Highly Demand Working Memory Intervention Weakens a Reactivated Threat Memory and the Associated Cognitive Biases.

Anxiety disorders are the most frequent type of mental disorder. Threat-conditioning memory plays a central role in anxiety disorders, impacting complex cognitive systems by modifying behavioral responses to fearful stimuli and inducing an overestimation of potential threats. Here, we analyzed the reminder-dependent amnesia on physiological responses, unconditioned stimulus (US) expectancy ratings, and measures of cognitive bias towards the threat of a threat-conditioning memory. Subjects received differential threat-conditioning. Twenty-four hours later, after reactivation of the memory of threat-conditioning, one group performed a high demand working memory task (HWM) and a second group a low demand working memory task (LWM). A third group only performed the HWM task. Retention of conditioned threat memory was tested on Day 3 in an extinction session followed by a reinstatement test. Tasks targeting stimulus representation, valuation, and attentional bias towards threat were performed. We show that the reminder-dependent intervention with an HWM weakened memory retention as expressed in skin conductance response (SCR) and faded the representation and valuation towards the threat, but it did not affect US expectancy or attentional bias. Our findings provide evidence for the experimental psychopathology approach opening the possibility to weaken both Threat conditioning memory and the systems associated with the maintenance of anxiety features.

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.

Psychological distress and mental health trajectories during the COVID-19 pandemic in Argentina: a longitudinal study.

Psychological-distress increased at the onset of the COVID-19 pandemic in Argentina. Longitudinal studies in developing countries are scarce. Particularly, Argentina had one of the longest lockdowns. Differences in preventive measures against the virus spread between countries may differentially affect the mental health of the populations. Here we aimed to characterize distinct psychological-distress and related-symptoms trajectories associated with the pandemic and explore risk/protective factors. In this longitudinal study, data from 832 Argentineans were collected every 3-5 months, between April 2020-August 2021. Mean psychological-distress levels and related-symptoms tended to increase over time. However, latent-class analysis identified four distinct psychological-distress trajectories. Most individuals had consistently good mental health (Resilient). Two classes showed psychological-distress worsening during the initial phase of the pandemic and recovered at different time points (Fast Recovery; Slow Recovery). The remaining class maintained a mild -level of psychological-distress and began to deteriorate in March 2021 (Deteriorating) continuously. Individuals who are younger, female, have pre-existing psychiatric diagnoses, or have high neuroticism or lower resilience were more likely to experiencing fluctuations in psychological-distress. The mental health trajectory during the pandemic had a complex dynamic. Although most participants remained resilient, a vulnerable group was detected, which deteriorated over time and should be considered by health-services.

Improvement of episodic memory retention by a memory reactivation intervention across the lifespan: from younger adults to amnesic patients.

Spontaneous reactivation of recently acquired memories is a fundamental mechanism of memory stabilization. Re-exposure to specific learned cues during sleep or awake states, namely targeted memory reactivation, has been shown to improve memory retention at long delays. Manipulation of memory reactivation could have potential clinical value in populations with memory deficits or cognitive decline. However, no previous study investigated a target memory reactivation approach on those populations. Here we tested the hypothesis that a reactivation-based intervention would improve episodic memory performance in healthy adults and amnestic patients. On Day 1, young adults, old adults and amnestic Mild Cognitive Impairment patients (n = 150) learned face-name pairs and 24 h later either received a reactivation intervention or a reactivation control (Day 2). On Day 3, associative and item memory were assessed. A robust Bayesian Generalized Mixed Model was implemented to estimate intervention effects on groups. Groups that underwent the reactivation-based intervention showed improved associative memory retention. Notably, amnestic patients benefited more from the intervention as they also had better item memory retention than controls. These findings support memory reactivation as stabilization and strengthening mechanism irrespectively of age and cognitive status, and provides proof-of-concept evidence that reactivation-based interventions could be implemented in the treatment and rehabilitation of populations with memory deficits.

Computational basis of decision-making impairment in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is commonly associated with decision-making, neurocognitive impairments, and mood and motivational symptoms. However, their relationship may be obscured by traditional scoring methods. OBJECTIVES: To study the computational basis underlying decision-making impairments in MS and their interaction with neurocognitive and neuropsychiatric measures. METHODS: Twenty-nine MS patients and 26 matched control subjects completed a computer version of the Iowa Gambling Task (IGT). Participants underwent neurocognitive evaluation using an expanded version of the Brief Repeatable Battery. Hierarchical Bayesian Analysis was used to estimate three established computational models to compare parameters between groups. RESULTS: Patients showed increased learning rate and reduced loss-aversion during decision-making relative to control subjects. These alterations were associated with: (1) reduced net gains in the IGT; (2) processing speed, executive functioning and memory impairments; and (3) higher levels of depression and current apathy. CONCLUSION: Decision-making deficits in MS patients could be described by the interplay between latent computational processes, neurocognitive impairments, and mood/motivational symptoms.

Social context shapes cognitive abilities: associative memories are modulated by fight outcome and social isolation in the crab Neohelice granulata.

Cognitive abilities of an animal can be influenced by distinct social experiences. However, the extent of this modulation has not been addressed in different learning scenarios: are all tasks similarly affected by social experiences? In the present study, we analyzed the effect of social dominance in aversive and appetitive memory processes in the crab Neohelice granulata. In addition, we studied the influence of social isolation on memory ability. Social dominance experiments consisted of an agonistic phase immediately followed by a memory phase. During the agonistic phase, matched pairs of male crabs were staged in 10-min encounters and the dominant or subordinate condition of each member of the dyad was determined. During the memory phase, crabs were trained to acquire aversive or appetitive memory and tested 24 h later. Results showed that the agonistic encounter can modulate long-term memory according to the dominance condition in such a way that memory retention of subordinates results higher than their respective dominant. Remarkably, this result was found for both aversive and appetitive memory tasks. In addition, we found that isolated animals showed no memory retention when compared with animals that remained grouped. Altogether this work emphasizes the importance of social context as a modulator of cognitive abilities.

Identification of a Novel Retrieval-dependent Memory Process in the Crab Neohelice granulata.

Fully consolidated associative memories may be altered by alternative retrieval dependent memory processes. While a brief exposure to the conditioned stimulus (CS) can trigger reconsolidation of the original memory, a prolonged CS exposure will trigger memory extinction. The conditioned response is maintained after reconsolidation, but is inhibited after extinction, presumably by the formation of a new inhibitory memory trace. In rats and humans, it has been shown that CS exposure of intermediate duration leave the memory in an insensitive or limbo state. Limbo is characterised by the absence of reconsolidation or extinction. Here we investigated the evolutionary conserved nature of limbo using a contextual Pavlovian conditioning (CPC) memory paradigm in the crab Neohelice granulata. In animals with fully consolidated CPC memory, systemic administration of the protein synthesis inhibitor cycloheximide after 1 CS presentation disrupted the memory, presumably by interfering with memory reconsolidation. The same intervention given after 320 CSs prevented CPC memory extinction. Cycloheximide had no behavioural effect when administered after 80 CS presentations, a protocol that failed to extinguish CPC memory. Also, we observed that a stronger CPC memory engaged reconsolidation after 80 CS instead of limbo, indicating that memory strength affects the parametrical conditions to engage either reconsolidation or limbo. Altogether, these results indicate that limbo is an evolutionary conserved memory process segregating reconsolidation from extinction in the number of CSs space. Limbo appears as an intrinsic component of retrieval dependent memory processing, with a key function in the transition from memory maintenance to inhibition.

Psychometric validation of the survey of autobiographical memory: confirmatory factor analysis and network analysis.

Autobiographical memory (AM) represents the ability to remember personal experiences. There are several laboratory or neuropsychological tasks to assess different aspects of memory function. However, there has been little research on self-reported AM ability. The Survey of Autobiographical Memory (SAM) is a self-report questionnaire, developed to assess individual differences in AM. Evidence for the factor structure and network properties of the SAM is still needed. Here, using an integral approach, we validated the SAM using a Multiple Correspondence Analysis (Study 1) as in the original study, a Confirmatory Factor Analysis (Study 2), and a Network Analysis (Study 3) using two large independent samples (total n = 2896). We first replicated the original findings, then confirmed the existence of 4 factors and found that the Episodic and Semantic categories were the most central ones. Finally, we found between "groups" differences for Gender and Anxiety. Overall, three different methods revealed a robust profile of the SAM.

Psychological distress associated with COVID-19 quarantine: Latent profile analysis, outcome prediction and mediation analysis.

BACKGROUND: Mental health of the population during COVID-19 quarantine could be at risk. Previous studies in short quarantines, found mood-related and anxiety symptomatology. Here we aimed to characterize the subtypes of psychological distress associated with quarantine, assess its prevalence, explore risk/protective factors, and possible mechanisms. METHODS: Online cross-sectional data (n = 4408) was collected during the Argentine quarantine, between 1st-17th April 2020 along a small replication study (n = 644). Psychological distress clusters were determined using latent profile analysis on a wide-range of symptoms using the complete Brief-Symptom Inventory-53. Multinomial and Elastic-net regression were performed to identify risk/protective factors among trait-measures (Personality and Resilience) and state-measures (COVID-19 related fear and coping-skills). RESULTS: Three latent-classes defined by symptom severity level were identified. The majority of individuals were classified in the mild (40.9%) and severe classes (41.0%). Participants reported elevated symptoms of Phobic-Anxiety (41.3%), Anxiety (31.8%), Depression (27.5%), General-Distress (27.1%), Obsession-Compulsion (25.1%) and Hostility (13.7%). Logistic-regressions analyses mainly revealed that women, young individuals, having a previous psychiatric diagnosis or trauma, having high levels of trait-neuroticism and COVID-related fear, were those at greater risk of psychological distress. In contrast, adults, being married, exercising, having upper-class income, having high levels of trait-resilience and coping-skills, were the most protected. Mediation analysis, showed that state-measures mediated the association between trait-measures and class-membership. CONCLUSIONS: Quarantine was associated intense psychological distress. Attention should be given to COVID-19-related fear and coping-skills as they act as potential mediators in emotional suffering during quarantine.

Author Correction: Retrieval of retrained and reconsolidated memories are associated with a distinct neural network.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

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.

Retrieval of retrained and reconsolidated memories are associated with a distinct neural network.

Consolidated memories can persist from a single day to years, and persistence is improved by retraining or retrieval-mediated plasticity. One retrieval-based way to strengthen memory is the reconsolidation process. Strengthening occurs simply by the presentation of specific cues associated with the original learning. This enhancement function has a fundamental role in the maintenance of memory relevance in animals everyday life. In the present study, we made a step forward in the identification of brain correlates imprinted by the reconsolidation process studying the long-term neural consequences when the strengthened memory is stable again. To reach such a goal, we compared the retention of paired-associate memories that went through retraining process or were labilizated-reconsolidated. Using functional magnetic resonance imaging (fMRI), we studied the specific areas activated during retrieval and analyzed the functional connectivity of the whole brain associated with the event-related design. We used Graph Theory tools to analyze the global features of the network. We show that reconsolidated memories imprint a more locally efficient network that is better at exchanging information, compared with memories that were retrained or untreated. For the first time, we report a method to elucidate the neural footprints associated with a relevant function of memory reconsolidation.

Contrasting dynamics of memory consolidation for novel word forms and meanings revealed by behavioral and neurophysiological markers.

Learning novel words is a challenging process for our memory systems; we must be able to recall new word forms and meanings in order to communicate. However, the dynamics of the word memory formation is still unclear. Here, we addressed the temporal profile of two key cognitive markers of memory consolidation in the domain of word learning: i) the susceptibility of recently learned novel words to memory interference; ii) their lexical integration using a semantic judgment task while recording the ERPs responses. Young adults acquired a set of novel picture-label-meaning associations. In a first experiment, we performed a temporal gradient of retroactive interference (5 min, 30 min, 4 h and 24 h) and evaluated the memory retention 48 h after learning. In a second experiment, we studied the dynamics of the integration of these novel words, by measuring their N400 modulation when preceded by semantically related words, at 30 min or 48 h after learning. Our results showed that the word-form memory was affected by the interference treatment when it was presented 5 min after learning, but not at later times. On the other hand, only 48 h after learning it was possible to observe a neurophysiological index of semantic-priming (reduced N400 response). These results point to the existence of two contrasting processes that help to build the memory for word forms and meanings. A rapid mechanism would enable word learning while mitigating forgetting, while a slow consolidation would allow the novel meanings to be integrated into previous semantic networks.

Effects of Threat Conditioning on the Negative Valanced Systems and Cognitive Systems.

Threat conditioning is held as a model of anxiety disorders. However, this approach is focused on implicit responses evaluated in a single day. Here, we evaluated negative-valence, positive-valence and cognitive-systems in order to evaluate the extent to which threat conditioning models anxiety disorders. Subjects underwent threat conditioning and five-minutes (Short-term evaluation) or 48 hs (Long-term evaluation) later, both groups performed several tasks targeting cognitive-systems and valenced-systems. In the short-term evaluation, successful conditioning maintained state-anxiety and increased the aversiveness representation of the CS+ and the valuation for negative events. Reaction-times for the CS+ were faster, reflecting an attentional bias toward threat. In the long-term evaluation, participants represented the CS+ as more aversive and generalized to all stimuli. Reaction-times showed a more restricted attentional bias. Threat conditioning alters the negative-valence systems and creates a cognitive bias, which is transformed by memory consolidation, suggesting that this protocol could be a useful resource to understand the deficits associated with anxiety disorders.

Does reconsolidation occur in natural settings? Memory reconsolidation and anxiety disorders.

In normal settings, our brain is able to update its stored representations in content, strength, and/or expectations by the memory reconsolidation process. Thus, a reactivated memory enters in a transient labile state (destabilization) followed by a re-stabilization phase in order to persist (memory reconsolidation). Cognitive neuroscience and its insight into psychiatric problems attributed a close relationship between memory (formation, maintenance, and utilization) and several mental disorders. In this framework, the reconsolidation process could be not only the mechanism for maintenance of some psychopathologies, but also open a novel therapeutic window. Here we aim to integrate recent experimental and theoretical research on memory reconsolidation and anxiety disorders maintenance. We propose a bayesian-like model about anxiety disorders persistence and postulate a new theoretical framework for how anxiety disorders are maintained through impaired memory updating due to a dysfunctional prediction error minimization strategy and anticipatory responses to threat.

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.

Toward a better understanding on the role of prediction error on memory processes: From bench to clinic.

Experimental psychology defines Prediction Error (PE) as a mismatch between expected and current events. It represents a unifier concept within the memory field, as it is the driving force of memory acquisition and updating. Prediction error induces updating of consolidated memories in strength or content by memory reconsolidation. This process has two different neurobiological phases, which involves the destabilization (labilization) of a consolidated memory followed by its restabilization. The aim of this work is to emphasize the functional role of PE on the neurobiology of learning and memory, integrating and discussing different research areas: behavioral, neurobiological, computational and clinical psychiatry.

Different dimensions of the prediction error as a decisive factor for the triggering of the reconsolidation process.

The reconsolidation process is the mechanism by which strength and/or content of consolidated memories are updated. Prediction error (PE) is the difference between the prediction made and current events. It is proposed as a necessary condition to trigger the reconsolidation process. Here we analyzed deeply the role of the PE in the associative memory reconsolidation in the crab Neohelice granulata. An incongruence between the learned temporal relationship between conditioned and unconditioned stimuli (CS-US) was enough to trigger the reconsolidation process. Moreover, after a partial reinforced training, a PE of 50% opened the possibility to labilize the consolidated memory with a reminder which included or not the US. Further, during an extinction training a small PE in the first interval between CSs was enough to trigger reconsolidation. Overall, we highlighted the relation between training history and different reactivation possibilities to recruit the process responsible of memory updating.

The fate of memory: Reconsolidation and the case of Prediction Error.

The ability to make predictions based on stored information is a general coding strategy. A Prediction-Error (PE) is a mismatch between expected and current events. It was proposed as the process by which memories are acquired. But, our memories like ourselves are subject to change. Thus, an acquired memory can become active and update its content or strength by a labilization-reconsolidation process. Within the reconsolidation framework, PE drives the updating of consolidated memories. Moreover, memory features, such as strength and age, are crucial boundary conditions that limit the initiation of the reconsolidation process. In order to disentangle these boundary conditions, we review the role of surprise, classical models of conditioning, and their neural correlates. Several forms of PE were found to be capable of inducing memory labilization-reconsolidation. Notably, many of the PE findings mirror those of memory-reconsolidation, suggesting a strong link between these signals and memory process. Altogether, the aim of the present work is to integrate a psychological and neuroscientific analysis of PE into a general framework for memory-reconsolidation.