Human Episodic Memory Research Articles

The Future Orientation of Past Memory: The Role of BA 10 in Prospective and Retrospective Retrieval Modes.

Klein made the provocative suggestion that the purpose of human episodic memory is to enable individuals to plan and prepare for the future. In other words, although episodic (retrospective) memory is about the past, it is not actually for the past; it is for the future. Within this focus, a natural subject for investigation is prospective memory, or memory to do things in the future. An important theoretical construct in the fields of both retrospective memory and prospective memory is that of a retrieval mode, or a neurocognitive set or readiness to treat environmental stimuli as potential retrieval cues. This construct was originally introduced in a theory of episodic (retrospective) memory and has more recently been invoked in a theory of how some prospective memory tasks are accomplished. To our knowledge, this construct has not been explicitly compared between the two literatures, and thus this is the purpose of the present article. Although we address the behavioral evidence for each construct, our primary goal is to assess the extent to which each retrieval mode appears to rely on a common neural region. Our review highlights the fact that a particular area of prefrontal cortex (BA 10) appears to play an important role in both retrospective and prospective retrieval modes. We suggest, based on this evidence and these ideas, that prospective memory research could profit from more active exploration of the relevance of theoretical constructs from the retrospective memory literature.

The hippocampus

The hippocampus

A Prefrontal-Hippocampal Comparator for Goal-Directed Behavior: The Intentional Self and Episodic Memory.

The hypothesis of this article is that the interactions between the prefrontal cortex and the hippocampus play a critical role in the modulation of goal-directed self-action and the strengthening of episodic memories. We describe various theories that model a comparator function for the hippocampus, and then elaborate the empirical evidence that supports these theories. One theory which describes a prefrontal-hippocampal comparator for voluntary action is emphasized. Action plans are essential for successful goal-directed behavior, and are elaborated by the prefrontal cortex. When an action plan is initiated, the prefrontal cortex transmits an efference copy (or corollary discharge) to the hippocampus where it is stored as a working memory for the action plan (which includes the expected outcomes of the action plan). The hippocampus then serves as a response intention-response outcome working memory comparator. Hippocampal comparator function is enabled by the hippocampal theta rhythm allowing the hippocampus to compare expected action outcomes to actual action outcomes. If the expected and actual outcomes match, the hippocampus transmits a signal to prefrontal cortex which strengthens or consolidates the action plan. If a mismatch occurs, the hippocampus transmits an error signal to the prefrontal cortex which facilitates a reformulation of the action plan, fostering behavioral flexibility and memory updating. The corollary discharge provides the self-referential component to the episodic memory, affording the personal and subjective experience of what behavior was carried out, when it was carried out, and in what context (where) it occurred. Such a perspective can be applied to episodic memory in humans, and episodic-like memory in non-human animal species.

Is episodic memory uniquely human? Evaluating the episodic-like memory research program

Recently, a research program has emerged that aims to show that animals have a memory capacity that is similar to the human episodic memory capacity. Researchers within this program argue that nonhuman animals have episodic-like memory of personally experienced past events. In this paper, I specify and evaluate the goals of this research program and the progress it has made in achieving them. I will examine some of the data that the research program has produced, as well as the operational definitions and assumptions that have gone into producing that data, in order to call into question the ultimate value of the episodic-like memory research program. I argue that there is a gap between the claims that the research program makes and the data it uses to support these claims, and that bridging this gap is essential if we want to claim that human episodic memory has a meaningful analog in animals. I end with some suggestions of how to potentially fix these problems.

Memory hierarchies map onto the hippocampal long axis in humans.

Memories, like the internal representation of space, can be recalled at different resolutions ranging from detailed events to more comprehensive, multi-event narratives. Single-cell recordings in rodents indicate that different spatial scales are represented as a gradient along the hippocampal axis. Here, we show that a similar organisation holds for human episodic memory: memory representations systematically vary in scale along the hippocampal long-axis, which may enable the formation of mnemonic hierarchies.

Genetic Analysis of Association Between Calcium Signaling and Hippocampal Activation, Memory Performance in the Young and Old, and Risk for Sporadic Alzheimer Disease.

Human episodic memory performance is linked to the function of specific brain regions, including the hippocampus; declines as a result of increasing age; and is markedly disturbed in Alzheimer disease (AD), an age-associated neurodegenerative disorder that primarily affects the hippocampus. Exploring the molecular underpinnings of human episodic memory is key to the understanding of hippocampus-dependent cognitive physiology and pathophysiology. To determine whether biologically defined groups of genes are enriched in episodic memory performance across age, memory encoding-related brain activity, and AD. In this multicenter collaborative study, which began in August 2008 and is ongoing, gene set enrichment analysis was done by using primary and meta-analysis data from 57 968 participants. The Swiss cohorts consisted of 3043 healthy young adults assessed for episodic memory performance. In a subgroup (n = 1119) of one of these cohorts, functional magnetic resonance imaging was used to identify gene set-dependent differences in brain activity related to episodic memory. The German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort consisted of 763 elderly participants without dementia who were assessed for episodic memory performance. The International Genomics of Alzheimer's Project case-control sample consisted of 54 162 participants (17 008 patients with sporadic AD and 37 154 control participants). Analyses were conducted between January 2014 and June 2015. Gene set enrichment analysis in all samples was done using genome-wide single-nucleotide polymorphism data. Episodic memory performance in the Swiss cohort and German Study on Aging, Cognition, and Dementia in Primary Care Patients cohort was quantified by picture and verbal delayed free recall tasks. In the functional magnetic resonance imaging experiment, activation of the hippocampus during encoding of pictures served as the phenotype of interest. In the International Genomics of Alzheimer's Project sample, diagnosis of sporadic AD served as the phenotype of interest. In the discovery sample, we detected significant enrichment for genes constituting the calcium signaling pathway, especially those related to the elevation of cytosolic calcium (P = 2 × 10-4). This enrichment was replicated in 2 additional samples of healthy young individuals (P = .02 and .04, respectively) and a sample of healthy elderly participants (P = .004). Hippocampal activation (P = 4 × 10-4) and the risk for sporadic AD (P = .01) were also significantly enriched for genes related to the elevation of cytosolic calcium. By detecting consistent significant enrichment in independent cohorts of young and elderly participants, this study identified that calcium signaling plays a central role in hippocampus-dependent human memory processes in cognitive health and disease, contributing to the understanding and potential treatment of hippocampus-dependent cognitive pathology.

Human hippocampus represents space and time during retrieval of real-world memories

Memory stretches over a lifetime. In controlled laboratory settings, the hippocampus and other medial temporal lobe brain structures have been shown to represent space and time on the scale of meters and seconds. It remains unclear whether the hippocampus also represents space and time over the longer scales necessary for human episodic memory. We recorded neural activity while participants relived their own experiences, cued by photographs taken with a custom lifelogging device. We found that the left anterior hippocampus represents space and time for a month of remembered events occurring over distances of up to 30 km. Although previous studies have identified similar drifts in representational similarity across space or time over the relatively brief time scales (seconds to minutes) that characterize individual episodic memories, our results provide compelling evidence that a similar pattern of spatiotemporal organization also exists for organizing distinct memories that are distant in space and time. These results further support the emerging view that the anterior, as opposed to posterior, hippocampus integrates distinct experiences, thereby providing a scaffold for encoding and retrieval of autobiographical memories on the scale of our lives.

Episodic memory in aspects of large-scale brain networks

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment.

Computational dissection of human episodic memory reveals mental process-specific genetic profiles

Episodic memory performance is the result of distinct mental processes, such as learning, memory maintenance, and emotional modulation of memory strength. Such processes can be effectively dissociated using computational models. Here we performed gene set enrichment analyses of model parameters estimated from the episodic memory performance of 1,765 healthy young adults. We report robust and replicated associations of the amine compound SLC (solute-carrier) transporters gene set with the learning rate, of the collagen formation and transmembrane receptor protein tyrosine kinase activity gene sets with the modulation of memory strength by negative emotional arousal, and of the L1 cell adhesion molecule (L1CAM) interactions gene set with the repetition-based memory improvement. Furthermore, in a large functional MRI sample of 795 subjects we found that the association between L1CAM interactions and memory maintenance revealed large clusters of differences in brain activity in frontal cortical areas. Our findings provide converging evidence that distinct genetic profiles underlie specific mental processes of human episodic memory. They also provide empirical support to previous theoretical and neurobiological studies linking specific neuromodulators to the learning rate and linking neural cell adhesion molecules to memory maintenance. Furthermore, our study suggests additional memory-related genetic pathways, which may contribute to a better understanding of the neurobiology of human memory.

Commentary: Merging of long-term memories in an insect.

Commentary: Merging of long-term memories in an insect.

Memory of occasional events in rats: individual episodic memory profiles, flexibility, and neural substrate.

In search for the mechanisms underlying complex forms of human memory, such as episodic recollection, a primary challenge is to develop adequate animal models amenable to neurobiological investigation. Here, we proposed a novel framework and paradigm that provides means to quantitatively evaluate the ability of rats to form and recollect a combined knowledge of what happened, where it happened, and when or in which context it happened (referred to as episodic-like memory) after a few specific episodes in situations as close as possible to a paradigm we recently developed to study episodic memory in humans. In this task, rats have to remember two odor-drink associations (what happened) encountered in distinct locations (where it happened) within two different multisensory enriched environments (in which context/occasion it happened), each characterized by a particular combination of odors and places. By analyzing licking behavior on each drinking port, we characterized quantitatively individual recollection profiles and showed that rats are able to incidentally form and recollect an accurate, long-term integrated episodic-like memory that can last ≥ 24 d after limited exposure to the episodes. Placing rats in a contextually challenging recollection situation at recall reveals the ability for flexible use of episodic memory as described in humans. We further report that reversible inactivation of the dorsal hippocampus during recall disrupts the animal's capacity to recollect the complete episodic memory. Cellular imaging of c-Fos and Zif268 brain activation reveals that episodic memory recollection recruits a specific, distributed network of hippocampal-prefrontal cortex structures that correlates with the accuracy of the integrated recollection performance.

New learning following reactivation in the human brain: Targeting emotional memories through rapid serial visual presentation

Once reactivated, previously consolidated memories destabilize and have to be reconsolidated to persist, a process that might be altered non-invasively by interfering learning immediately after reactivation. Here, we investigated the influence of interference on brain correlates of reactivated episodic memories for emotional and neutral scenes using event-related potentials (ERPs). To selectively target emotional memories we applied a new reactivation method: rapid serial visual presentation (RSVP). RSVP leads to enhanced implicit processing (pop out) of the most salient memories making them vulnerable to disruption. In line, interference after reactivation of previously encoded pictures disrupted recollection particularly for emotional events. Furthermore, memory impairments were reflected in a reduced centro-parietal ERP old/new difference during retrieval of emotional pictures. These results provide neural evidence that emotional episodic memories in humans can be selectively altered through behavioral interference after reactivation, a finding with further clinical implications for the treatment of anxiety disorders.

Telencephalic neurocircuitry and synaptic plasticity in rodent spatial learning and memory

Spatial learning and memory in rodents represent close equivalents of human episodic declarative memory, which is especially sensitive to cerebral aging, neurodegeneration, and various neuropsychiatric disorders. Many tests and protocols are available for use in laboratory rodents, but Morris water maze and radial-arm maze remain the most widely used as well as the most valid and reliable spatial tests. Telencephalic neurocircuitry that plays functional roles in spatial learning and memory includes hippocampus, dorsal striatum and medial prefrontal cortex. Prefrontal–hippocampal circuitry comprises the major associative system in the rodent brain, and is critical for navigation in physical space, whereas interconnections between prefrontal cortex and dorsal striatum are probably more important for motivational or goal-directed aspects of spatial learning. Two major forms of synaptic plasticity, namely long-term potentiation, a lasting increase in synaptic strength between simultaneously activated neurons, and long-term depression, a decrease in synaptic strength, have been found to occur in hippocampus, dorsal striatum and medial prefrontal cortex. These and other phenomena of synaptic plasticity are probably crucial for the involvement of telencephalic neurocircuitry in spatial learning and memory. They also seem to play a role in the pathophysiology of two brain pathologies with episodic declarative memory impairments as core symptoms, namely Alzheimer’s disease and schizophrenia. Further research emphasis on rodent telencephalic neurocircuitry could be relevant to more valid and reliable preclinical research on these most devastating brain disorders.This article is part of a Special Issue entitled SI: Brain and Memory.

Continuous theta burst stimulation of angular gyrus reduces subjective recollection.

The contribution of lateral parietal regions such as the angular gyrus to human episodic memory has been the subject of much debate following widespread observations of left parietal activity in healthy volunteers during functional neuroimaging studies of memory retrieval. Patients with lateral parietal lesions are not amnesic, but recent evidence indicates that their memory abilities may not be entirely preserved. Whereas recollection appears intact when objective measures such as source accuracy are used, patients often exhibit reduced subjective confidence in their accurate recollections. When asked to recall autobiographical memories, they may produce spontaneous narratives that lack richness and specificity, but can remember specific details when prompted. Two distinct theoretical accounts have been proposed to explain these results: that the patients have a deficit in the bottom-up capturing of attention by retrieval output, or that they have an impairment in the subjective experience of recollection. The present study aimed to differentiate between these accounts using continuous theta burst stimulation (cTBS) in healthy participants to disrupt function of specific left parietal subregions, including angular gyrus. Inconsistent with predictions of the attentional theory, angular gyrus cTBS did not result in greater impairment of free recall than cued recall. Supporting predictions of the subjective recollection account, temporary disruption of angular gyrus was associated with highly accurate source recollection accuracy but a selective reduction in participants’ rated source confidence. The findings are consistent with a role for angular gyrus in the integration of memory features into a conscious representation that enables the subjective experience of remembering.

When Eyewitnesses Misremember

Eyewitness testimony is a critical component of U.S. jurisprudence in both civil and criminal proceedings. Witnesses are relied on to recount key events, behaviors, and circumstances that contribute to findings of fact surrounding alleged criminal acts or circumstances that are the subject of civil dispute. The contribution of eyewitness testimony depends critically on the reliability of the witnesses’ memory of the events they are describing. Unfortunately, there are significant limits of human episodic memory that may degrade or distort these memories. Compounding this challenge is the poor metacognitive awareness of memory’s limitations. Eyewitnesses may overestimate the quality of their memory in accuracy and precision. They may be unaware of the potential for false details to merge into their episodic memories of an event. Jurists are similarly unaware of the limitations of memory and may rely too heavily on eyewitness testimony when resolving cases. But acknowledging and accounting for the limitations of memory has costs. Without eyewitness testimony many cases would not be viable, so there is a societal need to tolerate these limitations in order to have a working legal system. Human factors professionals, who are testifying as investigators in the case, may be the only source through which jurors can be informed of memory’s limitations when general memory experts are not admitted to testify solely for that purpose. When performed capably, this testimony can significantly improve the outcomes of legal proceedings.

Human single-unit recordings reveal a link between place-cells and episodic memory.

Human single-unit recordings reveal a link between place-cells and episodic memory.

A generic framework and methodology for extracting semantics from co-occurrences

Extracting semantic associations from text corpora is an important problem with several applications. It is well understood that semantic associations from text can be discerned by observing patterns of co-occurrences of terms. However, much of the work in this direction has been piecemeal, addressing specific kinds of semantic associations. In this work, we propose a generic framework, using which several kinds of semantic associations can be mined. The framework comprises a co-occurrence graph of terms, along with a set of graph operators. A methodology for using this framework is also proposed, where the properties of a given semantic association can be hypothesized and tested over the framework. To show the generic nature of the proposed model, four different semantic associations are mined over a corpus comprising of Wikipedia articles. The design of the proposed framework is inspired from cognitive science — specifically the interplay between semantic and episodic memory in humans.

Sleep benefits in parallel implicit and explicit measures of episodic memory

Research in rats using preferences during exploration as a measure of memory has indicated that sleep is important for the consolidation of episodic-like memory, i.e., memory for an event bound into specific spatio-temporal context. How these findings relate to human episodic memory is unclear. We used spontaneous preferences during visual exploration and verbal recall as, respectively, implicit and explicit measures of memory, to study effects of sleep on episodic memory consolidation in humans. During encoding before 10-h retention intervals that covered nighttime sleep or daytime wakefulness, two groups of young adults were presented with two episodes that were 1-h apart. Each episode entailed a spatial configuration of four different faces in a 3 × 3 grid of locations. After the retention interval, implicit spatio-temporal recall performance was assessed by eye-tracking visual exploration of another configuration of four faces of which two were from the first and second episode, respectively; of the two faces one was presented at the same location as during encoding and the other at another location. Afterward explicit verbal recall was assessed. Measures of implicit and explicit episodic memory retention were positively correlated (r = 0.57, P < 0.01), and were both better after nighttime sleep than daytime wakefulness (P < 0.05). In the sleep group, implicit episodic memory recall was associated with increased fast spindles during nonrapid eye movement (NonREM) sleep (r = 0.62, P < 0.05). Together with concordant observations in rats our results indicate that consolidation of genuinely episodic memory benefits from sleep.

Distinct slow and fast cortical theta dynamics in episodic memory retrieval

Brain oscillations in the theta frequency band (3–8Hz) have been shown to be critically involved in human episodic memory retrieval. In prior work, both positive and negative relationships between cortical theta power and retrieval success have been reported. This study examined the hypothesis that slow and fast cortical theta oscillations at the edges of the traditional theta frequency band are differentially related to retrieval success. Scalp EEG was recorded in healthy human participants as they performed a cued-recall episodic memory task. Slow (~3Hz) and fast (~7Hz) theta oscillations at retrieval were examined as a function of whether an item was recalled or not and as a function of the items' output position at test. Recall success typically declines with output position, due to increases in interference level. The results showed that slow theta power was positively related but fast theta power was negatively related to retrieval success. Concurrent positive and negative episodic memory effects for slow and fast theta oscillations were dissociable in time and space, showing different time courses and different spatial locations on the scalp. Moreover, fast theta power increased from early to late output positions, whereas slow theta power was unaffected by items' output position. Together with prior work, the results suggest that slow and fast theta oscillations have distinct functional roles in episodic memory retrieval, with slow theta oscillations being related to processes of recollection and conscious awareness, and fast theta oscillations being linked to processes of interference and interference resolution.

Divided Attention Improves Delayed, but Not Immediate Retrieval of a Consolidated Memory

A well-documented dissociation between memory encoding and retrieval concerns the role of attention in the two processes. The typical finding is that divided attention (DA) during encoding impairs future memory, but retrieval is relatively robust to attentional manipulations. However, memory research in the past 20 years had demonstrated that retrieval is a memory-changing process, in which the strength and availability of information are modified by various characteristics of the retrieval process. Based on this logic, several studies examined the effects of DA during retrieval (Test 1) on a future memory test (Test 2). These studies yielded inconsistent results. The present study examined the role of memory consolidation in accounting for the after-effect of DA during retrieval. Initial learning required a classification of visual stimuli, and hence involved incidental learning. Test 1 was administered 24 hours after initial learning, and therefore required retrieval of consolidated information. Test 2 was administered either immediately following Test 1 or after a 24-hour delay. Our results show that the effect of DA on Test 2 depended on this delay. DA during Test 1 did not affect performance on Test 2 when it was administered immediately, but improved performance when Test 2 was given 24-hours later. The results are consistent with other findings showing long-term benefits of retrieval difficulty. Implications for theories of reconsolidation in human episodic memory are discussed.