Emotion, Stress, and Memory

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will be part of Oxford's series in _; the series editors are _. Address correspondence to Siobhan Hoscheidt & Lynn Nadel,. Psychology Department, University of ...
Emotion, Stress, and Memory Siobhan M. Hoscheidt1 Bhaktee Dongaonkar1 Jessica Payne2 Lynn Nadel1


The University of Arizona 2 Notre Dame University

Running head: Emotional Memory Chapter to appear in Reisberg, D. (Eds.), Oxford Handbook of Cognitive Psychology, N.Y.:Oxford University Press, 2012 This volume will be part of Oxford’s series in _; the series editors are _. Address correspondence to Siobhan Hoscheidt & Lynn Nadel, Psychology Department, University of Arizona, Tucson, AZ 85721, or [email protected][email protected].


1. General introduction Emotional events are remembered from days to years, can be retrieved with little effort and are usually reported in vivid detail (Denburg et al., 2003;Kensinger & Schacter, 2006; Mickley & Kensinger, 2009a; Sharot, et al., 2007; Talarico, Berntsen, & Rubin,2009; Talarico, LaBar, & Rubin, 2004). By contrast, memoriesof non-emotional events may be subject to forgetting with time, and are characteristically hard to retrieve and vague. Storage and efficient recollection of memories for emotional events is highly adaptive (Nairne, 2007). Experience of past emotional events informs modification of future behaviors so that emotionally significant situations may be successfully avoided or addressed (Koster et al., 2007).The finding that emotional information is better remembered than nonemotional information has been widely reported across numerous studies and for a variety of different stimuli (e.g. word lists, scenes, and stories; Anderson et al., 2006;Harris &Pashler, 2005;Kensinger, Garoff-Eaton, &Schacter, 2007b; Payne et al., 2006, 2007; Segal & Cahill, 2009; Touryan, Marian, &Shimamura, 2007).Research conducted over the past two decades has contributed a wealth of new knowledge to the field’s understanding of how emotion affects memory,and has demonstrated that effects vary as a function of the valence and arousal of an emotional experience and the phase of memory processing influenced by emotion. We start by discussing the effects of mild to moderate emotion on different memory phases, and then discuss more severe emotion, or stress. This chapter aims to provide an integrated overview of (1) how mild to intense emotion modulates memory processesand (2) the underlying mechanisms that contribute to the formation of well-preserved emotional memory.

2. What Defines Emotion? Valence vs. Arousal


In memory research the word “emotion” has been predominantly used to describe affective states derived from stimuli with either positive or negative valence; however,there has been much debate as to whether valence itself, or the arousal invoked by stimuli with valence, or interactions of the two, are significant contributing factors tohowemotions modulate memory. Evidence suggests that arousal and valence significantly interact to modulate memory (Kensinger &Corkin, 2004; Kensinger &Schacter, 2006;Libkuman, Stabler&Otani, 2004; Mickley& Kensinger, 2008)however, there is also evidence that arousal strongly modulates memory processes (Anderson et al., 2006;Buchanan et al., 2006; Mather &Neisman, 2008)while the effects of valence alone appear to be minimal (Mather & Sutherland, 2009).Determining independent effects, or an interaction, of valence and arousal on memory has proved to be difficult, particularly in the case of negative items where valence and arousal are often confounded. Some studies have attempted to control for such confounds by equating experimental materials on levels of valence and arousal. One such study, a neuroimaging study conducted by Mickley& Kensinger (2009b),demonstrated thatbrain activation observed during encoding of highly arousing and negative images significantly overlapped, primarily eliciting activation in the hippocampus, amygdala and temporo-occipital cortex. Furthermore, the degree of activation in the hippocampus and amygdala strongly predicted enhanced subsequent memory of high arousal and negative items. By contrast, encoding of non-arousing and positive imageselicited activation primarily in frontal cortex and activation in this region was related to subsequent memory performance. The results of this study suggest that, when valence and arousal are equated, similar brain regions may be involved in processing highly arousing and negative materials. Another study showed similar results during encoding of arousing, versus valenced, non-arousing, items. Neuroimaging data showed robust activation in the amygdala and hippocampusduring encoding of arousing, versus valenced, non-arousing, items.


Activation in the hippocampus and amygdala predicted subsequent emotional memory performance, particularly when activation across these regions was correlated(Kensinger &Corkin, 2004).Although more studies are needed to determine the effects of valence and arousal on memory processes, concurrent activation between the amygdala and hippocampus during encoding of high arousing and negative information may be one of many reasons why negative items are typically associated with higher memory accuracy, compared to non-emotional and positive items, (Kensinger, Garoff-Eaton, &Schacter, 2007c; Ochsner, 2000) and hence continue to be a major focus of studies examining the effects of emotion on memory.

3. Modulation of Memory Processes by Moderate Emotion Emotion can modulate memory by influencing any phase of processing – attention/encoding, working memory, consolidation or retrieval. Studies have shown that the phase of processing influenced by emotion plays a significant role in how subsequent memory is affected, resulting in either memory enhancements or impairments (Liu, Graham, &Zorawski, 2008; Roozendaal, Barsegyan, & Lee, 2008; Talmi et al., 2008;van Stegeren et al., 2005;Waring et al., 2010). In this section, we will review the underlying mechanisms by which mild to moderate levels of emotion modulate 1) attention and encoding, 2) working memory, 3) consolidation and 4) retrieval.

3.1 Emotion-based Modulation of Attention and Encoding Emotionalstimuli are often referred to as “attention magnets” because they readily attract attentionand remain the focus of attention during encoding (Alpers, 2008; Calvo& Lang, 2005; Nummenmaa, Hyönä, &Calvo, 2006). Spontaneous preferential


processing of emotional information inperceptual and attentional systems, an effect commonly referred to as attention-narrowing, contributes to the overall effect of emotion on memory, allowing emotional information to have privileged access to working memory and beyond (see review by Mather, 2007). Eye tracking and ERP studies have provided evidence that automatic attentional shifts toward negatively arousing stimuli occur very early in emotion perception, within 100ms to 300ms after exposure to a stimulus (Bradley et al, 2007; Huang &Luo, 2006). Schaefer, Pottage, &Rickart, 2011). These effects appear to beautomatic andappear to be uninfluenced by attentional load during the earliest stages of encoding(Luo et al., 2010). Fast and efficient perceptual processing of arousing materials canachieve two things, both of which are adaptive and important for survival: (1) elicit an autonomic response; and (2) trigger the evaluation ofan affective stimulus before an individual is consciously aware of perceiving it.

Autonomic activation elicits the release of hormones that automatically and rapidly modulatesubcortical systems, causing pupil dilation (Sterpenich et al., 2006), and further biasing of perceptual and attentional systems towards processing emotionally relevant information (Brosch, Pourtois, & Sander, 2010; Ohman, 2005;Talmi et al., 2008).The amygdala plays a critical role in this process, directing eye movements, via projections to low-level visual areas,to selectively attend to (Adolphs, 2004) and encode emotionally salient information (Compton, 2003; Kensinger&Corkin, 2004; Pessoa &Ungerleider, 2004). Noradrenergic hormones modulate encoding of emotional materials by mediatingneural processes in the amygdala. Several neuroimaging studies have demonstrated the important role of noradrenergic mediation of amygdala activity during encoding of emotional material by administration of a betablocker (i.e. propranolol) just prior to encoding. Overall, these studies demonstrate that beta-blockade selectively disrupts normal activation


patterns in the amygdala during acquisition, selectively decreasing activation in this region. Critically, in these studies, decreased amygdala activation during encoding predictedselective subsequent memory retrieval impairment for emotional materials (Strange & Dolan, 2004; van Stegeren et al., 2005). The integral rolethe amygdalaplays in encoding emotional information has also been demonstrated in studies of patients with amygdala damage,whoat timesshow minimal physiological arousal to negative material (Bernston et al., 2007) and unbiased visual attention when encodingfearful faces or scenes withemotional and non-emotional components(Adolphs et al., 2005; Anderson & Phelps, 2001). An absence of emotion modulation of perceptualand attentional processes and impaired normal amygdala and noradrenergic functionmay be a few of the many reasons that memory for emotional information is not enhanced in amygdala patients, as it is in intact individuals.

Unlike emotional information, non-emotional information does not benefit from amygdala-driven modulation of perceptual and attention systems or arousal-evoked release of hormones (Kensinger &Corkin, 2004; Segal & Cahill, 2009). In fact, allocation of attention to favor emotional information diminishes resources, constraining attention that would be allocated across all aspects of an event in the absence of arousal. It has been shown that while viewing negative emotional stimuli the functional field of view (FFOV) dramatically narrows, thus making it less probable that attention will be allocated to non-emotional or positive stimuli (Nobata, Hakoda&Ninose, 2010). As a result, subsequent memory for non-emotional and positive information is typically poor,compared to memory for negative emotional information, particularly when presented within or in close proximity to a negatively emotionally arousing stimulus or event (Kensinger, Garoff-Eaton, &Schacter,2007b;Touryan, Marian, & Shimamura, 2007).


Preferential remembering ofemotional information at the expense of non-emotional information is often referred to as an emotion-induced memory trade-off (see Buchanan &Adolphs, 2002; Kensinger, 2009;Reisberg&Heuer, 2004 for reviews). For instance, if one sees a picture of a car accident on a street, one tends to have excellent memory for the car accident but poor memory for the street. In fact, memory for the street is often worse if onesaw a car accident on the street than if onesaw a non-emotional version of the scene, such as an intact car parked on the street. Such trade-offs can occur not only for non-emotional information presented in close spatial proximity to an emotional item but also for non-emotional information presented in temporal proximity to emotional information (Hurlemann et al., 2005).These findings suggest that memory trade-off effects may be tied to the strength of the emotional “attention magnet” in a scene.

Exceptions to this pattern of findings are seen when non-emotional and emotional information are integrated spatially (e.g. the font color or spatial location of an emotional word; Kensinger, Garoff-Eaton, &Schacter, 2007a), temporally or conceptually (Adolphs, Denburg, &Tranel, 2001; Schmidt, 2002) or are equally relevant to goal attainment (Compton, 2003; Gable & Harmon-Jones, 2008;Levine & Pizarro, 2004; Levine & Edelstein, 2009, review). In such cases non-emotional information appears to be remembered as well as emotional information (Adolphs, Denburg, &Tranel, 2001).For example, studies have shown that encoding processes can be manipulated by altering instructions that directparticipants to allocate their attention towardsparticular aspects of scenes. The logic behind these studies is that if focal effects arise due to attention focusing during encoding, it should be possible to alter the types of details that are remembered by manipulating how people process the information. Kensinger et al (2005) demonstrated that when young


adults intentionally encoded scenes with instructions to remember all aspects of the scenes, their ability to remember the non-emotional background (e.g., the street) was as good as their ability to remember the negative object (e.g., the car accident). Similar reductions of memory trade-off effects can occur if participants are asked to describe a scene so that an artist could reproduce it accurately. With this type of focused encoding task, most people are just as good at remembering the nonemotional background details of a negative scene than of an entirely non-emotional scene. Additionally, it has been shown that memory for thematically induced arousal, or arousal produced by empathy instead of a salient visual stimulus, enhancesmemory for an event overall with no memory narrowing effects (Laney, Heuer, &Reisberg, 2003; Laney et al., 2004).These data suggest that although perceptual processes may initially be automatically biased towards emotionally salient stimuli, controlled shifts in attention to intentionally encode non-emotional aspects of an emotional scene can alter later memory performance, eliminating emotion-induced memory trade-offs.

Successful encoding of emotional memories has been shown to critically depend on interactions between the hippocampus and amygdala (Dolcos, LaBar, &Cabeza, 2004; Richardson, Strange, & Dolan, 2004) and arousal-induced release of hormones. Neuroimaging studieshighlight the important role of emotional arousal on activation in the hippocampus and amygdala during encoding of emotional stimuli. Some studies have suggested that an affective attentional network (amygdala, orbitofrontal cortex, ventral striatum, and anterior cingulate gyrus) focuses and guides encoding processes, assuring that negative information is attended to and encoded in the hippocampus, often at the cost of non-emotional elements (Kensinger, Garoff-Eaton &Schacter, 2007a) in the absence of intentional encoding instructions.Interestingly, implicitly driven emotion-induced memory trade-offs may


vary depending on individual differences, particularly levels of anxiety, working memory capacity and executive function abilities. A study recently conducted by Waring et al., (2010)demonstrated that individuals with greater anxiety, poor visuospatial working memory and poor executive function show more prominent emotion-induced memory trade-offs than individuals without these traits. Further research is needed to understand additional factors that may influence and modulate attentional resources and encoding of emotional scenes, however, regardless of such differences, emotion-induced memory trade-off has been demonstrated across many studies and is a robust effect. Preferential processing of emotional information in perceptual and attentional networks creates ideal conditions for emotional information to have privileged access to working memory.

3.2 Emotion-based modulation of Working Memory Working memory is a limited-capacity system that regulates and maintains information through conscious rehearsal or rumination (Baddeley, 2001).Only a handful of studies have examined the effects of emotion on working memory and findings remain mixed (Kensinger &Corkin, 2003; Edelstein, 2006).Some find that working memory capacity appears greater for emotional (both positive and negative) than non-emotional words (Edelstein, 2006), while others reportthat working memory performance does not differ for emotional and non-emotional information (Kensinger &Corkin, 2003b). Mixed results may arise, in part,fromtask demanddifferences across studies. Working memory tasks incorporating instructions that require individuals to remember both non-emotional and emotional items typically result in no memory differences while emotional items show enhancement if individuals are not provided with task instructions(Kensinger &Corkin, 2003b).High task demands appear to negatively impact working memory performance, most likely by straining its limited capacity,while emotional information is more likely to be


maintained in working memory than non-emotional information in the absence of specific instructions to the contrary.

Although it is known that rehearsal is the primary means by which information is maintained and processed in working memory, it has been shown that rehearsal alone does not account for emotional memory enhancement in working memory tasks. Studies have demonstrated that eliminating the opportunity for rehearsal does not eliminate the memory advantage for emotional information in working memory (Harris &Pashler, 2005; Hulse et al., 2007).Similar to emotion modulation of perceptual and attentional systems, emotional memory advantages in working memory may reflect the influence of arousal-induced release of hormones (i.e. norepinephrine). Indeed it has been shown that drugs that block arousal-induced hormone release selectively impair emotional memory in working memory tasks (Chamberlain et al., 2006).Given that information is maintained in working memory, it can then beconsolidated into long-term memory storage. Emotion has been shown to modulate consolidation processes as well.

3.3. Emotion-based modulation of Consolidation Memory consolidation involves a complex set of neurobiological processes that occur over time andthat can be modulated by emotion (see McGaugh, 2000 for a review). Animal studies have provided evidence that arousal-induced activation of the noradrenergic system (i.e. norepinephrine) and activation of the amygdala, which promotes consolidation, drive the preferential consolidation of emotional memory (Ashby, Isen, &Turken, 1999; Cahill, Gorski, & Le, 2003; Canli et al., 2000; Hurlemann et al., 2005; McGaugh, 2004). Although much of the research in this area has been conducted with animals, human research has also demonstratedthat emotional memory is consolidated into long-term memory more efficiently than

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memory for non-emotional information, particularly under conditions of arousal. Research has shown that memory consolidation is facilitated by both pleasant and aversive post-learning arousal for positive and negative, but not non-emotional, stimuli (Liu, Graham, &Zorawski, 2008; Nielson &Powless, 2007). Moreover, once encoded, emotional memories have been shown to be susceptible to strengthening by post-learning arousal from 30 minutes (Nielson &Powless, 2007) to 50 minutes and in some cases up to 2 hours (Pelletier et al., 2005) after learning. Although some studies have focused on the effects of endogenous increases in arousal hormones, studies have shown that memory consolidation is enhanced by exogenous increases in norepinephrine as well (Cahill &Alkire, 2003). Memory traces for negatively arousing events are additionallystrengthened over time; enhancement effects are observed after brief delays from hours to days (Sharot& Phelps, 2004), and especially following post-learning nocturnal sleep (Payne et al., 2008; Payne & Kensinger, 2010; Payne & Kensinger, 2011).An extended window of time for emotion to influence consolidation processes after initial acquisition, and preferential consolidation of emotional memory traces during sleep, serve important adaptive functions, ensuring that memory for emotionally salient events is well preserved.

3.4 Emotion-based modulation of Retrieval Clearly, research has shown that the more arousing an event is, the better it is remembered. Preferential processing of emotional information in perception/attention, working memory, consolidation and long-term memory systems culminates in emotional information being more reliably and accurately retrieved than non-emotional information. Memories laden with great emotional

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intensity or of personal significance are remembered more accurately than memories that are emotionally neutral or are of little personal relevance (Buchanan, 2007; Reisberg&Hertel, 2005; Sharot et al., 2007)

Overall, there is less conclusive evidence regarding how emotion influences retrieval, wheninduced just prior to or during remembering. It has been suggested thatretrieval of emotional information may be facilitated by reactivation of affective states similar to those experienced during encoding. In this sense, affective states act as an internalretrievalcue and could aid in remembering past emotionalexperiences.Reactivation of affective states may additionally elicit activation in the amygdala, including release of noradrenergic hormones (Murchinson et al., 2004), which may aid in memory retrieval. Pharmacology studies support this notion, demonstrating that beta-adrenergic blockade during memory retrieval abolishes enhanced declarative memory for emotional materials (Kroes, Strange, & Dolan, 2010). Numerous studies have demonstrated that the amygdala is activated during retrieval of emotional information and that activation in this regioncorresponds tosuccessful remembering of emotional, but not neutral, materials (Dolcos, LaBar, &Cabeza, 2005; Keightley et al., 2011). Amygdala involvement in retrieval of emotional memories is critical and persists over time. Dolcos, LaBar, &Cabeza (2005) demonstrated that after a retention interval of a year memory for emotional versus neutral items was greater overall, and that successful retrieval of emotional items elicited greater activation in the hippocampus and amygdala, than did successful retrieval of neutral items. Furthermore, emotional items reported as being recollected, as opposed to being familiar, elicited greater activation in the amygdala and hippocampus, suggesting that these regions may somehow contribute to the accuracy with which emotional information is retrieved as well as the phenomenological experience of remembering emotional events. The hippocampus

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and amygdala not only play an integral role in retrieval of emotional information but also, as discussed earlier, show correlated activation during the encoding of emotional events. Thus, activation in these regions during encoding and reactivation during subsequent retrieval may contribute to the accuracy and efficiency with which emotional memories are remembered.

In summary, moderate emotion facilitates processing of emotional information in attention & perception (i.e. encoding), working memory, consolidation, and retrieval systems. As a result, subsequent memory for emotional materials is enhanced. By comparison, under conditions of moderate emotion,memory for non-emotional information is often impaired. Impairments are thought to result from a lack of attention allocated to non-emotional items, when in the presence of emotional materialduring acquisition, as well as a failure to engage norepinephrine and amygdala mechanisms that selectively promote the encoding and consolidation of emotionalmaterials.

4. Modulation of Memory Processes by Intense Emotion (i.e. Stress) The effects of intense emotion, or stress, on memory processes are similar to those discussed for moderate emotion; however, memory impairments and enhancements are more pronounced. These effects are primarily driven by the releaseof cortisol, a stress hormone shown tomodulatethe neural processing in memory regions including the hippocampus and amygdala. Cortisol effects on memory processes are mediated by two factors 1) the degree to which an individual is emotionally arousedand 2) the phase of memory processes influenced by elevation in cortisol levels (i.e. acquisition/encoding, consolidation, or retrieval).

4.1 The Physiological Stress Response & Learning

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In response to stress, cortisol is released into the blood by the adrenal cortex, travels through the circulatory system, crosses the blood-brain barrier and bindsto mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in various brain regions. The frontal cortex, hippocampus and amygdalahave an abundance of these receptors; however, cortisol activation of MRs and GRs modulates processes quite differentlyin these regions. For the purpose of this discussion, we will focus on the effects of cortisol on the hippocampus and amygdala, however, it is important to note that stress has also been shown to modulate frontal lobe function (see Dedovic, D’Aguair, &Pruessner, 2009 for review; van Stegeren et al., 2010). In the medial temporal lobes, cortisol facilitates neural processes in the amygdala and impairs neural processes in the hippocampus.

Cortisol facilitates amygdala function by influencing both intracellular and extracellular neural processes. In the presence of high cortisol levels, amygdala neurons become more excitable, showing a positive shift in resting membrane potential and enhancedinput resistance. Additionally, GABA-A receptors within this region show overalldecreasedamplitude of inhibitory post-synaptic potential (IPSPs).These cortisol-driven shifts of amygdala neurons were reported in a study conducted by Duvarci&Paré(2007) who administered varying amounts of cortisol, in vitro, to basal lateral amygdala (BLA) slices. Larger dosages of cortisol resulted in greater facilitation of synaptic plasticity. The functional implication of these effects seems clear: learning and memory can be facilitated in the amygdala when stress levels are high.

Facilitation of amygdala plasticity is not solely dependent on cortisol activation of GRs and MRs.Similar to what is known regarding the necessary release of norepinephrine for enhanced emotional learning in the amygdala,the facilitating

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effects of cortisol on BLA plasticity aremodulated by, and perhaps even dependent upon, arousal-induced noradrenergic activation within the BLA. Animal studies have provided support for this notion, demonstrating that blockade of betaadrenoceptorsin the BLA prevents the memory enhancing effects of cortisol on amygdala function (McGaugh&Roozendaal, 2002; Roozendaal et al., 2006b).These findings suggest that emotional arousal and stress must co-occur for subsequent memory of emotional materials to be enhanced. This is particularly true regarding stress modulation of encoding and consolidation processes, which will be discussed in the next section.

In contrast to what appears to be a positive linear correlation observed between cortisol levels and amygdala function, cortisol effectson hippocampal learning are more complex, and depend on the ratio of cortisol-bound MRs to GRs. There are important differences in affinity between these two receptor types: MRs have a much higher affinity for cortisol than GRs. Thus, at low and moderate levels of stress, binding of cortisol can belimited primarily to MRs, whichfacilitates hippocampal LTP processes (Joëls& de Kloet, 1990; 1991). When this occurs, hippocampal-plasticity is at its maximum and performance on hippocampal-dependent tasks is optimal. However, when stress levels are high cortisol levels increase, MRs saturate, andGRs become activated. Activation of GRs leads to the instantiation of long-term depression (LTD) in the hippocampus. As a result, hippocampal plasticity and hippocampal-dependent tasks are impaired (Kim &Diamond, 2002). Given the dissociative effects of cortisol on hippocampal plasticity, the relationship between stress and performance on hippocampal-dependent tasks is traditionally described as an inverted U-shaped function (Yerkes & Dodson, 1908). Optimal behavioral performance occurs when cortisol levels are moderate (MRs are largely occupied but GR activation is minimal) and impaired behavioralperformance occurs when cortisol

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levels are too low or is high (in the latter case, MRs are fully saturated and a large proportion of GRs are occupied).

4.2 Severe Emotion Modulation of Encoding & Consolidation Disentangling the effects of stress on encoding and consolidation has proved to be difficult. Traditionally the effects of stress on encoding are examined by inducing stress immediately prior to acquisition. Although these methods allow examination of the effects of stress on encoding processes, they also influence early consolidation processes, which are thought to begin immediately after encoding.By contrast, stress induction immediately after acquisition allows for the examination of the effects of stress on consolidation processes relatively independent of those on encoding. In this section we will discuss the effects of stress on encoding and consolidation.

4.2.1 Intense Emotion and the Modulation of Encoding Behavioral studies have shown that stress induction,just prior to acquisition of emotional and non-emotional materials,typically results in enhanceddeclarative memory performance (Abercrombie et al., 2003). In particular, enhanced emotional memory, but impaired memoryfor non-emotional informationhas been shown (de Quervain et al., 2009, review; Payne et al., 2006; 2007).Dissociative effects of stress on memory for emotional versus non-emotional information is perhaps best understood in terms of the dissociative effects of cortisol on hippocampal versus amygdala function,discussed in the previous section. Neuroimaging studies have provided evidence for impairing effects of cortisol on hippocampal function and enhancing effectsof cortisol on amygdala function in humans during encoding, in that hippocampal activation decreases (Dedovic et al., 2009; Henckens et al., 2009; Pruessner et al., 2008), whereas amygdala activation increases (van Stegeren et al., 2010), under conditions of elevated stress.Furthermore, hippocampal activation and

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cortisol levels are negatively correlated; thus, as cortisol levels increase activation in the hippocampus decreases (Pruessner et al., 2008).

Behavioral studies that have examined the effects of stress under conditions of arousal versus non-arousal have demonstrated the critical role arousal plays in stress modulation of encoding processes. Studies have shown that arousal and physiological stress must be co-activated for emotional memory enhancement effects to arise (Roozendaal et al., 2006a; 2006b; Segal & Cahill, 2009). Under conditions of stress and arousal, cortisol and norepinephrine appear to work within the BLA synergistically, facilitating amygdala learning during encoding. Payne et al. (2007) examined memory for arousing versus non-arousing episodes using identical visual stimuli. A slideshow depicting a car accident and subsequent injuries (cf., Cahill &McGaugh, 1995) was presented to all participants; the arousal group heard an emotionally arousing narrative while the non-arousal group heard a non-emotional narrative (i.e. participants are told that the injuries depicted are not real but rather part of a mock hospital drill). Results showed that memory for the events in the slide show was enhanced in the stress-arousal group, but impaired in the stress/nonarousal group. These results suggest that, when all things are held equal, arousal must be present for stress to enhance emotional memory while stress alone can cause memory impairment for non-arousing materials.

Pharmacological studies have examined independent contributions of cortisol and norepinephrine on amygdala function,providingfurther evidence for the importance of co-occurring stress and arousal in the facilitation of emotional memory encoding. These studies have demonstrated that blockage of norepinephrine release or administration of a noradrenergic antagonist results in impaired long-term memory for emotionally arousing material (Maheu et al., 2004; van Steregen et al., 2005;

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2007). Results of neuroimaging studies support these results, showing that the administration of a noradrenergic antagonist decreases amygdala activation, even under conditions of extreme stress(van Steregen et al., 2005; 2007). Together, these results support the notion that arousal plays an integral role in modulation of amygdala processes during encoding of emotionally salient information to produce emotional memory enhancement under high levels of stress.

Clearly, cortisol and norepinephrine interact in important ways to produce memory enhancement effects in the amygdala during encoding. However, research has also shownthat enhanced BLA activation, during arousal, in turn mediates the effects of cortisol within areas of the hippocampus (McGaugh&Roozendaal, 2002; Roozendaal, 2002; Nathan et al., 2004;Strange & Dolan, 2004) allowing this region to successfully encode emotional information under stress (Richter-Levin, 2004; Lupien et al., 2007; Roozendaal, Barsegyan, & Lee, 2008; de Quervain et al., 2009).Although elevated cortisol levels can impair hippocampal plasticity,impaired hippocampal function may be most predominant in the absence of amygdala-driven noradrenegic modulation of hippocampal function during encoding under stress. Research has provided evidence that this region is capable of preferentially encoding emotionally relevant information via interactions with the amygdala and release of norepinephrine, under conditions of stress (van Stegeren et al., 2010). In fact, at least one animal study hasdemonstrated that an intact hippocampus is necessary for the modulation of learning by stress, showing that hippocampal lesions prevented stress-induced enhancements as well asstress-induced impairments of learning after stress (Bangasser&Shors,2007).Few human studies have investigated emotional memory in hippocampal-damaged individuals and findings remain mixed. One study, conducted by Buchanan, Tranel, &Adolphs (2005) demonstrated that unpleasant autobiographical memory reports of hippocampal patients were strikingly similar to

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those of brain-damaged and healthy controls. By contrast, patients with damage to the hippocampus and surrounding cortical regions (e.g. amygdala) reported fewer unpleasant memories, overall. A critical component for interpreting these results is determining whether or not these structures were intact at the time the reported emotional events were encoded and the extent of damage to these regions. Provided what is known regarding the critical role of the amygdala and hippocampus in encoding and retrievingemotional memories, one might suspect that patients with partial hippocampal damage and an intact amygdala are able to report a number of remote emotional memories while individuals with hippocampal and amygdala damage would produce fewer emotional memories, overall. Additionally, research suggests that results may vary depending on whether the right or left medial temporal lobe region is damaged. Patients with right-sided anteromedial temporal lobe (i.e. anterior hippocampus and amygdala) damage demonstrate severely impaired recollection of unpleasant memories compared to right temporal lobectomy patients who perform similarly to intact individuals (Buchanan, Tranel&Adolphs, 2006b).

4.2.2 Severe Emotion Modulation of Consolidation Similar to the facilitating effects of stress administered prior to encoding, increased cortisol levels after encoding are positively correlated with enhanced memory for emotionally laden information in emotionally aroused individuals (Abercrombie et al. 2003; Buchanan &Lovallo, 2001;Cahill, Gorski& Le, 2003).Numerousstudies have demonstrate that endogenous and exogenousincreases in cortisol after training lead to enhanced memory consolidation of emotionallyarousingmaterials (Kuhlmann & Wolf, 2006a ; McGaugh&Roozendaal, 2002 ; Roozendaal, 2002). It is postulated that the emotional memory enhancement effect is the product of a ‘special’ consolidation process involving interactions between cortisol and norepinephrine within the BLA

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and concomitant BLA modulation of hippocampal activity that promotes consolidation of emotional material (Richardson, Strange, & Dolan, 2004; Richter-Levin, 2004; Lupien et al., 2007; Roozendaal, Barsegyan, & Lee, 2008; de Quervain et al., 2009).

However, the effects of stress on consolidation processes remain unclear. Some studies have reported mixed results showing impaired emotional memory or enhanced non-emotional memory when cortisol levels are elevated after encoding. Buchanan, Tranel, &Adolphs (2006a) subjected participants to a cold pressor stress task one hour after learning negative and neutral words. This task, which involves submerging one’s arm in very cold water, reliably elevates cortisol in human participants. Stress responders showed impaired memory for moderately arousing negative words while memory for highly arousing negative words and neutral words was unaffected.Mixed results may exist, in part, due to the phase of memory consolidation (i.e. early vs. late) modulated by cortisol. Neural mechanisms that underlie early consolidation processes, believed to begin immediately after encoding, may significantly differ from those involved in late consolidation processes. Thus, the effects of stress, induced a few hours after encoding, may produce very different memory effects compared to the effects of stress on early consolidation processes. It may be the case that once the optimal window of time during which cortisol can modulate consolidation processes has passed emotional memory enhancement is not observed. Additionally, the time between stress induction and memory testing is critical in determining the effects of stress on consolidation processes without affecting retrieval. In the study of Buchanan, Tranel, &Adolphs (2006a) memory was tested 10 minsafter the cold pressor task, thus cortisol levels were likely elevated during retrieval and, as we will discuss in the next section, stress has been shown to impair memory retrieval.

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4.3 Severe Emotion Modulation of Memory Retrieval Contrary to facilitatory effects ofcortisol on encoding and consolidation of emotional materials, increased cortisol levels at retrieval typicallyresults in memory impairments overall(de Quervain et al., 2009; Kuhlmann, Piel, & Wolf, 2005; Tollenaar et al., 2008b; Merz, Wolf, &Hennig, 2010). Impairing effects of stress on retrieval are robust,generalizingacross various types of stimuli with varying levels of valence and arousal (e.g. words (Domes et al., 2004; Kuhlmann, Piel, & Wolf, 2005), word pair associations (Tollenaar et al., 2008a; 2008b), slideshows (Buchanan &Tranel, 2008), and socially relevantinformation(Merz, Wolf, &Hennig, 2010)). Studies examining the effects of exogenous increases in cortisol levels, through the oral administration of hydrocortisone, show that cortisol increases at the time of retrieval not only impair memory for experimental materials but also generally impair episodic memory performance (Tollenaar et al., 2009a; 2009b). The driving factor of impaired retrieval under conditions of stress is thought to be disrupted hippocampal function via binding cortisol to both GRs and MRs. Neuroimaging studies examining the effects of stress on activation in regions involved in retrieval processes have provided evidence for this notion, demonstrating that activity in the hippocampus is significantly reduced when cortisol levels are high (Dedovic et al., 2005; Wang et al., 2005). Additionally, it has been shown that the degree of hippocampal deactivation significantly correlates with impaired declarative memory retrieval (Dedovic et al., 2009) as well as the cortisol stress response (Pruessner et al., 2008). Although impairing effects of stress on memory retrieval appear to be primarily driven by cortisol (Buchanan, Tranel, &Adolphs, 2006a) whether or not arousal-induced release of hormones modulates cortisol effects on memory retrieval, driving impairing effects, is still under debate. Some studies suggest that this is the case, demonstrating that non-arousing testing situations (Kuhlmann& Wolf, 2006b) and

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non-arousing materials (Kuhlmann, Kirschbaum& Wolf, 2005) are unaffected by exogenous cortisol administration prior to retrieval.

Although impaired memory retrieval may seem maladaptive, impaired memory retrieval under conditions of stress may serve an adaptive purpose. Hippocampal deactivation may prevent previously stored information from being retrieved at a time when it couldinterfere with the encoding and consolidation of salientnew emotional information. Thus, stress-induced retrieval impairmentsmight allowstressful experienceto be encoded fast and efficiently. Additionally, impaired retrieval may prevent remote memories for traumatic events from being updated through reconsolidation mechanisms during new stressful situations. This would guaranteethat emotional memories remain distinct from one another (Roozendaal, Barsegyan, & Lee, 2008), an important feature for adaptive future behavior. Provided the stress is not chronic, such retrieval impairments are usually temporary and memory performance is reinstated once the cortisol effects wear off (de Quervain, Aerni, &Roozendaal, 2007).

5. Conclusions All the effects we described abovereflect acute emotion or stress. While there is not a great deal known about the effects of chronic stress it is worth briefly discussing what is known.

For obvious reasons, the effects of chronic stress have been studied mostly in animals. Elevating stress levels for long periods of time impair hippocampal and prefrontal functions (de Kloet et al., 1998; see Herbert et al., 2006 for review; Liston, Casey,& McEwen, 2009; McEwen, 1998; 2005), causing profound disruption of long-term potentiation and reduced density of dendritic spines in the hippocampus

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(Chen et al., 2010) that results in hippocampal volume loss. By contrast, chronic stress has been shown to enhance sensitivity of the amygdala (Vyas et al., 2002;Vyas, Bernal, &Chattarji, 2003), making this region more active, overall.For example, heightened activity of the amygdala after traumatic stress has been shown to increase sensitivity to information related to the trauma (Bremner et al., 1999) and also to fear inducing information (Shin et al., 2005). Deleterious effects of chronic stress on the hippocampus and enhanced sensitivity in the amygdala may be two of many reasons some individuals develop pathological conditions such as depression and posttraumatic stress disorder (PTSD). One possible mechanism at play in stress related disorders may be that inhibitory controlthe medial prefrontal cortex normally exerts over the amygdala is diminished, resulting in increased basal activity within this region (McEwen, 2005; Shekhar et al., 2005). As a result, individuals may become more responsive to stressful situations and less able to moderate things such as mood and anxiety levels.

Little is known about the relationship between stress hormones and depression but what is known is that acorrelation exists. Although the underlying neural mechanisms of the relationship between chronic stress and depression remains unknown it is plausiblethat depression and chronic stress are related at least in terms of decreased prefrontal and hippocampal function and increased amygdala activity. Long periods of depression have been shown to decrease volume in hippocampal and prefrontal cortex (Sheline, Gado, & Kraemer, 2003; MacQueen et al., 2003) while amygdala volume has been observed to increase, particularly after the first bout of depression (Frodl et al., 2003).

Finally, chronic stress suppresses long term changes in the input pathways to and within sub-regions of the hippocampus that are implicated in long term memory

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(Alkadhi, Srivareerat, & Tran, 2010;Pavlides, Nivon, & McEwen, 2002) as well as hippocampal neurogenesis, which may result in age-related memory deficits (Borcel et al., 2008). It is interesting to note, in this light, that acute prenatal stress can diminish the neurogenesis typically triggered by learning (Lemaire et al., 2000), an effect that can be reversed by providing rich learning environments in early postnatal life (Yang et al., 2007).

Although there has been relatively little work in humans, chronic stress in animals does seem to have a number of negative effects on neural structures subject to modulation by stress hormones. While some of these effects are reversible, normal function is frequently impaired. Given that amygdala, hippocampus, and frontal cortex are prominent amongst the affected structures, learning and memory is not surprisingly compromised and disorders such as posttraumatic stress disorder and depression develop in some individuals. Clearly, more research in humans is needed, although the difficulties involved in obtaining such information are clear.

The situation is much better understood with respect to acute stress. Our review suggests that low to moderate levels of emotion enhance memory for emotional, relative to non-emotional, information. These effects are observed across all phases of memory and appear to be norepinephrine-driven. By contrast, intense levels of emotion (i.e. stress) cause the release of the stress hormone cortisol which modulates the facilitating effects of norepinephrine, resulting in enhanced encoding of emotional vs. non-emotional items, facilitated consolidation of emotional items and impaired memory retrieval, overall. These impairing and enhancing effects can be best understood in terms of how cortisol affects neuronal function in the hippocampus and amygdala, impairing learning in the former and facilitating learning it in the latter.

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