Differential effects of clonazepam on declarative memory formation and face recognition.

Benzodiazepines are commonly used drugs to treat anxiety in crime witnesses. These increase GABA inhibitory effects, which impairs aversive memory encoding and consolidation. Eyewitness memory is essential in justice. However, memory is malleable leading to false memories that could cause a selection of an innocent in a lineup. Here, we studied whether a low dose of Clonazepam impairs memory encoding as well as consolidation of faces and narrative of the event. We performed two experiments using a double-blind and between subject design (N = 216). Day 1: subjects watched a crime video and received Clonazepam 0.25 mg (CLZ group) or placebo (PLC group) before (Exp. 1) or after the video (Exp. 2) to assess the effect on encoding and consolidation. One week later, the memory was assessed using a present and absent target lineup and asking for a free recall. Regarding encoding, we found that in the CLZ group memory was impaired in the free recall task, while no differences were found for recognition memory. Regarding consolidation, we did not observe memory measures that were affected by this dose of benzodiazepines. The results suggest that while some aspects of eyewitness memory could be modulated even with low doses of benzodiazepine, others could not be affected. More studies should be performed with higher doses of CLZ similar to those administered in real life. These results are relevant in the judicial field to assess the reliability of the eyewitness elections under the effects of this drug.

Spontaneous and induced out-of-body experiences during sleep paralysis: Emotions, "AURA" recognition, and clinical implications.

Sleep paralysis is characterized by the incapacity to perform voluntary movements during sleep/wake transitions, and could bring great discomfort. During sleep paralysis, out-of-body experiences can occur. Out-of-body experiences refers to the sensation of being outside of the physical body and perceiving the world from this outside perspective; however, they are pleasant in comparison with other sleep paralysis hallucinations. Lucid dreams are dreams in which a subject becomes aware of being dreaming while the dream occurs. Here, we designed an online survey to study the predominant and specific emotions during sleep paralysis and/or out-of-body experience events as well as the somatosensory perceptions that preceded their occurrence. The sample (N = 329) was divided into experimental groups depending on the presence/absence of out-of-body experiences, capacity to induce (or not) out-of-body experiences, and perception/no-perception of the sleep paralysis. We showed that more positive emotions were associated with out-of-body experiences and more negative emotions were associated with sleep paralysis episodes, and for those who claim the ability to induce out-of-body experiences, positive emotions were more frequent in their episodes. We found that subjects perceived auditory, tactile and visual sensations before sleep paralysis episodes, and we proposed that these could be an "aura" of sleep paralysis. Furthermore, subjects that had out-of-body experiences but had never felt the sleep paralysis, perceived tactile and visual sensations to the same extent as subjects with out-of-body experiences that felt the sleep paralysis. Therefore, we proposed that the "aura" recognition could be used under controlled conditions for out-of-body experiences induction in patients with sleep paralysis to diminish the negative symptoms associated with sleep paralysis episodes.

Impairment of aversive episodic memories during Covid-19 pandemic: The impact of emotional context on memory processes.

The threatening context of the COVID-19 pandemic provided a unique setting to study the effects of negative psychological symptoms on memory processes. Episodic memory is an essential function of the human being related to the ability to store and remember experiences and anticipate possible events in the future. Studying this function in this context is crucial to understand what effects the pandemic will have on the formation of episodic memories. To study this, the formation of episodic memories was evaluated by free recall, recognition, and episode order tasks for an aversive and neutral content. The results indicated that aversive episodic memory is impaired both in the free recall task and in the recognition task. Even the beneficial effect that emotional memory usually has for the episodic order was undermined as there were no differences between the neutral and aversive condition. The present work adds to the evidence that indicates that the level of activation does not modify memory processes in a linear way, which also depends on the type of recall and the characteristics of the content to be encoded.

Learning new words: Memory reactivation as a mechanism for strengthening and updating a novel word's meaning.

In the present study we explored the postlearning changes in a novel word's definition using a cue-induced memory reactivation. Native speakers of Spanish (N = 373) learned low-frequency words with their corresponding definitions. The following day, reactivated groups were exposed to a reminder and provided a subjective assessment of reactivation for each word, while control groups did not receive a reactivation. Study A demonstrated that memory reactivation enhances both explicit recall and semantic integration of new meanings. Study B investigated the effect of memory reactivation in the modification of the new meanings, through three different experiments. Results show an improvement of the updated definitions according to each word's reactivation strength. In addition, congruence with previous knowledge was suggested to be a boundary condition, while consolidation time had a positive modulatory effect. Our findings call attention to reactivation as a factor allowing for malleability as well as persistence of long-term memories for words.

The effect of zolpidem on targeted memory reactivation during sleep.

According to the active system consolidation theory, memory consolidation during sleep relies on the reactivation of newly encoded memory representations. This reactivation is orchestrated by the interplay of sleep slow oscillations, spindles, and theta, which are in turn modulated by certain neurotransmitters like GABA to enable long-lasting plastic changes in the memory store. Here we asked whether the GABAergic system and associated changes in sleep oscillations are functionally related to memory reactivation during sleep. We administered the GABAA agonist zolpidem (10 mg) in a double-blind placebo-controlled study. To specifically focus on the effects on memory reactivation during sleep, we experimentally induced such reactivations by targeted memory reactivation (TMR) with learning-associated reminder cues presented during post-learning slow-wave sleep (SWS). Zolpidem significantly enhanced memory performance with TMR during sleep compared with placebo. Zolpidem also increased the coupling of fast spindles and theta to slow oscillations, although overall the power of slow spindles and theta was reduced compared with placebo. In an uncorrected exploratory analysis, memory performance was associated with slow spindle responses to TMR in the zolpidem condition, whereas it was associated with fast spindle responses in placebo. These findings provide tentative first evidence that GABAergic activity may be functionally implicated in memory reactivation processes during sleep, possibly via its effects on slow oscillations, spindles and theta as well as their interplay.

Positive and neutral updating reconsolidate aversive episodic memories via different routes.

Aversive memories are long-lasting and prone to burden our emotional wellbeing and mental health. Yet, how to remedy the maladaptive effects of aversive memories remains elusive. Using memory reactivation and emotional updating manipulations, we investigated how positive and neutral emotion may update aversive memories for reconsolidation in humans. We found that positive updating after reactivation was equivalent to neutral updating in impairing true memories of a previous aversive event after a 12-hour wakeful delay, but induced more false memory. Moreover, additional 12-hour delay with overnight sleep did not further enlarge true memory differences, but attenuated the effect of reactivation and updating on false memory. Interestingly, the neutral rather than the positive updating reduced the emotional arousal of the aversive memory 24 h later. Our findings could serve as a reference for real-world therapeutic applications regarding how positive and neutral updating may reshape aversive memories, especially when taking wake- and sleep-filled reconsolidation into account.

Sleep accelerates re-stabilization of human declarative memories.

Consolidated memories can return to a labile state upon presentation of a reminder, followed by a period of re-stabilization known as reconsolidation. This period can take several hours, and if an amnesic agent (e.g. new learning) is administered inside the time window of reconsolidation (when the memory is still labile) the memory is impaired, whereas the memory remains unaffected if the amnesic agent is administered outside this time window. Sleep plays a fundamental role in the consolidation and integration of new memories, and recently sleep has also been implicated in memory reconsolidation. Here, we studied the role of sleep in accelerating the reconsolidation time window. On day 1, participants learned a list of syllable-pairs (List 1). On day 2, they received a reminder, followed by interference learning (List 2) administered either after 90 min of wakefulness, after 90 min of sleep, or after 10 h of wakefulness. On day 3, participants had to recall List 1 first, followed by List 2, and we assessed the Retrieval-Induced-Forgetting Effect (RIF) on List 2 as a measure of List 1 memory stability. We found that the 90 min sleep group showed an intact RIF effect similar to the 10 h wake group, reflecting stable List 1 memory after 90 min of sleep and after 10 h of wakefulness. However, the RIF effect was absent after 90 min of wakefulness, suggesting that the List 1 memory was still labile at that time. Moreover, the RIF effect in the 90 min sleep group was associated with power density in the slow oscillation frequency band (0.5-1 Hz) during SWS and S2. These findings suggest that 90 min of sleep accelerate memory re-stabilization after reminder presentation, shortening the reconsolidation time window and protecting the memory against subsequent interference. This rapid memory re-stabilization may depend on slow oscillation activity during NREM sleep.

The role of GABAA in the expression of updated information through the reconsolidation process in humans.

Consolidated memory can be again destabilized by the presentation of a memory cue (reminder) of the previously acquired information. During this process of labilization/restabilization memory traces can be either impaired, strengthened or updated in content. Here, we study if a consolidated memory can be updated by linking one original cue to two different outcomes and whether this process was modulated by the GABAergic system. To aim that, we designed two experiments carried out in three consecutive days. All participants learned a list of non-sense syllable pairs on day 1. On day 2 the new information was introduced after the reminder or no-reminder presentation. Participants were tested on day 3 for the updated or original list (Exp. 1). In Exp. 2 we tested whether this new information was incorporated by an inhibitory process mediated by the GABAergic system. For that, participants retrieved the original information before being taken Clonazepam 0.25mg (GABAA agonist) or Placebo pill. We found that the groups that received the reminder correctly recalled the old and new information. However, the no reminder groups only correctly recalled the original information. Furthermore, when testing occurred in the presence of Clonazepam, the group that received the reminder plus the new information showed an impaired original memory performance compared to the group that received only Clonazepam (without reminder) or the reminder plus Placebo pill. These results show that new information can be added to a reactivated declarative memory in humans by linking one cue to two different outcomes. Furthermore, we shed light on the mechanisms of memory updating being the GABAergic system involved in the modulation of the old and new information expression.

The dynamic nature of the reconsolidation process and its boundary conditions: Evidence based on human tests.

The reconsolidation process is the mechanism by which the strength and/or content of consolidated memories are updated. This process is triggered by the presentation of a reminder (training cues). It is not always possible to trigger the reconsolidation process. For example, memory age and strength are boundary conditions for the reconsolidation process. Here, we investigated the dynamic changes in these conditions. We propose that the boundary conditions of the reconsolidation process are not fixed and vary as a consequence of the interaction between memory features and reminder characteristics. To modify memory properties, participants received a threatening social protocol that improves memory acquisition or a control condition (fake, without social interaction) prior to learning pairs of meaningless syllables. To determine whether a strong young or old declarative memory undergoes the reconsolidation process, we used an interference task (a second list of pairs of meaningless syllables) to disrupt memory re-stabilization. To assess whether the older memory could be strengthened, we repeated the triggering of reconsolidation. Strong young or old memories modulated by a threatening experience could be interfered during reconsolidation and updated (strengthened) by reconsolidation. Rather than being fixed, boundary conditions vary according to the memory features (strong memory), which indicates the dynamic nature of the reconsolidation process. Our findings demonstrate that it is possible to modify these limits by recruiting the reconsolidation process and making it functionally operative again. This novel scenario opens the possibility to new therapeutically approaches that take into account the reconsolidation process.

Positive modulation of a neutral declarative memory by a threatening social event.

Memories can be altered by negative or arousing experiences due to the activation of the stress-responsive sympatho-adrenal-medullary axis (SYM). Here, we used a neutral declarative memory that was acquired during multi-trial training to determine the effect of a threatening event on memory without emotional valence. To this end, participants received a new threatening social protocol before learning pairs of meaningless syllables and were tested either 15 min, 2 days or 8 days after acquisition. We first demonstrated that this threatening social situation activates not only the SYM axis (Experiment 1) and the hypothalamus-pituitary-adrenal axis (HPA; Experiment 2), but also, it improves the acquisition or early consolidation of the syllable pairs (Experiment 3). This improvement is not a transient effect; it can be observed after the memory is consolidated. Furthermore, this modulation increases the persistence of memory (Experiment 4). Thus, it is possible to affect memories with specific events that contain unrelated content and a different valence.

Changing maladaptive memories through reconsolidation: A role for sleep in psychotherapy?

Like Lane et al., we believe that change in psychotherapy comes about by updating dysfunctional memories with new adaptive experiences. We suggest that sleep is essential to (re-)consolidate such corrective experiences. Sleep is well-known to strengthen and integrate new memories into pre-existing networks. Targeted sleep interventions might be promising tools to boost this process and thereby increase therapy effectiveness.

Comparing targeted memory reactivation during slow wave sleep and sleep stage 2.

Sleep facilitates declarative memory consolidation, which is assumed to rely on the reactivation of newly encoded memories orchestrated by the temporal interplay of slow oscillations (SO), fast spindles and ripples. SO as well as the number of spindles coupled to SO are more frequent during slow wave sleep (SWS) compared to lighter sleep stage 2 (S2). But, it is unclear whether memory reactivation is more effective during SWS than during S2. To test this question, we applied Targeted Memory Reactivation (TMR) in a declarative memory design by presenting learning-associated sound cues during SWS vs. S2 in a counterbalanced within-subject design. Contrary to our hypothesis, memory performance was not significantly better when cues were presented during SWS. Event-related potential (ERP) amplitudes were significantly higher for cues presented during SWS than S2, and the density of SO and SO-spindle complexes was generally higher during SWS than during S2. Whereas SO density increased during and after the TMR period, SO-spindle complexes decreased. None of the parameters were associated with memory performance. These findings suggest that the efficacy of TMR does not depend on whether it is administered during SWS or S2, despite differential processing of memory cues in these sleep stages.

One-week sleep hygiene education improves episodic memory in young but not in older adults during social isolation.

Memory formation is a dynamic process that comprises different phases, such as encoding, consolidation and retrieval. It could be altered by several factors such as sleep quality, anxiety, and depression levels. In the last years, due to COVID-19 pandemic, there was a reduction in sleep quality, an increase in anxiety and depressive symptoms as well as an impairment in emotional episodic memory encoding, especially in young adults. Taking into account the profound impact of sleep quality in daily life a series of rules has been developed that are conducive to consistently achieving good sleep, known as sleep hygiene education. These interventions have been shown to be effective in improving sleep quality and duration and reducing depressive and anxiety symptoms. Here we propose the implementation of a brief sleep hygiene education to improve sleep quality and memory performance as well as to diminish anxiety and depressive scores. For that, participants were divided into two groups: Sleep hygiene education and control group. After that, they were evaluated for anxiety, depression, and sleep quality levels and trained on an episodic memory task. They were tested immediately after (short-term test) and also 1 week later (long-term test). This procedure was also performed before the sleep hygiene education and was taken as baseline level. We found that episodic memory performance for young adults improved for the SHE group after intervention but not for older adults, and no improvements in emotional variables were observed. Despite not observing a significant effect of the intervention for young and older adults regarding the sleep quality scores, we consider that there may be an improvement in sleep physiology that is not subjectively perceived, but would also have a positive impact on memory processes. These results show that even a sleep hygiene education of 1 week could improve cognition in young adults when acute memory and sleep impairment occurs, in this case, due to the isolation by COVID-19 pandemic. However, we suggest that longer interventions should be implemented for older adults who already experience a natural decline in cognitive processes such as episodic memory formation.

Fake news and false memory formation in the psychology debate.

Fake news can generate memory distortions and influence people's behavior. Within the framework of the great debates, the tendency to generate false memories from fake news seems to be modulated by the ideological alignment of each individual. This effect has been observed mainly around issues involving large sectors of society, but little is known about its impact on smaller-scale discussions focused on more specific populations. In this work we examine the formation of false memories from fake news in the debate between psychological currents in Argentina. For this, 326 individuals aligned to psychoanalysis (PSA) or Evidence-Based Practices (EBP) observed a series of news (12 true and 8 fabricated). The EBP group remembered or believed more fake news that damaged PSA. They also remembered with greater precision the statements of the news that harmed their own school, than those referring to others. These results could be understood as the product of an imbalance in the commitment between the different parties, since the group that proposes the paradigm shift (EBP) exhibited a congruence effect, while the group whose orientation is hegemonic in this field (PSA) did not show any effect of ideological alignment. The fact that the congruence effect is manifested to some extent in settings as relevant as the education of mental health professionals, highlights the need to move towards more careful practices in the consumption and production of media.

Structural differences between non-lucid dreams, lucid dreams and out-of-body experience reports assessed by graph analysis.

Dreaming is a complex phenomenon that occurs during sleep, involving various conscious dream experiences. Lucid dreams (LDs) involve heightened awareness within the dream environment, while out-of-body experiences (OBEs) involve the sensation of being outside one's physical body. OBEs occur during sleep paralysis (SP), where voluntary movements are inhibited during sleep/wake transitions while remaining aware of the surroundings. The relationship between LDs and OBEs is debated, with some viewing them as distinct phenomena and others considering them different manifestations of the same underlying experience. This study aimed to characterize non-lucid dreams, LDs, and OBEs by analyzing dream reports' structural properties. OBE reports displayed a condensed and interconnected network structure compared to non-lucid dreams and LDs. Additionally, OBE reports exhibited a specialized network structure, with specific nodes playing a more central role. These findings suggest that OBE dreams may have a more coherent and unified narrative, with certain nodes being pivotal in the network structure.

Odor cueing during sleep improves consolidation of a history lesson in a school setting.

Sleep is a key factor in memory consolidation. During sleep, information is reactivated, transferred, and redistributed to neocortical areas, thus favoring memory consolidation and integration. Although these reactivations occur spontaneously, they can also be induced using external cues, such as sound or odor cues, linked to the acquired information. Hence, targeted memory reactivation during sleep represents an advantageous tool for improving memory consolidation in real-life settings. In this study, our goal was to improve the consolidation of complex information such as that of a history lesson, using a school study session in the presence of an odor, and a reactivation round while sleeping at home on the same night of the acquisition, without using additional study sessions. We found that complex information can be associated with an odor in the classroom and that one session of reactivation during the first night of sleep in the students' houses improves its consolidation. These results bring new evidence for the implementation of reactivation during sleep in real-life settings.

Non-linear susceptibility to interferences in declarative memory formation.

After encoding, memories go through a labile state followed by a stabilization process known as consolidation. Once consolidated they can enter a new labile state after the presentation of a reminder of the original memory, followed by a period of re-stabilization (reconsolidation). During these periods of lability the memory traces can be modified. Currently, some studies show a rapid stabilization after 30 min, while others show that stabilization occurs after longer periods (e.g. > 6 h). Here we investigate the effect of an interference treatment on declarative memory consolidation, comparing distinct time intervals after acquisition. On day 1, participants learned a list of non- syllable pairs (List 1). 5 min, 30 min, 3 h or 8 h later, they received an interference list (List 2) that acted as an amnesic agent. On day 2 (48 h after training) participants had to recall List 1 first, followed by List 2. We found that the List 1 memory was susceptible to interference when List 2 was administered 5 min or 3 h after learning but not when it was administered 30 min or 8 h after. We propose the possibility that this rapid memory protection could be induced by a fast and transient neocortical integration. Our results open a discussion about the contribution of molecular and systemic aspects to memory consolidation.

Identification Performance During Quarantine by COVID-19 Pandemic: Influence of Emotional Variables and Sleep Quality.

The COVID-19 pandemic has caused major disruptions in people's lives around the globe. Sleep habits and emotional balance have been disturbed in a way that could be comparable to the havoc caused by a deep personal crisis or a traumatic experience. This unfortunate situation provides a unique context in which to study the impact of these imbalances on cognitive processes. In particular, the field of eyewitness science could benefit from these conditions, since they are also often present in crime victims, but can only be generated in the laboratory up to a certain ethical and practical limit. For several decades, eyewitness studies have tried to discover what variables affect people's ability to properly recognize faces. However, the disparity of experimental designs and the limitations of laboratory work could be contributing to the lack of consensus around several factors, such as sleep, anxiety, and depression. Therefore, the possibility of observing the influence of these agents in natural contexts could shed light on this discussion. Here, we perform simple and repeated lineups with witnesses of mock-crime, considering the conditions related to the COVID-19 pandemic, which to some extent allow emulating the deterioration in general well-being that often afflicts crime victims. For this, 72 participants completed symptomatology scales, and watched a video portraying a staged violent episode. Subsequently, they gave testimony and participated in two lineups, in which we manipulated the presence/absence of the perpetrator, to recreate critical scenarios for the appearance of false recognitions. We found an increase in recognition errors in those individuals who did not have access to the perpetrator during the Initial lineup. Additionally, the conditions of the pandemic appear to have adversely affected the ability to witness and accurately perform lineups. These results reaffirm the need to move toward the standardization of research practices and methods for assessing testimonial evidence, especially in relation to the results of the lineups. Considering the degree of fallibility of these processes can lead to a reduction of wrongful convictions.

Reconsolidation in humans opens up declarative memory to the entrance of new information.

A consolidated memory recalled by a reminder enters a vulnerability phase (labilization), followed by a process of stabilization (reconsolidation). Several authors have suggested that the labilization of the consolidated memory makes the incorporation of new information possible. Here, we demonstrate updating in the framework of memory declarative reconsolidation in humans by giving an opportune verbal instruction. Volunteers learn an association between five cue-syllables (L1) and their respective response-syllables. Twenty-four hours later, the paired-associate verbal memory is labilized by exposing the subjects to the reminder, and then they receive the verbal Instruction of adding three new cue-response syllables (INFO) with their respective responses to the former list of five. The new information is incorporated into the single former L1-memory and both INFO and L1 are successfully retrieved on the third day. However, when the Instruction is not preceded by a proper reminder, or when the instruction omits the order of adding the INFO into the former L1-memory, we observed interference in retrieval of both the original and the new information, suggesting that they are encoded independently and coexist as separate memories.

Reactivation during sleep with incomplete reminder cues rather than complete ones stabilizes long-term memory in humans.

Reactivation by reminder cues labilizes memories during wakefulness, requiring reconsolidation to persist. In contrast, during sleep, cued reactivation seems to directly stabilize memories. In reconsolidation, incomplete reminders are more effective in reactivating memories than complete reminders by inducing a mismatch, i.e. a discrepancy between expected and actual events. Whether mismatch is likewise detected during sleep is unclear. Here we test whether cued reactivation during sleep is more effective for mismatch-inducing incomplete than complete reminders. We first establish that only incomplete but not complete reminders labilize memories during wakefulness. When complete or incomplete reminders are presented during 40-min sleep, both reminders are equally effective in stabilizing memories. However, when extending the retention interval for another 7 hours (following 40-min sleep), only incomplete but not complete reminders stabilize memories, regardless of the extension containing wakefulness or sleep. We propose that, during sleep, only incomplete reminders initiate long-term memory stabilization via mismatch detection.