Pre-learning Stress Research Articles

Pre-Learning Stress That Is Temporally Removed from Acquisition Impairs Fear Learning.

Few studies have examined the time-dependent effects of stress on fear learning. Previously, we found that stress immediately before fear conditioning enhanced fear learning. Here, we aimed to extend these findings by assessing the effects of stress 30 min prior to fear conditioning on fear learning and fear generalization. Two hundred and twenty-one healthy adults underwent stress (socially evaluated cold pressor test) or a control manipulation 30 min before completing differential fear conditioning in a fear-potentiated startle paradigm. One visual stimulus (CS+), but not another (CS-), was associated with an aversive airblast to the throat (US) during acquisition. The next day, participants were tested for their fear responses to the CS+, CS-, and several generalization stimuli. Stress impaired the acquisition of fear on Day 1 but had no significant impact on fear generalization. The stress-induced impairment of fear learning was particularly evident in participants who exhibited a robust cortisol response to the stressor. These findings are consistent with the notion that stress administered 30 min before learning impairs memory formation via corticosteroid-related mechanisms and may help us understand how fear memories are altered in stress-related psychological disorders.

Acute pre-learning stress selectively impairs hippocampus-dependent fear memory consolidation: Behavioral and molecular evidence

Despite compelling evidence that stress or stress-related hormones influence fear memory consolidation processes, the understanding of molecular mechanisms underlying the effects of stress is still fragmentary. The release of corticosterone in response to pre-learning stress exposure has been demonstrated to modulate positively or negatively memory encoding and/or consolidation according to many variables such as stress intensity, the emotional valence of the learned material or the interval between stressful episode and learning experience. Here, we report that contextual but not cued fear memory consolidation was selectively impaired in male mice exposed to a 50 min-period of restraint stress just before the unpaired fear conditioning session. In addition to behavioral impairment, acute stress down-regulated activated/phosphorylated ERK1/2 (pERK1/2) in dorsal hippocampal area CA1 in mice sacrificed 60 min and 9 h after unpaired conditioning. In lateral amygdala, although acute stress by itself increased the level of pERK1/2 it nevertheless blocked the peak of pERK1/2 that was normally observed 15 min after unpaired conditioning. To examine whether stress-induced corticosterone overflow was responsible of these detrimental effects, the corticosterone synthesis inhibitor, metyrapone, was administered 30 min before stress exposure. Metyrapone abrogated the stress-induced contextual fear memory deficits but did not alleviate the effects of stress on pERK1/2 and its downstream target phosphorylated CREB (pCREB) in hippocampus CA1 and lateral amygdala. Collectively, our observations suggest that consolidation of hippocampus-dependent memory and the associated signaling pathway are particularly sensitive to stress. However, behavioral normalization by preventive metyrapone treatment was not accompanied by renormalization of the canonical signaling pathway. A new avenue would be to consider surrogate mechanisms involving proper metyrapone influence on both nongenomic and genomic actions of glucocorticoid receptors.

Frontal lobe and long-term memory retrieval analysis during pre-learning stress using EEG signals

This paper uses the EEG analysis to investigate the relationship between pre-learning stress, frontal lope and long-term memory in the brain. The stress on learning stage is a challenge, especially in academic life. Stress also on learning stage affects the retrieval or recall from the memory. Nowadays; there are many recent works have discovered the relationship between stress, learning and memory performance based on different techniques. Some of these techniques are biological methods. Moreover, these methods have discovered the effect of stress based on hormones levels such as cortisol, or based on physiological effects such as blood pressure. However, these techniques have given conflicting discoveries because of the instability of hormones and an extensive number of related elements. The main aim of this research is to discover the relationship between Pre-learning stress, frontal lope, and long-term memory retrieval using EEG signals. The experimental results indicate that there is a relationship between theta rhythm in the frontal lobe and long-term memory retrieval during Pre-learning stress.

Immediate pre-learning stress enhances baseline startle response and fear acquisition in a fear-potentiated startle paradigm

Extensive work has shown that stress time-dependently influences hippocampus-dependent learning and memory. In particular, stress that is administered immediately before learning enhances long-term memory, while stress that is temporally separated from learning impairs long-term memory. We have extended these findings by examining the impact of immediate, pre-learning stress on an amygdala-dependent fear conditioning task. One hundred and forty-one healthy participants underwent a stress (socially evaluated cold pressor test) or control manipulation immediately before completing differential fear conditioning in a fear-potentiated startle paradigm. Participants then completed extinction and extinction memory testing sessions 24 and 48 h later, respectively. Stress administered immediately before acquisition increased baseline startle responses and enhanced fear learning, as evidenced by greater fear-potentiated startle to the CS + . Although no group differences were observed during extinction training on Day 2, stressed participants exhibited evidence of impaired extinction processes on Day 3, an effect that was driven by group differences in acquisition. Importantly, stressed participants’ cortisol responses to the stressor on Day 1 were positively associated with CS discrimination on Days 2 and 3. These findings suggest that stress immediately before fear conditioning strengthens fear memory formation and produces a more enduring fear memory, perhaps via corticosteroid activity. Such a paradigm could be useful for understanding factors that influence traumatic memory formation.

Effects of acute psychosocial stress on the neural correlates of episodic encoding: Item versus associative memory.

Acute stress is known to modulate episodic memory, but little is known about the extent to, and the circumstances under, which stress affects encoding of item vs. inter-item associative information for words of different valences. Furthermore, the precise neuro-cognitive mechanisms underlying stress effects on episodic encoding in humans are largely unknown. To address these questions, in the present study we recorded EEG activity while male participants encoded neutral, negative and positive words, each paired with another word that was always neutral. Immediately before encoding, half of the participants experienced a psychosocial stressor, the Trier Social Stress Test, while the other half underwent a control procedure. Twenty-four hours later, participants completed separate item and associative recognition tests. Pre-learning stress enhanced item recognition accuracy for the positive, but not for the negative words. By contrast, there was no evidence for stress effects on associative recognition. The increase in item recognition was accompanied by a higher familiarity-, but not recollection-, based item retrieval of positive and neutral, but not negative words. Crucially, in the event-related potential (ERP) stress affected the amplitude of the frontal slow wave in general, and the frontal slow wave subsequent memory effect for positive words in specific, and the subsequent memory effect was correlated with cortisol levels after the stress manipulation. Our results suggest that positive words are encoded more elaboratively under stress, leading to a higher likelihood of subsequent item retrieval. An interaction of cortisol with frontal-lobe dependent control processes as well as a shift in attentional biases may contribute to this stress-induced modulation of episodic encoding.

Women with high estradiol status are protected against declarative memory impairment by pre-learning stress.

Stress is a potent modulator of learning and memory. Factors contributing to whether stress aids or impairs memory are timing of the stressor, memory stage, form of memory studied, and sex of the subjects. The female sex hormone 17-beta-estradiol (E2) has widespread effects in the brain and affects hippocampus-dependent memory in animals. In humans, the interaction between stress effects and E2 has not been widely studied. We report data from a healthy sample divided into 3 hormone-status groups: free-cycling women in the early follicular phase (EF: low E2, low progesterone [P4]), or during midcycle (MC: high E2, low P4), and men. Participants within each hormone-status group were randomly assigned to a psychosocial stressor or a control treatment 37 min before encoding a short story of neutral content. We found a Hormone status × Stress × Time (immediate, 35-min, 24-h delayed recall) interaction. Irrespective of time, hormone status mattered only after stress treatment: stressed early follicular women had poorer recall compared to stressed men and midcycle women. Only in the early follicular group, recall was negatively correlated with increases in salivary cortisol, but not with blood levels of E2 and P4. To uncover changes beyond immediate recall, we computed the individual percent change relative to immediate recall and repeated the analysis for these adjusted 35-min and 24-h data. Despite the lack of a stress effect in raw data, memory in stressed men was more stable over time (35-min and 24-h delay) than in unstressed men. In contrast, stressed EF-women (vs. control) recalled less at the 35-min and (as a trend) at the 24-h delay. Stressed MC-women (vs. control) showed less recall only at the 35-min delay while compensating this stress effect after a 24-h consolidation interval. Overall, results suggest that women in high-E2 midcycle phase could be less vulnerable to effects of pre-learning stress on declarative memory encoding and consolidation.

Interactive influence of sex, stressor timing, and the BclI glucocorticoid receptor polymorphism on stress-induced alterations of long-term memory

Certain susceptibility factors, such as genetic variants or specific physiological responses to stress, can dictate the effects of stress on learning and memory. Here, we examined the influence of the BclI polymorphism of the glucocorticoid receptor gene on the time-dependent effects of pre-learning stress on long-term memory. Healthy individuals were exposed to the socially evaluated cold pressor test or a control condition immediately or 30 min before word list learning. Participants’ memory for the words was tested immediately and 24 h after learning, and saliva samples were collected to genotype participants for the BclI polymorphism and to assess cortisol responses to the stressor. Results revealed that stress immediately before learning enhanced memory, while stress 30 min before learning impaired memory; these effects were largely selective to males and non-arousing words. Additionally, stress, independent of when it was administered, enhanced memory in non-carriers of the BclI polymorphism, while impairing memory in carriers; these effects were largely selective to males and participants exhibiting a robust cortisol response to stress. These results provide further evidence for time-dependent effects of stress on long-term memory and suggest that carriers of the BclI polymorphism might be more sensitive to the negative effects of corticosteroids on learning.

Preextinction Stress Prevents Context-Related Renewal of Fear

Extinction learning, which creates new safety associations, is thought to be the mechanism underlying exposure therapy, commonly used for the treatment of anxiety disorders and posttraumatic stress disorder. The relative strength and availability for retrieval of both the fear and safety memories determine the response in a given situation. While the fear memory is often context-independent and may easily generalize, extinction memory is highly context-specific. “Renewal” of the extinguished fear memory might thus occur following a shift in context. The aim of the current work was to create an enhanced and generalized extinction memory to a discrete stimulus using stress exposure before extinction learning, thereby preventing renewal. In our contextual fear conditioning paradigm, 40 healthy men acquired (Day 1), retrieved and extinguished (Day 2) the fear memories, with no differences between the stress and the control group. A significant difference between the groups emerged in the renewal test (Day 3). A renewal effect was seen in the control group (N = 20), confirming the context-dependency of the extinction memory. In contrast, the stress group (N = 20) showed no renewal effect. Fear reduction was generalized to the acquisition context as well, suggesting that stress rendered the extinction memory more context-independent. These results are in line with previous studies that showed contextualization disruption as a result of pre-learning stress, mediated by the rapid effects of glucocorticoids on the hippocampus. Our findings support research investigating the use of glucocorticoids or stress induction in exposure therapy and suggest the right timing of administration in order to optimize their effects.

Blunted cortisol response to acute pre-learning stress prevents misinformation effect in a forced confabulation paradigm

Research examining the effects of stress on false memory formation has been equivocal, partly because of the complex nature of stress-memory interactions. A major factor influencing stress effects on learning is the timing of stress relative to encoding. Previous work has shown that brief stressors administered immediately before learning enhance long-term memory. Thus, we predicted that brief stress immediately before learning would decrease participants' susceptibility to subsequent misinformation and reduce false memory formation. Eighty-four male and female participants submerged their hand in ice cold (stress) or warm (no stress) water for 3min. Immediately afterwards, they viewed an 8-min excerpt from the Disney movie Looking for Miracles. The next day, participants were interviewed and asked several questions about the video, some of which forced them to confabulate responses. Three days and three weeks later, respectively, participants completed a recognition test in the lab and a free recall test via email. Our results revealed a robust misinformation effect, overall, as participants falsely recognized a significant amount of information that they had confabulated during the interview as having occurred in the original video. Stress, overall, did not significantly influence this misinformation effect. However, the misinformation effect was completely absent in stressed participants who exhibited a blunted cortisol response to the stress, for both recognition and recall tests. The complete absence of a misinformation effect in non-responders may lend insight into the interactive roles of autonomic arousal and corticosteroid levels in false memory development.

ADRA2B deletion variant influences time-dependent effects of pre-learning stress on long-term memory

Extensive work over the past few decades has shown that certain genetic variations interact with life events to confer increased susceptibility for the development of psychological disorders. The deletion variant of the ADRA2B gene, which has been associated with enhanced emotional memory and heightened amygdala responses to emotional stimuli, might confer increased susceptibility for the development of post-traumatic stress disorder (PTSD) or related phenotypes by increasing the likelihood of traumatic memory formation. Thus, we examined whether this genetic variant would predict stress effects on learning and memory in a non-clinical sample. Two hundred and thirty-five individuals were exposed to the socially evaluated cold pressor test or a control condition immediately or 30min prior to learning a list of words that varied in emotional valence and arousal level. Participants’ memory for the words was tested immediately (recall) and 24h after learning (recall and recognition), and saliva samples were collected to genotype participants for the ADRA2B deletion variant. Results showed that stress administered immediately before learning selectively enhanced long-term recall in deletion carriers. Stress administered 30min before learning impaired recognition memory in male deletion carriers, while enhancing recognition memory in female deletion carriers. These findings provide additional evidence to support the idea that ADRA2B deletion variant carriers retain a sensitized stress response system, which results in amplified effects of stress on learning and memory. The accumulating evidence regarding this genetic variant implicates it as a susceptibility factor for traumatic memory formation and PTSD-related phenotypes.

The Influence of Stress on Human Memory: Differences among Subjected Timing of Acute Stress

<p>In this study, we compared the differences in influence of three stress subjection timings on memory using words stimuli with three valences, positive, negative, and neutral. Sixty-three participants were divided into four conditions, pre-learning stress, on-learning stress, post-learning stress, and control condition. Participants in stress conditions were exposed to acute white noise stress. The results showed differences in the delayed recall memory performances among the three stress timing conditions, and definite valence influences. Compared to the non-stressed condition, impaired neutral delayed recall was observed in the post-learning stress condition. Pre- and on-learning stress showed lower positive memory compared to the other valences within their condition. Since memory performance was not significantly different from the control condition in either the pre-learning or on-learning stress timing conditions, learning after/or under stress did not seem to impair memory performance. Among the three stress timing conditions, post-learning stress seems to most affect human memory.</p>

Brief, pre-learning stress reduces false memory production and enhances true memory selectively in females

Some of the previous research on stress–memory interactions has suggested that stress increases the production of false memories. However, as accumulating work has shown that the effects of stress on learning and memory depend critically on the timing of the stressor, we hypothesized that brief stress administered immediately before learning would reduce, rather than increase, false memory production. In the present study, participants submerged their dominant hand in a bath of ice cold water (stress) or sat quietly (no stress) for 3min. Then, participants completed a short-term memory task, the Deese–Roediger–McDermott paradigm, in which they were presented with 10 different lists of semantically related words (e.g., candy, sour, sugar) and, after each list, were tested for their memory of presented words (e.g., candy), non-presented unrelated “distractor” words (e.g., hat), and non-presented semantically related “critical lure” words (e.g., sweet). Stress, overall, significantly reduced the number of critical lures recalled (i.e., false memory) by participants. In addition, stress enhanced memory for the presented words (i.e., true memory) in female, but not male, participants. These findings reveal that stress does not unequivocally enhance false memory production and that the timing of the stressor is an important variable that could mediate such effects. Such results could have important implications for understanding the dependability of eyewitness accounts of events that are observed following stress.

Acute pre-learning stress and declarative memory: impact of sex, cortisol response and menstrual cycle phase

This study explores the influence of pre-learning stress on performance on declarative memory tasks in healthy young adults in relation to sex and menstrual cycle phase. The sample was composed of 119 students (32 men and 87 women) from 18 to 25years of age. The women were tested in different hormonal stages (30 in follicular phase, 34 in luteal phase, and 23 using oral contraceptives). The participants were exposed to the Trier Social Stress Test (TSST) or a control condition. Afterwards, their memory performance was measured using a standardized memory test (Rey's Auditory Verbal Learning Test). In the control condition, all groups of women recalled more words than men, but these differences disappeared in the group exposed to TSST because men's performance on the memory test improved, but only to the level of women. In addition, our data suggest that in women the relationship between cortisol and memory can be modulated by sex hormone levels, since in luteal women a negative relationship was found between memory performance and peak cortisol level. These results confirm that sex differences need to be considered in the relationship between pre-learning stress and memory performance.

Pre-learning stress that is temporally removed from acquisition exerts sex-specific effects on long-term memory

We have examined the influence of sex and the perceived emotional nature of learned information on pre-learning stress-induced alterations of long-term memory. Participants submerged their dominant hand in ice cold (stress) or warm (no stress) water for 3min. Thirty minutes later, they studied 30 words, rated the words for their levels of emotional valence and arousal and were then given an immediate free recall test. Twenty-four hours later, participants’ memory for the word list was assessed via delayed free recall and recognition assessments. The resulting memory data were analyzed after categorizing the studied words (i.e., distributing them to “positive-arousing”, “positive-non-arousing”, “negative-arousing”, etc. categories) according to participants’ valence and arousal ratings of the words. The results revealed that participants exhibiting a robust cortisol response to stress exhibited significantly impaired recognition memory for neutral words. More interestingly, however, males displaying a robust cortisol response to stress demonstrated significantly impaired recall, overall, and a marginally significant impairment of overall recognition memory, while females exhibiting a blunted cortisol response to stress demonstrated a marginally significant impairment of overall recognition memory. These findings support the notion that a brief stressor that is temporally separated from learning can exert deleterious effects on long-term memory. However, they also suggest that such effects depend on the sex of the organism, the emotional salience of the learned information and the degree to which stress increases corticosteroid levels.

Pre-learning stress differentially affects long-term memory for emotional words, depending on temporal proximity to the learning experience

Stress exerts a profound, yet complex, influence on learning and memory and can enhance, impair or have no effect on these processes. Here, we have examined how the administration of stress at different times before learning affects long-term (24-hr) memory for neutral and emotional information. Participants submerged their dominant hand into a bath of ice cold water (Stress) or into a bath of warm water (No stress) for 3min. Either immediately (Exp. 1) or 30min (Exp. 2) after the water bath manipulation, participants were presented with a list of 30 words varying in emotional valence. The next day, participants' memory for the word list was assessed via free recall and recognition tests. In both experiments, stressed participants exhibited greater blood pressure, salivary cortisol levels, and subjective pain and stress ratings than non-stressed participants in response to the water bath manipulation. Stress applied immediately prior to learning (Exp. 1) enhanced the recognition of positive words, while stress applied 30min prior to learning (Exp. 2) impaired free recall of negative words. Participants' recognition of positive words in Experiment 1 was positively associated with their heart rate responses to the water bath manipulation, while participants' free recall of negative words in Experiment 2 was negatively associated with their blood pressure and cortisol responses to the water bath manipulation. These findings indicate that the differential effects of pre-learning stress on long-term memory may depend on the temporal proximity of the stressor to the learning experience and the emotional nature of the to-be-learned information.

Effects of pre-learning stress on memory for neutral, positive and negative words: Different roles of cortisol and autonomic arousal

Stress can have enhancing or impairing effects on memory. Here, we addressed the effect of pre-learning stress on subsequent memory and asked whether neutral and emotionally valent information are differentially affected by specific stress components, autonomic arousal and stress-induced cortisol. Ninety-six healthy men and women underwent either a stressor (modified cold pressor test) or a control warm water exposure. During stress, participants showed comparable autonomic arousal (heart rate, blood pressure), while 60 percent showed an increase of cortisol (responders vs. 40 percent non-responders). Ten minutes after the cold pressor test neutral, positive and negative words were presented. Free recall was tested 1 and 24h later. Overall, positive and negative words were better recalled than neutral words. Stress enhanced the recall of neutral words independently of cortisol response. In contrast, the free recall of negative words was enhanced in cortisol responders in the 1-h but not 24-h test which might suggest different effects of cortisol on consolidation and reconsolidation processes. Recall for positive words was unaffected by stress-induced cortisol. To summarize, (i) pre-learning stress can enhance memory for neutral words independently of cortisol and (ii) stress effects on memory for negative words appear to rely on stress-induced cortisol elevations, the absence of this effect for positive words might be at least partly due to differences in arousal evoked by positive vs. negative words.