Can neutral episodic memories become emotional? Evidence from facial expressions and subjective feelings.

Maladaptive emotional memories are a transdiagnostic feature of mental health problems. Therefore, understanding whether and how emotional memories can change might help to prevent and treat mental disorders. We tested whether neutral memories of naturalistic events can retroactively acquire positive or negative affect, in a preregistered three-day Modification of Valence in Episodes (MOVIE) paradigm. On Day 1, participants (N = 41) encoded memories of neutral movie scenes, representing lifelike naturalistic experiences. On Day 2, they retrieved each episode before viewing a happy, sad, or neutral scene from the same movie (yielding a within-subjects design with a neutral-negative, neutral-positive, and neutral-neutral condition). On Day 3, participants again retrieved each memory from Day 1. We assessed the affective tone of episodes through facial expressions of positive and negative affect (using facial electromyography, fEMG) and through self-reported feelings. Positive updating of neutral episodes led to increased expressions of positive affect, whereas negative updating led to increased self-reported negative feelings. These results suggest that complex neutral episodic memories can retroactively acquire an affective tone, but the effects were modest and inconsistent across affect readouts. Future research should investigate alternative approaches to updating emotional memories that produce more profound changes in the valence of memories.

No evidence that arousal affects reactivated memories.

Memory for inherently neutral elements of emotional events is often enhanced on delayed tests - an effect that has been attributed to noradrenergic arousal. Reactivation of a memory is thought to return its corresponding neural ensemble to a state that is similar to when it was originally experienced. Therefore, we hypothesized that neutral elements of memories, too, can be enhanced through reactivation concurrent with heightened arousal. Participants (n = 94) visited the lab for three sessions. During the first session, they encoded 120 neutral memories consisting of an object presented in unique context images. In session two, the 80 objects were reactivated by presenting their corresponding context images, 40 of which were immediately followed by an arousal-inducing shock. Finally, recognition memory for all objects was tested. It was found that memory for reactivated objects was enhanced, but even though the shocks elicited elevations in arousal as indexed by skin conductance, there was no difference between memory of objects reactivated with and without heightened arousal. We thus conclude that arousal, when isolated from other cognitive and affective variables that might impact memory, has no enhancing effect on reactivated memories.

Bayesian evaluation of diverging theories of episodic and affective memory distortions in dysphoria.

People suffering from dysphoria retrieve autobiographical memories distorted in content and affect, which may contribute to the aetiology and maintenance of depression. However, key memory difficulties in dysphoria remain elusive because theories disagree how memories of different valence are altered. Here, we assessed the psychophysiological expression of affect and retrieved episodic detail while participants with dysphoria (but without a diagnosed mental illness) and participants without dysphoria relived positive, negative, and neutral memories. We show that participants with dysphoria retrieve positive memories with diminished episodic detail and negative memories with enhanced detail, compared to participants without dysphoria. This is in line with negativity bias but not overgeneral memory bias theories. According to confirmatory analyses, participants with dysphoria also express diminished positive affect and enhanced negative affect when retrieving happy memories, but exploratory analyses suggest that this increase in negative affect may not be robust. Further confirmatory analyses showed that affective responses to memories are not related to episodic detail and already present during the experience of new emotional events. Our results indicate that affective memory distortions may not emerge from mnemonic processes but from general distortions in positive affect, which challenges assumptions of memory theories and therapeutics. Protocol registration: The Stage 1 protocol for this Registered Report was accepted in principle on the 18rd of March 2021. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.14605374.v1 .

A brief treatment for veterans with PTSD: an open-label case-series study.

Introduction: Despite the positive outcomes observed in numerous individuals undergoing trauma-focused psychotherapy for PTSD, veterans with this condition experience notably diminished advantages from such therapeutic interventions in comparison to non-military populations. Methods: In a preliminary study we investigated the efficacy of an innovative treatment approach in a small sample of veterans (n = 7). Recognizing that accessing and targeting trauma memory in veterans with PTSD may be more challenging compared to other patient populations, we employed unique and personalized retrieval cues that engaged multiple senses and were connected to the context of their trauma. This was followed by a session focused on memory reconsolidation, which incorporated both psychological techniques (i.e., imagery rescripting) and a pharmacological component (i.e., 40 mg of propranolol). Results: The findings from this small-scale case series cautiously indicate that this brief intervention, typically consisting of only one or two treatment sessions, shows promise in producing significant effects on symptoms of PTSD, distress and quality of life.This is particularly noteworthy given the complex symptomatology experienced by the veterans in this study. Conclusion: To summarize, there are grounds for optimism regarding this brief treatment of combat-related PTSD. It appears that the potential for positive outcomes is far greater than commonly believed, as demonstrated by the encouraging results of this pilot study.

Context reexposure to bolster contextual dependency of emotional episodic memory.

Contextual overgeneralization of emotional memory is a core aspect of anxiety disorders. Identifying methods to enhance contextual dependency of emotional memory is therefore of significant clinical interest. Animal research points to a promising approach: reexposure to the context in which fear is acquired reduces generalization to other contexts. However, the exact conditions for this effect are unknown, complicating translation to effective interventions. Most notably, exposure to a context that resembles-but is not identical to-the learning context may diminish contextual dependency of memory by integration of additional contextual cues. Here, we therefore assessed in a large-scale study (N = 180) whether context reexposure enhances contextual dependency of emotional episodic memory whereas exposure to a similar context impairs it. We also tested whether relatively strong memory retrieval during context (re)exposure amplifies these effects. We replicated prior research showing that correct recognition depends on context and contextual dependency is lower for emotional than neutral memories. However, exposure to the encoding context or a similar context did not affect contextual dependency of memory, and retrieval strength did not interact with such effects. Thorough insight into factors underlying the effects of context (re)exposure on contextual dependency seems key to eventually attain a memory recontextualization intervention.

Manipulating expectancy violations to strengthen the efficacy of human fear extinction.

Recent theoretical and clinical articles have emphasized a role for expectancy violations in improving the effectiveness of exposure therapy. Expectancy violations are critical to extinction learning and strengthening these violations has been suggested to improve the formation and retention of extinction memories, which should result in lasting symptom reductions after treatment. However, more detailed mechanistic insights in this process are needed to better inform clinical interventions. In two separate fear-conditioning experiments, we investigated whether stronger expectancy violations (Exp1) or fostering awareness of expectancy violations (Exp2) during extinction could reduce the subsequent return of fear. We measured fear potentiated startle (FPS) and skin conductance responses (SCR) as physiological indices of fear, and US expectancy ratings to assess our manipulations. While we successfully created stronger expectancy violations in Exp1, we found no evidence that these stronger violations reduced the return of fear at test. Interestingly, fostering awareness of violations (Exp2) reduced differential SCRs, but not FPS responses. These findings provide novel insights into the effect of US expectancies on fear extinction in the lab, but they also illustrate the complexity of capturing clinically relevant processes of change with fear-conditioning studies.

Time-dependent emotional memory transformation: Divergent pathways of item memory and contextual dependency.

Emotional memory can persist strikingly long, but it is believed that not all its elements are protected against the fading effects of time. So far, studies of emotional episodic memory have mostly investigated retention up to 24h postencoding and revealed that central emotional features (items) are usually strengthened, while contextual binding of the event is reduced. However, even though it is known for neutral memories that central versus contextual elements evolve differently with longer passage of time, the time-dependent evolution of emotional memories remains unclear. Hypothetically, compared to neutral memories, emotional item memory becomes increasingly stronger, accompanied by accelerated decay of-already fragile-links with their original encoding contexts, resulting in progressive reductions in contextual dependency. Here, we tested these predictions in a large-scale study. Participants encoded emotional and neutral episodes, and were assessed 30 minutes (N = 40), 1 day (N = 40), 1 week (N = 39), or 2 weeks (N = 39) later on item memory, contextual dependency, and subjective quality of memory. The results show that, with the passage of time, emotional memories were indeed characterized by increasingly stronger item memory and weaker contextual dependency. Interestingly, analyses of the subjective quality of memories revealed that stronger memory for emotional items with time was expressed in familiarity, whereas increasingly smaller contextual dependency for emotional episodes was reflected in recollection. Together, these findings uncover the time-dependent transformation of emotional episodic memories, thereby shedding light on the ways healthy and maladaptive human memories may develop. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Emotional memory in the lab: Using the Trier Social Stress Test to induce a sensory-rich and personally meaningful episodic experience.

A myriad of clinical theories places emotional memory or mental representations at the root of mental disorders. Various cognitive-behavioural interventions are based on the assumption that targeting the underlying emotional memory is the working mechanism of treatment efficacy. To test the assumptions about the role of emotional memory in the development, maintenance, and treatment of mental disorders, we first need to establish ecologically valid paradigms that can induce emotional memory in the lab. For this, we used the Trier Social Stress Test (TSST), a standardized protocol to elicit social distress, paired with a neutral unfamiliar ambient odour, to create a sensory-rich and personally meaningful episodic experience. Seven days later, participants (N = 132) reactivated the memory of the TSST with the aid of auditory, olfactory, and visual retrieval cues, during which their heart rate and self-reported affective responses were collected. Although increases in heart rate were only observed during encoding, and not at retrieval, self-report ratings showed that cues which directly referred to the aversive experience evoked more negative valence, arousal, and feelings of lack of control during memory reactivation compared to control cues across sensory modalities. These findings are indicative of successful memory induction and corroborate the utility of ambient odours as retrieval aids. Moreover, the self-reported response to the reactivated emotional memory correlated with individual differences in indices of (social) anxiety and depression. Thereby, we provide preliminary evidence of the translational significance of this paradigm that offers potential for being a model to induce ecologically valid emotional memory in the lab.

A paradigm shift in the treatment of emotional memory disorders: Lessons from basic science.

Experiments demonstrating post-reactivation amnesia for learned fear in animals have generated a novel and influential hypothesis on the plasticity of memory, usually referred to as memory reconsolidation. The clinical potential of pharmacologically disrupting the process of memory reconsolidation has sparked a wave of interest into whether this phenomenon can also be demonstrated in humans, and ultimately harnessed for therapeutic purposes. In this essay we outline how the work of Karim Nader and colleagues has moved the field forward from a focus on extinction learning to the prospect of disrupting memory reconsolidation. We then review some promising findings on the necessary conditions, as well as potential boundary conditions, of pharmacologically disrupting the process of memory reconsolidation obtained in our laboratory. Even though laboratory experiments in animals and humans suggest that we may be at the brink of a breakthrough in fundamentally changing emotional memories, the necessary and sufficient conditions for targeting and disrupting memory reconsolidation in clinical practice are largely unknown. There is likely no universally effective reactivation procedure for triggering the reconsolidation of clinically significant emotional memories, and the impact of subtle boundary conditions observed in basic experiments compounds this issue. Notwithstanding these challenges, the discovery of changing emotional memory through disrupting the process of memory reconsolidation has unquestionably invigorated the field.

Threat learning impairs subsequent associative inference.

Despite it being widely acknowledged that the most important function of memory is to facilitate the prediction of significant events in a complex world, no studies to date have investigated how our ability to infer associations across distinct but overlapping experiences is affected by the inclusion of threat memories. To address this question, participants (n = 35) encoded neutral predictive associations (A → B). The following day these memories were reactivated by pairing B with a new aversive or neutral outcome (B → CTHREAT/NEUTRAL) while pupil dilation was measured as an index of emotional arousal. Then, again 1 day later, the accuracy of indirect associations (A → C?) was tested. Associative inferences involving a threat learning memory were impaired whereas the initial memories were retroactively strengthened, but these effects were not moderated by pupil dilation at encoding. These results imply that a healthy memory system may compartmentalize episodic information of threat, and so hinders its recall when cued only indirectly. Malfunctioning of this process may cause maladaptive linkage of negative events to distant and benign memories, and thereby contribute to the development of clinical intrusions and anxiety.

Do your troubles today seem further away than yesterday? On sleep's role in mitigating the blushing response to a reactivated embarrassing episode.

The "sleep to forget and sleep to remember hypothesis" proposes that sleep weakens the emotional tone of an experience while preserving or even enhancing its content. Prior experimental research however shows contradictory findings on how emotional reactivity changes after a period of sleep, likely explained by methodological variations. By addressing these inconsistencies, we investigated the mitigating effect of overnight sleep on emotional reactivity triggered by memory reactivation. Using a karaoke paradigm, we recorded participants' singing of two songs, followed by exposing them to one of the recordings (rec1) to induce an embarrassing episode. After a 12-hr period of either day-time wakefulness (N = 20) or including nighttime sleep (N = 20), we assessed emotional reactivity to the previously exposed recording (rec1) and the newly exposed recording (rec2). Emotional reactivity was assessed with a physiological measure of facial blushing as the main outcome and subjective ratings of embarrassment and valence. Sleep and wake were monitored with diaries and actigraphy. The embarrassing episode was successfully induced as indicated by objective and subjective measures. After controlling for an order effect in stimulus presentation, we found a reduction in blushing response to the reactivated recording (rec1) from pre- to post-sleep compared to wakefulness. However, emotional reactivity to the reactivated recording (rec1) and the new recording (rec2) did not differ after sleep and wakefulness. This study shows that facial blushing was reduced following overnight sleep, while subjective ratings were unaffected. Whether the beneficial effect of sleep is due to changes in memory representation or rather emotion regulation remains elusive.

Imagery Rescripting as a stand-alone treatment for posttraumatic stress disorder related to childhood abuse: A randomized controlled trial.

BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder (PTSD) related to childhood abuse (CA) is associated with high symptom complexity. This study examined the efficacy of Imagery Rescripting (ImRs) as a stand-alone treatment versus a sequenced approach with Skills training in Affective and Interpersonal Regulation (STAIR) followed by ImRs for CA-related PTSD. METHODS: Outpatients of two mental health clinics with CA-related PTSD (N = 61) were randomly assigned to ImRs (16 sessions; n = 21), STAIR/ImRs (8 STAIR-sessions followed by 16 ImRs-sessions; n = 20), or Waitlist (8 weeks; n = 20). Patients of the waitlist condition were also randomized to the two active conditions for comparison of STAIR/ImRs (total n for this condition = 31) and ImRs (total n for this condition = 30) and started treatment after waitlist completion. Assessments took place at pre-treatment, after each treatment phase and at 12-week post-intervention follow-up. PTSD symptoms and diagnosis were primary outcome measures, and depression, emotion regulation and interpersonal functioning were secondary outcomes. RESULTS: ImRs showed greater reduction of PTSD severity (effect sizes [ES] 1.40-1.63) than STAIR (ES, 0.23-0.33) as compared to waitlist. When comparing STAIR/ImRs and ImRs directly, (i.e. including re-randomized Waitlist-patients), PTSD symptoms reduced significantly (within condition ES, 1.64-2.10) and improved further to 12-week follow-up (within-condition ES, 2.33-2.66), with no significant difference between both conditions (between-condition ES, 0.21-0.45). Loss of PTSD diagnosis was achieved by 70% in the ImRs condition and 86% in the STAIR/ImRs condition. LIMITATIONS: The sample size was relatively small. CONCLUSIONS: Results show that ImRs is an effective treatment for CA-related PTSD, whereby the current data do not convincingly show an additive effect of STAIR.

Pupil dilation and skin conductance as measures of prediction error in aversive learning.

Notwithstanding the success of CBT, it is relatively unknown how individuals can better profit from corrective learning experiences. Various theories postulate that prediction errors - the difference between what is occurring and what is expected - are the driving force of associative (re)learning. While prediction errors are typically operationalized as violations of cognitive outcome expectancies, direct physiological indices of prediction errors could capture potentially more essential automatic and emotional processes in associative learning. Although physiological responses have previously been suggested to reflect prediction errors, it remains elusive if these measures actually predict changes in subsequent conditioned responding. In three fear-conditioning experiments, we compared pupil dilation and skin conductance responses to unexpected outcomes - unconditioned stimulus (US) presentations or omissions - with expected outcomes, and tested whether outcome responses predicted actual changes in subsequent conditioned responding. We found evidence for increased physiological responses to unexpected outcomes, but the results were inconsistent across experiments. Furthermore, only pupil responses to US presentations consistently predicted an increase in conditioned responding, making it difficult to reconcile our findings with associative learning models. Both pupil dilation and skin conductance can thus index unexpected outcomes, but the relationship of these responses to future learning is not evident and requires further investigation.

Jumping back onto the giants' shoulders: Why emotional memory should be considered in a network perspective of psychopathology.

Clinical psychology finds itself with a paradox: On the one hand, there is abundant empirical evidence showing that aversive experiences increase the risk for psychopathology. In fact, a learning and memory framework forms the foundation of numerous psychological theories and treatments. For example, various CBT approaches aim to target maladaptive emotional memories (e.g., schemas or cognitions) that are deemed to lie at the core of mental health conditions. On the other hand, a new approach - the network theory - is gaining ground, which ignores underlying causes for mental disorders and instead dictates a focus on symptoms and their causal interactions. While radical shifts are sometimes necessary in science, we argue why completely neglecting common causes, such as emotional memory, is not justified. We critically discuss the strengths and limitations of the network approach: While its transdiagnostic nature and recognition of symptom interactions have the potential to invigorate the field, the framework is merely descriptive, its concepts not well defined, and its clinical utility still to be established. To move forward, we propose an incorporation of latent constructs into the network model, starting with clearer definitions and operationalisations of concepts in both network and latent variable models.

More than just fear: Development and psychometric evaluation of the Spider Distress Scale to assess spider fear and spider-related disgust.

Spider fear is an excellent model to experimentally study processes in the maintenance and treatment of long-lasting fears. A valid, reliable, and practical tool to assess spider-related distress dimensionally, and to differentiate between spider-related fear and disgust in a time-sensitive manner, may help to better understand individual differences in these two emotions and to tailor treatments accordingly. We developed a concise self-report questionnaire, the Spider Distress Scale (SDS), that combines the strengths of established spider fear questionnaires and addresses their shortcomings. We explored (study 1 and 2) and confirmed (study 3) a two-factor structure of the SDS in samples from the general population (n = 370; n = 360; n = 423), recruited online via Prolific Academic from the United Kingdom, the Netherlands, and the United States. The fear and disgust factors of the SDS are highly internally consistent and the SDS has excellent test-retest reliability. We found good convergent and discriminant validity, based on self-report measures and spider behavioural approach tasks, and the SDS successfully differentiated between individuals with and without spider fear (study 4, n = 75). Our series of studies suggests that fear and disgust are functionally related, but that disgust towards spiders can be differentially assessed when focussing on unique elements of disgust-related information.

Interfering With Contextual Fear Memories by Post-reactivation Administration of Propranolol in Mice: A Series of Null Findings.

Post-reactivation amnesia of contextual fear memories by blockade of noradrenergic signaling has been shown to have limited replicability in rodents. This is usually attributed to several boundary conditions that gate the destabilization of memory during its retrieval. How these boundary conditions can be overcome, and what neural mechanisms underlie post-reactivation changes in contextual fear memories remain largely unknown. Here, we report a series of experiments in a contextual fear-conditioning paradigm in mice, that were aimed at solving these issues. We first attempted to obtain a training paradigm that would consistently result in contextual fear memory that could be destabilized upon reactivation, enabling post-retrieval amnesia by the administration of propranolol. Unexpectedly, our attempts were unsuccessful to this end. Specifically, over a series of experiments in which we varied different parameters of the fear acquisition procedure, at best small and inconsistent effects were observed. Additionally, we found that propranolol did not alter retrieval-induced neural activity, as measured by the number of c-Fos+ cells in the hippocampal dentate gyrus. To determine whether propranolol was perhaps ineffective in interfering with reactivated contextual fear memories, we also included anisomycin (i.e., a potent and well-known amnesic drug) in several experiments, and measures of synaptic glutamate receptor subunit GluA2 (i.e., a marker of memory destabilization). No post-retrieval amnesia by anisomycin and no altered GluA2 expression by reactivation was observed, suggesting that the memories did not undergo destabilization. The null findings are surprising, given that the training paradigms we implemented were previously shown to result in memories that could be modified upon reactivation. Together, our observations illustrate the elusive nature of reactivation-dependent changes in non-human fear memory.

Over the Edge: Extending the duration of a reconsolidation intervention for spider fear.

Pharmacologically disrupting fear memory reconsolidation dramatically reduces fear behaviour. For example, 2-3 min of tarantula exposure followed by 40 mg of propranolol HCl (i.e., a reconsolidation intervention) abruptly decreased spider avoidance, an effect that persisted one year later. However, the success of reconsolidation interventions is not guaranteed: Pavlovian fear-conditioning research shows that the window to target memory reconsolidation is small and easy to miss. If exposure is too long to trigger reconsolidation, but too short for extinction learning, an inactive transitional limbo state occurs, rendering the fear memory unchanged and insensitive to amnesic agents. In this pre-registered study, we aimed to find this behaviourally-controlled boundary condition. Spider-fearful participants underwent a ~3 min (n = 23) or ~14 min (n = 20) exposure to a tarantula, intended to trigger reconsolidation or the limbo state respectively, followed by 40 mg of propranolol. We expected greater spider fear reduction after 3 than 14 min of exposure. Unexpectedly, there were no group differences on any outcome measures. In both groups, Bayesian analysis revealed a marked reduction in fear behaviour towards a generalisation stimulus (a house spider) accompanied by lower self-reported distress, with a sharp decline in spider fear scores two days after treatment that persisted one year later. Possible explanations include that the boundary conditions of reconsolidation are wider in older and stronger memories than experimentally-induced fears, or that alternative processes caused the treatment effects. Although the mechanism is unclear, these results carry a tentative promising message for the potential of brief reconsolidation-targeting interventions to mitigate irrational fears.

A new science of mental disorders: Using personalised, transdiagnostic, dynamical systems to understand, model, diagnose and treat psychopathology.

The core ideas of a 10-year research program 'New Science of Mental Disorders' are outlined. This research program moves away from the disorder-based 'one-model-fits-all' approach to treating mental disorders, and adopts the network approach to psychopathology as its foundation of research. Its core assumption is that dynamically interacting symptoms constitute the disorder. Our goal is to further develop the network approach by studying (1) dynamic networks of symptoms and other variables (i.e., elements) in a large number of individuals with a wide range of mental disorders from a transdiagnostic perspective (network-based diagnosis; mapping), including both Ecological Momentary Assessment (EMA) and digital phenotyping, (2) the transdiagnostic mechanisms reflecting potential causal relations among elements of the networks by performing experimental (pre-)clinical studies (zooming), and (3) the effectiveness of personalised network-informed interventions (targeting). Challenges to overcome in this research program are discussed, which relate to data collection (e.g., selection of EMA variables) and data analyses (e.g., power considerations), the development and application of network-informed diagnoses and network-informed interventions (e.g., what characteristic(s) of the network to target in interventions), and the implementation in clinical practice (e.g., train therapists in the use of networks in therapy).

In search of the behavioral effects of fear: A paradigm to assess conditioned suppression in humans.

Conditioned fear can substantially reduce the likelihood that an individual will engage in reward-related behavior--a phenomenon coined conditioned suppression. Despite the unmistakable relevance of conditioned suppression for excessive fears and their adverse consequences, the phenomenon has primarily been observed in animal models and is not yet well understood. Here, we aimed to develop a conditioned suppression paradigm that enables a robust quantification of the effect of Pavlovian fear on subsequent reward-related behavior in humans and assess its potential relation to physiological measures of fear. In phase 1, an instrumental response was incentivized with monetary rewards. In phase 2, one of two conditioned stimuli (CS+) was reinforced with an aversive unconditioned stimulus (US, i.e., electric stimulus). During Pavlovian fear learning we assessed differential skin conductance (SCR) and fear- potentiated startle responses (FPS). Lastly, we tested the effect of the fear conditioned CS+ on the response rate of the instrumental response in a transfer phase. Despite strong Pavlovian fear conditioning, as indicated by large effect sizes in differential SCR and FPS, we did not find any evidence for conditioned suppression: that is, there was no significant reduction of instrumental responding in the presence of the CS+ compared to a new control stimulus. This lack of conditioned suppression is in line with previous studies that reported difficulties inducing conditioned suppression and points toward a general challenge in investigating conditioned suppression in humans. Implications and directions for future research on the highly relevant behavioral effects of fear and anxiety are discussed.

Demarcating the boundary conditions of memory reconsolidation: An unsuccessful replication.

Disrupting memory reconsolidation provides an opportunity to abruptly reduce the behavioural expression of fear memories with long-lasting effects. The success of a reconsolidation intervention is, however, not guaranteed as it strongly depends on the destabilization of the memory. Identifying the necessary conditions to trigger destabilization remains one of the critical challenges in the field. We aimed to replicate a study from our lab, showing that the occurrence of a prediction error (PE) during reactivation is necessary but not sufficient for destabilization. We tested the effectiveness of a reactivation procedure consisting of a single PE, compared to two control groups receiving no or multiple PEs. All participants received propranolol immediately after reactivation and were tested for fear retention 24 h later. In contrast to the original results, we found no evidence for a reconsolidation effect in the single PE group, but a straightforward interpretation of these results is complicated by the lack of differential fear retention in the control groups. Our results corroborate other failed reconsolidation studies and exemplify the complexity of experimentally investigating this process in humans. Thorough investigation of the interaction between learning and memory reactivation is essential to understand the inconsistencies in the literature and to improve reconsolidation interventions.