CS+G and CS+N. Insula and dorsal anterior cingulate cortex (dACC) activation for CS+G as compared to CS+N extending to the second half of extinction training indicated prolonged fear processing during extinction training for the CS+G on day two. During retrieval on day three, an activation of the anterior hippocampus occurred for CS+N minus CS+G in the cortisol but not in the placebo group. Additionally, a more posterior hippocampal activation (compared to the other hippocampal activation) was observed for the contrast CS+G minus CS+N. In accordance with our hypotheses, amygdala and dACC responding during reinstatement test was reduced for the CS+G as compared to CS+N. However, cortisol did not modulate amygdala responding, but abolished the CS+G/CS+N differentiation in the dACC relative to placebo. Generalization and cortisol effects were not mirrored in skin conductance responses. In conclusion, extinction generalization processes appear to rely on prolonged fear processing still present in the second half of extinction training that in turn leads to reduced fear-related processing after reinstatement. Cortisol administration prior to extinction training, however, selectively reduced fear-related activation for standard extinction but did not further reduce fear-related activation for extinction generalization.

Stimulus-Based Extinction Generalization: Neural Correlates and Modulation by Cortisol.

BACKGROUND: While healthy individuals and patients with anxiety disorders easily generalize fear responses, extinction learning is more stimulus specific. Treatments aiming to generalize extinction learning are urgently needed, since they comprise the potential to overcome stimulus specificity and reduce relapses, particularly in the face of stressful events. METHODS: In the current 3-day functional magnetic resonance imaging fear conditioning paradigm, we aimed to create a generalized extinction memory trace in 60 healthy men and women by presenting multiple sizes of 1 conditioned stimulus during extinction training (CS+G; generalized), whereas the other conditioned stimulus was solely presented in its original size (CS+N; nongeneralized). Recall was tested on the third day after pharmacological administration of either the stress hormone cortisol or placebo. RESULTS: After successful fear acquisition, prolonged activation of the amygdala and insula and deactivation of the ventromedial prefrontal cortex for CS+G compared with CS+N during extinction learning indicated sustained fear to the generalization stimuli. In line with our hypotheses, reduced amygdala activation was observed after extinction generalization on the third day in the contrast CS+G minus CS+N, possibly reflecting an attenuated return of fear. Cortisol administration before recall, however, blocked this effect. CONCLUSIONS: Taken together, the findings show that extinction generalization was associated with decreased activation of the fear network during recall after prolonged activation of the fear network during extinction learning. However, the generalization of the extinction memory did not counteract the detrimental effects of stress hormones on recall. Thus, stimulus-based extinction generalization may not be sufficient to reduce relapses after stressful experiences.

Acute stress improves the effectivity of cognitive emotion regulation in men.

Emotion regulation is crucial for coping with stressors but in turn can also be influenced by stress. Initial studies provided mixed evidence showing either beneficial or impairing stress effects on cognitive emotion regulation depending on stress timing, sex or the regulatory strategy. Here, we investigated the impact of acute stress on different emotion regulation strategies in men and women. N = 118 healthy participants were subjected to the Trier Social Stress Test or a control condition after which they completed an emotion regulation paradigm, requiring them to regulate their emotions in response to negative pictures using reappraisal or distraction. Cortisol levels were repeatedly measured to quantify changes in HPA axis activity. Affective ratings and pupil dilation served to measure emotion regulation success and the cognitive effort to regulate emotions. Stress reduced arousal and increased valence and success ratings for reappraisal in men, whereas no significant stress effects were found in women. Moreover, stressed men displayed a significant expansion of pupil diameter during reappraisal suggesting enhanced cognitive regulatory engagement, which ultimately may have led to better emotion regulation outcomes. Cortisol secretion positively correlated with subjective reappraisal success in men, suggesting a glucocorticoid-driven mechanism that may promote emotion regulatory performance in the aftermath of stress.

An oral presentation causes stress and memory impairments.

Laboratory experiments revealed the stress hormone cortisol to decrease memory retrieval of emotional material, but a translation to real-life settings is missing so far. In this study, 51 students encoded a list of neutral, positive, and negative words as well as two neutral, biographical notes one day before attendance at a seminar at the university. In the stress condition, students gave a graded oral presentation, whereas they just attended the same seminar in the control condition immediately before retrieval took place. Measures of state anxiety, salivary cortisol and alpha-amylase confirmed the oral presentation to constitute a potent stressor. Importantly, stress significantly impaired retrieval of negative words, but not retrieval of the biographical notes. These results indicate that a real-life stressor decreases memory retrieval for negative items. In contrast, delayed memory retrieval of neutral information and interrelated details of biographical notes seems to be less prone to stress effects. These results have critical implications for educational settings.