Stability of emotional dysfunctions? A long-term fMRI study in first-episode schizophrenia

OBJECTIVE: Patients with schizophrenia are characterized by emotional symptoms such as flattened affect which are accompanied by cerebral dysfunctions. This study aimed at determining changes of mood-related neural correlates under standardized pharmacological therapy in first-episode schizophrenia. METHOD: Using fMRI in a longitudinal approach, 10 first-episode schizophrenia patients (6 males) and 10 healthy subjects (same education, gender and age) were investigated during sad and happy mood induction using facial expressions. Reassessments were carried out following 6 months of standardized antipsychotic treatment. Data analysis focussed on therapy-related changes in cerebral activation and on stable, therapy-independent group differences. RESULTS: According to self ratings, mood induction was successful in both groups and did not reveal time-dependent changes. Patients revealed stable hypoactivations in core brain regions of emotional processing like the anterior cingulate cortex, orbitofrontal and temporal areas as well as the hippocampus. Therapy-related signal increases in pre- and postcentral, inferior temporal and frontal areas were restricted to sadness. DISCUSSION: Stable dysfunctions which are unaffected by therapy and symptom improvement were found in cortico-limbic regions crucially involved in emotion processing. They presumably reflect patients' difficulties in emotion regulation and emotional memory processes. However, therapy-related activation changes were also observed and demonstrate efficacy of antipsychotic therapy on improving emotion functionality. They may represent an increased usage of autobiographic emotional memories and an improved strategy to experience an emotion by mirroring someone else's emotions.     

Ketamine alters neural processing of facial emotion recognition in healthy men: an fMRI study

Disruption of facial emotion perception occurs in neuropsychiatric disorders where the expression of emotion is dulled or blunted, for example depersonalization disorder and schizophrenia. It has been suggested that, in the clinical context of emotional blunting, there is a shift in the relative contribution of brain regions subserving cognitive and emotional processing. The non-competitive glutamate receptor antagonist ketamine produces such emotional blunting in healthy subjects. Therefore, we hypothesised that in healthy subjects ketamine would elicit neural responses to emotional stimuli which mimicked those reported in depersonalization disorder and schizophrenia. Thus, we predicted that ketamine would produce reduced activity in limbic and visual brain regions involved in emotion processing, and increased activity in dorsal regions of the prefrontal cortex and cingulate gyrus, both associated with cognitive processing and, putatively, with emotion regulation. Measuring BOLD signal change in fMRI, we examined the neural correlates of ketamine-induced emotional blunting in eight young right-handed healthy men receiving an infusion of ketamine or saline placebo while viewing alternating 30 s blocks of faces displaying fear versus neutral expressions. The normal pattern of neural response occurred in limbic and visual cortex to fearful faces during the placebo infusion. Ketamine abolished this: significant BOLD signal change was demonstrated only in left visual cortex. However, with ketamine, neural responses were demonstrated to neutral expressions in visual cortex, cerebellum and left posterior cingulate gyrus. Emotional blunting may be associated with reduced limbic responses to emotional stimuli and a relative increase in the visual cortical response to neutral stimuli.     

Emotion–cognition interactions in schizophrenia

Abstract

Objectives. Negative emotion exerts a considerable influence on cognitive processes. This may have clinical implications in mental illnesses, such as schizophrenia, where negative emotions often prevail. Experimentally this influence can be studied by using olfactory emotion induction. Methods. Fourteen schizophrenia patients and 14 healthy volunteers were investigated with functional magnetic resonance imaging with respect to the neural correlates of emotion–cognition interactions. Emotion was induced by odorants during an n-back working memory task. Results. Similar detrimental effects of negative stimulation on working memory performance were observed in patients and control subjects. Among the neural correlates modulating this interaction a decreased activation emerged in patients in the anterior cingulate and the medial superior frontal cortex and increased activation in the medial orbitofrontal and middle frontal area. Conclusions. During emotion–cognition interaction hypoactivations were found in regions crucial for the monitoring/control of ongoing processes but also for emotion regulation. Decreased activations may reflect failure to adapt to higher task requirements. In contrast, increased activations could be indicative of a greater emotional response and irritation induced by the odour. These patterns may represent the neural correlates of an inefficient control of emotional influences on cognitive processes in patients with schizophrenia.     

Supramodal representation of emotions

Supramodal representation of emotion and its neural substrates have recently attracted attention as a marker of social cognition. However, the question whether perceptual integration of facial and vocal emotions takes place in primary sensory areas, multimodal cortices, or in affective structures remains unanswered yet. Using novel computer-generated stimuli, we combined emotional faces and voices in congruent and incongruent ways and assessed functional brain data (fMRI) during an emotional classification task. Both congruent and incongruent audiovisual stimuli evoked larger responses in thalamus and superior temporal regions compared with unimodal conditions. Congruent emotions were characterized by activation in amygdala, insula, ventral posterior cingulate (vPCC), temporo-occipital, and auditory cortices; incongruent emotions activated a frontoparietal network and bilateral caudate nucleus, indicating a greater processing load in working memory and emotion-encoding areas. The vPCC alone exhibited differential reactions to congruency and incongruency for all emotion categories and can thus be considered a central structure for supramodal representation of complex emotional information. Moreover, the left amygdala reflected supramodal representation of happy stimuli. These findings document that emotional information does not merge at the perceptual audiovisual integration level in unimodal or multimodal areas, but in vPCC and amygdala.     

Neural correlates of alexithymia: A meta-analysis of emotion processing studies

Alexithymia is a personality trait characterized by difficulties in the experience and cognitive processing of emotions. It is considered a risk factor for a range of psychiatric and neurological disorders. Functional neuroimaging studies investigating the neural correlates of alexithymia have reported inconsistent results. To integrate previous findings, we conducted a parametric coordinate-based meta-analysis including fifteen neuroimaging studies on emotion processing in alexithymia. During the processing of negative emotional stimuli, alexithymia was associated with a diminished response of the amygdala, suggesting decreased attention to such stimuli. Negative stimuli additionally elicited decreased activation in supplementary motor and premotor brain areas and in the dorsomedial prefrontal cortex, possibly underlying poor empathic abilities and difficulties in emotion regulation associated with alexithymia. Positive stimuli elicited decreased activation in the right insula and precuneus, suggesting reduced emotional awareness in alexithymia regarding positive affect. Independent of valence, higher (presumably compensatory) activation was found in the dorsal anterior cingulate possibly indicating increased cognitive demand. These results suggest valence-specific as well as valence-independent effects of alexithymia on the neural processing of emotions.     

Modulation of affective face processing deficits in Schizophrenia by congruent emotional sounds

Schizophrenia is a psychiatric disorder resulting in prominent impairments in social functioning. Thus, clinical research has focused on underlying deficits of emotion processing and their linkage to specific symptoms and neurobiological dysfunctions. Although there is substantial research investigating impairments in unimodal affect recognition, studies in schizophrenia exploring crossmodal emotion processing are rare. Therefore, event-related potentials were measured in 15 patients with schizophrenia and 15 healthy controls while rating the expression of happy, fearful and neutral faces and concurrently being distracted by emotional or neutral sounds. Compared with controls, patients with schizophrenia revealed significantly decreased P1 and increased P2 amplitudes in response to all faces, independent of emotion or concurrent sound. Analyzing these effects with regard to audiovisual (in)congruence revealed that P1 amplitudes in patients were only reduced in response to emotionally incongruent stimulus pairs, whereas similar amplitudes between groups could be observed for congruent conditions. Correlation analyses revealed a significant negative correlation between general symptom severity (Brief Psychiatric Rating Scale-V4) and P1 amplitudes in response to congruent audiovisual stimulus pairs. These results indicate that early visual processing deficits in schizophrenia are apparent during emotion processing but, depending on symptom severity, these deficits can be restored by presenting concurrent emotionally congruent sounds.     

Brain dysfunctions during facial discrimination in schizophrenia: Selective association to affect decoding

Schizophrenia patients exhibit impaired facial affect perception, yet the exact nature of this impairment remains unclear. We investigated neural activity related to processing facial emotional and non-emotional information and complex images in 12 schizophrenia patients and 15 healthy controls using functional magnetic resonance imaging. All subjects performed a facial information processing task with three conditions: matching facial emotion, matching facial identity, and matching complex visual patterns. Patients and controls showed comparable behavioral performance in all task conditions. The neural activation patterns in schizophrenia patients and healthy controls were distinctly different while processing affect-related facial information but not other non-emotional facial features. During emotion matching, orbital frontal cortex and left amydala activations were found in controls but not in patients. When comparing emotion versus identity matching, controls activated the fusiform and middle temporal gyri, left superior temporal gyrus, and right inferior and middle frontal gyrus, whereas schizophrenia patients only activated the middle and inferior frontal gyri, the frontal operculi and the right insular cortex. Our findings suggest that schizophrenia patients and healthy controls may utilize different neural networks when processing facial emotional information.     

Neural responses associated with positive and negative emotion processing in patients with left versus right temporal lobe epilepsy

Studies on emotion processing in patients with temporal lobe epilepsy have dealt mainly with the processing of negative emotions. To further understand the neural basis of emotional disorders in temporal lobe epilepsy, we studied patterns of brain activation induced by implicit processing of negative and positive emotions perceived through facial expressions and emotionally salient stimuli in candidates for surgical treatment of intractable epilepsy. Using functional MRI, we compared, in patients with mesial temporal lobe epilepsy and healthy subjects, the patterns of brain activation elicited by the implicit processing of fearful, sad, and happy faces and pleasant and unpleasant scenes. The results revealed different patterns of activation in patients with left and right mesial temporal lobe epilepsy, compared with healthy subjects, suggesting that the left and right mesial temporal regions are involved differently in emotion processing, which could be related to different contributions in emotional arousal.     

Cerebral dysfunctions of emotion-cognition interactions in adolescent-onset schizophrenia

ObjectiveSchizophrenia is among the most severe of psychiatric disorders, leading to impairments of affective and cognitive abilities. These dysfunctions affect each other mutually. Adolescent-onset schizophrenia (AOS) constitutes a particularly severe form of the disorder. In this study, possible dysfunctions of the neural correlates underlying the interaction of negative emotion and working memory in AOS were investigated.MethodDuring functional magnetic resonance imaging, 12 patients with AOS and 12 non-AOS adolescents performed a verbal n-back task. Intermittently, negative and neutral emotions were induced by olfactory stimulation. Group differences in working memory, emotion, and their interaction were evaluated.ResultsIn patients with AOS, lower performance sensitivity was observed, along with dorsolateral prefrontal, anterior cingulate, and inferior parietal hypoactivation during working memory demands. For negative versus neutral emotion induction, patients with AOS mainly showed increased brain activation compared with control subjects in widespread brain regions including the left orbitofrontal cortex and the medial frontal gyrus. Finally, during the interaction of emotion and cognition, altered patterns of activation in patients with AOS were found in the thalamocortical network, including the angular and the middle cingulate gyri extending to the precuneus. These activation differences were further decomposed by parameter estimates.ConclusionsOur results provide new insights into the neural correlates underlying the mutual influence of affective and cognitive symptoms in AOS. During the n-back task, areas typically associated with working memory performance were found hypoactivated in patients relative to the control subjects, including the dorsolateral prefrontal and parietal cortex and the anterior cingulate. However, patients with AOS mainly demonstrated increased activation in key areas of emotion processing, such as the left orbitofrontal cortex and medial frontal areas, during negative emotion induction. A dysfunctional thalamocortical network during the interaction mainly included regions involved in the integration of converging information—either on the subcortical (thalamus) or on a higher-order cortical level (comprising the angular gyrus). These findings point to dysfunctional emotion-cognition interactions in AOS, which may explain its poor prognosis. J. Am. Acad. Child Adolesc. Psychiatry, 2008;47(11): 1299–1310.     

Negative bias effects during audiovisual emotional processing in major depression disorder

Aberrant affective neural processing and negative emotional bias are trait‐marks of major depression disorders (MDDs). However, most research on biased emotional perception in depression has only focused on unimodal experimental stimuli, the neural basis of potentially biased emotional processing of multimodal inputs remains unclear. Here, we addressed this issue by implementing an audiovisual emotional task during functional MRI scanning sessions with 37 patients with MDD and 37 gender‐, age‐ and education‐matched healthy controls. Participants were asked to distinguish laughing and crying sounds while being exposed to faces with different emotional valences as background. We combined general linear model and psychophysiological interaction analyses to identify abnormal local functional activity and integrative processes during audiovisual emotional processing in MDD patients. At the local neural level, MDD patients showed increased bias activity in the ventromedial prefrontal cortex (vmPFC) while listening to negative auditory stimuli and concurrently processing visual facial expressions, along with decreased dorsolateral prefrontal cortex (dlPFC) activity in both the positive and negative visual facial conditions. At the network level, MDD exhibited significantly decreased connectivity in areas involved in automatic emotional processes and voluntary control systems during perception of negative stimuli, including the vmPFC, dlPFC, insula, as well as the subcortical regions of posterior cingulate cortex and striatum. These findings support a multimodal emotion dysregulation hypothesis for MDD by demonstrating that negative bias effects may be facilitated by the excessive ventral bottom‐up negative emotional influences along with incapability in dorsal prefrontal top‐down control system.     

Alexithymia influences brain activation during emotion perception but not regulation

Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes.     

Neural substrates of olfactory processing in schizophrenia patients and their healthy relatives

Odorants represent powerful stimuli capable of eliciting various emotional responses. In schizophrenia patients and their non-affected relatives, olfactory and emotional functions are impaired, revealing a familial influence on these deficits. We aimed at determining the neural basis of emotional olfactory dysfunctions using odors of different emotional valence for mood induction and functional magnetic resonance imaging (fMRI) by comparing 13 schizophrenia patients, their non-affected brothers and 26 matched healthy controls. Blood-oxygen-level-dependent (BOLD) effects and subjective mood changes were assessed during negative (rotten yeast), positive (vanilla) and neutral (ambient air) olfactory stimulation. Group comparisons of brain activation were performed in regions of interest. Subjective ratings were comparable between groups and indicated successful mood induction. However, during stimulation with the negative odor, hypofunctional activity emerged in regions of the right frontal and temporal cortex in the patients. A familial influence in the neural substrates of negative olfactory dysfunction was indicated by a similar reduced frontal brain activity in relatives. Dysfunctions therefore appeared to be located in regions involved in higher cognitive processes associated with olfaction. No familial influences were indicated for cerebral dysfunctions during positive olfactory stimulation. Results point to a differentiation between trait and state components in cerebral dysfunctions during emotional olfactory processing in schizophrenia.     

Early visual ERPs are influenced by individual emotional skills

Processing information from faces is crucial to understanding others and to adapting to social life. Many studies have investigated responses to facial emotions to provide a better understanding of the processes and the neural networks involved. Moreover, several studies have revealed abnormalities of emotional face processing and their neural correlates in affective disorders. The aim of this study was to investigate whether early visual event-related potentials (ERPs) are affected by the emotional skills of healthy adults. Unfamiliar faces expressing the six basic emotions were presented to 28 young adults while recording visual ERPs. No specific task was required during the recording. Participants also completed the Social Skills Inventory (SSI) which measures social and emotional skills. The results confirmed that early visual ERPs (P1, N170) are affected by the emotions expressed by a face and also demonstrated that N170 and P2 are correlated to the emotional skills of healthy subjects. While N170 is sensitive to the subject’s emotional sensitivity and expressivity, P2 is modulated by the ability of the subjects to control their emotions. We therefore suggest that N170 and P2 could be used as individual markers to assess strengths and weaknesses in emotional areas and could provide information for further investigations of affective disorders.     

Neural correlates of processing emotional prosody in unipolar depression

Major depressive disorder (MDD) is characterized by a biased emotion perception. In the auditory domain, MDD patients have been shown to exhibit attenuated processing of positive emotions expressed by speech melody (prosody). So far, no neuroimaging studies examining the neural basis of altered processing of emotional prosody in MDD are available. In this study, we addressed this issue by examining the emotion bias in MDD during evaluation of happy, neutral, and angry prosodic stimuli on a five‐point Likert scale during functional magnetic resonance imaging (fMRI). As expected, MDD patients rated happy prosody less intense than healthy controls (HC). At neural level, stronger activation in the middle superior temporal gyrus (STG) and the amygdala was found in all participants when processing emotional as compared to neutral prosody. MDD patients exhibited an increased activation of the amygdala during processing prosody irrespective of valence while no significant differences between groups were found for the STG, indicating that altered processing of prosodic emotions in MDD occurs rather within the amygdala than in auditory areas. Concurring with the valence‐specific behavioral effect of attenuated evaluation of positive prosodic stimuli, activation within the left amygdala of MDD patients correlated with ratings of happy, but not neutral or angry prosody. Our study provides first insights in the neural basis of reduced experience of positive information and an abnormally increased amygdala activity during prosody processing.     

Influence of Emotional Processing on Working Memory in Schizophrenia

Research on emotional processing in schizophrenia suggests relatively intact subjective responses to affective stimuli “in the moment.” However, neuroimaging evidence suggests diminished activation in brain regions associated with emotional processing in schizophrenia. We asked whether given a more vulnerable cognitive system in schizophrenia, individuals with this disorder would show increased or decreased modulation of working memory (WM) as a function of the emotional content of stimuli compared with healthy control subjects. In addition, we examined whether higher anhedonia levels were associated with a diminished impact of emotion on behavioral and brain activation responses. In the present study, 38 individuals with schizophrenia and 32 healthy individuals completed blocks of a 2-back WM task in a functional magnetic resonance imaging scanning session. Blocks contained faces displaying either only neutral stimuli or neutral and emotional stimuli (happy or fearful faces), randomly intermixed and occurring both as targets and non-targets. Both groups showed higher accuracy but slower reaction time for negative compared to neutral stimuli. Individuals with schizophrenia showed intact amygdala activity in response to emotionally evocative stimuli, but demonstrated altered dorsolateral prefrontal cortex (DLPFC) and hippocampal activity while performing an emotionally loaded WM-task. Higher levels of social anhedonia were associated with diminished amygdala responses to emotional stimuli and increased DLPFC activity in individuals with schizophrenia. Emotional arousal may challenge dorsal-frontal control systems, which may have both beneficial and detrimental influences. Our findings suggest that disturbances in emotional processing in schizophrenia relate to alterations in emotion-cognition interactions rather than to the perception and subjective experience of emotion per se.     

Lower effective connectivity between amygdala and parietal regions in response to fearful faces in schizophrenia

Behavioral abnormalities related to processing negative emotions such as fear have been demonstrated in schizophrenia. The amygdala is strongly associated with fear processing, and alterations in amygdala function and structure have been demonstrated in schizophrenia. Further, functional disconnectivity has been attributed as key to the etiology of schizophrenia, with a number of lines of evidence supporting this theory. In the present study, we examine the effective connectivity corresponding to fear processing, from the amygdala to the whole brain, and compare this between patients with schizophrenia and control participants. An implicit facial emotion processing task was performed by 19 patients with schizophrenia and 24 matched controls during fMRI scanning. During the task, participants made gender judgments from facial images with either neutral or fearful emotion. Neural response to fearful images versus neutral was used as contrast of interest to estimate effective connectivity between the amygdala and the whole brain using the psycho-physiological interactions approach. This connectivity was compared between patients with schizophrenia and healthy controls. We show that when looking at fearful compared to neutral faces patients with schizophrenia show significantly reduced effective connectivity from the amygdala to a large cluster of regions including parts of the precuneus and parietal lobe, compared to healthy controls. These regions have been associated with emotion processing and high level social cognition tasks involving self related processing and mental representations about other people. The reduced amygdala connectivity in schizophrenia shown here further illuminates the neural basis for the behavioral abnormalities in emotional and social function found in the disorder.     

Neural representation and clinically relevant moderators of individualised self-criticism in healthy subjects

Many people routinely criticise themselves. While self-criticism is largely unproblematic for most individuals, depressed patients exhibit excessive self-critical thinking, which leads to strong negative affects. We used functional magnetic resonance imaging in healthy subjects (N = 20) to investigate neural correlates and possible psychological moderators of self-critical processing. Stimuli consisted of individually selected adjectives of personally negative content and were contrasted with neutral and negative non-self-referential adjectives. We found that confrontation with self-critical material yielded neural activity in regions involved in emotions (anterior insula/hippocampus–amygdala formation) and in anterior and posterior cortical midline structures, which are associated with self-referential and autobiographical memory processing. Furthermore, contrasts revealed an extended network of bilateral frontal brain areas. We suggest that the co-activation of superior and inferior lateral frontal brain regions reflects the recruitment of a frontal top–down pathway, representing cognitive reappraisal strategies for dealing with evoked negative affects. In addition, activation of right superior frontal areas was positively associated with neuroticism and negatively associated with cognitive reappraisal. Although these findings may not be specific to negative stimuli, they support a role for clinically relevant personality traits in successful regulation of emotion during confrontation with self-critical material.     

Regional cerebral changes and functional connectivity during the observation of negative emotional stimuli in subjects with post-traumatic stress disorder

Patients with post-traumatic stress disorder (PTSD) exhibit exaggerated brain responses to emotionally negative stimuli. Identifying the neural correlates of emotion regulation in these subjects is important for elucidating the neural circuitry involved in emotional dysfunction. The aim of this study was to investigate the functional connectivity between the areas activated during emotional processing of negative stimuli in a sample of individuals affected by PTSD compared to a group of healthy subjects. Ten subjects with PTSD (who survived the L’Aquila 2009 earthquake) and ten healthy controls underwent fMRI during which the participants observed 80 images: 40 pictures with negative emotional valence and 40 neutral (scrambled) stimuli. A higher activation was found in the left posterior (LP) insula for PTSD group and in the ventromedial prefrontal cortex (vmPFC) for the healthy group. Two sets of Granger causality modeling analyses were performed to examine the directed influence from LP-insula and vmPFC to other brain regions. Activity in the vmPFC in the healthy group while observing negative stimuli predicted activity in several subcortical regions and insula, while in the PTSD group the LP-insula exerted a positive directed influence on several cortical regions. The hyperactivation in PTSD subjects of subcortical areas such as the insula would underlie the emotional, social, and relational difficulties of PTSD patients.     

Functional imaging of emotions and emotional dysfunctions in schizophrenia patients

Emotions have been discussed in earliest psychiatric literature as core characteristics of psychiatric patients. More recently emotions got back into the focus of modern neuropsychiatric imaging research. This is due to the outstanding importance of emotions for psychiatric symptomatology and also to recent technical developments in neuroimaging, which lay the ground for more complex paradigms. Especially schizophrenic patients show deficits in emotional functioning, such as in mood induction or emotion discrimination. It is subject to discussion how stable these dysfunctions are over the course of schizophrenia, e.g. in prodromal stage. Therefore research also deals with juvenile patients with schizophrenia-like symptoms. In the future it will be essential to characterize the effect of emotions on cognitive functions in healthy subjects and psychiatric patients.     

Neural long-term effects of emotion regulation on episodic memory processes

Emotions can enhance memory which is on the one hand advantageous, but on the other hand may be detrimental in the long term, for example in the case of traumatic events. Although cognitive emotion regulation may reduce emotion experience and corresponding neural activation, at present little is known about its influence on long-term memory. We investigated memory for emotional pictures in healthy female subjects 1 year after voluntary emotion regulation using fMRI. Whereas memory performance was not affected by regulation, our data revealed a dissociation of brain regions involved in memory encoding and recognition depending on whether emotional engagement during encoding had been downregulated. Emotional engagement during encoding resulted in a long-term subsequent memory effect in mesolimbic brain regions and hippocampus, and in recognition-related activation in the amygdala. In contrast, when negative emotions had been downregulated during encoding memory performance was predicted by prefrontal activation. Our data suggest that memory for emotionally encoded stimuli is supported by emotional re-activation, whereas memory for successfully encoded items during emotion regulation is rather supported by recognition of features and cognitive contents. These results contribute to research on long-term effects of emotion regulation in everyday life and open new avenues to understand and possibly influence traumatic memory traces.