Impaired free recall of neutral but not negative material tested 105 min after cortisol administration.

Pharmacological studies have consistently shown memory retrieval impairment after administration of cortisol, particularly pronounced for emotional laboratory material (i.e. list of emotional words). However, it is unclear how pharmacological elevation of cortisol affects memory retrieval of ecologically-relevant emotional material (i.e. similar to a newspaper article about an emotional event). In the present study, we aimed to explore whether cortisol administration affects the recall of ecologically-relevant emotional and neutral material, and when memory retrieval occurs after a longer delay (105 min). In this double-blind, pseudo-randomized, placebo-control study, 79 participants learned a negative text and a neutral text. Twenty-four hours later, they were administrated either 10 mg of hydrocortisone or placebo. After 105 min, participants engaged in free recall of both texts. The group with cortisol administration showed significantly reduced free recall compared to the placebo group. Interestingly, this memory retrieval impairment was driven by significantly lower recall after cortisol vs. placebo administration for neutral texts, but not negative texts. The current finding suggests that cortisol administration impairs neutral ecologically-relevant material while leaving emotional material unaffected. These divergent findings, compared to existing literature, emphasize the necessity of employing more ecologically validated material to gain a more comprehensive understanding of the intricate interplay between cortisol administration and memory for ecological material.

Opposite effects of emotion and event segmentation on temporal order memory and object-context binding.

Our daily lives unfold continuously, yet our memories are organised into distinct events, situated in a specific context of space and time, and chunked when this context changes (at event boundaries). Previous research showed that this process, termed event segmentation, enhances object-context binding but impairs temporal order memory. Physiologically, peaks in pupil dilation index event segmentation, similar to emotion-induced bursts of autonomic arousal. Emotional arousal also modulates object-context binding and temporal order memory. Yet, these two critical factors have not been systematically studied together. To address this gap, we ran a behavioural experiment using a paradigm validated to study event segmentation and extended it with emotion manipulation. During encoding, we sequentially presented greyscale objects embedded in coloured frames (colour changes defining events), with a neutral or aversive sound. During retrieval, we tested participants' memory of temporal order memory and object-colour binding. We found opposite effects of emotion and event segmentation on episodic memory. While event segmentation enhanced object-context binding, emotion impaired it. On the contrary, event segmentation impaired temporal order memory, but emotion enhanced it. These findings increase our understanding of episodic memory organisation in laboratory settings, and potentially in real life with perceptual changes and emotion fluctuations constantly interacting.

Suppressing the Morning Cortisol Rise After Memory Reactivation at 4 A.M. enhances Episodic Memory Reconsolidation in Humans.

Evidence from animal and human research shows that established memories can undergo changes after reactivation through a process called reconsolidation. Alterations of the level of the stress hormone cortisol may provide a way to manipulate reconsolidation in humans. Here, in a double-blind, within-subject design, we reactivated a 3-d-old memory at 3:55 A.M. in sixteen men and four women, immediately followed by oral administration of metyrapone versus placebo, to examine whether metyrapone-induced suppression of the morning cortisol rise may influence reconsolidation processes during and after early morning sleep. Crucially, reactivation followed by cortisol suppression versus placebo resulted in enhanced memory for the reactivated episode tested 4 d after reactivation. This enhancement after cortisol suppression was specific for the reactivated episode versus a non-reactivated episode. These findings suggest that when reactivation of memories is immediately followed by suppression of cortisol levels during early morning sleep in humans, reconsolidation processes change in a way that leads to the strengthening of episodic memory traces.SIGNIFICANCE STATEMENT How can we change formed memories? Modulation of established memories has been long debated in cognitive neuroscience and remains a crucial question to address for basic and clinical research. Stress-hormone cortisol and sleep are strong candidates for changing consolidated memories. In this double-blind, placebo-controlled, within-subject pharmacological study, we investigate the role of cortisol on the modulation of reconsolidation of episodic memories in humans. Blocking cortisol synthesis (3 g metyrapone) during early morning sleep boosts memory for a reactivated but not for a non-reactivated story. This finding contributes to our understanding of the modulatory role of cortisol and its circadian variability on reconsolidation, and moreover can critically inform clinical interventions for the case of memory dysfunctions, and trauma and stress-related disorders.

The Longitudinal Relationship of Perceived Stress Predicting Subsequent Decline in Executive Functioning in Old Age Is Attenuated in Individuals with Greater Cognitive Reserve.

BACKGROUND: Cognitively stimulating activities contribute to the accumulation of cognitive reserve that is proposed to be instrumental for maintaining cognitive functioning in aging. Adopting a novel, more general conceptual perspective including models of vulnerability, we argue that cognitive reserve may modify the longitudinal association between perceived stress and the rate of subsequent decline in executive functioning. OBJECTIVE: The present study set out to investigate the longitudinal relationship between perceived stress and subsequent decline in executive functioning over 6 years as measured through performance changes in the Trail Making Test (TMT) and whether this longitudinal relationship differed by key markers of cognitive reserve (education, occupation, and leisure activities), taking into account age, sex, and chronic diseases as covariates. METHODS: We used latent change score modeling based on longitudinal data from 897 older adults tested on TMT parts A and B in two waves 6 years apart. Mean age in the first wave was 74.33 years. Participants reported information on perceived stress, education, occupation, leisure activities, and chronic diseases. RESULTS: The longitudinal relationship between greater perceived stress in the first wave of data collection and steeper subsequent decline in executive functioning over 6 years was significantly reduced in individuals who had pursued a higher frequency of leisure activities in the first wave. CONCLUSION: The longitudinal relationship between perceived stress and subsequent decline in executive functioning may be attenuated in individuals who have accumulated greater cognitive reserve through an engaged lifestyle. Implications for current cognitive reserve and gerontological research are discussed.

The relation of low cognitive abilities to low well-being in old age is attenuated in individuals with greater cognitive reserve and greater social capital accumulated over the life course.

Objectives: The present study sets out to investigate the relation of cognitive abilities to well-being and its interplay with key life course proxies of cognitive reserve and social capital in a large sample of older adults.Method: Three thousand eighty older adults served as sample for the present study. Physical well-being (EuroQoL-5D questionnaire) and psychological well-being (Satisfaction with Life Scale) as well as cognitive performance in terms of verbal abilities (Mill Hill vocabulary scale), processing speed (Trail Making Test part A), and cognitive flexibility (Trail Making Test part B) were assessed. Participants reported information on education, occupation, cognitively stimulating leisure activities, the different languages regularly spoken as well as family and close friends.Results: Moderation analyses showed that the relation of cognitive performance to physical and psychological well-being was significantly attenuated in individuals with a higher cognitive level of the first job after education, a larger number of midlife and current cognitively stimulating leisure activities, a larger number of languages regularly spoken, a larger number of significant family members and friends, and more frequent contact with and more confidence in significant family members.Conclusion: Present data suggest that the relation of low cognitive abilities to low well-being in old age is attenuated in individuals with greater cognitive reserve and greater social capital accumulated over the life course.

Better memory for intrinsic versus extrinsic details underlies the enhanced recollective experience of negative events.

Why we remember emotional events with an increased subjective sense of remembering (SSR) is unclear. SSR for neutral events is linked to memory for various kinds of details. Using the Remember/Know paradigm, participants provided written justifications of their Remember responses indicating what they specifically recollected about a negative or neutral photo seen during encoding. Crucially, Remember responses for negative photos were more often linked to memory for details of the stimuli (intrinsic details) versus details related to external associations (extrinsic details) or emotional reaction at encoding, suggesting that memory for intrinsic details underlies the enhanced SSR of negative stimuli.

Stress and prospective memory: What is the role of cortisol?

Studies investigating effects of acute stress on Prospective Memory (PM) so far yielded heterogeneous findings. Although results were commonly attributed to stress-induced changes in cortisol, past research did not disentangle effects of cortisol from the effects of sympathetic nervous system (SNS) activation and cognitive reappraisal. The present study therefore aimed at investigating the mere effect of cortisol on PM tasks that differently involve prefrontal brain regions (nonfocal vs. focal PM tasks) via a placebo-controlled oral pharmacological intake of 10 mg hydrocortisone mimicking physiological responses to stress. Contrary to our prediction, enhanced levels of cortisol did not affect PM accuracy and monitoring costs, neither for the focal nor the nonfocal PM tasks. These results suggest that changes of cortisol levels do not underlie potential stress effects on PM. Further exploratory results revealed that PM performance was higher in the 3 pm than in the 1 pm placebo group. This means that PM performance, independently of effects of cortisol, seem to vary throughout the day.

Suppressing cortisol at encoding reduces the emotional enhancement in subjective sense of recollection.

The stress hormone cortisol, released when encountering an emotional event, contributes to form a strong emotional memory. Such emotionally arousing memories are recalled with an enhanced subjective sense of recollection, i.e. experienced in memory as more vivid and richer in details. We examined here whether cortisol plays a role in this emotional enhancement in subjective sense of recollection for a set of learned scenes. Suppressing cortisol at encoding decreased the emotional enhancement in subjective sense of recollection at a test 28 h later, but did not affect familiarity and memory for a contextual detail. Individual cortisol levels were significantly correlated to emotional enhancement in subjective sense of recollection. These findings indicate that cortisol plays a modulatory role for enhanced subjective sense of recollection for emotional events.

Cognitive Reserve and Social Capital Accrued in Early and Midlife Moderate the Relation of Psychological Stress to Cognitive Performance in Old Age.

AIMS: The present study set out to investigate the relation of psychological stress to cognitive performance and its interplay with key life course markers of cognitive reserve and social capital in a large sample of older adults. METHODS: We assessed cognitive performance (verbal abilities and processing speed) and psychological stress in 2,812 older adults. The Participants reported information on education, occupation, leisure activities, family, and close friends. RESULTS: Greater psychological stress was significantly related to lower performance in verbal abilities and processing speed. Moderation analyses suggested that the relations of psychological stress to cognitive performance were reduced in individuals with higher education, a higher cognitive level of the first profession practiced after education, a larger number of midlife leisure activities, a larger number of significant family members, and a larger number of close friends. CONCLUSION: Cognitive reserve and social capital accrued in early and midlife may reduce the detrimental influences of psychological stress on cognitive functioning in old age.

Beta-adrenergic Blockade at Memory Encoding, but Not Retrieval, Decreases the Subjective Sense of Recollection.

Humans remember emotional events not only better but also exhibit a qualitatively distinct recollective experience-that is, emotion intensifies the subjective vividness of the memory, the sense of reliving the event, and confidence in the accuracy of the memory [Phelps, E. A., & Sharot, T. How (and why) emotion enhances the subjective sense of recollection. Current Directions in Psychological Science, 17, 147-152, 2008]. Although it has been demonstrated that activation of the beta-adrenergic system, linked to increases in stress hormone levels and physiological arousal, mediates enhanced emotional memory accuracy, the mechanism underlying the increased subjective sense of recollection is unknown. Behavioral evidence suggests that increased arousal associated with emotional events, either at encoding or retrieval, underlies their increased subjective sense of recollection. Using a double-blind, placebo-controlled, within-subject design, we showed that reducing arousal at encoding through oral intake of 80-mg of the beta-adrenergic receptor antagonist propranolol decreases the subjective sense of recollection for both negative and neutral stimuli 24 hr later. In contrast, administration of propranolol before memory retrieval did not alter the subjective sense of recollection. These results suggest that the neurohormonal changes underlying increased arousal at the time of memory formation, rather than the time of memory retrieval, modulate the subjective sense of recollection.

Emotional memory can be persistently weakened by suppressing cortisol during retrieval.

Cortisol's effects on memory follow an inverted U-shaped function such that memory retrieval is impaired with very low concentrations, presumably due to insufficient activation of high-affine mineralocorticoid receptors (MR), or with very high concentrations, due to predominant low-affine glucocorticoid receptor (GR) activation. Through corresponding changes in re-encoding, the retrieval effect of cortisol might translate into a persistent change of the retrieved memory. We tested whether partial suppression of morning cortisol synthesis by metyrapone, leading to intermediate, circadian nadir-like levels with presumed predominant MR activation, improves retrieval, particularly of emotional memory, and persistently changes the memory. In a randomized, placebo-controlled, double-blind, within-subject cross-over design, 18 men were orally administered metyrapone (1g) vs. placebo at 4:00 AM to suppress the morning cortisol rise. Retrieval of emotional and neutral texts and pictures (learned 3 days earlier) was assessed 4h after substance administration and a second time one week later. Metyrapone suppressed endogenous cortisol release to circadian nadir-equivalent levels at the time of retrieval testing. Contrary to our expectations, metyrapone significantly impaired free recall of emotional texts (p<.05), whereas retrieval of neutral texts or pictures remained unaffected. One week later, participants still showed lower memory for emotional texts in the metyrapone than placebo condition (p<.05). Our finding that suppressing morning cortisol to nadir-like concentrations not only impairs acute retrieval, but also persistently weakens emotional memories corroborates the concept that retrieval effects of cortisol produce persistent memory changes, possibly by affecting re-encoding.

Adult age differences in the psychophysiological response to acute stress.

Age-related differences in the psychophysiology of the acute stress response are poorly understood given the limited number of studies and the high heterogeneity of findings. The present study contributes by investigating age differences in both the psychological and physiological responses to acute stress in a sample of healthy younger (N = 50; 18-30; Mage = 23.06; SD = 2.90) and older adults (N = 50; 65-84; Mage = 71.12; SD = 5.02). Specifically, the effects of psychosocial stress (i.e., age-adapted Trier Social Stress Test) were investigated at numerous timepoints throughout the stress response phases (i.e., baseline, anticipation, reactivity, recovery) on cortisol, heart rate, subjective stress, and anticipatory appraisal of the stressful situation. The study was conducted in a between-subject (younger vs. older) cross-over (stress vs. control) design. Results revealed age-related differences in both physiological and psychological variables: older adults had overall lower salivary cortisol levels in the stress and control conditions and lower stress-induced cortisol increase (i.e., AUCi). In addition, older adults' cortisol reactivity was delayed compared to younger adults. Older adults showed a lower heart rate response in the stress condition while no age differences were observed in the control condition. Finally, older adults reported less subjective stress and a less negative stress appraisal during the anticipation phase than younger adults, which could potentially explain lower physiological reactivity in this age group. Results are discussed in relation to the existing literature, potential underlying mechanisms, and future directions for the field.

Tackling childbirth-related intrusive memories with a single-session behavioural intervention involving a visuospatial task: protocol for a single-blind, waitlist-controlled randomised trial.

INTRODUCTION: Approximately 12.3% of mothers experience childbirth-related post-traumatic stress symptoms (CB-PTSS). However, evidence-based interventions to treat CB-PTSS are lacking. Intrusive memories (IM), a key CB-PTSS, are distressing and can trigger other PTSS by reliving the traumatic event. Emerging evidence shows that a behavioural intervention involving a visuospatial task (BI-VT) can reduce the number of IM and PTSS, supposedly by interfering with the reconsolidation of the trauma memory. This study aims to test the efficacy of a single-session BI-VT targeting IM to reduce the number of childbirth-related (CB-)IM and PTSS, in comparison to a waitlist control group (WCG). METHODS AND ANALYSIS: In this multicentre, single-blind, randomised controlled trial being undertaken at one regional and one university hospital in Switzerland, 60 participants will be allocated to the Immediate Intervention Group (IIG), receiving the immediate intervention on day 15, and 60 participants to the WCG receiving the delayed intervention on day 30. All participants will report their CB-IM during the 2 weeks preimmediate and postimmediate intervention in diaries. The IIG will additionally report their CB-IM over weeks 5 and 6 postimmediate intervention. Self-report questionnaires will assess CB-PTSS at 2 weeks preimmediate and postimmediate intervention in both groups, and at 6 weeks postimmediate intervention in the IIG. A feedback questionnaire will evaluate the intervention acceptability. The primary outcome will be group differences in the number of CB-IM between the 2 weeks preimmediate and postimmediate intervention. Secondary outcomes will be CB-PTSS at 2 and 6 weeks postimmediate intervention, the number of CB-IM at weeks 5 and 6 postimmediate intervention, and intervention acceptability. ETHICS AND DISSEMINATION: Ethical approval was granted by the Human Research Ethics Committee of the Canton of Vaud (study number 202200652). Participants will provide an informed consent before study participation. Results will be presented in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: NCT05381155.

In Older Adults, Perceived Stress and Self-Efficacy Are Associated with Verbal Fluency, Reasoning, and Prospective Memory (Moderated by Socioeconomic Position).

Despite evidence that stress relates negatively to cognitive functioning in older adults, little is known how appraisal of stress and socioeconomic meso-level factors influence different types of cognitive functions in older adults. Here, we assess the relationship between perceived stress (PSS scale) and a battery of cognitive functions, including prospective memory in 1054 older adults (65+). A moderator analysis assessed whether this relationship varies with neighborhood socioeconomic status using an area-based measure of Socioeconomic Position (SEP). Perceived stress was associated with worse processing speed, verbal fluency, and inductive reasoning. The perceived self-efficacy subscale of the PSS is related to better performance in these measures. Higher self-efficacy was also associated with better prospective memory; this relationship was more pronounced for people with high neighborhood SEP. These findings indicate that not only do perceived stress and perceived self-efficacy relate to cognitive functioning in older age but also that neighborhood SEP is a moderator of this relationship.

Does older adults' cognition particularly suffer from stress? A systematic review of acute stress effects on cognition in older age.

This literature review provides the first comprehensive qualitative and quantitative systematic synthesis of acute laboratory stress effects on older adults' cognition by specifying the direction and magnitude of those effects both overall and for different cognitive processes separately. A systematic literature search was performed, and effect sizes estimated whenever possible. We found meta-analytical evidence that stress has negative effects on older adults' verbal fluency (gadj = -0.53, 95 % CI [-2.70, 1.63]), null-to-negative effects on episodic memory (gadj = -0.26, 95 % CI [-0.44, -0.08]), null effects on executive functions (gadj = 0.07, 95 % CI [-0.31, 0.46]), and enhancing effects on working memory (gadj = 0.16, 95 % CI [-0.01, 0.33]). Relating these findings to those in young adults, notable differences emerged for some cognitive functions, such as opposing effects on working memory between age groups. Our review further reveals that stress effects on older adults' memory retention, associative memory, prospective memory, interference control or cognitive flexibility are heavily understudied. We provide a conceptual and methodological framework for future studies in older adults.

Pharmacologically increased cortisol levels impair recall of associative background context memory in males, but not females.

Laboratory studies have consistently shown that stress impairs memory retrieval of individual parts (items) of a memory. The stress-hormone cortisol has been particularly linked to this impairment. However, it is unclear whether cortisol similarly affects the binding of items to associative context information in memory, i.e. the constituents of episodic memory. Here, we examine memory retrieval of item and associative memory under pharmacologically elevated cortisol vs. normal levels. Given that previous studies have indicated potential sex differences in the stress- and cortisol-induced memory modulation, we additionally assessed whether there may be sex differences for the cortisol effect on memory retrieval. Eighty-four female and male participants were tested in a placebo controlled, double-blind between-subject design, assigned to either a cortisol (10 mg hydrocortisone) or a placebo group. Participants of both groups were presented foreground images of negative and neutral valence on different neutral background scenes. Twenty-four hours later, participants' memory for the images and their associated background scene was tested with a recognition task 20 min after substance administration. Among the 78 participants of both groups included in the final analysis, cortisol levels were higher in the cortisol group in comparison to the placebo group, and female participants had higher cortisol levels after hydrocortisone intake in comparison to male participants. Item memory did not differ between the placebo and cortisol group. In contrast, in males, but not females, associative memory for the background scene of emotional foreground images was lower in the cortisol vs. placebo group. Moreover, the individual cortisol increase during the recognition task was negatively correlated to memory for the background scenes of the emotional foreground images only in male participants of the cortisol group. This study shows that pharmacologically increased cortisol levels distinctly affect associative memory in female and male participants, but have no effect on item memory, indicating a complex interaction for the stress effects on memory.

Quarreling After a Sleepless Night: Preliminary Evidence of the Impact of Sleep Deprivation on Interpersonal Conflict.

Although poor sleep has been found to correlate with deteriorations in romantic relationships, its causal impact on interpersonal conflict has not previously been studied. Therefore, 30 couples were randomly assigned to either a single night of total sleep deprivation or a night of normal sleep to test the effects of sleep deprivation on couples' conflict. After the experimental night, all participants discussed a topic of recurrent conflict for 15 min. We collected pre- and post-conflict measures of cortisol, self-reports of feelings, and satisfaction with the conflictual discussion. Multilevel analyses revealed higher cortisol levels during conflict and less positive affect prior to and after the conflict for sleep-deprived couples compared to couples in the control condition. These findings provide initial evidence for a causal negative impact of sleep deprivation on couples' conflicts. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00076-4.

Suppressing the morning rise in cortisol impairs free recall.

Elevated glucocorticoid levels impair memory retrieval. We investigated whether retrieval under naturally elevated glucocorticoid levels, i.e., during the morning rise in cortisol can be improved by suppressing cortisol. In a crossover study 16 men retrieved emotional and neutral texts and pictures (learned 3 d earlier) 30 min after morning awakening, following administration of the cortisol synthesis inhibitor metyrapone or placebo. Unexpectedly, the metyrapone-induced cortisol suppression significantly impaired free recall of both materials. Recognition remained unaffected. Thus, not only high, but also very low glucocorticoid levels impair retrieval, with the latter effect possibly reflecting insufficient occupation of hippocampal/amygdalar mineralocorticoid receptors (MRs).

Oxytocin makes a face in memory familiar.

Social recognition is the basis of all social interactions. Here, we show that, in humans, the evolutionarily highly conserved neuropeptide oxytocin, after intranasal administration, specifically improves recognition memory for faces, but not for nonsocial stimuli. With increased oxytocin levels, previously presented faces were more correctly assessed as "known," whereas the ability of recollecting faces was unchanged. This pattern speaks for an immediate and selective effect of the peptide strengthening neuronal systems of social memory.

The level of physical activity affects adrenal and cardiovascular reactivity to psychosocial stress.

Physical activity plays a key role in the control of neuroendocrine, autonomic, and behavioral responses to physical and psychosocial stress. However, little is known about how the level of physical activity modulates stress responsiveness. Here, we test whether different levels of physical activity are associated with different adrenal, cardiovascular, and psychological responses to psychosocial stress. In addition, competitiveness is assessed as a personality trait that possibly modulates the relationship between physical activity and stress reactivity. Eighteen elite sportsmen, 50 amateur sportsmen, and 24 untrained men were exposed to a standardized psychosocial laboratory stressor (Trier Social Stress Test). Repeated measures of salivary free cortisol, heart rate, and psychological responses to psychosocial stress were compared among the 3 study groups. Elite sportsmen exhibited significantly lower cortisol, heart rate, and state anxiety responses compared with untrained subjects. Amateur sportsmen showed a dissociation between sympathetic and hypothalamic-pituitary-adrenal responsiveness to stress, with significantly reduced heart rate responses but no difference in cortisol responses compared with untrained men. Different levels of competitiveness among groups did not mediate stress reactivity. Our results are in line with previous studies indicating reduced reactivity of the autonomic nervous system to psychosocial stress in trained individuals. More importantly, these findings imply a differential effect of the level of physical activity on different stress-related neurophysiological systems in response to psychosocial stress.