Hormonal contraceptive usage influences stress hormone effects on cognition and emotion.

Men and women partially differ in how they respond to stress and how stress in return affects their cognition and emotion. The influence of hormonal contraceptives (HCs) on this interaction has received little attention, which is surprising given the prevalence of HC usage. This selective review illustrates how HC usage modulates the effects of stress hormones on cognition and emotion. As three examples, we discuss stress hormone effects on episodic memory, fear conditioning and cognitive emotion regulation. The identified studies revealed that stress effects on cognitive-emotional processes in women using HCs were at times reduced or even absent when compared to men or naturally cycling women. Especially striking were the few examples of reversed effects in HC women. As underlying neuroendocrine mechanisms, we discuss influences of HCs on the neuroendocrine stress response and effects of HCs on central glucocorticoid sensitivity. The summarized findings emphasize the need for additional translational research.

Cortisol promotes the cognitive regulation of high intensive emotions independent of timing.

Failures to cognitively downregulate negative emotions are a crucial risk factor for mental disorders. Previous studies provide evidence for a stress-induced improvement of cognitive emotion regulation possibly mediated via glucocorticoid actions. Cortisol can initialize immediate non-genomic as well as delayed genomic effects on cognitive control functioning, but its distinct effects on emotion regulation processes remain to be shown. Here, we sought to characterize time-dependent effects of oral cortisol administration on cognitive emotion regulation outcomes. We expected cortisol to improve emotion regulation success. Possible interactions with the delay between cortisol treatment and emotion regulation, strategy use and intensity of the emotional stimuli were examined. Eighty-five healthy men received either 10 mg hydrocortisone or a placebo in a double-blind, randomized design 30 or 90 min prior to an emotion regulation paradigm, in which they were asked to downregulate their emotional responses towards low and high intensive negative pictures via reappraisal or distraction. Affective ratings and pupil dilation served as outcome measures. Reduced arousal, enhanced valence ratings as well as increases in pupil dilations indexing the cognitive regulatory effort indicated successful downregulation of negative emotions evoked by high intensive but not low intensive negative pictures. Cortisol significantly reduced arousal ratings when downregulating high intensive negative emotions via distraction and (at a trend level) via reappraisal, independent of timing, demonstrating a beneficial effect of cortisol on subjective regulatory outcomes. Taken together, this study provides initial evidence suggesting that cortisol promotes the cognitive control of high intensive negative emotions both, 30 and 90 min after treatment.

Acute physical exercise promotes the consolidation of emotional material.

Physical exercise can improve cognitive functions and promote learning and memory, especially when performed in close temporal proximity to the encoding of information. This benefit may occur due to circulating stress hormones released in response to acute exercise. When administered after encoding, acute stress typically enhances the consolidation of emotional stimuli. However, whether acute exercise also selectively modulates emotional memories remains to be explored. Likewise, the potential role of sex in moderating these effects has not been addressed so far. Here, we tested whether a single bout of aerobic exercise after learning boosts the consolidation and thus long-term memory for emotional versus neutral visuospatial stimuli. Healthy men and women learned an object-location task and subsequently were exposed to a vigorous-treadmill running task or control intervention. Memory was assessed 24 h later. Acute exercise significantly increased heart rate and salivary cortisol in both sexes and selectively facilitated the consolidation of emotional stimuli. In particular, we found improved memory for negative items in women and better recall of positive items in men following exercise exposure. This memory benefit was positively related to the increase in heart rate and cortisol in both men and women, suggesting that the favorable effects of acute exercise on emotional memory may be mediated via a co-activation of the sympathetic nervous system and the hypothalamus-pituitary-adrenocortical axis. Our findings thereby provide first evidence for the improvement of emotional memory consolidation by acute physical exercise that appears to rely on similar neuroendocrine mechanisms as psychosocial stressors. Given that exercise is healthy, cost-effective and practical in nature, it constitutes an ideal behavioral intervention strategy for boosting memory in clinical and educational settings alike.

Rapid effects of acute stress on cognitive emotion regulation.

Acute stress has been shown to either enhance or impair emotion regulation (ER) performances. Besides sex, strategy use and stimulus intensity, another moderating factor appears to be timing of the ER task relative to stress exposure. Whereas somewhat delayed increases in the stress hormone cortisol have been shown to improve ER performances, rapid sympathetic nervous system (SNS) actions might oppose such effects via cognitive regulatory impairments. Here, we thus investigated rapid effects of acute stress on two ER strategies: reappraisal and distraction. N = 80 healthy participants (40 men & 40 women) were exposed to the Socially Evaluated Cold-Pressor Test or a control condition immediately prior to an ER paradigm which required them to deliberately downregulate emotional responses towards high intensity negative pictures. Subjective ratings and pupil dilation served as ER outcomes measures. Increases in salivary cortisol and cardiovascular activity (index of SNS activation) verified successful induction of acute stress. Unexpectedly, stress reduced subjective emotional arousal when distracting from negative pictures in men indicating regulatory improvements. However, this beneficial effect was particularly pronounced in the second half of the ER paradigm and fully mediated by already rising cortisol levels. In contrast, cardiovascular responses to stress were linked to decreased subjective regulatory performances of reappraisal and distraction in women. However, no detrimental effects of stress on ER occurred at the group level. Yet, our findings provide initial evidence for rapid, opposing effects of the two stress systems on the cognitive control of negative emotions that are critically moderated by sex.

The impact of physical exercise on the consolidation of fear extinction memories.

Based on the mechanisms of fear extinction, exposure therapy is the most common treatment for anxiety disorders. However, extinguished fear responses can reemerge even after successful treatment. Novel interventions enhancing exposure therapy efficacy are therefore critically needed. Physical exercise improves learning and memory and was also shown to enhance extinction processes. This study tested whether physical exercise following fear extinction training improves the consolidation of extinction memories. Sixty healthy men underwent a differential fearconditioning paradigm with fear acquisition training on day 1 and fear extinction training followed by an exercise or resting control intervention on day 2. On day 3, retrieval and reinstatement were tested including two additional but perceptually similar stimuli to explore the generalization of exercise effects. Exercise significantly increased heart rate, salivary alpha amylase, and cortisol, indicating successful exercise manipulation. Contrary to our expectations, exercise did not enhance but rather impaired extinction memory retrieval on the next day, evidenced by significantly stronger differential skin conductance responses (SCRs) and pupil dilation (PD). Importantly, although conditioned fear responses were successfully acquired, they did not fully extinguish, explaining why exercise might have boosted the consolidation of the original fear memory trace instead. Additionally, stronger differential SCRs and PD toward the novel stimuli suggest that the memory enhancing effects of exercise also generalized to perceptually similar stimuli. Together, these findings indicate that physical exercise can facilitate both the long-term retrievability and generalization of extinction memories, but presumably only when extinction was successful in the first place.

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.

Acute stress influences strategy preference when dealing with high intensity emotions in men.

Stress has been shown to initiate a shift from flexible to rigid, less demanding cognitive processes. Reappraisal and distraction are two emotion regulation strategies varying in their cognitive demands. Previous studies indicate that stress improves regulatory performances of high arousal stimuli. We thus investigated whether acute stress alters the preference for reappraisal or distraction when downregulating emotions of different intensities and further explored its influence on regulatory outcomes. Eighty males were either socially stressed (n = 40) or exposed to a control condition (n = 40) prior to an emotion regulation choice paradigm. Stress increased the probability to prefer distraction for downregulating high intensity emotions. Stressed (vs. control) participants reported to be generally more successful in regulating high intensity emotions, which was positively associated with cortisol but not alpha-amylase increases. Our findings provide initial evidence that stress fosters a preference for less demanding regulatory options, suggesting favorable strategy choices in response to acute stressors.

Delayed effects of acute stress on cognitive emotion regulation.

Acute stress has been shown to modulate cognitive emotion regulation. Besides interactions with strategy use or sex, another critical modulating factor appears to be stress timing. Exposure to acute stress initiates immediate and delayed glucocorticoid effects on cognitive control functions. Previous studies indicated a delayed increase in prefrontal activity after stress and cortisol elevations, which might also improve the ability to cognitively regulate emotions when the acute stress state has subsided. In this study, we investigated the delayed impact of acute stress on the two emotion regulation strategies reappraisal and distraction. Eighty-one healthy males and free-cycling females were exposed to the Trier Social Stress Test or a control condition 90 min before they were tested in an emotion regulation paradigm, which required them to up- and downregulate their emotional responses towards negative pictures. Affective ratings served to measure emotion regulation success, whereas pupil dilation was included to additionally assess the cognitive effort required to deliberately regulate emotions. Stress affected neither arousal, valence or success ratings nor pupil dilation. However, cortisol increases were significantly associated with reduced arousal and enhanced valence ratings when regulating negative emotions via distraction. Exploratory mediation analyses revealed an indirect effect of stress on arousal and valence ratings for distraction that was mediated by cortisol increase. Our findings thereby provide further evidence that cortisol is positively related to emotion regulation success, which might be driven by a glucocorticoid-mediated mechanism facilitating attentional shifting.

The impact of emotion regulation on cardiovascular, neuroendocrine and psychological stress responses.

Emotion regulation (ER) is vital for healthy adaptation and influences how individuals respond to and recover from stress. We investigated whether ER improves cardiovascular, neuroendocrine and psychological stress responses, while taking into account the moderating role of habitual ER tendencies. Eighty-six women applied either cognitive reappraisal or expressive suppression (vs. control) while undergoing a stressor. Reappraisal decreased heart rate variability (HRV) during stress, but also initiated a stronger post-stress HRV-recovery relative to suppression. This reappraisal-induced cardiac-vagal-flexibility was particularly observed in habitual reappraisers. Furthermore, the reappraisal group reported enhanced positive affect, whereas the suppression group experienced more unpleasantness and expressed higher cortisol levels than controls. Heightened cortisol reactivity was also found in the reappraisal group, but only for individuals scoring low or mean on trait reappraisal. These results provide preliminary evidence that reappraisal fosters psychophysiological adaptation in response to stress, but also suggest that ER-strategy-efficacy critically depends on its habitual use.

Temporal dynamics of conditioned skin conductance and pupillary responses during fear acquisition and extinction.

Fear acquisition manifests in the development of conditioned fear responses (CRs), whereas a decrement in CRs as a consequence of unconditioned stimulus (UCS) omission is referred to as extinction learning. Time windows for CR scoring in physiological readouts are subject to discussion, especially regarding the subdivision of skin conductance responses (SCRs) into first- (FIR) and second-interval responses (SIR). However, distinct temporal CR trajectories within or across measures may reflect specific characteristics of the underlying associative processes. In this study, 41 participants underwent fear acquisition and extinction, while SCRs and pupillary responses were recorded and separated into different time bins to explore the temporal dynamics of CRs across both learning phases. For SCRs, we observed a shift from early (FIR) to late (SIR) time intervals during fear acquisition most likely reflecting subsequent learning processes, in which CS-UCS associations and their relative timing are formed. During extinction, only the FIR exhibited a CR decline and was thus able to track the learning progress. These results indicate that conditioned SCRs follow a dynamic temporal pattern that may be related to different learning dimensions. By contrast, pupillary CRs were generally better captured by a late pupillary response component, suggesting a rather stable temporal CR pattern for the pupil in both learning phases. Our findings underscore the importance of specifying CR quantification for different physiological readouts when evaluating learning performance in the context of fear acquisition and extinction and may motivate further investigation of time-specific CR patterns and their relation to specific associative dimensions.

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.

Restoring emotional stability: Cortisol effects on the neural network of cognitive emotion regulation.

Effective emotion regulation in stressful contexts is a key feature of mental health. Acute stress, however, impairs prefrontal top-down control, probably leading to a decline of emotion regulatory capacities. By contrast, the delayed cortisol increase in response to a stressor or after a pharmacological manipulation has been linked to mood-protecting effects and emotion regulation success. In this functional magnetic resonance imaging study, healthy men and women received either 30 mg cortisol or placebo 90 min before they were exposed to an emotion regulation paradigm involving neutral and negative pictures. As expected, behavioural and brain imaging data indicated successful induction and downregulation of negative emotions via cognitive reappraisal and distraction. Cortisol enhanced regulatory activity in the ventrolateral prefrontal cortex when participants used distraction and reduced emotion-related activation in the amygdala when regulating emotions via cognitive reappraisal. Together, these findings provide first evidence for a delayed glucocorticoid-induced facilitation of cognitive emotion regulation processes that might be beneficial for restoring emotional stability in the aftermath of stressful events.

How stress and glucocorticoids timing-dependently affect extinction and relapse.

In recent years, various research groups aimed to augment extinction learning (the most important underlying mechanism of exposure therapy) using glucocorticoids (GCs), in particular the stress hormone cortisol. In this review, we introduce the STaR (Stress Timing affects Relapse) model, a theoretical model of the timing-dependent effects of stress/GCs treatment on extinction and relapse. In particular, we show that (1) pre-extinction stress/GCs promote memory consolidation in a context-independent manner, making extinction memory more resistant to relapse following context change. (2) Post-extinction stress also enhances extinction consolidation, but in a context-bound manner. These differences may result from the timing-dependent effects of cortisol on emotional memory contextualization. At the neural level, extinction facilitation is reflected in alterations in the amygdala-hippocampal-prefrontal cortex network. (3) Stress/GCs before a retrieval test impair extinction retrieval and promote relapse. This may result from strengthening amygdala signaling or disruption of the inhibitory functioning of the prefrontal cortex. The STaR model can contribute to the understanding and prevention of relapse processes.

Navigating the garden of forking paths for data exclusions in fear conditioning research.

In this report, we illustrate the considerable impact of researcher degrees of freedom with respect to exclusion of participants in paradigms with a learning element. We illustrate this empirically through case examples from human fear conditioning research, in which the exclusion of 'non-learners' and 'non-responders' is common - despite a lack of consensus on how to define these groups. We illustrate the substantial heterogeneity in exclusion criteria identified in a systematic literature search and highlight the potential problems and pitfalls of different definitions through case examples based on re-analyses of existing data sets. On the basis of these studies, we propose a consensus on evidence-based rather than idiosyncratic criteria, including clear guidelines on reporting details. Taken together, we illustrate how flexibility in data collection and analysis can be avoided, which will benefit the robustness and replicability of research findings and can be expected to be applicable to other fields of research that involve a learning element.