Background and objectives: Episodic specific induction (ESI) is a manipulation shown to enhance episodic memory function. Episodic specificity induction involves thoroughly unpacking a recently encoded memory, with this enhanced retrieval-induced process helping to facilitate subsequent cognitions. In addition to ESI, emerging work suggests that acute exercise may also help to facilitate episodic memory function. The purpose of this study was to evaluate the potential individual and combined effects of acute exercise and ESI on subsequent episodic memory performance. Materials and Methods: Participants (n = 120) were randomly assigned into one of four groups, (1) ESI and exercise (ESI + E), (2) ESI only (ESI), (3) exercise only (E), and (4) no ESI and no exercise (Control; C). The ESI protocol involved watching a short video and then recalling details about the setting, people, and actions in the video. The exercise protocol involved an acute bout (15 min) of treadmill exercise. After these tasks, episodic memory function was evaluated with an autobiographical interview assessment and a computerized episodic memory task involving what-where-when integration. Results: We did not observe significant main effects for exercise or ESI on memory function but did observe some suggestive evidence of an interaction effect of these two parameters on episodic memory. That is, for the exercise group, memory performance was higher when combined with ESI as opposed to without ESI. Conclusions: Acute exercise and ESI may interact to influence episodic memory function.

Men as a group have been shown to have larger variances than women in several areas pertaining to both biological and psychological traits, but no investigation has been performed in regard to episodic memory. We conducted an analysis on sex differences in episodic memory variance on 535 studies, representing 962,946 individuals, conducted between 1973 and 2013. Results showed that men had larger variances than women in verbal episodic memory tasks as well as episodic memory tasks having to do with spatial locations. Women, on the other hand, had larger variance than men for tasks involving remembering routes. These effects were for the most part small, and exploratory analyses suggest that they might come about, at least in part, because of measures not sufficiently controlled for ceiling effects. This means that the effects should be interpreted with caution and that further research on sex differences in episodic memory variance is needed.

A fundamental question in memory research is how different forms of memory interact. Previous research has shown that people rely on working memory (WM) in short-term recognition tasks; a common view is that episodic memory (EM) only influences performance on these tasks when WM maintenance is disrupted. However, retrieval of memories from EM has been widely observed during brief periods of quiescence, raising the possibility that EM retrievals during maintenance-critically, before a response can be prepared-might affect short-term recognition memory performance even in the absence of distraction. We hypothesized that this influence would be mediated by the lingering presence of reactivated EM content in WM. We obtained support for this hypothesis in three experiments, showing that delay-period EM reactivation introduces incidentally associated information (context) into WM, and that these retrieved associations negatively impact subsequent recognition, leading to substitution errors (Experiment 1) and slowing of accurate responses (Experiment 2). FMRI pattern analysis showed that slowing is mediated by the content of EM reinstatement (Experiment 3). These results expose a previously hidden influence of EM on WM, raising new questions about the adaptive nature of their interaction.

The medial temporal lobe supports both navigation and declarative memory. On this basis, a theory of phylogenetic continuity has been proposed according to which episodic and semantic memories have evolved from egocentric (e.g., path integration) and allocentric (e.g., map-based) navigation in the physical world, respectively. Here, we explored the behavioral significance of this neurophysiological model by investigating the relationship between the performance of healthy individuals on a path integration and an episodic memory task. We investigated the path integration performance through a proprioceptive Triangle Completion Task and assessed episodic memory through a picture recognition task. We evaluated the specificity of the association between performance in these two tasks by including in the study design a verbal semantic memory task. We also controlled for the effect of attention and working memory and tested the robustness of the results by including alternative versions of the path integration and semantic memory tasks. We found a significant positive correlation between the performance on the path integration the episodic, but not semantic, memory tasks. This pattern of correlation was not explained by general cognitive abilities and persisted also when considering a visual path integration task and a non-verbal semantic memory task. Importantly, a cross-validation analysis showed that participants' egocentric navigation abilities reliably predicted episodic memory performance. Altogether, our findings support the hypothesis of a phylogenetic continuity between egocentric navigation and episodic memory and pave the way for future research on the potential causal role of egocentric navigation on multiple forms of episodic memory.

The aim of this study was to determine the neural correlates of different stages of episodic memory function and their modulation by Alzheimer's disease (AD). Several decades of work has supported the role of the medial temporal lobes (MTL) in episodic memory function. However, a more recent work, derived in part from functional neuroimaging studies, has suggested that other brain structures make up a large-scale network that appears to support successful encoding and retrieval of episodic memories. Furthermore, controversy exists as to whether dissociable MTL regions support qualitatively different aspects of memory (hippocampus: contextual memory or 'recollection'; perirhinal/lateral entorhinal cortex: item memory or 'familiarity'). There is limited neuropsychological support for these models and most work in AD only has examined free recall memory measures. We studied the relationship between performance on different stages of the Rey Auditory Verbal Learning Test (AVLT), a 15-item word list learning task, and structural MRI measures in mild AD patients. Structural measures included hippocampal volume and cortical thickness of several ROIs known to undergo atrophy in AD. Correlation and multiple regression analyses, controlling for age, education, and gender, were performed in 146 mild AD patients (MMSE 23.3±2.0). To evaluate the robustness of these relationships, similar analyses were performed with additional standardized verbal memory measures. Early immediate recall trials (e.g. Trial 1 of the AVLT) were not associated with the size of MTL regions, but correlated most strongly with inferior parietal, middle frontal gyrus, and temporal pole ROIs. After repeated exposure (e.g. Trial 5 of the AVLT), immediate recall was correlated with both MTL and a similar distribution of isocortical structures, but most strongly the temporal pole. For delayed recall, only the hippocampus correlated with performance. In contrast, for delayed recognition discrimination, the perirhinal/entorhinal cortex correlated more strongly than the hippocampus; no other isocortical regions were strongly associated with performance. Convergent results were found for immediate and delayed trials of other memory tests. The current results suggest that a richer understanding of the memory deficits in AD can be gained by examining multiple measures, which tap different aspects of memory function. Furthermore, the present findings are consistent with models hypothesizing different stages of verbal list learning map onto dissociable brain regions. These data have implications for understanding the anatomic basis of processes underlying episodic memory, particularly related to a division of labor within the medial temporal lobes and within the large-scale MTL-cortical memory network.

Episodic memories are long lasting and full of detail, yet imperfect and malleable. We quantitatively evaluated recollection of short audiovisual segments from movies as a proxy to real-life memory formation in 161 subjects at 15 minutes up to a year after encoding. Memories were reproducible within and across individuals, showed the typical decay with time elapsed between encoding and testing, were fallible yet accurate, and were insensitive to low-level stimulus manipulations but sensitive to high-level stimulus properties. Remarkably, memorability was also high for single movie frames, even one year post-encoding. To evaluate what determines the efficacy of long-term memory formation, we developed an extensive set of content annotations that included actions, emotional valence, visual cues and auditory cues. These annotations enabled us to document the content properties that showed a stronger correlation with recognition memory and to build a machine-learning computational model that accounted for episodic memory formation in single events for group averages and individual subjects with an accuracy of up to 80%. These results provide initial steps towards the development of a quantitative computational theory capable of explaining the subjective filtering steps that lead to how humans learn and consolidate memories.

Cytoplasmic polyadenylation element-binding (CPEB) proteins are crucial for synaptic plasticity and memory in model organisms. A highly conserved, mammalian-specific short intronic sequence within CPEB3 has been identified as a ribozyme with self-cleavage properties. In humans, the ribozyme sequence is polymorphic and harbors a single nucleotide polymorphism that influences cleavage activity of the ribozyme. Here we show that this variation is related to performance in an episodic memory task and that the effect of the variation depends on the emotional valence of the presented material. Our data suggest a role for human CPEB3 in human episodic memory.

It has been suggested that the simulation of hypothetical episodes and the recollection of past episodes are supported by fundamentally the same set of brain regions. The present article specifies this core network via Activation Likelihood Estimation (ALE). Specifically, a first meta-analysis revealed joint engagement of expected core-network regions during episodic memory and episodic simulation. These include parts of the medial surface, the hippocampus and parahippocampal cortex within the medial temporal lobes, and the temporal and inferior posterior parietal cortices on the lateral surface. Both capacities also jointly recruited additional regions such as parts of the bilateral dorsolateral prefrontal cortex. All of these core regions overlapped with the default network. Moreover, it has further been suggested that episodic simulation may require a stronger engagement of some of the core network's nodes as well as the recruitment of additional brain regions supporting control functions. A second ALE meta-analysis indeed identified such regions that were consistently more strongly engaged during episodic simulation than episodic memory. These comprised the core-network clusters located in the left dorsolateral prefrontal cortex and posterior inferior parietal lobe and other structures distributed broadly across the default and fronto-parietal control networks. Together, the analyses determine the set of brain regions that allow us to experience past and hypothetical episodes, thus providing an important foundation for studying the regions' specialized contributions and interactions.

Memory is often conceived as a dynamic process that involves substantial transformations of mental representations. However, the neural mechanisms underlying these transformations and their role in memory formation and retrieval have only started to be elucidated. Combining intracranial EEG recordings with deep neural network models, we provide a detailed picture of the representational transformations from encoding to short-term memory maintenance and long-term memory retrieval that underlie successful episodic memory. We observed substantial representational transformations during encoding. Critically, more pronounced semantic representational formats predicted better subsequent long-term memory, and this effect was mediated by more consistent item-specific representations across encoding events. The representations were further transformed right after stimulus offset, and the representations during long-term memory retrieval were more similar to those during short-term maintenance than during encoding. Our results suggest that memory representations pass through multiple stages of transformations to achieve successful long-term memory formation and recall.

Polymorphisms in the gene encoding catenin-β-like 1 (CTNNBL1) were recently reported to be associated with verbal episodic memory performance--in particular, delayed verbal free recall assessed between 5 and 30 min after encoding--in a genome-wide association study on healthy young adults. To further examine the genetic effects of CTNNBL1, we tested for association between 455 single-nucleotide polymorphisms (SNPs) in or near CTNNBL1 and 14 measures of episodic memory performance from three different tasks in 1743 individuals. Probands were part of a population-based study of mentally healthy adult men and women, who were between 20 and 70 years old and were recruited as participants for the Berlin Aging Study II. Associations were assessed using linear regression analysis. Despite having sufficient power to detect the previously reported effect sizes, we found no evidence for statistically significant associations between the tested CTNNBL1 SNPs and any of the 14 measures of episodic memory. The previously reported effects of genetic polymorphisms in CTNNBL1 on episodic memory performance do not generalize to the broad range of tasks assessed in our cohort. If not altogether spurious, the effects may be limited to a very narrow phenotypic domain (that is, verbal delayed free recall between 5 and 30 min). More studies are needed to further clarify the role of CTNNBL1 in human memory.

Episodic memory formation requires the binding of multiple associations to a coherent episodic representation, with rich detail of times, places, and contextual information. During postnatal development, the ability to recall episodic memories emerges later than other types of memory such as object recognition. However, the precise developmental trajectory of episodic memory, from weaning to adulthood has not yet been established in rats. Spontaneous object exploration tasks do not require training, and allow repeated testing of subjects, provided novel objects are used on each trial. Therefore, these tasks are ideally suited for the study of the ontogeny of episodic memory and its constituents (e.g., object, spatial, and contextual memory).

Our memories enable us to form expectations for our future experiences, yet the precise neural mechanisms underlying how we compare any experience to our memory remain unknown. Here, using intracranial EEG recordings, we show that episodic memories formed after a single visual experience establish expectations for future experience within neocortical-medial temporal lobe circuits. When subsequent experiences violate these expectations, we find a 80-120 Hz prediction error signal that emerges in both visual association areas and the medial temporal lobe. Critically, this error signal emerges in visual association areas first and then propagates to the medial temporal lobe. This error signal is accompanied by alpha coherence between the two regions. Our data therefore suggest that internal models formed from episodic memories are generated throughout the visual hierarchy after just a single exposure, and that these internal models are then used for comparison with future experiences.

Episodic memory enables humans to encode and later vividly retrieve information about our rich experiences, yet the neural representations that support this mental capacity are poorly understood. Using a large fMRI dataset (n = 468) of face-name associative memory tasks and principal component analysis to examine neural representational dimensionality (RD), we found that the human brain maintained a high-dimensional representation of faces through hierarchical representation within and beyond the face-selective regions. Critically, greater RD was associated with better subsequent memory performance both within and across participants, and this association was specific to episodic memory but not general cognitive abilities. Furthermore, the frontoparietal activities could suppress the shared low-dimensional fluctuations and reduce the correlations of local neural responses, resulting in greater RD. RD was not associated with the degree of item-specific pattern similarity, and it made complementary contributions to episodic memory. These results provide a mechanistic understanding of the role of RD in supporting accurate episodic memory.

Contemporary models of episodic memory posit that remembering involves the reenactment of encoding processes. Although encoding-retrieval similarity has been consistently reported and linked to memory success, the nature of neural pattern reinstatement is poorly understood. Using high-resolution fMRI on human subjects, our results obtained clear evidence for item-specific pattern reinstatement in the frontoparietal cortex, even when the encoding-retrieval pairs shared no perceptual similarity. No item-specific pattern reinstatement was found in the ventral visual cortex. Importantly, the brain regions and voxels carrying item-specific representation differed significantly between encoding and retrieval, and the item specificity for encoding-retrieval similarity was smaller than that for encoding or retrieval, suggesting different nature of representations between encoding and retrieval. Moreover, cross-region representational similarity analysis suggests that the encoded representation in the ventral visual cortex was reinstated in the frontoparietal cortex during retrieval. Together, these results suggest that, in addition to reinstatement of the originally encoded pattern in the brain regions that perform encoding processes, retrieval may also involve the reinstatement of a transformed representation of the encoded information. These results emphasize the constructive nature of memory retrieval that helps to serve important adaptive functions.SIGNIFICANCE STATEMENT Episodic memory enables humans to vividly reexperience past events, yet how this is achieved at the neural level is barely understood. A long-standing hypothesis posits that memory retrieval involves the faithful reinstatement of encoding-related activity. We tested this hypothesis by comparing the neural representations during encoding and retrieval. We found strong pattern reinstatement in the frontoparietal cortex, but not in the ventral visual cortex, that represents visual details. Critically, even within the same brain regions, the nature of representation during retrieval was qualitatively different from that during encoding. These results suggest that memory retrieval is not a faithful replay of past event but rather involves additional constructive processes to serve adaptive functions.

A number of studies have provided evidence that animals, including rats, remember past episodes. However, few experiments have addressed episodic-like memory from a social perspective. In the present study, we evaluated Wistar rats in the WWWhen/ELM task as single setups and in dyads, applying a long retention interval. We also investigated behaviors that could subserve the emergence of this type of memory. We found that only rats tested in the social setting were able to recollect an integrated episodic-like memory that lasted 24 h. Additionally, rats in dyads presented higher levels of exploration during the task. When exposed to the testing environment, the dyads exhibited affiliative behavior toward each other and presented fewer anxiety-like responses. Our findings indicate that the presence of a conspecific could act as a facilitating factor in memory evaluations based on spontaneous exploration of objects and provide empirical support for applying more naturalistic settings in investigations of episodic-like memory in rats.

Temporal lobe epilepsy (TLE) affects brain networks and is associated with impairment of episodic memory. Temporal and extratemporal reorganization of memory functions is described in functional magnetic resonance imaging (fMRI) studies. Functional reorganizations have been shown at the local activation level, but network-level alterations have been underinvestigated. We aim to investigate the functional anatomy of memory networks using memory fMRI and determine how this relates to memory function in TLE.

Episodic memory is the memory for experienced events. A peak competence of episodic memory is the mental combination of events to infer commonalities. Inferring commonalities may proceed with and without consciousness of events. Yet what distinguishes conscious from unconscious inference? This question inspired nine experiments that featured strongly and weakly masked cartoon clips presented for unconscious and conscious inference. Each clip featured a scene with a visually impenetrable hiding place. Five animals crossed the scene one-by-one consecutively. One animal trajectory represented one event. The animals moved through the hiding place, where they might linger or not. The participants' task was to observe the animals' entrances and exits to maintain a mental record of which animals hid simultaneously. We manipulated information load to explore capacity limits. Memory of inferences was tested immediately, 3.5 or 6 min following encoding. The participants retrieved inferences well when encoding was conscious. When encoding was unconscious, the participants needed to respond intuitively. Only habitually intuitive decision makers exhibited a significant delayed retrieval of inferences drawn unconsciously. Their unconscious retrieval performance did not drop significantly with increasing information load, while conscious retrieval performance dropped significantly. A working memory network, including hippocampus, was activated during both conscious and unconscious inference and correlated with retrieval success. An episodic retrieval network, including hippocampus, was activated during both conscious and unconscious retrieval of inferences and correlated with retrieval success. Only conscious encoding/retrieval recruited additional brain regions outside these networks. Hence, levels of consciousness influenced the memories' behavioral impact, memory capacity, and the neural representational code.

Episodic memory deficits are a common consequence of aging and are associated with a number of neurodegenerative disorders (e.g., Alzheimer's disease). Given the importance of episodic memory, a great deal of research has investigated how we can improve memory performance. Transcranial electrical stimulation (TES) represents a promising tool for memory enhancement but the optimal stimulation parameters that reliably boost memory are yet to be determined. In our double-blind, randomised, sham-controlled study, 42 healthy adults (36 females; 23.3 ± 7.7 years of age) received anodal transcranial direct current stimulation (tDCS), theta transcranial alternating current stimulation (tACS) and sham stimulation during a list-learning task, over three separate sessions. Stimulation was applied over the left temporal lobe, as encoding and recall of information is typically associated with mesial temporal lobe structures (e.g., the hippocampus and entorhinal cortex). We measured word recall within each stimulation session, as well as the average number of intrusion and repetition errors. In terms of word recall, participants recalled fewer words during tDCS and tACS, compared to sham stimulation, and significantly fewer words recalled during tACS compared with tDCS. Significantly more memory errors were also made during tACS compared with sham stimulation. Overall, our findings suggest that TES has a deleterious effect on memory processes when applied to the left temporal lobe.

Episodic memory, remembering past experiences based on unique what-where-when components, declines during ageing in humans, as does episodic-like memory in non-human mammals. By contrast, semantic memory, remembering learnt knowledge without recalling unique what-where-when features, remains relatively intact with advancing age. The age-related decline in episodic memory likely stems from the deteriorating function of the hippocampus in the brain. Whether episodic memory can deteriorate with age in species that lack a hippocampus is unknown. Cuttlefish are molluscs that lack a hippocampus. We test both semantic-like and episodic-like memory in sub-adults and aged-adults nearing senescence (n = 6 per cohort). In the semantic-like memory task, cuttlefish had to learn that the location of a food resource was dependent on the time of day. Performance, measured as proportion of correct trials, was comparable across age groups. In the episodic-like memory task, cuttlefish had to solve a foraging task by retrieving what-where-when information about a past event with unique spatio-temporal features. In this task, performance was comparable across age groups; however, aged-adults reached the success criterion (8/10 correct choices in consecutive trials) significantly faster than sub-adults. Contrary to other animals, episodic-like memory is preserved in aged cuttlefish, suggesting that memory deterioration is delayed in this species.

There is marked variability in both onset and rate of episodic-memory decline in aging. Structural magnetic resonance imaging studies have revealed that the extent of age-related brain changes varies markedly across individuals. Past studies of whether regional atrophy accounts for episodic-memory decline in aging have yielded inconclusive findings. Here we related 15-year changes in episodic memory to 4-year changes in cortical and subcortical gray matter volume and in white-matter connectivity and lesions. In addition, changes in word fluency, fluid IQ (Block Design), and processing speed were estimated and related to structural brain changes. Significant negative change over time was observed for all cognitive and brain measures. A robust brain-cognition change-change association was observed for episodic-memory decline and atrophy in the hippocampus. This association was significant for older (65-80 years) but not middle-aged (55-60 years) participants and not sensitive to the assumption of ignorable attrition. Thus, these longitudinal findings highlight medial-temporal lobe system integrity as particularly crucial for maintaining episodic-memory functioning in older age.