Disruption of relapse to cocaine and morphine seeking by LiCl-induced aversive counterconditioning following memory retrieval.

Substance use disorder is conceptualized as a form of maladaptive learning, whereby drug-associated memories, elicited by the presence of stimuli related to drug contexts or cues, contribute to the persistent recurrence of craving and the reinstatement of drug-seeking behavior. Hence, use of pharmacology or non-pharmacology way to disrupt drug-related memory holds promise to prevent relapse. Several studies have shown that memories can be unstable and susceptible to modification during the retrieval reactivation phase, termed the "reconsolidation time window". In this study, we use the classical conditioned place preference (CPP) model to investigate the role of aversive counterconditioning on drug-related memories during reconsolidation. Specifically, we uncovered that reconditioning drug cues through counterconditioning with LiCl-induced aversive outcomes following drug memory retrieval reduces subsequent drug-seeking behavior. Notably, the recall of cocaine- or morphine-CPP was eliminated when LiCl-induced aversive counterconditioning was performed 10 min, but not 6 h (outside the reconsolidation time window) after cocaine or morphine memory retrieval. In addition, the effect of LiCl-induced aversive counterconditioning could last for about 14 days. These results suggest that aversive counterconditioning during the reconsolidation of cocaine or morphine memory can prevent the re-seeking of cocaine or morphine, presumably by updating or replacing cocaine or morphine memories with aversive information.

Exercise and Fear and Safety Learning.

Fear conditioning paradigms have been studied for over 100 years and are of great interest to the behavioral and clinical sciences given that several safety learning processes (e.g., extinction learning and recall) are thought to be fundamental to the success of exposure-based therapies for anxiety and related disorders. This chapter provides an overview of preclinical and clinical investigations that examined the effects of exercise on initial fear acquisition, fear extinction learning and consolidation, and return of fear outcomes. This chapter highlights the collective body of evidence suggesting that exercise administered after extinction learning enhances the consolidation and subsequent recall of extinction memories to a greater extent than exercise administered prior to extinction learning. This suggests that the addition of exercise after exposure therapy sessions may improve treatment outcomes for people with anxiety and related disorders. Potential mechanisms are discussed in addition to suggestions for future research to improve our understanding of the effects of exercise on fear conditioning and extinction outcomes.

Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

The effect of a Schema-based method on correcting persistent errors in mental arithmetic: an experimental study.

Introduction: Arithmetic calculation is a fundamental skill for mathematical learning and daily life. However, elementary school students often make errors in practice. Methods: Grounded in the schema theory and the memory retrieval theory of mental arithmetic, this study employs a controlled experiment to investigate the effect of a schema-based method in correcting persistent errors in mental arithmetic, specifically in the context of simple addition operations. The experimental group utilizes a schema-based method to help participants rectify incorrect answers in memory retrieval, while the control group did not receive this treatment. Results: The results showed that significant differences emerged between the experimental and control groups in both the post-test performance and the reduction of persistent error count, indicating that the experimental group had rectified incorrect answers in memory; and persistent errors in simple addition were indeed caused by interference from incorrect answers during memory retrieval; and the schema-based method proves to be effective. Discussion: The findings of this study contribute to enhancing practical mental arithmetic instruction, assisting students in correcting relevant errors, and improving their mental arithmetic abilities. Not only does it offer directive guidance for teaching practices, but it also provides an enlightening reference for promoting innovative teaching methods.

Proactive interference of visual working memory chunks implicates long-term memory.

Visual working memory (VWM) is a limited cognitive resource that can be functionally expanded through chunking (Miller, 1956). For example, participants can hold an increasing number of colours in mind as they learn to chunk reliably paired combinations (Brady et al., 2009). We investigated whether this benefit is mediated through the in situ compression of VWM representations (Brady et al., 2009) or the offloading of chunks to long-term memory (LTM; Huang & Awh, 2018; Ngiam et al., 2019) by asking if a vulnerability of LTM - proactive interference - influences VWM performance. We adapted previous designs using deterministic (Experiment 1, N = 60) and probabilistic pairings (Experiments 2 and 3, N = 64 and 80, respectively), to include colour pairings that swapped in sequence along with pairings that were consistent in sequence. Generally, participants reported colours from consistent pairs more accurately than from swapping pairs, which we designed to drive interference in LTM (Experiments 1 and 2). The error profiles also pointed to proactive interference between swapping pairs in all three experiments. Moreover, participants who had explicit awareness of frequent colour pairings had higher VWM accuracy, and their errors reflected more proactive interference than their unaware counterparts (Experiment 3). This pattern of long-term proactive interference in a VWM task lends support for accounts of VWM chunking that propose LTM offloading.

Training semantic long-term memory retrieval transfers to executive function and reading fluency.

The retrieval of information from long-term memory is a fundamental cognitive ability, crucial for most aspects of successful human functioning. Whether and how long-term memory retrieval (LTMR) can be improved with training has clear societal importance but also theoretical value for furthering our understanding of underlying mechanisms. Here, we provide electrophysiological evidence for the plasticity of semantic LTMR. Thirty-five university students were randomly assigned to adaptive semantic LTMR training (using a Posner task) or to a non-adaptive version of the training. Before and after training they were assessed on measures of semantic LTMR, working memory, central executive function (interference control, switching), reading fluency, and fluid intelligence. Adaptive LTMR training (relative to non-adaptive training) led to significant improvements in semantic LTMR. The intervention group (in contrast to the control group) also showed a significant reduction in the mean amplitude of the N400 ERP component and 700-1000 ms measured during a semantic LTMR task, suggesting that changes in retrieval occurred at an early/automatic point and retrieval processing in semantic processing. Moreover, transfer effects were observed for switching, working memory and reading fluency, but not for interference control or fluid intelligence. These results point to the plasticity of semantic LTMR, and suggest that improvement in this ability can transfer to other domains for which LTMR is key.

Reconciling categorization and memory via environmental statistics.

How people represent categories and how those representations change over time is a basic question about human cognition. Previous research has demonstrated that people categorize objects by comparing them to category prototypes in early stages of learning but consider the individual exemplars within each category in later stages. However, these results do not seem consistent with findings in the memory literature showing that it becomes increasingly easier to access representations of general knowledge than representations of specific items over time. Why would one rely more on exemplar-based representations in later stages of categorization when it is more difficult to access these exemplars in memory? To reconcile these incongruities, our study proposed that previous findings on categorization are a result of human participants adapting to a specific experimental environment, in which the probability of encountering an object stays uniform over time. In a more realistic environment, however, one would be less likely to encounter the same object if a long time has passed. Confirming our hypothesis, we demonstrated that under environmental statistics identical to typical categorization experiments the advantage of exemplar-based categorization over prototype-based categorization increases over time, replicating previous research in categorization. In contrast, under realistic environmental statistics simulated by our experiments the advantage of exemplar-based categorization over prototype-based categorization decreases over time. A second set of experiments replicated our results, while additionally demonstrating that human categorization is sensitive to the category structure presented to the participants. These results provide converging evidence that human categorization adapts appropriately to environmental statistics.

The effect of target detection on memory retrieval.

Attention and memory are fundamental cognitive processes that closely interact. In the attentional boost effect (ABE), the stimuli that co-occur with targets are remembered better than those that co-occur with distractors in target detection tasks performed during memory encoding. In target detection tasks performed during retrieval, the stimuli that co-occur with targets are recognized as 'old' more easily than the stimuli that co-occur with distractors. This study mainly explored the internal mechanism of the effect of target detection on recognition. In Experiment 1, the full attention (FA; where participants performed only the memory task) condition was used to compare with divided attention (DA; where participants performed target detection while performing memory retrieval) condition to explore the impact of target detection and distraction inhibition on recognition. In Experiment 2, the proportion of old and new words in the retrieval stage was adjusted to 1:1 to eliminate the possible reaction tendency caused by the high proportion of old words. In Experiment 3, the presentation time of words was extended to 1.5 s and 3 s to eliminate the possible impact of rapid processing. The results indicated that the effect of target detection on recognition was attributed to both target detection and distraction rejection and is not affected by the ratio of old and new words and the word presentation time. The effect of target detection on recognition may be owing to temporal yoking of the dual tasks, which is different from the effect of target detection on memory encoding.

Cost-benefit Tradeoff Mediates the Rule- to Memory-based Processing Transition during Practice.

Practice not only improves task performance, but also changes task execution from rule- to memory-based processing by incorporating experiences from practice. However, how and when this change occurs is unclear. We tested the hypothesis that strategy transition in task learning results from cost-benefit analysis. Participants learned two task sequences and were then queried about the task type at a cued sequence and position. Behavioral improvement with practice can be accounted for by a computational model implementing cost-benefit analysis. Model-predicted strategy transition points are related to behavioral slowing and changes in fMRI activation patterns in the dorsolateral prefrontal cortex. Strategy transition is also related to increased pattern separation in the ventromedial prefrontal cortex. The cost-benefit analysis model outperforms alternative models (e.g., both strategies racing for being expressed in behavior) in accounting for empirical data. These findings support cost-benefit analysis as a mechanism of practice-induced strategy shift.

forager: a Python package and web interface for modeling mental search.

Analyzing data from the verbal fluency task (e.g., "name all the animals you can in a minute") is of interest to both memory researchers and clinicians due to its broader implications for memory search and retrieval. Recent work has proposed several computational models to examine nuanced differences in search behavior, which can provide insights into the mechanisms underlying memory search. A prominent account of memory search within the fluency task was proposed by Hills et al. (2012), where mental search is modeled after how animals forage for food in physical space. Despite the broad potential utility of these models to scientists and clinicians, there is currently no open-source program to apply and compare existing foraging models or clustering algorithms without extensive, often redundant programming. To remove this barrier to studying search patterns in the fluency task, we created forager, a Python package ( https://github.com/thelexiconlab/forager ) and web interface ( https://forager.research.bowdoin.edu/ ). forager provides multiple automated methods to designate clusters and switches within a fluency list, implements a novel set of computational models that can examine the influence of multiple lexical sources (semantic, phonological, and frequency) on memory search using semantic embeddings, and also enables researchers to evaluate relative model performance at the individual and group level. The package and web interface cater to users with various levels of programming experience. In this work, we introduce forager's basic functionality and use cases that demonstrate its utility with pre-existing behavioral and clinical data sets of the semantic fluency task.

Towards a conflict account of déjà vu: The role of memory errors and memory expectation conflict in the experience of déjà vu.

Déjà vu can be defined as conflict between a subjective evaluation of familiarity and a concurrent evaluation of novelty. Accounts of the déjà vu experience have not explicitly referred to a "conflict account of déjà vu" despite the acceptance of conflict-based definitions of déjà vu and relatively recent neuroimaging work that has implicated brain areas associated with conflict as underpinning the experience. Conflict monitoring functioning follows a similar age-related trajectory to déjà vu with a peak in young adulthood and a subsequent age-related decline. In this narrative review of the literature to date, we consider how déjà vu is defined and how this has influenced the understanding of déjà vu. We also review how déjà vu can be understood within theories of recognition memory and cognitive control. Finally, we summarise the conflict account of déjà vu and propose that this account of the experience may provide a coherent explanation as to why déjà vu experiences tend to decrease with age in the non-clinical population.

Parietal cortical alpha/beta suppression during prospective memory retrieval.

Prospective memory (PM) impairment is among the most frequent memory complaints, yet little is known about the underlying neural mechanisms. PM for a planned intention may be achieved through strategic monitoring of the environment for cues, involving ongoing attentional processes, or through spontaneous retrieval. We hypothesized that parietal spectral power modulation accompanies prospectively encoded intention retrieval, irrespective of PM retrieval approach. A cognitively engaging arithmetic-based ongoing task (OGT) was employed to encourage spontaneous retrieval, with a focal, internally generated PM cue to eliminate OGT/PM trial differentiation based on perceptual or conceptual PM cue features. Two PM repetition frequencies were used to vary the extent of strategic monitoring. We observed a transient parietal alpha/beta spectral power reduction directly preceding the response, which was distinguishable on a single trial basis, as revealed by an OGT/PM trial classification rate exceeding 70% using linear discriminant analysis. The alpha/beta idling rhythm reflects cortical inhibition. A disengagement of task-relevant neural assemblies from this rhythm, reflected in alpha/beta power reduction, is deemed to increase information content, facilitate information integration, and enable engagement of neural assemblies in task-related cortical networks. The observed power reduction is consistent with the Dual Pathways model, where PM strategies converge at the PM retrieval stage.

Effects of cueing multiple memories of eating on people's judgments about their diet.

Past research shows that recalling a single positive health-related experience, such as exercising, can encourage people's subsequent healthy behaviours. In contrast, we reasoned that attempting to recall many healthy experiences might elicit a metacognitive experience of difficulty that would lead people to perceive themselves as less healthy, and perhaps to make other health-related judgments based on this perception. In two pre-registered experiments (combined N = 729), participants recalled either "few" or "many" instances of eating either healthily or unhealthily, before rating the healthiness of their diets and completing measures of their eating preferences and choices. Contrary to our predictions, our pre-registered analyses provided minimal evidence that the number of memories people retrieved affected their judgments. However, exploratory mediation analyses suggested that two counteracting effects may have occurred, whereby retrieving more (un)healthy memories led people to identify as more (un)healthy, yet also created a sense of subjective difficulty that partially or wholly negated these effects. These findings suggest that whereas probing people's dietary memories might sometimes lead to healthier self-perceptions and dietary choices, we should also consider the possibility of backfire effects.

Cholinergic deficit induced memory retrieval impairment and hippocampal CaMKII-alpha deregulation is counteracted by sub-chronic agmatine treatment in mice.

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disease characterized by brain cholinergic dysfunction. Evidence suggests the impairment of memory retrieval phase in AD. It has been shown that CaMKII-α expressing neurons are selectively reduced in the hippocampus in AD brains. The present study aimed to investigate the effect of scopolamine on the memory retrieval phase and the hippocampal CaMKII-α signaling. In addition, the effect of sub-chronic administration of agmatine against scopolamine induced memory and possible hippocampal CaMKII-α deregulation was investigated in mice. Adult male NMRI mice were administered with agmatine at the doses of 5, 10, 20, 30 and 40 mg/kg/i.p. or saline for 11 days. Acquisition and retrieval tests of passive avoidance task were performed on days 10 and 11, respectively (30 Min following agmatine treatment). Scopolamine (1 mg/kg/i.p.) was administered once, 30 Min before retrieval test. Upon completion of the behavioral tasks, the hippocampi were isolated for western blot analysis to detect the phosphorylated and total levels of CaMKII-α and beta actin proteins. The results showed that scopolamine induced memory retrieval deficit and decreased the phosphorylated level of hippocampal CaMKII-α. Sub-chronic agmatine treatment at the dose of 40 mg/kg prevented scopolamine induced memory retrieval deficit and restored the level of hippocampal phosphorylated CaMKII-α. This study suggests that hippocampal CaMKII-α might play a role in scopolamine induced amnesia and sub-chronic agmatine prevents the impairing effect of scopolamine on the retrieval phase of memory and the phosphorylation of hippocampal CaMKII-α protein.

Why and when do you look away when trying to remember? Gaze aversion as a marker of the attentional switch to the internal world during memory retrieval.

It is common to look away while trying to remember specific information, for example during autobiographical memory retrieval, a behavior referred to as gaze aversion. Given the competition between internal and external attention, gaze aversion is assumed to play a role in visual decoupling, i.e., suppressing environmental distractors during internal tasks. This suggests a link between gaze aversion and the attentional switch from the outside world to a temporary internal mental space that takes place during the initial stage of memory retrieval, but this assumption has never been verified so far. We designed a protocol where 33 participants answered 48 autobiographical questions while their eye movements were recorded with an eye-tracker and a camcorder. Results indicated that gaze aversion occurred early (median 1.09 s) and predominantly during the access phase of memory retrieval-i.e., the moment when the attentional switch is assumed to take place. In addition, gaze aversion lasted a relatively long time (on average 6 s), and was notably decoupled from concurrent head movements. These results support a role of gaze aversion in perceptual decoupling. Gaze aversion was also related to higher retrieval effort and was rare during memories which came spontaneously to mind. This suggests that gaze aversion might be required only when cognitive effort is required to switch the attention toward the internal world to help retrieving hard-to-access memories. Compared to eye vergence, another visual decoupling strategy, the association with the attentional switch seemed specific to gaze aversion. Our results provide for the first time several arguments supporting the hypothesis that gaze aversion is related to the attentional switch from the outside world to memory.

Corticosterone injection into the basolateral amygdala before and after memory reactivation impairs the subsequent expression of fear memory in rats: An interaction of glucocorticoids and ß-adrenoceptors.

Glucocorticoid administration, before or after fear memory reactivation, impairs subsequent fear memory expression, but the underlying mechanisms are not well understood. The present study examined the role of basolateral amygdala (BLA) ß-adrenoceptors in the effects of intra-BLA corticosterone injection on fear memory in rats. Bilateral cannulae were implanted in the BLA of Wistar male rats. The rats were trained and tested using an inhibitory avoidance task (1 mA footshock for 3 s). Forty-eight hours after training, corticosterone (CORT, 5, 10, or 20 ng/0.5 µl/side) and the ß2-adrenoceptor agonist clenbuterol (CLEN, 10 or 20 ng/0.5 µl/side) or the ß-adrenoceptor antagonist propranolol (PROP, 250 or 500 ng/0.5 µl/side) were injected into the BLA before or right after memory reactivation (retrieval, Test 1). We performed subsequent tests 2 (Test 2), 5 (Test 3), 7 (Test 4), and 9 (Test 5) days after Test 1. The results demonstrated that CORT injection before Test 1 disrupted memory retrieval and reduced fear expression in Tests 2-5, possibly due to enhanced extinction or impaired reconsolidation. CORT injection after Test 1 also impaired reconsolidation and reduced fear expression in Tests 2-5. CLEN prevented, but PROP exacerbated, the effects of CORT on fear expression. The reminder shock did not recover fear memory in CORT-treated animals, suggesting that reconsolidation, not extinction, was affected. These results indicate that glucocorticoids and ß-adrenoceptors in the BLA jointly modulate fear memory reconsolidation and expression. Comprehending the neurobiology of stress and the impact of glucocorticoids on fear memory may lead to new treatments for stress and trauma-induced disorders such as PTSD.

Neural retrieval processes occur more rapidly for visual mental images that were previously encoded with high-vividness.

Visual mental imagery refers to our ability to experience visual images in the absence of sensory stimulation. Studies have shown that visual mental imagery can improve episodic memory. However, we have limited understanding of the neural mechanisms underlying this improvement. Using electroencephalography, we examined the neural processes associated with the retrieval of previously generated visual mental images, focusing on how the vividness at generation can modulate retrieval processes. Participants viewed word stimuli referring to common objects, forming a visual mental image of each word and rating the vividness of the mental image. This was followed by a surprise old/new recognition task. We compared retrieval performance for items rated as high- versus low-vividness at encoding. High-vividness items were retrieved with faster reaction times and higher confidence ratings in the memory judgment. While controlling for confidence, neural measures indicated that high-vividness items produced an earlier decrease in alpha-band activity at retrieval compared with low-vividness items, suggesting an earlier memory reinstatement. Even when low-vividness items were remembered with high confidence, they were not retrieved as quickly as high-vividness items. These results indicate that when highly vivid mental images are encoded, the speed of their retrieval occurs more rapidly, relative to low-vivid items.

The role of middle frontal gyrus in working memory retrieval by the effect of target detection tasks: a simultaneous EEG-fMRI study.

Maintained working memory (WM) representations have been shown to influence visual target detection selection, while the effect of the visual target detection process on WM retrieval remains largely unknown. In the current research, we used the dual-paradigm of the visual target detection task and the delayed matching task (DMT), which contained the following four conditions: the match condition: the DMT target contained the detection target; the mismatch condition: the DMT target contained the detection distractor; the neutral condition: only the detection target was presented; the catch condition: only the DMT target was presented. Twenty-six subjects were recruited in the experiment with simultaneous EEG-fMRI data. Behaviorally, faster responses were found in the mismatch condition than in the match and neutral conditions. The EEG data found a greater parieto-occipital N1 component in the mismatch condition compared to the neutral condition, and a greater frontal N2 component in the match condition than in the mismatch condition. Moreover, compared to the match and neutral conditions, weaker activations of the bilateral middle frontal gyrus (MFG) were observed in the mismatch condition. And the representational similarity analysis (RSA) revealed significant differences in the representational patterns of the bilateral MFG between mismatch and match conditions, as well as in the representational patterns of the left MFG between mismatch and neutral conditions. Additionally, the left MFG may be the brain source of the N1 component in the mismatch condition. These findings suggest that the mismatch between the DMT target and detection target affects early attention allocation and attentional control in WM retrieval, and the MFG may play an important role in WM retrieval by the effect of the target detection task. In conclusion, our work deepens the understanding of the neural mechanisms by which visual target detection affects WM retrieval.

Protecting against mental impasses: Evidence of selective retrieval mitigating the impact of fixation in creative problem solving.

A common issue in creative problem solving is the unintended fixation on strongly associated, yet inappropriate solutions. In two experiments, we investigated whether lowering their accessibility by means of selective retrieval can positively affect subsequent problem-solving performance in a Compound Remote Associate test. Misleading associates were strengthened by letting participants memorize them alongside with neutral words. Half of the participants then selectively retrieved the neutral words in a cued recall test, temporarily weakening the activation level of induced fixation. In both experiments, this resulted in less impairment of subsequent performance for fixated CRA problems in early problem-solving stages (0-30 s). Additional results further revealed that participants who had engaged in prior selective retrieval perceived an increased feeling of having had immediate access to target solutions. These findings correspond to the assumption of inhibitory processes being a critical factor in both retrieval-induced forgetting and overcoming fixation in creative problem solving or preventing it from occurring in the first place. Also, they provide important insight into how strongly problem solving success is influenced by fixation.