Implications of psychosocial stress on memory formation in a typical male versus female student sample.

Stress is known to differentially modulate memory function. Memory can be impaired or strengthened by stress, depending on e.g. the memory type and phase under study, the emotional value of the learned information and the sex of the subjects. Here, we addressed the latter and investigated the impact of psychosocial stress on long-term memory for neutral and emotional pictures and working memory in typical samples of male versus female students. In total, 77 subjects (54 women of which 39 used oral contraceptives) were exposed to either the Trier Social Stress Test (TSST) or a control condition, and then engaged in a long-term memory task (emotionally arousing and neutral pictures; surprise recall after one week) and a working memory (n-back) task. During the experiment salivary cortisol and alpha-amylase levels as well as subjective affect state were assessed. As expected, stress hormone concentrations as well as subjective negative affect states increased significantly in response to the stress task. Men reacted more to the stressor in terms of cortisol responses than women, probably due to oral contraceptive use of the latter. Results show that, in male as well as in female students, memory for emotional arousing information was better than for neutral information, in both the stress and control condition. Stress enhanced recognition memory for emotional versus neutral pictures only in male subjects. Moreover, stress enhanced working memory, particularly in males, during the first block of a 2-back task. The lack of stress effects on memory in women might be explained by oral contraceptive use, leading to blunted HPA-axis responses and secondary to reduced stress effects on memory. The results emphasize that stress affects both long-term and working memory differentially in male versus female students.

Emotional stimuli modulate readiness for action: a transcranial magnetic stimulation study.

Emotional stimuli may prime the motor system and facilitate action readiness. Direct evidence for this effect has been shown by recent studies using transcranial magnetic stimulation (TMS). When administered over the primary motor cortex involved in responding, TMS pulses elicit motor-evoked potentials (MEPs) in the represented muscles. The amplitudes of these MEPs reflect the state of corticospinal excitability. Here, we investigated the dynamic effects of induced emotions on action readiness, as reflected by corticospinal excitability. Subjects performed a choice task while viewing task-irrelevant emotional and neutral pictures. The pattern of MEP amplitudes showed a typical increase as the TMS pulse was presented closer in time to the imminent response. This dynamic pattern was amplified by both pleasant and unpleasant emotional stimuli, but more so when unpleasant pictures were viewed. These patterns present novel evidence in support of the notion that emotional stimuli modulate action readiness.

Interacting noradrenergic and corticosteroid systems shift human brain activation patterns during encoding.

Emotionally arousing experiences are usually well retained, an effect that depends on the release of adrenal stress hormones. Animal studies have shown that corticosterone and noradrenaline - representing the two main stress hormone systems - act in concert to enhance memory formation by actions involving the amygdala, hippocampus and prefrontal cortex (PFC). Here we test whether interactions between these two stress hormone systems also affect human memory formation as well as the associated pattern of brain activation. To this end, forty-eight male human subjects received hydrocortisone, yohimbine or both before presentation of emotional and neutral pictures. Activity in the amygdala, hippocampus and PFC was monitored with functional Magnetic Resonance Imaging (fMRI) during encoding of these stimuli, when hormonal levels were elevated. Memory performance was tested 1 week later. We investigated whether an increased level of one of the two hormone systems would lead to differential effects compared to the combined application of the drugs on brain activation and memory performance. We report that the application of cortisol led to an overall enhancing effect on recognition memory, with no significant additional effect of yohimbine. However, during encoding the brain switched from amygdala/hippocampus activation with either hormone alone, to a strong deactivation of prefrontal areas under the influence of the combination of both exogenous hormones. Although we did not find evidence that exogenous stimulation of the noradrenergic and corticosteroid systems led to significant interaction effects on memory performance in this experiment, we conclude that stress hormone levels during encoding did differentially determine the activation pattern of the brain circuits here involved.

Imaging stress effects on memory: a review of neuroimaging studies.

OBJECTIVE: To review and give an overview of neuroimaging studies that look at the role of stress (hormones) on memory. METHOD: An overview will be given of imaging studies that looked at the role of stress (hormones) on memory. Stress is here defined as the acute provocation of the sympathetic adrenal medullar system and the hypothalamic-pituitary-adrenal axis in experimental designs. Stress hormone levels can be raised endogenously in response to stimulus material (for example, pictures and films) or social evaluative threat situations (stress tasks). Other studies use the exogenous application of drugs to enhance or decrease stress hormone levels. Finally, we review studies on chronic stress and memory. RESULTS: Stress or emotional arousal, leading to increased noradrenaline or cortisol levels, led to better memory performance when it is applied during perception or encoding. Brain regions involved in this process were medial temporal lobe regions such as amygdala and hippocampus, and several parts of the prefrontal cortex (PFC). High stress levels accompanied by high cortisol levels during retrieval led to impaired memory performance. Sex effects on memory as well as lateralization effects on brain activation were found. CONCLUSION: High stress levels during encoding and consolidation of emotional material involve increased amygdala and hippocampus activation. The role of the anterior cingulate cortex and other parts of the PFC during perception and encoding of arousing material appears to be a modulating one. However, additional research is needed to shed more light on the nature of the brain changes during stress, especially during retrieval.

Salivary alpha amylase and cortisol responses to different stress tasks: impact of sex.

Neuro-endocrine markers such as salivary alpha amylase (sAA) and cortisol (CORT) play an important role in establishing human responses to stressful events. Whereas sAA levels reflect sympathetic system activity, salivary cortisol appears to be a valid measure for HPA axis activity. Although many studies looked at either sAA or CORT responses in reaction to stress, work still has to be done to look at the way these systems interact, especially when both systems are activated. Additionally, sex effects in CORT responses have been investigated relatively often, but possible sex differences in sAA levels and responses, or the way both systems interact has not been the focus of sufficient studies to yield a univocal conclusion. In this study we presented a group of healthy participants (n=80) with two mildly stressful tasks, consisting of an aversive picture rating task and a cold pressor stress (CPS) task. The second task was compared with a control task. We expected a rise in sAA level in response to the first task and sAA as well as CORT responses on the second task and explored the interaction between the two responses. Results indicate that sAA is indeed a sensitive marker in both psychologically and physically induced arousal paradigms, whereas a cortisol response was only observed in the CPS task. Men had higher sAA levels than women during the complete course of the study, but men and women were comparable in their responsivity to the tasks. No strong correlations between sAA and CORT responses were found.

The role of the noradrenergic system in emotional memory.

This contribution is an overview on the role of noradrenaline as neurotransmitter and stress hormone in emotional memory processing. The role of stress hormones in memory formation of healthy subjects can bear significance for the derailment of memory processes, for example, in post traumatic stress disorder (PTSD). Increased noradrenaline levels lead to better memory performance, whereas blocking the noradrenergic receptors with a betablocker attenuates this enhanced memory for emotional information. Noradrenaline appears to interact with cortisol in emotional memory processes, varying from encoding to consolidation and retrieval. Imaging studies show that confronting human subjects with emotional stimuli results in increased amygdala activation and that this activation is noradrenergic dependent. The role of noradrenaline in other brain areas, such as hippocampus and prefrontal cortex, is shortly summarized. Finally, the pros and cons of a therapeutic application of betablockers in the (secondary) prevention of PTSD will be discussed.

Interaction of endogenous cortisol and noradrenaline in the human amygdala.

Animal studies show that glucocorticoid effects on memory depend on noradrenergic activation within an intact amygdala. Testing this model in humans is the subject of the present fMRI study. Healthy subjects watched emotional and neutral stimuli after having received a betablocker or placebo. Cortisol levels of all subjects were determined and served as a marker of the subject's (endogenous) cortisol level during the experiment. Viewing emotional pictures resulted in increased amygdala activation compared to neutral pictures and this effect was enhanced in subjects with a high versus low cortisol level under placebo condition. Betablockade with propranolol, lowering the noradrenergic level in the amygdala, disrupted this effect and apparently the interaction with cortisol. These data support the hypothesis that high endogenous cortisol levels at the time of encoding interact with noradrenergic activation in the amygdala in man.

Endogenous cortisol level interacts with noradrenergic activation in the human amygdala.

Animal studies show that high cortisol levels exert their effect on stressful task performance via modulation of the amygdala. Availability of noradrenaline in this brain region appears to be a critical prerequisite for this effect. This relationship between noradrenaline and cortisol is explained by an animal model where the amygdala constitutes a crucial region for this interaction. In humans this model has not been extensively tested so far. In a previously reported study human subjects (aged 20.93+/-2.38) were scanned using fMRI when watching sets of emotional and neutral pictures after taking the beta-adrenergic antagonist propranolol or placebo. Stimulus sets consisted of 92 pictures, divided in four emotional categories that ranged from neutral scenes of domestic objects (CAT1) to extremely negative scenes of mutilation or accidents (CAT4). Confrontation with arousing emotional pictures, accompanied by increased noradrenaline levels, evoked increased amygdala activation under placebo but not under betablocker condition. This new and additional analysis of this data set was carried out to determine the effect of differential endogenous cortisol levels on amygdala activation. Cortisol levels during scanning were determined using salivary samples and subjects were post hoc divided in a High (n=14) and Low cortisol group (n=14). When subjects were watching emotional stimuli, presumably associated with enhanced noradrenaline (NA) levels, amygdala activation was contrasted between the two cortisol groups. We hypothesized that emotional stimuli would elicit more amygdala activation in the High than in the Low cortisol group. Here we demonstrate indeed a significant interaction effect of the endogenous cortisol level with increasing activation in the amygdala under placebo but not under betablocker condition, thereby extending the rodent based model of a synergistic effect of the two stress hormones to the human.

Noradrenaline mediates amygdala activation in men and women during encoding of emotional material.

The amygdala is a pivotal structure in humans for encoding of emotional information, as shown by recent imaging studies. It is unknown which neurotransmitters are specifically involved in the human amygdala, although in animal studies noradrenaline was shown to be essential. In our study, participants received the betablocker propranolol (which blocks the noradrenergic response) or placebo when watching neutral to highly negative arousing pictures. Amygdala activation, monitored with functional magnetic resonance imaging (fMRI), increased with emotional intensity of the pictures under placebo condition. Betablockade selectively decreased amygdala activation for emotional pictures of the second highest category, but not for the highest or lower (neutral) category pictures. Two findings add to the existing knowledge in this area. First, the activation pattern in the amygdala under placebo condition shows a nonlinearity related to the emotional categories of the pictures. Second, propranolol disturbs this activation pattern in the amygdala. Explorations with respect to gender show a similar effect of betablockade on amygdala activation in both men and women, but a difference in its effect on long-term memory for emotional pictures. This study supports the hypothesis that the neurotransmitter noradrenaline also mediates amygdala activity in humans when processing emotional stimuli and that betablockers can disrupt the normal activation pattern in the amygdala.

The effect of beta-adrenergic blockade after encoding on memory of an emotional event.

RATIONALE: Animal and human studies lend support to the hypothesis that enhanced memory associated with emotional experiences involves activation of the beta-adrenergic system. Evidence for the role of noradrenaline in emotional memory in humans has been gathered from experimental studies where blockade of the beta-adrenergic system with a beta-blocker selectively impaired long-term memory for an emotionally arousing story (a slide show), when the beta-blocker was given before subjects were confronted with the emotional stimuli. OBJECTIVE: The purpose of this study was to test whether effective beta-adrenergic blockade occurring only after the stage of encoding has a similar impairing effect on memory. METHODS: In a double blind experimental design, 60 healthy adult subjects received randomly one tablet of either propranolol (Inderal, 40 mg) or placebo. Drugs were administered just before the slide show begun and (in view of its pharmacokinetics) propranolol reaches peak levels 1 h after drug intake. Physiological arousal was monitored by heart rate and blood pressure. Half of the beta-blocker and placebo groups watched either a neutral or an arousal version of an 11-slide presentation. Memory performance was tested with a surprise free recall and recognition test 1 week later. RESULTS: Memory performance, specifically for the second phase in which emotional elements were introduced, was better in subjects who viewed the arousal version than subjects who saw the neutral version of the slide show. However, no effect of the beta-blocker condition was found. CONCLUSION: This experiment does not support a role for noradrenaline in the post-encoding phase and on the later processes of consolidation and retrieval. Although it remains possible that with a different dosage or timing protocol a post-treatment effect of noradrenaline in humans can be found, this experiment could not find support for it.