Memory Retrieval Research Articles

Cholinergic regulation of dendritic Ca2+ spikes controls firing mode of hippocampal CA3 pyramidal neurons

Active dendritic integrative mechanisms such as regenerative dendritic spikes enrich the information processing abilities of neurons and fundamentally contribute to behaviorally relevant computations. Dendritic Ca2+ spikes are generally thought to produce plateau-like dendritic depolarization and somatic complex spike burst (CSB) firing, which can initiate rapid changes in spatial coding properties of hippocampal pyramidal cells (PCs). However, here we reveal that a morpho-topographically distinguishable subpopulation of rat and mouse hippocampal CA3PCs exhibits compound apical dendritic Ca2+ spikes with unusually short duration that do not support the firing of sustained CSBs. These Ca2+ spikes are mediated by L-type Ca2+ channels and their time course is restricted by A- and M-type K+ channels. Cholinergic activation powerfully converts short Ca2+ spikes to long-duration forms, and facilitates and prolongs CSB firing. We propose that cholinergic neuromodulation controls the ability of a CA3PC subtype to generate sustained plateau potentials, providing a state-dependent dendritic mechanism for memory encoding and retrieval.

Transcranial Direct Current Stimulation over the Posterior Parietal Cortex Increases Non-target Retrieval during Visual Working Memory.

Visual working memory (VWM) requires precise feature binding. Previous studies have revealed a close relationship between the posterior parietal cortex (PPC) and feature binding during VWM, this study further examined their causal relationship through three transcranial direct current stimulation (tDCS) experiments. In Experiment 1 (N = 57), participants underwent three sessions of tDCS separately, including PPC stimulation, occipital cortex stimulation, and sham stimulation, and completed delayed estimation tasks for orientations before and after stimulation. Results showed that tDCS over PPC selectively prolonged recall response time (RT) and increased the probability of non-target responses (a.k.a. failure of feature binding, pNT). In Experiment 2 (N = 29), combining metacognition estimation, we further investigated whether the effects of PPC stimulation were attributed to mis-binding (i.e., participants self-reported "remembered" in non-target responses) or informed guessing trials (participants self-reported "forgotten" in non-target responses). We replicated the main findings in Experiment 1, and observed greater tDCS effects of PPC on RT in informed guessing trials while comparable effects on pNT in these two types of trials. In Experiment 3 (N = 28), we then examined whether the tDCS effects over PPC specifically influenced the memory retrieval process by using a change detection task. We found that PPC stimulation did not influence the recognition RT or accuracy. Together, this study provided direct causal evidence supporting the specific involvement of PPC in feature binding during VWM retrieval, from both aspects of speed and response preference, expanding our understanding of the neural basis of feature binding in VWM.Significance Statement Visual working memory (VWM) enables humans to temporarily store and process visual information, which requires accurate binding of items to their unique context. Accumulating studies posited that the posterior parietal cortex (PPC) is closely related to this binding process, the current study further examined their causal relationship. Through three strictly within-subject well-designed non-invasive neural stimulation experiments, we found that PPC stimulation selectively increased response time (RT) and binding error during VWM. Moreover, we found these changes were modulated by individual metacognition and only occurred during memory recall instead of recognition. Together, our results provided strong evidence that PPC is causally involved in the binding process during visual working memory retrieval.

Hippocampal contextualization of social rewards in mice

Acquiring and exploiting memories of rewarding experiences is critical for survival. The spatial environment in which a rewarding stimulus is encountered regulates memory retrieval. The ventral hippocampus (vH) has been implicated in contextual memories involving rewarding stimuli such as food, social cues or drugs. Yet, the neuronal representations and circuits underlying contextual memories of socially rewarding stimuli are poorly understood. Here, using in vivo electrophysiological recordings, in vivo one-photon calcium imaging, and optogenetics during a social reward contextual conditioning paradigm in male mice, we show that vH neurons discriminate between contexts with neutral or acquired social reward value. The formation of context-discriminating vH neurons following learning was contingent upon the presence of unconditioned stimuli. Moreover, vH neurons showed distinct contextual representations during the retrieval of social reward compared to fear contextual memories. Finally, optogenetic inhibition of locus coeruleus (LC) projections in the vH selectively disrupted social reward contextual memory by impairing vH contextual representations. Collectively, our findings reveal that the vH integrates contextual and social reward information, with memory encoding of these representations supported by input from the LC.

Activation, but not inactivation, of the medial or lateral orbitofrontal cortex impaired context-specific fear encoding

In laboratories, classical fear conditioning and extinction procedures are commonly used to study the behavioral and neural mechanisms underlying fear regulation. Contextual fear conditioning involves the association of an aversive event with the environment where it occurs, which engages the hippocampus and its interactions with the amygdala. The orbitofrontal cortex (OFC), divided into the lateral OFC (lOFC) and medial OFC (mOFC) subregions, plays a crucial role in integrating contextual information from the hippocampus and modulating behavioral responses based on the anticipated outcomes of the context. Because of the extensive anatomical connections of the OFC with the fear circuit, including the hippocampus, the amygdala, and the medial prefrontal cortex, and the reasoning that proper retrieval of fear-related memory is context-dependent, we raised the question to investigate the ability of the animals to discriminate between contexts when they were trained under differential OFC activation levels during the encoding of contextual fear memory. In this study, we conducted a contextual fear conditioning procedure in rats using footshock as an unconditioned stimulus (US), followed by the test of their fear levels in contexts same (dangerous) or different (safe) from the conditioning context. We used a pharmacological approach to modulate the activation levels of the lOFC or the mOFC during conditioning to examine their roles on context-specific fear encoding. Our findings showed that the animals could accurately distinguish between the two contexts in control and OFC hypoactivation groups, but failed to do so if they were trained under OFC hyperactivation. Therefore, OFC hyperactivity disturbed the encoding of contextual information during fear acquisition.

Age-related differences in memory encoding and retrieval during referential processing: A time-frequency analysis.

We investigated how lexical form similarity of referential candidates and ambiguity of following pronouns impact the encoding and retrieval of words from memory during sentence processing in younger and older adults. Critical sentences included two noun phrases (henceforth NPs) that were either phonologically and orthographically similar (Jason and Jacob/Jade) or dissimilar (Jason and Matt/Hannah), followed by a pronoun (e.g., he) that was either ambiguous or unambiguous (depending on the genders of the preceding NPs). We analyzed brain activity time-locked to the onsets of the second NP (NP2) and the pronoun to investigate the encoding and the retrieval of the NPs, respectively. During encoding NP2, older adults exhibited greater alpha power when NP1 had the same-gender, whereas younger adults showed no such effect, suggesting an increased need for inhibition for older adults during encoding. Moreover, although both groups exhibited an increase in alpha power for similar NPs, only younger adults exhibited a theta power increase, suggesting similarity-induced inhibition for both groups, but an additional maintenance cost only for younger adults. During retrieval (i.e., on the pronoun), we found that both pronominal ambiguity and form similarity resulted in greater theta power for younger adults, suggesting full pronominal processing and therefore more difficult retrieval, but smaller theta/alpha power for older adults, suggesting good-enough processing and therefore easier retrieval. Together with complementary behavioral results, our findings suggest that older adults resort to good-enough referential processing when the retrieval of relevant representations is cognitively demanding. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The power of one: A single flanker produces compatibility effects in the episodic flanker task

AbstractThe episodic flanker task is an episodic version of the Eriksen and Eriksen (Perception & Psychophysics, 16 (1), 143–149, 1974) perceptual flanker task, showing the same compatibility and distance effects. Subjects are presented with a list followed by a probe display in which one item is cued. The task, to indicate whether the probed letter appeared in the same position in the memory list, requires focusing attention on a single item in memory. The probe display contains flanking items to be ignored. They are same as the memory list or different. Same flankers are compatible with “yes” responses and incompatible with “no” responses. Different flankers are incompatible with “yes” responses and compatible with “no” responses. Previously, we presented multiple flankers in the probe, allowing a global matching strategy. Here, we report two episodic flanker experiments with just one flanker in the probe to encourage focusing sharply on the target. We found flanker compatibility effects in both experiments when a single flanker appeared immediately adjacent to the target. Experiment 2 varied the distance between the flanker and the target in the probe and the memory list and found the compatibility effect in response time only when the flanker was immediately adjacent to the target in both the probe and the memory list. The effect in accuracy also appeared when the flanker was two positions away in both the probe and the memory list. These results show that attention is focused sharply on elements of a memory structure during retrieval, suggesting that memory retrieval is perceptual attention turned inward.

I Have Decided to Read Out Loud for the Rest of My Life! Cognitive Health and the StrongerMemory Program

The StrongerMemory program aims to improve cognitive health in older adults through three daily brain exercises stimulating the prefrontal cortex: reading aloud, writing, and math activities. The brain’s prefrontal cortex governs memory retrieval, decision-making, concentration, planning, insight, and judgment. This paper reports on focus groups conducted to understand participants’ perspectives of the StrongerMemory program and their continuation of the exercises post-study. Thirty older adults, mostly female, white, married, and holding advanced degrees, participated. Rigorous data analysis involving coding, memoing, and constant comparative analysis generated 132 codes leading to the emergence of five themes: motivating, appreciating, taxing, committing, and enhancing. Social work practitioners can gain valuable insights from this study to enhance the creation and implementation of accessible and meaningful brain health interventions for older adults.

EXPRESS: The lexical boost is not an automatic part of sentence production: Evidence from Japanese structural priming.

The lexical boost is an increase in structural priming with overlapping elements like verbs. Residual activation priming theories argue that the boost is an automatic side effect of sentence planning. In contrast, explicit memory theories of the boost argue that it is the result of a non-automatic explicit memory retrieval. These theories were contrasted in Japanese by including a prime memory task in a structural priming study. Structural priming was found for both datives and passives, but no lexical boost was found and one possible reason was that explicit memory for the prime structure was weak. In a follow-up study, priming was found in a sentence completion task, but there was no lexical boost. The existence of abstract priming and the lack of a lexical boost in these studies falsifies theories that argue that verb overlap automatically creates a boost under conditions that exhibit abstract priming.

How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.

Non-sentential responses to requests for information.

When faced with requests for information ("Where did you go last night?"), why do speakers make non-sentential replies ("The movies") rather than full sentence replies ("I went to the movies")? We examine the role that pragmatic factors (politeness and formality) and memory factors (the speaker's ability to retrieve the answer to the question) play in determining whether speakers generate a non-sentential reply. Participants answered a series of questions about their lives. Pragmatic factors affected the participants' responses. Speakers instructed to be polite or formal made fewer non-sentential replies than speakers who did not receive specific instructions. Memory retrieval (indexed both by the time required for the participant to begin their response and by the presence of disfluencies at the beginning of the response) did not have a straightforward relationship to the production of non-sentential replies. The effect of response latency and disfluencies depended on whether the participants were told to be polite or formal (or if they were given no instruction at all).

Cross-cultural linguistic adaptation and development of three alternate forms of the Free and Cued Selective Reminding Test to the Brazilian context: The role of word familiarity

In spite of its importance, studies presenting detailed development procedures of alternate forms of verbal memory paradigms remains limited and unclear in terms of word selection criteria, while failing to consider word familiarity factors, despite its crucial role on episodic memory retrieval and encoding mechanisms. The present study aims to present the cross-cultural linguistic adaptation and development procedures of alternate forms of the Free and Cued Selective Reminding Test to the Brazilian context (FCSRT) based on word familiarity. After translation and backtranslation procedures, 231 new words were gathered and underwent a step-by-step familiarity analysis. Initially, overall familiarity feel of each word was assessed through the Familiarity Form (FF) during phase 1, and exposure frequency to words were later assessed through the Familiarity Questionnaire (FQ) completed by healthy controls during phase 2 with the remaining words considered ambiguous in terms of familiarity. Three alternate forms of the FCRST were then developed and assessed in terms of familiarity by the FQ during phase 3, and later administered in healthy control groups during phase 4. Repeated measures analysis revealed no significant differences in terms of familiarity and memory performance among the developed forms. Limitations are discussed, and recommendations are offered for future studies.

The retrieval of neutral and positive autobiographical memories: a pilot study

Background Several studies have shown that the retrieval of positive memories may play a role in emotional regulation. However, it is unclear whether the effects of neutral and positive autobiographical memories differ. It is necessary to confirm whether genuinely neutral autobiographical memories can be retrieved without bias when prompted to recall neutral memories. Methods In this pilot study, using “home” and “study” as cue words, we investigated whether participants were able to retrieve appropriate autobiographical memories when asked to recall a limited number of neutral or positive memories. Results Although participants were asked to recall neutral autobiographical memories, they tended to recall positive memories. Conclusions Our results support the concept of positive memory bias and suggest that future work should consider combining neutral and positive autobiographical memories by asking participants to recall neutral–positive memories.

Executive control can query hidden human memories.

When we try to retrieve a representation from visual long-term memory there is a chance that we will fail to recall seeing it even though the memory is stored in our brain. Here we show that although mechanisms of explicit memory retrieval are sometimes unable to retrieve stored memories, that mechanisms of executive control can quickly query memory and determine if a representation is stored therein. Our findings suggest that the representations stored in human memory that cannot be accessed explicitly at that moment are nonetheless directly accessible by the brain's higher level control mechanisms.

Temporal recall in the shadow of emotion: separate emotional contexts during encoding enhance the temporal source memory retrieval.

Episodic memory, with its emphasis on temporal-spatial contexts, has been a longstanding focus in memory research. While previous studies have investigated the role of emotion in temporal source memory using emotionally charged stimuli, such as emotional words or images, the influence of a separated emotional context remains less explored. This study sought to understand the impact of separate emotional contexts on temporal source memory. Participants were shown Chinese characters alongside separate emotional contexts (i.e. a neutral or negative picture) and then engaged in either a retrieval practice or a control condition. Finally, they were tested for recognition, temporal source memory, and emotional source memory for all the learned characters. Results revealed that a negative emotional context, unlike a neutral setting, enhanced the accuracy of temporal memory for adjacent neutral characters. However, this negative context reduced the accuracy of recalling the associated emotion. Importantly, the boost in temporal memory due to the emotional context remained even when participants were unsure or mistaken about the associated emotion. This study demonstrates the complex interplay between emotion and temporal memory, underscoring the enhancement effect of separated emotional contexts on temporal recall, irrespective of explicit emotional memory retrieval.

Pattern separation during encoding and Subsequent Memory Effect

Memory retrieval has been extensively studied in relation to the encoding processes that precede access to stored information. Event related potentials (ERP) research has compared brain potentials elicited during the study phase of successful and unsuccessful retrieval, finding greater activation for the subsequent retrieval information. In this work we were interested in exploring the neural markers associated to subsequent recognition when similar memories are subsequently encoded. We used a Subsequent Memory paradigm in which we manipulated the number of similar items within a category (2 or 6) that participants encoded. Manipulating the number of similar encoded items within a category allowed us to test whether encoding markers of subsequent recognition depend solely on memory trace strength or, on the contrary, successful recognition is influenced by subsequently presented similar memories, and consequently may not be reflected in higher activation in such cases. After a 20-minute period, participants performed a recognition task providing one of a three-option judgement: “old”, “similar” and “new”, which allowed us to test if the amplitude of ERP waveforms varied based on the similarity judgement of the unrecognized encoded item. We did not observe a significant parietal subsequent memory effect, however, old hits and similar false alarms were both significantly different from similar correct rejections and old false alarms in ERP retrieval. These findings suggest that differences in brain responses between conditions are specifically related to the retrieval process and not the encoding process, indicating potential differential effects on memory during retrieval. Moreover, it is also possible that differences in brain responses develop or change over the rest time between phases, influencing how these conditions manifest across different stages of information processing.

The Infralimbic, but not the Prelimbic Cortex is needed for a Complex Olfactory Memory Task.

The medial prefrontal cortex (mPFC) plays a key role in memory and behavioral flexibility, and a growing body of evidence suggests that the prelimbic (PL) and infralimbic (IL) subregions contribute differently to these processes. Studies of fear conditioning and goal-directed learning suggest that the PL promotes behavioral responses and memory retrieval, while the IL inhibits them. Other studies have shown that the mPFC is engaged under conditions of high interference. This raises the possibility that the PL and IL play differing roles in resolving interference. To examine this, we first used chemogenetics (DREADDs) to suppress mPFC neuronal activity and tested subjects on a conditional discrimination task known to be sensitive to muscimol inactivation. After confirming the effectiveness of the DREADD procedures, we conducted a second experiment to examine the PL and IL roles in a high interference memory task. We trained rats on two consecutive sets of conflicting odor discrimination problems, A and B, followed by test sessions involving a mid-session switch between the problem sets. Controls repeatedly performed worse on Set A, suggesting that learning Set B inhibited the rats' ability to retrieve Set A memories (i.e. retroactive interference). PL inactivation rats performed similarly to controls. However, IL inactivation rats did not show this effect, suggesting that the IL plays a critical role in suppressing the retrieval of previously acquired memories that may interfere with retrieval of more recent memories. These results suggest that the IL plays a critical role in memory control processes needed for resolving interference.

The role of the claustrum in the acquisition, consolidation and reconsolidation of memories in mice

The claustrum is a brain structure that remains shrouded in mystery due to the limited understanding of its cellular structure, neural pathways, functionality and physiological aspects. Significant research has unveiled connections spanning from the claustrum to the entire cortex as well as subcortical areas. This widespread connectivity has led to speculations of its role in integrating information from different brain regions, possibly contributing to processes such as attention, consciousness, learning and memory. Our working hypothesis posits that claustrum neural activity contributes to the acquisition, consolidation and reconsolidation of long-term memories in mice. We found evidence in CF-1 mice of a decline in behavioral performance in an inhibitory avoidance task due to intra-claustral administration of 2% lidocaine immediately after a training session or memory recall. Nevertheless, this does not seem to be the case for the acquisition or retrieval of this type of memory, although its neural activity is significantly increased after training, evaluated through c-Fos expression. Moreover, inhibition of the claustrum’s synaptic activity appears to impair the consolidation but not acquisition or retrieval of an unconditioned memory formed in a nose-poke habituation task.

Mechanisms of memory-supporting neuronal dynamics in hippocampal area CA3.

Hippocampal CA3 is central to memory formation and retrieval. Although various network mechanisms have been proposed, direct evidence is lacking. Using intracellular Vm recordings and optogenetic manipulations in behaving mice, we found that CA3 place-field activity is produced by a symmetric form of behavioral timescale synaptic plasticity (BTSP) at recurrent synapses among CA3 pyramidal neurons but not at synapses from the dentate gyrus (DG). Additional manipulations revealed that excitatory input from the entorhinal cortex (EC) but not the DG was required to update place cell activity based on the animal's movement. These data were captured by a computational model that used BTSP and an external updating input to produce attractor dynamics under online learning conditions. Theoretical analyses further highlight the superior memory storage capacity of such networks, especially when dealing with correlated input patterns. This evidence elucidates the cellular and circuit mechanisms of learning and memory formation in the hippocampus.

Personalized Model-Driven Interventions for Decisions From Experience.

Cognitive models that represent individuals provide many benefits for understanding the full range of human behavior. One way in which individual differences emerge is through differences in knowledge. In dynamic situations, where decisions are made from experience, models built upon a theory of experiential choice (instance-based learning theory; IBLT) can provide accurate predictions of individual human learning and adaptivity to changing environments. Here, we demonstrate how an instance-based learning (IBL) cognitive model, implemented in a cognitive architecture (Adaptive Control of Thought-Rational), can be used to model an individual's decisions in a cybersecurity defense task, accounting for both population average and individual variances. The same IBL model structure with identical architectural parameters generates the full range of human behavior through stochastic memory retrieval processes operating over and contributing to unique experiences. Recurrence quantification analyses allow us to look beyond average behavior between and within individuals to sequential patterns of trial-to-trial behavior. We show how model-tracing and knowledge-tracing techniques can be used to align the model to an individual in real time to drive adaptive and personalized signaling algorithms for a cybersecurity defense system. We also present a method for introspecting into the cognitive model to gain further insight into the cognitive salience of features factored into individual decisions. The combination of techniques provides a blueprint for personalized modeling of individuals. We discuss the results and implications of this adaptive and personalized method for cybersecurity defense and more generally for intelligent artifacts tailored to individual differences in domains such as human-machine teaming.

Distinct Roles of Medial Prefrontal Cortex Subregions in the Consolidation and Recall of Remote Spatial Memories.

It is a common belief that memories, over time, become progressively independent of the hippocampus and are gradually stored in cortical areas. This view is mainly based on evidence showing that prefrontal cortex (PFC) manipulations impair the retrieval of remote memories, while hippocampal inhibition does not. More controversial is whether activity in the medial PFC is required immediately after learning to initiate consolidation. Another question concerns functional differences among PFC subregions in forming and storing remote memories. To address these issues, we directly contrasted the effects of loss-of-function manipulations of the anterior cingulate cortex (aCC) and the ventromedial PFC, which includes the infralimbic (IL) and prelimbic (PL) cortices, before testing and immediately after training on the ability of CD1 mice to recall the hidden platform location in the Morris water maze. We injected an AAV carrying the hM4Di receptor into the PL-IL or aCC. Interestingly, pretest administrations of clozapine-N-oxide (CNO; 3 mg/kg) revealed that the aCC, but not the PL-IL, was necessary to recall remote spatial information. Furthermore, systemic post-training administration of CNO impaired memory recall at remote, but not recent, time points in both groups. These findings revealed a functional dissociation between the two prefrontal areas, demonstrating that both the PL-IL and the aCC are involved in early consolidation of remote spatial memories, but only the aCC is engaged in their recall.