Retrieval Session Research Articles

Remote digital memory assessment in middle‐aged and older adults: Feasibility, reliability, and construct validity

AbstractBackgroundFrequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). Our objective was to evaluate the feasibility, reliability, and construct validity of repeated remote memory assessment in late middle‐aged and older adults.MethodParticipants were recruited from longitudinal aging cohorts to complete medial temporal lobe‐based memory paradigms (Object‐In‐Room Recall [ORR], Mnemonic Discrimination for Objects and Scenes [MDT‐OS], Complex Scene Recognition [CSR]) using the neotiv application on a smartphone or tablet at repeated intervals over one year. Participants were randomized to a task schedule (biweekly or bimonthly burst) for a total of 24 ten‐minute remote sessions. Feasibility metrics included participation, retention, compliance, and acceptability. Intraclass correlation coefficients (ICC) assessed test‐retest reliability over an 8‐week period. Analysis of covariance (ANCOVA) models including covariates of demographics, device type, and task schedule were used to evaluate relationships between neotiv baseline performance and traditional memory scores (Rey Auditory Verbal Learning Test [RAVLT]; Preclinical Alzheimer’s Cognitive Composite [PACC]).ResultOf 280 potentially eligible adults, n = 180 consented (64% participation rate). Of 180 consented, n = 133 completed at least one session and n = 119 completed or nearly completed all sessions (retention rate = 66% for all consented and 89% for all completed 1+ session). Delayed retrieval sessions were completed within expected timeframes in 72% of sessions. Greater than 90% of respondents felt the application was easy to use, instructions were understood, and the frequency and length of remote sessions were appropriate. 60% enjoyed completing the tasks (34% felt neutral) and 40% preferred mobile tests to traditional cognitive testing (42% felt neutral). Test‐retest reliability was moderate (ICC = 0.54‐0.70). RAVLT and PACC were significantly associated with MDT‐OS, CSR, and ORR performance (p’s <.001).ConclusionChallenges to participation occurred primarily during enrollment; future studies may allocate additional support facilitating registration and initial task completion within the application. Acceptability of the mobile tasks was high. The mobile memory paradigms exhibited moderate test‐retest reliability and were significantly related to gold‐standard cognitive tests. Overall, findings support preliminary feasibility, reliability, and validity of the neotiv tasks in assessing memory function in cognitively healthy adults enriched for AD risk.

An Ecological Momentary Assessment and Intervention Tool for Memory in Chronic Traumatic Brain Injury: Development and Usability of Memory Ecological Momentary Intervention.

Memory and learning deficits are among the most impactful and longest-lasting symptoms experienced by people with chronic traumatic brain injury (TBI). Despite the persistence of post-TBI memory deficits and their implications for community reintegration, memory rehabilitation is restricted to short-term care within structured therapy sessions. Technology shows promise to extend memory rehabilitation into daily life and to increase the number and contextual diversity of learning opportunities. Ecological momentary assessment and intervention frameworks leverage mobile phone technology to assess and support individuals' behaviors across contexts and have shown benefits in other chronic conditions. However, few studies have used regular outreach via text messaging for adults with chronic TBI, and none have done so to assess and support memory. This study aimed to develop and test the usability of memory ecological momentary intervention (MEMI), a text message-based assessment and intervention tool for memory in daily life. MEMI is designed to introduce new information, cue retrieval of the information, and assess learning across time and contexts. We tested MEMI via an iterative, user-centered design process to ready it for a future trial. We developed MEMI by leveraging automated text messages for prompts using a REDCap (Research Electronic Data Capture)/Twilio interface linking to the Gorilla web-based behavioral experimental platform. We recruited 14 adults with chronic, moderate-severe TBI from the Vanderbilt Brain Injury Patient Registry to participate in 3 rounds of usability testing: one round of ThinkAloud sessions using the platform and providing real-time feedback to an experimenter (n=4) and 2 rounds of real-world usability testing in which participants used MEMI in their daily lives for a week and provided feedback (n=5/round). We analyzed engagement and quantitative and qualitative user feedback to assess MEMI's usability and acceptability. Participants were highly engaged with MEMI, completing an average of 11.8 out of 12 (98%) possible sessions. They rated MEMI as highly usable, with scores on the System Usability Scale across all rounds equivalent to an A+ on a standardized scale. In semistructured interviews, they stated that MEMI was simple and easy to use, that daily retrieval sessions were not burdensome, and that they perceived MEMI as helpful for memory. We identified a few small issues (eg, instruction wording) and made improvements between usability testing rounds. Testing MEMI with adults with chronic TBI revealed that this technology is highly usable and favorably rated for this population. We incorporated feedback regarding users' preferences and plan to test the efficacy of this tool in a future clinical trial.

Perineuronal Nets in the Rat Medial Prefrontal Cortex Alter Hippocampal-Prefrontal Oscillations and Reshape Cocaine Self-Administration Memories.

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. The output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets. We previously showed that treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Furthermore, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse.

Leveraging interindividual variability in threat conditioning of inbred mice to model trait anxiety.

Trait anxiety is a major risk factor for stress-induced and anxiety disorders in humans. However, animal models accounting for the interindividual variability in stress vulnerability are largely lacking. Moreover, the pervasive bias of using mostly male animals in preclinical studies poorly reflects the increased prevalence of psychiatric disorders in women. Using the threat imminence continuum theory, we designed and validated an auditory aversive conditioning-based pipeline in both female and male mice. We operationalised trait anxiety by harnessing the naturally occurring variability of defensive freezing responses combined with a model-based clustering strategy. While sustained freezing during prolonged retrieval sessions was identified as an anxiety-endophenotype biomarker in both sexes, females were consistently associated with an increased freezing response. RNA-sequencing of CeA, BLA, ACC, and BNST revealed massive differences in phasic and sustained responders' transcriptomes, correlating with transcriptomic signatures of psychiatric disorders, particularly post-traumatic stress disorder (PTSD). Moreover, we detected significant alterations in the excitation/inhibition balance of principal neurons in the lateral amygdala. These findings provide compelling evidence that trait anxiety in inbred mice can be leveraged to develop translationally relevant preclinical models to investigate mechanisms of stress susceptibility in a sex-specific manner.

Feasibility, satisfaction, and test‐retest reliability of repeated remote memory assessments with older adults

AbstractBackgroundFrequent, remote cognitive assessments may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). To gain insight on how use of this technology can be optimized, the objective of this study is to determine if feasibility, satisfaction, or test‐retest reliability (TRR) vary depending on task frequency schedules or demographic characteristics.MethodParticipants were recruited from a longitudinal aging cohort to complete three memory tasks via smartphone or tablet using the neotiv application: Object‐In‐Room Recall (ORR), Mnemonic Discrimination for Objects and Scenes (MDT‐OS), and Complex Scene Recognition (CSR). Participants were randomly assigned to complete 24 remote sessions over one year either: (1) every other week or (2) for multiple days within one week every other month. Each session lasted approximately 10 minutes, including one memory task followed by a delayed retrieval session 90 minutes later. Chi‐square tests were used to assess differences in feasibility, acceptability for participants who completed at least 3 sessions, and satisfaction based on task schedule, gender, age, or education. ICC was used to determine TRR of visit 2 to 3 (“V2‐V3”) and an average of visits 1+2 and 3+4 (“V1+2‐V3+4”).Result115 participants (mean age = 68.4, 66% women) enrolled; 49 completed all remote sessions to date (Table 1). Willingness to enroll differed by education (X2 = 4.2, p = .04), such that participants with at least a bachelor’s degree were more likely to enroll. Withdrawal from the study occurred more often for those scheduled to the every other week condition (X2 = 6.2, p = .01) than the every other month condition. Measures of acceptability and satisfaction did not differ by task schedule or demographics. TRR from V2‐V3 and V1+2‐V3+4 were adequate, (CSR: ICC = 0.56 and 0.64, ORR: ICC = 0.58 and 0.66, MDT‐OS: ICC = 0.38 and 0.52).ConclusionParticipants with a bachelor’s degree or higher were more likely to enroll. Reported satisfaction was similar for both task frequency schedules; however, drop‐outs occurred more frequently in those assigned to complete tasks every other week, which could suggest that it is a less optimal task schedule. TRR was moderate for all three tasks. Altogether, results suggest that repeated mobile cognitive testing can be utilized to track cognitive performance remotely.

90 Feasibility of Repeated Remote Memory Assessment with Mobile Devices to Detect Subtle Cognitive Decline in Older Adults

Objective:Frequent and remote cognitive assessment may improve sensitivity to subtle cognitive decline associated with preclinical Alzheimer’s disease (AD). The objective of this study was to evaluate the feasibility and acceptability of repeated remote memory assessment in late middle-aged and older adults.Participants and Methods:We recruited participants from a longitudinal aging cohort to complete three medial temporal lobe-based memory paradigms (Object-In-Room Recall [ORR], Mnemonic Discrimination for Objects and Scenes [MDT-OS], Complex Scene Recognition [CSR]) using the neotiv application at repeated intervals over one year. We conducted initial telephone calls to perform screening, consent, and download instructions. Participants were assigned 24 remote sessions on a smartphone or tablet and were alerted via push notification when an assignment was ready to complete. Participants were randomly assigned to: (1) complete memory tests every other week or (2) complete memory tests for multiple days within one week every other month. Each remote session lasts approximately 10 minutes and includes one memory paradigm and brief usability/acceptability questionnaires followed by a delayed retrieval session 90 minutes later. Feasibility metrics examined included participation, retention, compliance, and usability/acceptability.Results:Of 150 participants recruited, 113 consented and were enrolled into the study (participation rate = 75%). Current retention rate is 75%, with 85/113 currently active (n=73) or completed (n=12). Of the 85 active or completed participants, the mean age is 68.7 (range = 4882), 64% are women, 70% used a smartphone (30% tablet), 84 are cognitively unimpaired and 1 has mild cognitive impairment. The primary threat to retention was participants consenting into the study but never registering in the app or completing their first scheduled assignment. After enrollment, 130 telephone calls were made by study staff to facilitate registration into the app or to remind participants to complete tasks. 74-80% of participants completed delayed retrieval tasks within 30 minutes of push notification, but average retrieval time was 125137 minutes post-learning trials. Regarding acceptability/usability, 94% agreed the application was easy to use, 56% enjoyed completing the mobile memory tests (36% felt neutral), 40% prefer remote mobile memory tests to standard in-person paper and pencil tests, and 50% understood the test instructions. 87% felt the frequency of tests assigned was “just right” (13% “too often”) and 90% felt the test length was “just right” (7% too short, 3% too long). Participants who completed all 24 sessions to date (n=12) all endorsed being “satisfied” or “very satisfied” with the platform and visit schedule, as well as recommended continued use of this type of cognitive testing.Conclusions:Remote memory assessment using smartphones and tablets is feasible and acceptable for cognitively unimpaired late middle-aged and older adults. Follow-up by study staff was needed to ensure adequate retention. Comprehension of instructions and compliance with completing delayed retrieval tasks within the expected timeframe was lower than expected. These feedback will be incorporated into an updated version of the app to improve compliance and retention. Longitudinal data collection is ongoing and results will be updated with a larger sample. Results will be compared across frequency schedule groups.

Solidity Meets Surprise: Cerebral and Behavioral Effects of Learning from Episodic Prediction Errors.

How susceptible a memory is to later modification might depend on how stable the episode has been encoded. This stability was proposed to increase when retrieving information more (vs. less) often and in a spaced (vs. massed) practice. Using fMRI, we examined the effects of these different pre-fMRI retrieval protocols on the subsequent propensity to learn from episodic prediction errors. After encoding a set of different action stories, participants came back for two pre-fMRI retrieval sessions in which they encountered original episodes either 2 or 8 times in either a spaced or a massed retrieval protocol. One week later, we cued episodic retrieval during the fMRI session by using original or modified videos of encoded action stories. Recurrent experience of modified episodes was associated with increasing activity in the episodic memory network including hippocampal and cortical areas, when leading to false memories in a post-fMRI memory test. While this observation clearly demonstrated learning from episodic prediction errors, we found no evidence for a modulatory effect of the different retrieval protocols. As expected, the benefit of retrieving an episode more often was reflected in better memory for originally encoded episodes. In addition, frontal activity increased for episodic prediction errors when episodes had been less frequently retrieved pre-fMRI. A history of spaced versus massed retrieval was associated with increased activation throughout the episodic memory network, with no significant effect on behavioral performance. Our findings show that episodic prediction errors led to false memories. The history of different retrieval protocols was reflected in memory performance and brain responses to episodic prediction errors, but did not interact with the brain's episodic learning response.

Blockade of dopamine D3 receptor in ventral tegmental area attenuating contextual fear memory

The abnormal fear memory will lead to the onset of stress disorders, such as post-traumatic stress disorder (PTSD) and so on. Therefore, the intervention in the formation of abnormal fear memory will provide a new strategy for the prevention and treatment of PTSD. In our previous studies, we found that blockade of dopamine D3 receptor (DRD3) with highly selective antagonist YQA14 or knockout of DRD3 was able to attenuate the expression or retrieval of fear memory in PTSD animal models. However, the neurobiological mechanism of regulation of DRD3 in fear is unclear. In the present research, we clarified that DRD3 was expressed in the dopaminergic (DAergic) neurons in the ventral tegmental area (VTA). Then, we identified that microinjection of YQA14 (1 μg/0.2 μl/side) in VTA before the aversive stimuli in the training session or during days subsequent to the shock significantly meliorated the freezing behaviors in the inescapable electric foot-shock model. At last, using fiber photometry system, we found that microinjection of YQA14 in VTA promoted the dopamine neurotransmitter release in the basolateral amygdala (BLA), and pre-training YQA14 infusion in VTA lowered the increase of dopamine (DA) in BLA induced by shock during the training session or by context during the retrieval session. All above the results demonstrated that YQA14 attenuated the fear learning through the blockade of DRD3 in VTA decreasing the excitability of the projection to BLA. This study may provide new mechanisms and potential intervention targets for stress disorders with abnormal fear memory.

Recall of Vocabulary from a Second Language: Picture Naming vs. Word Definition

The present study investigated the differences between early and late-acquired words from a second language in terms of the method of recall, speed and accuracy. This involved comparing the performance of 24 native Arabic participants on two different recall methods: picture naming vs. word definition. Each participant attended two sessions, with a 24-hour interval: a learning session, in which they learned new words, and a retrieval session, in which they performed the picture-naming and word-definition tasks while their ERP signals were recorded. The main results showed a significant main effect of age of acquisition on both accuracy and reaction time. Additionally, the N400 ERP component showed a significant interaction between age of acquisition and method of recall in the N400 values recorded in the left frontal area. Together, these findings indicate that both accuracy and reaction time measures can detect differences between early and late-acquired words, recalled through either a picture-naming or word-definition task.

Sounding the Alarm: Sex Differences in Rat Ultrasonic Vocalizations during Pavlovian Fear Conditioning and Extinction.

Pavlovian fear conditioning is a prevalent tool in the study of aversive learning, which is a key component of stress-related psychiatric disorders. Adult rats can exhibit various threat-related behaviors, including freezing, motor responses, and ultrasonic vocalizations (USVs). While these responses can all signal aversion, we know little about how they relate to one another. Here we characterize USVs emitted by male and female rats during cued fear acquisition and extinction, and assess the relationship between different threat-related behaviors. We found that males consistently emitted >22 kHz calls (referred to here as "alarm calls") than females, and that alarm call frequency in males, but not females, related to the intensity of the shock stimulus. Interestingly, 25% of males and 45% of females did not emit any alarm calls at all. Males that did make alarm calls had significantly higher levels of freezing than males who did not, while no differences in freezing were observed between female Alarm callers and Non-alarm callers. Alarm call emission was also affected by the predictability of the shock; when unpaired from a tone cue, both males and females started emitting alarm calls significantly later. During extinction learning and retrieval sessions, males were again more likely than females to emit alarm calls, which followed an extinction-like reduction in frequency. Collectively these data suggest sex dependence in how behavioral readouts relate to innate and conditioned threat responses. Importantly, we suggest that the same behaviors can signal sex-dependent features of aversion.

Re-exposures in the Dark Cycle Promote Attenuation of Fear Memory: Role of the Circadian Cycle and Glucocorticoids

It has been shown that a previously consolidated memory can incorporate either new external information or a novel internal emotional state following a labile state induced by retrieval. This updating process allows editing unwanted fear memory, leading to the reduction of the fear response. Memory can be modulated by the circadian cycle. Considering that rodents are more active during the night, expressing less fearful behavior, we investigated whether fear memory can be updated when reactivated during the dark cycle. We found that rats expressed lower freezing levels during a single retrieval session in the dark cycle, but not in the test. However, three retrieval sessions in the dark cycle were able to update fear memory, reducing freezing response in the test performed in the light cycle. This effect was blocked when the glucocorticoid synthesis inhibitor metyrapone was administered before retrieval. This approach opens new avenues to explore interventions that consider the circadian cycle in the treatment of fear memories based on non-pharmacological interventions.

Evidence on the impairing effects of Ayahuasca on fear memory reconsolidation.

To uncover whether psychedelic drugs attenuate fear memory responses would advance the development of better psychedelic-based treatments for posttraumatic stress disorder (PTSD). Ayahuasca (AYA), a psychedelic brew containing indolamine N, N-dimethyltryptamine (DMT) and β-carbolines, facilitates fear extinction and improves neural plasticity. Upon retrieval, fear memory undergoes labilization and reconsolidation; however, the effects of AYA on this memory stabilization phase are unknown. We aimed to investigate the effects of AYA treatment on fear memory reconsolidation. Fear-conditioned Wistar rats received AYA (60, 120, or 240mg/kg) or H2O orally via gavage o.g. 20min before, immediately, or 3h after a short retrieval session. Analysis of AYA through liquid chromatography-tandem mass spectrometry was used to determine the content of DMT and β-carbolines in AYA. AYA impaired fear memory reconsolidation when given 20min before or 3h after memory retrieval, with the dose of 60mg/kg being effective at both moments. This dose of AYA was devoid of anxiolytic effect. Importantly, during retrieval, AYA did not change fear expression. The lack of retrieval abolished the reconsolidation impairing effect of AYA. The effects of AYA treatment 20min before or 3h aftermemory retrieval lasted at least 22days, suggesting no spontaneous recovery of fear memory. Fear memory impairments induced by AYA treatment, at both moments, do not show reinstatement. Our findings support the view that a low dose of AYA treatment impairs early and late stages of memory reconsolidation instead of facilitating fear extinction.

N-Methyl-D-Aspartate (NMDA) Receptors in the Prelimbic Cortex Are Required for Short- and Long-Term Memory Formation in Trace Fear Conditioning.

Accumulating evidence suggests that the medial prefrontal cortex (mPFC) has been implicated in the acquisition of fear memory during trace fear conditioning in which a conditional stimulus (CS) is paired with an aversive unconditional stimulus (UCS) separated by a temporal gap (trace interval, TI). However, little is known about the role of the prefrontal cortex for short- and long-term trace fear memory formation. Thus, we investigated how the prelimbic (PL) subregion within mPFC in rats contributes to short- and long-term trace fear memory formation using electrolytic lesions and d,l,-2-amino-5-phosphonovaleric acid (APV), an N-methyl-D-aspartate receptor (NMDAR) antagonist infusions into PL. In experiment 1, pre-conditioning lesions of PL impaired freezing to the CS as well as TI during the acquisition and retrieval sessions, indicating that PL is critically involved in trace fear memory formation. In experiment 2, temporary blockade of NMDA receptors in PL impaired the acquisition, but not the expression of short- and long-term trace fear memory. In addition, the inactivation of NMDAR in PL had little effect on locomotor activity, pre-pulse inhibition (PPI), or shock sensitivity. Taken together, these results suggest that NMDA receptor-mediated neurotransmission in PL is required for the acquisition of trace fear memory.

TDCS-Induced Memory Reconsolidation Effects: Analysis of Prominent Predicting Factors.

BackgroundMemory impairment is among one of the greatest cognitive complaints in midlife and in old age. Considering the importance of good memory functioning in everyday life, it is crucial to study interventions that can reduce the natural decline in this cognitive function. Transcranial Magnetic Stimulation (TMS) studies have demonstrated that the lateral prefrontal cortex (PFC) plays a causal role in enhancing episodic memory recall through reconsolidation. Using a similar paradigm with transcranial direct current stimulation (tDCS) over the left lateral PFC, facilitation effects were observed in delayed memory retrieval in older adults with subjective memory complaints (SMCs) and amnestic Mild Cognitive Impairment (aMCI). However, it remains unclear which potential factors (i.e., tDCS group, cognitive reserve, education level, diagnosis and encoding performance) directly and/or indirectly modulate the tDCS-induced memory reconsolidation effects.MethodsWe reanalyzed data acquired in our previous tDCS studies with 22 SMC and 18 aMCI participants from the perspective of predicting delayed memory retrieval performance. These studies included a learning session on Day 1, a reactivation by a contextual reminder followed by 15 min of tDCS session on Day 2 (24 h after Day 1), and two retrieval sessions (free recall and recognition) tested on Days 3 and 30 (48 h and 30 Days after Day 1).ResultsUnivariate models showed that tDCS group (sham vs. active) significantly predicted memory recognition (but not free recall), evidenced by higher scores in the active tDCS group than in sham group, confirming our previous results. Encoding performance and diagnosis (SMC vs. aMCI) significantly predicted memory retrieval, suggesting higher performances in individuals with SMC than in those with aMCI. Regarding cognitive reserve, higher leisure time activity subscores significantly predicted better memory recognition. Finally, multiple models did not show any tDCS group × predictor interaction effects, indicating that the effects of the predictors on retrieval occurred irrespective of tDCS group.ConclusionOur results shed light on predicting factors of episodic memory retrieval in this reconsolidation paradigm in individuals with SMC and aMCI. The findings suggest that multifactorial interventions program may be most promising to slow cognitive decline and delay the onset of dementia.

High trait anxiety in mice is associated with impaired extinction in the contextual fear conditioning paradigm

Trait anxiety is a form of chronic state anxiety that can be part of the individual’s personality and one of the individual factors that increase the risk of developing PTSD. To be able to distinguish between trait and state anxiety in animal models might be challenging, since the tests themselves are often anxiogenic. One possible approach is the use of the free exploratory paradigm (FEP), a model that consists of providing the animal the choice to explore both a familiar and a novel environment. High trait anxiety animals choose to explore more the familiar environment. Thus, the objective of this study was to evaluate if differences in trait anxiety could lead to impairments in acquisition and extinction of fear memory in a contextual fear conditioning protocol. First, Swiss mice were divided into high trait anxiety (HTA) or low trait anxiety (LTA) based on their exploration of the novel environment (%TNS) in the FEP. We observed that the %TNS was stable across three testing sessions. Also, we observed that freezing behavior was not different between HTA and LTA mice in a retrieval session 1 day after the conditioning, which indicates that acquisition was not impaired. However, HTA presented higher freezing time during extinction training and test. Also, HTA presented higher freezing in reinstatement test, but this might be related to the poor extinction learning. Moreover, diazepam (0.25 or 1.0 mg/kg, i.p.) did not prevent the differences in extinction training and test when administer 30 min before conditioning training or 30 min before extinction training, even though diazepam (1.0 mg/kg) had anxiolytic effect in the elevated plus-maze. These results demonstrate that HTA mice presented increase in freezing during extinction training and test, as well as during reinstatement. These results indicate that increased freezing time in HTA mice is not explained by high state anxiety in a specific phase of the fear conditioning, but more likely, the overall high trait anxiety throughout the entire experiment.

NMDA receptor-mediated synaptic transmission in prefrontal neurons underlies social memory retrieval in female mice

Social memory is the ability to discriminate familiar conspecific from the unknown ones. Prefrontal neurons are essentially required for social memory, but the mechanism associated with this regulation remains unknown. It is also unclear to what extent the neuronal representations of social memory formation and retrieval events overlap in the prefrontal cortex (PFC) and which event drives social memory strength. Here we asked these questions by using a repeated social training paradigm for social recognition in FosTRAP mice. We found that after 4 days’ repeated social training, female mice developed stable social memory. Specifically, repeated social training activated more cells that were labeled with tdTomato during memory retrieval compared with the first day of memory encoding. Besides, combining TRAP with c-Fos immunostaining, we found about 30% of the FosTRAPed cells were reactivated during retrieval. Moreover, the number of retrieval-induced but not first-day encoding-induced tdTomato neurons correlates with the social recognition ratio in the prelimbic but not other subregions. The activated cells during the retrieval session also showed increased NMDA receptor-mediated synaptic transmission compared with that in non-labeled pyramidal neurons. Blocking NMDA receptors by MK-801 impaired social memory but not sociability. Therefore, our results reveal that repetitive training elevates mPFC involvement in social memory retrieval via enhancing NMDA receptor-mediated synaptic transmission, thus rendering stable social memory.

Role of prediction error and the cholinergic system on memory reconsolidation processes in mice

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. 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. In the past our lab has made key progresses showing that a blockade in the central cholinergic system during reconsolidation can cause memory impairment, while reinforcement of cholinergic activity enhances it. In the present work we determined that PE is a necessary condition for memory to reconsolidate in an inhibitory avoidance task using both male and female mice. Depending on the intensity of the unconditioned stimulus (US) used during training, a negative (higher US intensity) or positive (lower US intensity/no US) PE on a retrieval session modified the behavioral response on a subsequent testing session. Furthermore, we demonstrated that the cholinergic system modulates memory reconsolidation only when PE is detected. In this scenario administration of oxotremorine, scopolamine or nicotine after memory reactivation either enhanced or impaired memory reconsolidation in a sex-specific manner.

Out-of-body experience favors emotional memory consolidation

Body ownership reflects our ability to recognise our body at a certain location, enabling us to interact with the world. Emotion has a strong impact on memory and body ownership; interestingly, skin temperature may at least in part mediate this impact. Previous studies have found that out-of-body experiences (OBE) impair memory encoding and cause skin temperature to drop. In the present study a new method for inducing OBE was designed and their impact on a different stage and type of memory processing (emotional memory consolidation) and on skin temperature was investigated. In our experiment, we presented three types of emotional pictures (neutral, pleasant, unpleasant) before inducing OBE and testing our participants’ recognition memory in a retrieval session. Throughout the whole experiment, both neck and hand skin temperature were measured using iButtons. Participants’ performance was calculated using d-prime and statistical analyses included one-way ANOVA, probing the relationship between the score on the OBE questionnaire, performance and skin temperature; we also compared the differences between the experimental and a control group. Results showed that OBE favour emotional memory consolidation and cause a temperature increase, supporting the embodied cognition theory as proposed by Anderson (2003). Future studies should expand our findings, to rule out that participants experiencing OBE could have a better memory at baseline or that temperature could be increased due to other reasons.

Hemispheric Asymmetries in Electroencephalogram Oscillations for Long-Term Memory Retrieval in Healthy Individuals.

The hemispherical encoding retrieval asymmetry (HERA) model, established in 1991, suggests that the involvement of the right prefrontal cortex (PFC) in the encoding process is less than that of the left PFC. The HERA model was previously validated for episodic memory in subjects with brain traumas or injuries. In this study, a revised HERA model is used to investigate long-term memory retrieval from newly learned video-based content for healthy individuals using electroencephalography. The model was tested for long-term memory retrieval in two retrieval sessions: (1) recent long-term memory (recorded 30 min after learning) and (2) remote long-term memory (recorded two months after learning). The results show that long-term memory retrieval in healthy individuals for the frontal region (theta and delta band) satisfies the revised HERA asymmetry model.

The power of children\u2019s sleep - Improved declarative memory consolidation in children compared with adults

Post-learning slow wave sleep (SWS) is known to support declarative memory consolidation. As SWS is more abundant in young population, we suggested that sleep-dependent memory consolidation processes could occur at a faster pace in school-aged children. After learning new associations between non-objects and their functions, retrieval performance was tested in 30 children (7–12 years) and 34 adults (20–30 years) during an immediate (IR) and a delayed retrieval (DR) session separated by either a Sleep or a Wake condition. Sleep led to stabilized memory retrieval performance only in children, not in adults, whereas no age-related difference was observed after a similar period of wakefulness. Hence, our results suggest more efficient sleep-dependent declarative memory consolidation processes in children compared with adults, an effect potentially ascribed to more abundant and deeper SWS during childhood.