Human Episodic Memory Research Articles

Repulsion of CA3 / dentate gyrus representations is driven by distinct internal beliefs in the face of ambiguous sensory input.

Recent human neuroimaging studies of episodic memory have revealed a counterintuitive phenomenon in the hippocampus: when events are highly similar, corresponding hippocampal activity patterns are sometimes less correlated than activity patterns associated with unrelated events. This phenomenon- repulsion- is not accounted for by most theories of the hippocampus, and the conditions that trigger repulsion remain poorly understood. Here, we used a spatial route-learning task and high-resolution fMRI in humans to test whether hippocampal repulsion is fundamentally driven by internal beliefs about the environment. By precisely measuring participants' internal beliefs and actively manipulating them, we show that repulsion selectively occurred in hippocampal subfields CA3 and dentate gyrus when visual input was ambiguous-or even identical -but internal beliefs were distinct. These findings firmly establish conditions that elicit repulsion and have broad relevance to theories of hippocampal function and to the fields of human episodic memory and rodent spatial navigation.

A third kind of episodic memory: Context familiarity is distinct from item familiarity and recollection.

Memory for past events is widely believed to operate through two different processes: one called 'recollection' when retrieving confident, specific details of a memory, and another called 'familiarity' when only having an unsure but conscious awareness that an item was experienced before. When people successfully retrieve details such as the source or context of a prior event, it has been assumed to reflect recollection. We demonstrate that familiarity of context is functionally distinct from familiarity of items and recollection and offer a new, tri-component model of memory. The three memory responses were differentiated across multiple behavioral and brain wave measures. What has traditionally been thought to be two kinds of memory processes are actually three, becoming evident when using sensitive enough multi-measures. Results are independently replicated across studies from different labs. These data reveal that context familiarity is a third process of human episodic memory.

Theta phase precession supports memory formation and retrieval of naturalistic experience in humans.

Associating different aspects of experience with discrete events is critical for human memory. A potential mechanism for linking memory components is phase precession, during which neurons fire progressively earlier in time relative to theta oscillations. However, no direct link between phase precession and memory has been established. Here we recorded single-neuron activity and local field potentials in the human medial temporal lobe while participants (n = 22) encoded and retrieved memories of movie clips. Bouts of theta and phase precession occurred following cognitive boundaries during movie watching and following stimulus onsets during memory retrieval. Phase precession was dynamic, with different neurons exhibiting precession in different task periods. Phase precession strength provided information about memory encoding and retrieval success that was complementary with firing rates. These data provide direct neural evidence for a functional role of phase precession in human episodic memory.

Synthesizing the temporal self: robotic models of episodic and autobiographical memory.

Episodic memories are experienced as belonging to a self that persists in time. We review evidence concerning the nature of human episodic memory and of the sense of self and how these emerge during development, proposing that the younger child experiences a persistent self that supports a subjective experience of remembering. We then explore recent research in cognitive architectures for robotics that has investigated the possibility of forms of synthetic episodic and autobiographical memory. We show that recent advances in generative modeling can support an understanding of the emergence of self and of episodic memory, and that cognitive architectures which include a language capacity are showing progress towards the construction of a narrative self with autobiographical memory capabilities for robots. We conclude by considering the prospects for a more complete model of mental time travel in robotics and the implications of this modeling work for understanding human episodic memory and the self in time. This article is part of the theme issue 'Elements of episodic memory: lessons from 40 years of research'.

Human-unique brain cell clusters are associated with learning disorders and human episodic memory activity.

The advanced evolution of the human cerebral cortex forms the basis for our high-level cognitive functions. Through a comparative analysis of single-nucleus transcriptome data from the human neocortex and that of chimpanzees, macaques, and marmosets, we discovered 20 subgroups of cell types unique to the human brain, which include 11 types of excitatory neurons. Many of these human-unique cell clusters exhibit significant overexpression of genes regulated by human-specific enhancers. Notably, these specific cell clusters also express genes associated with disease risk, particularly those related to brain dysfunctions like learning disorders. Furthermore, genes linked to cortical thickness and human episodic memory encoding activities show heightened expression within these cell subgroups. These findings underscore the critical role of human brain-unique cell clusters in the evolution of human brain functions.

Neuroscientist's Behavioral Toolbox for Studying Episodic-Like Memory.

Episodic memory, the ability to recall specific events and experiences, is a cornerstone of human cognition with profound clinical implications. While animal studies have provided valuable insights into the neuronal underpinnings of episodic memory, research has largely relied on a limited subset of tasks that model only some aspects of episodic memory. In this narrative review, we provide an overview of rodent episodic-like memory tasks that expand the methodological repertoire and diversify the approaches used in episodic-like memory research. These tasks assess various aspects of human episodic memory, such as integrated what-where-when or what-where memory, source memory, free recall, temporal binding, and threshold retrieval dynamics. We review each task's general principle and consider whether alternative non-episodic mechanisms can account for the observed behavior. While our list of tasks is not exhaustive, we hope it will guide researchers in selecting models that align with their specific research objectives, leading to novel advancements and a more comprehensive understanding of mechanisms underlying specific aspects of episodic memory.

Validation of a rodent model of episodic memory replay.

Vivid episodic memories in humans have been described as the replay of the flow of past events in sequential order. Recently, Panoz-Brown et al. Current Biology, 28, 1628-1634, (2018) developed an olfactory memory task in which rats were presented with a list of trial-unique odors in an encoding context; next, in a distinctive memory assessment context, the rats were rewarded for choosing the second to last item from the list while avoiding other items from the list. In a different memory assessment context, the fourth to last item was rewarded. According to the episodic memory replay hypothesis, the rat remembers the list items and searches these items to find the item at the targeted locations in the list. However, events presented sequentially differ in memory trace strength, allowing a rat to use the relative familiarity of the memory traces, instead of episodic memory replay, to solve the task. Here, we directly manipulated memory trace strength by manipulating the odor intensity of target odors in both the list presentation and memory assessment. The rats relied on episodic memory replay to solve the memory assessment in conditions in which reliance on memory trace strength is ruled out. We conclude that rats are able to replay episodic memories.

Episodic-like memory in wild free-living blue tits and great tits

Episodic-like memory in non-human animals represents the behavioral characteristics of human episodic memory-the ability to mentally travel backward in time to "re-live" past experiences. A focus on traditional model species of episodic-like memory may overlook taxa possessing this cognitive ability and consequently its evolution across species. Experiments conducted in the wild have the potential to broaden the scope of episodic-like memory research under the natural conditions in which they evolved. We combine two distinct yet complementary episodic-like memory tasks (the what-where-when memory and incidental encoding paradigms), each targeting a different aspect of human episodic memory, namely the content (what-where-when) and process (incidental encoding), to comprehensively test the memory abilities of wild, free-living, non-caching blue tits (Cyanistes caeruleus) and great tits (Parus major). Automated feeders with custom-built programs allowed for experimental manipulation of spatiotemporal experiences on an individual-level basis. In the what-where-when memory experiment, after learning individualized temporal feeder rules, the birds demonstrated their ability to recall the "what" (food type), "where" (feeder location), and "when" (time since their initial visit of the day) of previous foraging experiences. In the incidental encoding experiment, the birds showed that they were able to encode and recall incidental spatial information regarding previous foraging experiences ("where" test), and juveniles, but not adults, were also able to recall incidentally encoded visual information ("which" test). Consequently, this study presents multiple lines of converging evidence for episodic-like memory in a wild population of generalist foragers, suggesting that episodic-like memory may be more taxonomically widespread than previously assumed.

Eurasian jays (Garrulus glandarius) show episodic-like memory through the incidental encoding of information.

Episodic memory describes the conscious reimagining of our memories and is often considered to be a uniquely human ability. As these phenomenological components are embedded within its definition, major issues arise when investigating the presence of episodic memory in non-human animals. Importantly, however, when we as humans recall a specific experience, we may remember details from that experience that were inconsequential to our needs, thoughts, or desires at that time. This 'incidental' information is nevertheless encoded automatically as part of the memory and is subsequently recalled within a holistic representation of the event. The incidental encoding and unexpected question paradigm represents this characteristic feature of human episodic memory and can be employed to investigate memory recall in non-human animals. However, without evidence for the associated phenomenology during recall, this type of memory is termed 'episodic-like memory'. Using this approach, we tested seven Eurasian jays (Garrulus glandarius) on their ability to use incidental visual information (associated with observed experimenter made 'caches') to solve an unexpected memory test. The birds performed above chance levels, suggesting that Eurasian jays can encode, retain, recall, and access incidental visual information within a remembered event, which is an ability indicative of episodic memory in humans.

Sex differences in the context dependency of episodic memory.

Context contributes to multiple aspects of human episodic memory including segmentation and retrieval. The present studies tested if, in adult male and female mice, context influences the encoding of odors encountered in a single unsupervised sampling session of the type used for the routine acquisition of episodic memories. The three paradigms used differed in complexity (single vs. multiple odor cues) and period from sampling to testing. Results show that males consistently encode odors in a context-dependent manner: the mice discriminated novel from previously sampled cues when tested in the chamber of initial cue sampling but not in a distinct yet familiar chamber. This was independent of the interval between cue encounters or the latency from initial sampling to testing. In contrast, female mice acquired both single cues and the elements of multi-cue episodes, but recall of that information was dependent upon the surrounding context only when the cues were presented serially. These results extend the list of episodic memory features expressed by rodents and also introduce a striking and unexpected sex difference in context effects.

Inhibition of Cpeb3 ribozyme elevates CPEB3 protein expression and polyadenylation of its target mRNAs and enhances object location memory.

A self-cleaving ribozyme that maps to an intron of the cytoplasmic polyadenylation element-binding protein 3 (Cpeb3) gene is thought to play a role in human episodic memory, but the underlying mechanisms mediating this effect are not known. We tested the activity of the murine sequence and found that the ribozyme's self-scission half-life matches the time it takes an RNA polymerase to reach the immediate downstream exon, suggesting that the ribozyme-dependent intron cleavage is tuned to co-transcriptional splicing of the Cpeb3 mRNA. Our studies also reveal that the murine ribozyme modulates maturation of its harboring mRNA in both cultured cortical neurons and the hippocampus: inhibition of the ribozyme using an antisense oligonucleotide leads to increased CPEB3 protein expression, which enhances polyadenylation and translation of localized plasticity-related target mRNAs, and subsequently strengthens hippocampal-dependent long-term memory. These findings reveal a previously unknown role for self-cleaving ribozyme activity in regulating experience-induced co-transcriptional and local translational processes required for learning and memory.

Replay of incidentally encoded episodic memories in the rat

Although events are not always known to be important when they occur, people can remember details about such incidentally encoded information using episodic memory. Importantly, when information is explicitly encoded for use in an expected test of retention (as in most assessments in animals), it is possible that it is used to generate a planned action1,2,3; thus, the remembered action can occur without remembering the earlier episode. By contrast, when a test is unexpected, transforming information into an action plan is unlikely because the importance of the information and the nature of the test are not yet known. Thus, accurate performance in an unexpected test after incidental encoding documents episodic memory.1,2,3,4,5,6,7,8 Here, we present evidence that rats replay episodic memories of incidentally encoded information in an unexpected assessment of memory. In one task,9 rats reported the third-last item in an explicitly encoded list of trial-unique odors. In a second task,10 rats foraged in a radial maze in the absence of odors. On a critical test, rats foraged in the radial maze, but scented lids covered the food. Next, memory of the third-last odor was assessed. All participating rats correctly answered the unexpected question. These results suggest that rats encoded multiple pieces of putatively unimportant information, and later they replayed a stream of episodic memories when that information was needed to solve an unexpected problem. We propose that rats replay episodic memories of incidentally encoded information, which documents a critical aspect of human episodic memory in a non-human animal.

A computational model of current control mechanism for long-term potentiation (LTP) in human episodic memory based on gene-gene interaction.

The establishment of long-term potentiation (LTP) is a prime process for the formation of episodic memory. During the establishment of LTP, activations of various components are required in the signaling cascade of the LTP pathway. Past efforts to determine the activation of components relied extensively on the cellular or molecular level. In this paper, we have proposed a computational model based on gene-level cascading and interaction in LTP signaling for the establishment and control of current signals for achieving the desired level of activation in the formation of episodic memory. This paper also introduces a model for a generalized signaling pathway in episodic memory. A back-propagation feedback mechanism is used for updating the interaction levels in the signaling cascade starting from the last stage and ending at the start stage of the signaling cascade. Simulation of the proposed model has been performed for the LTP signaling pathway in the context of human episodic memory. We found through simulation that the qualifying genes correction factors of all stages are updated to their maximum limit. The article explains the signaling pathway for episodic memory and proves its effectiveness through simulation results.

Sparse attentional subsetting of item features and list-composition effects on recognition memory

Although knowledge is extremely high-dimensional, human episodic memory performance appears extremely low-dimensional, focused largely on stimulus-features that distinguish list items from one another. A cognitively plausible way this tension could be addressed is if selective attention selects a small number of features from each item. I consider an ongoing debate about whether stronger items (better encoded) interfere more than weaker items (less well encoded) with probe items during old/new episodic recognition judgements. This is called the list-strength effect, concerning whether or not effects of encoding strength are larger in lists of mixed strengths than in pure lists of a single strength. Analytic derivations with Anderson’s (1970) matched filter model show how storing only a small subset of features within high-dimensional representations, and assuming those same subsets tend to reiterate themselves item-wise at test, can support high recognition performance. In the sparse regime, the model produces a list-strength effect that is small in magnitude, resembling previous findings of so-called null list-strength effects. When the attended feature space is compact, such as for phonological features, attentional subsetting cannot be sparse. This introduces non-negligible cross-talk from other list items, producing a large-magnitude list-strength effect, similar to what is observed for the production effect (better recognition when reading aloud). This continuum-based account implies the existence of a continuous range of magnitudes of list-composition effects, including occasional inverted list-strength effects. This lays the foundation for propagating effects of task-relevant attention to sparse subsets of features through a broad range of models of memory behaviour.

Altering stimulus timing via fast rhythmic sensory stimulation induces STDP-like recall performance in human episodic memory

Episodic memory provides humans with the ability to mentally travel back to the past,1 where experiences typically involve associations between multimodal information. Forming a memory of the association is thought to be dependent on modification of synaptic connectivity.2,3 Animal studies suggest that the strength of synaptic modification depends on spike timing between pre- and post-synaptic neurons on the order of tens of milliseconds, which is termed "spike-timing-dependent plasticity" (STDP).4 Evidence found in human invitro studies suggests different temporal scales in long-term potentiation (LTP) and depression (LTD), compared with the critical time window of STDP in animals.5,6 In the healthy human brain, STDP-like effects have been shown in the motor cortex, visual perception, and face identity recognition.7,8,9,10,11,12,13 However, evidence in human episodic memory is lacking. We investigated this using rhythmic sensory stimulation to drive visual and auditory cortices at 37.5Hz with four phase offsets. Visual relative to auditory cued recall accuracy was significantly enhanced in the 90° condition when the visual stimulus led at the shortest delay (6.67ms). This pattern was reversed in the 270° condition when the auditory stimulus led at the shortest delay. Within cue modality, recall was enhanced when a stimulus of the corresponding modality led the shortest delay (6.67ms) compared with the longest delay (20ms). Our findings provide evidence for STDP in human episodic memory, which builds an important bridge from invitro studies in animals to human memory behavior.

Seven Ambiguities in Explaining the Human Memory System in the Principles of Neural Science Book.

The human memory system is not yet well identified.Imaging studies are not able to locate the memory storage sites of the brain.Current theories cannot explain the huge amount of memory storage in the brain.Episodic memories of animals should be different with a human episodic memory? The human memory system is very complex, and we still have many questions on that. One of the questions is about the location of episodic memory storage in humans. Is that really happening in the brain? One other question is about studying the episodic memory in animals: do they really have an episodic memory similar to the humans? Prof. Kandel in his very valuable book has explained the memory system; however, many ambiguities are still unsolved. For example, the neuroimaging methods are nearly never able to speak of the site of memory "storage" in the brain, whereas many of their results are used as evidence for identifying the location of memory storage in the brain. Also, the hippocampus is emphasized to be responsible for the storage of episodic memories in animals, whereas a human whore hippocampus is resected is still able to retrieve his memories from before the surgery. As a result, we speculate that, despite all the very precious findings of Prof. Kandel, we still have to work in this field to reveal its mysteries.

Constructing condensed memories in functorial time

ABSTRACT If episodic memory is constructive, experienced time is also a construct. We develop an event-based formalism that replaces the traditional objective, agent-independent notion of time with a constructive, agent-dependent notion of time. We show how to make this agent-dependent time entropic and hence well-defined. We use sheaf-theoretic techniques to render agent-dependent time functorial and to construct episodic memories as sequences of observed and constructed events with well-defined limits that maximise the consistency of categorisations assigned to objects appearing in memories. We then develop a condensed formalism that represents episodic memories as pure constructs from single events. We formulate an empirical hypothesis that human episodic memory implements a particular time-symmetric constructive functor, and discuss possible experimental tests.

Gamma amplitude is coupled to opposed hippocampal theta-phase states during the encoding and retrieval of episodic memories in humans

Computational models and invivo studies in rodents suggest that the emergence of gamma activity (40-140Hz) during memory encoding and retrieval is coupled to opposed-phase states of the underlying hippocampal theta rhythm (4-9Hz).1,2,3,4,5,6,7,8,9,10 However, direct evidence for whether human hippocampal gamma-modulated oscillatory activity in memory processes is coupled to opposed-phase states of the ongoing theta rhythm remains elusive. Here, we recorded local field potentials (LFPs) directly from the hippocampus of 10 patients with epilepsy, using depth electrodes. We used a memory encoding and retrieval task whereby trialunique sequences of pictures depicting real-life episodes were presented, and 24h later, participants were asked to recall them upon the appearance of the first picture of the encoded episodic sequence. Wefound theta-to-gamma cross-frequency coupling that was specific to the hippocampus during both the encoding and retrieval of episodic memories. We also revealed that gamma was coupled to opposing theta phases during both encoding and recall processes. Additionally, we observed that the degree of theta-gamma phase opposition between encoding and recall was associated with participants' memory performance, so gamma power was modulated by theta phase for both remembered and forgotten trials, although only for remembered trials the dominant theta phase was different for encoding and recall trials. The current results offer direct empirical evidence in support of hippocampal theta-gamma phase opposition models in human long-term memory and provide fundamental insights into mechanistic predictions derived from computational and animal work, thereby contributing to establishing similarities and differences across species.

Interaction between Theta Phase and Spike Timing-Dependent Plasticity Simulates Theta-Induced Memory Effects.

Rodent studies suggest that spike timing relative to hippocampal theta activity determines whether potentiation or depression of synapses arise. Such changes also depend on spike timing between presynaptic and postsynaptic neurons, known as spike timing-dependent plasticity (STDP). STDP, together with theta phase-dependent learning, has inspired several computational models of learning and memory. However, evidence to elucidate how these mechanisms directly link to human episodic memory is lacking. In a computational model, we modulate long-term potentiation (LTP) and long-term depression (LTD) of STDP, by opposing phases of a simulated theta rhythm. We fit parameters to a hippocampal cell culture study in which LTP and LTD were observed to occur in opposing phases of a theta rhythm. Further, we modulated two inputs by cosine waves with 0° and asynchronous phase offsets and replicate key findings in human episodic memory. Learning advantage was found for the in-phase condition, compared with the out-of-phase conditions, and was specific to theta-modulated inputs. Importantly, simulations with and without each mechanism suggest that both STDP and theta phase-dependent plasticity are necessary to replicate the findings. Together, the results indicate a role for circuit-level mechanisms, which bridge the gap between slice preparation studies and human memory.

Distinct brain networks for remote episodic memory depending on content and emotional experience

Memories of life episodes are the heart of individual stories. However, modelling episodic memory is a major challenge in both humans and animals when considering all its characteristics. As a consequence, the mechanisms that underlie the storage of old nontraumatic episodic memories remain enigmatic. Here, using a new task in rodents that models human episodic memory including odour/place/context components and applying advances behavioural and computational analyses, we show that rats form and recollect integrated remote episodic memories of two occasionally encountered complex episodes occurring in their daily life. Similar to humans, the information content and accuracy of memories vary across individuals and depend on the emotional relationship with odours experienced during the very first episode. We used cellular brain imaging and functional connectivity analyses, to find out the engrams of remote episodic memories for the first time. Activated brain networks completely reflect the nature and content of episodic memories, with a larger cortico-hippocampal network when the recollection is complete and with an emotional brain network related to odours that is critical in maintaining accurate and vivid memories. The engrams of remote episodic memories remain highly dynamic since synaptic plasticity processes occur during recall related to memory updates and reinforcement.