Role In Episodic Memory Research Articles

Integrity of the uncinate fasciculus is associated with emotional pattern separation-related fMRI signals in the hippocampal dentate and CA3

Alterations in white matter integrity have been demonstrated in a number of psychiatric disorders involving emotional disruptions. One such pathway – the uncinate fasciculus – connects the orbitofrontal cortex (OFC) to the medial temporal lobes (MTL) and has been associated with early life adversity, maltreatment, anxiety, and depression. While it is purported to play a role in episodic memory and discrimination, its exact function remains poorly understood. We have previously described the role of the amygdala and dentate (DG)/CA3 fields of the hippocampus in the mnemonic discrimination of emotional experiences (i.e. emotional pattern separation). However, how this computation may be modulated by connectivity with the orbitofrontal cortex remains unknown. Here we asked if the uncinate fasciculus plays a role in influencing MTL subregional activity during emotional pattern separation. By combining diffusion imaging with high-resolution fMRI, we found that reduced integrity of the UF is related to elevated BOLD fMRI activation of the DG/CA3 subregions of the hippocampus during emotional lure discrimination. We additionally report that higher levels of DG/CA3 activity are associated with poorer memory performance, suggesting that greater activation in this network (possibly driven by CA3 recurrent collaterals) is associated with memory errors. Based on this work we suggest that the UF is one pathway that may allow the OFC to exert control on this network and improve discrimination of emotional experiences, although further work is necessary to fully evaluate this possibility. This work provides novel insight into the role of prefrontal interactions with the MTL, particularly in the context of emotional memory.

Links between autobiographical memory richness and temporal discounting in older adults

When making choices between smaller, sooner rewards and larger, later ones, people tend to discount future outcomes. Individual differences in temporal discounting in older adults have been associated with episodic memory abilities and entorhinal cortical thickness. The cause of this association between better memory and more future-oriented choice remains unclear, however. One possibility is that people with perceptually richer recollections are more patient because they also imagine the future more vividly. Alternatively, perhaps people whose memories focus more on the meaning of events (i.e., are more “gist-based”) show reduced temporal discounting, since imagining the future depends on interactions between semantic and episodic memory. We examined which categories of episodic details – perception-based or gist-based – are associated with temporal discounting in older adults. Older adults whose autobiographical memories were richer in perception-based details showed reduced temporal discounting. Furthermore, in an exploratory neuroanatomical analysis, both discount rates and perception-based details correlated with entorhinal cortical thickness. Retrieving autobiographical memories before choice did not affect temporal discounting, however, suggesting that activating episodic memory circuitry at the time of choice is insufficient to alter discounting in older adults. These findings elucidate the role of episodic memory in decision making, which will inform interventions to nudge intertemporal choices.

Correlation Between Hippocampal Volume and Autobiographical Memory Depending on Retrieval Frequency in Healthy Individuals and Patients with Alzheimer's Disease.

The hippocampus plays an indispensable role in episodic memory, particularly during the consolidation process. However, its precise role in retrieval of episodic memory is still ambiguous. In this study, we investigated the correlation of hippocampal morphometry and the performance in an autobiographical memory task in 27 healthy controls and 24 patients suffering from Alzheimer's disease (AD). Most importantly, correlations were defined separately and comparatively for memory contents with different retrieval frequency in the past. In healthy subjects, memory performance for seldom retrieved autobiographical events was significantly associated with gray matter density in the bilateral hippocampus, whereas this correlation was not present for events with high retrieval frequency. This pattern of findings confirms that retrieval frequency plays a critical role in the consolidation of episodic autobiographical memories, thereby making them more independent of the hippocampal system. In AD patients, on the other hand, successful memory retrieval appeared to be related to hippocampal morphometry irrespective of the contents' retrieval frequency, comprising events with high retrieval frequency, too. The observed differences between patients and control subjects suggest that AD-related neurodegeneration not only impairs the function, but also decreases the functional specialization of the hippocampal memory system, which, thus, may be considered as marker for AD.

The hippocampus as a visual area organized by space and time: A spatiotemporal similarity hypothesis

The hippocampus is the canonical memory system in the brain and is not typically considered part of the visual system. Yet, it sits atop the ventral visual stream and has been implicated in certain aspects of vision. Here I review the place of the hippocampal memory system in vision science. After a brief primer on the local circuity, external connectivity, and computational functions of the hippocampus, I explore what can be learned from each field about the other. I first present four areas of vision science (scene perception, imagery, eye movements, attention) that challenge our current understanding of the hippocampus in terms of its role in episodic memory. In the reverse direction, I leverage this understanding to inform vision science in other ways, presenting a working hypothesis about a unique form of visual representation. This spatiotemporal similarity hypothesis states that the hippocampus represents objects according to whether they co-occur in space and/or time, and not whether they look alike, as elsewhere in the visual system. This tuning may reflect hippocampal mechanisms of pattern separation, relational binding, and statistical learning, allowing the hippocampus to generate visual expectations to facilitate search and recognition.

Neural Representation of Overlapping Path Segments and Reward Acquisitions in the Monkey Hippocampus.

Disambiguation of overlapping events is thought to be the hallmark of episodic memory. Recent rodent studies have reported that when navigating overlapping path segments in the different routes place cell activity in the same overlapping path segments were remapped according to different goal locations in different routes. However, it is unknown how hippocampal neurons disambiguate reward delivery in overlapping path segments in different routes. In the present study, we recorded monkey hippocampal neurons during performance of three virtual navigation (VN) tasks in which a monkey alternately navigated two different routes that included overlapping path segments (common central hallway) and acquired rewards in the same locations in overlapping path segments by manipulating a joystick. The results indicated that out of 106 hippocampal neurons, 57 displayed place-related activity (place-related neurons), and 18 neurons showed route-dependent activity in the overlapping path segments, consistent with a hippocampal role in the disambiguation of overlapping path segments. Moreover, 75 neurons showed neural correlates to reward delivery (reward-related neurons), whereas 56 of these 75 reward-related neurons showed route-dependent reward-related activity in the overlapping path segments. The ensemble activity of reward-related neurons represented reward delivery, locations, and routes in the overlapping path segments. In addition, ensemble activity patterns of hippocampal neurons more distinctly represented overlapping path segments than non-overlapping path segments. The present results provide neurophysiological evidence of disambiguation in the monkey hippocampus, consistent with a hippocampal role in episodic memory, and support a recent computational model of “neural differentiation,” in which overlapping items are better represented by repeated retrieval with competitive learning.

Scenes facilitate associative memory and integration.

How do we form mental links between related items? Forming associations between representations is a key feature of episodic memory and provides the foundation for learning and guiding behavior. Theories suggest that spatial context plays a supportive role in episodic memory, providing a scaffold on which to form associations, but this has mostly been tested in the context of autobiographical memory. We examined the memory boosting effect of spatial stimuli in memory using an associative inference paradigm combined with eye-tracking. Across two experiments, we found that memory was better for associations that included scenes, even indirectly, compared to objects and faces. Eye-tracking measures indicated that these effects may be partly mediated by greater fixations to scenes compared to objects, but did not explain the differences between scenes and faces. These results suggest that scenes facilitate associative memory and integration across memories, demonstrating evidence in support of theories of scenes as a spatial scaffold for episodic memory. A shared spatial context may promote learning and could potentially be leveraged to improve learning and memory in educational settings or for memory-impaired populations.

Positive reward prediction errors during decision-making strengthen memory encoding.

Dopamine is thought to provide reward prediction errors signals to temporal lobe memory systems, but their role in episodic memory has not been fully characterized. We developed an incidental memory paradigm to 1) estimate the influence of reward prediction errors on formation of episodic memories, 2) dissociate this influence from surprise and uncertainty, 3) characterize the role of temporal correspondence between prediction error and memoranda presentation, and 4) determine the extent to which this influence is consolidation-dependent. We found that people encoded incidental memoranda more strongly when they gambled for potential rewards. Moreover, this strengthened encoding scaled with the reward prediction error experienced when memoranda were presented (and not before or after). This encoding enhancement was detectable within minutes and did not differ substantially after twenty-four hours, indicating that it is not consolidation-dependent. These results suggest a computationally and temporally specific role for reward prediction error signaling in memory formation.

Internal representation of hippocampal neuronal population spans a time-distance continuum

The hippocampus plays a critical role in episodic memory: the sequential representation of visited places and experienced events. This function is mirrored by hippocampal activity that self organizes into sequences of neuronal activation that integrate spatiotemporal information. What are the underlying mechanisms of such integration is still unknown. Single cell activity was recently shown to combine time and distance information; however, it remains unknown whether a degree of tuning between space and time can be defined at the network level. Here, combining daily calcium imaging of CA1 sequence dynamics in running head-fixed mice and network modeling, we show that CA1 network activity tends to represent a specific combination of space and time at any given moment, and that the degree of tuning can shift within a continuum from 1 day to the next. Our computational model shows that this shift in tuning can happen under the control of the external drive power. We propose that extrinsic global inputs shape the nature of spatiotemporal integration in the hippocampus at the population level depending on the task at hand, a hypothesis which may guide future experimental studies.

Out and about: Subsequent memory effect captured in a natural outdoor environment with smartphone EEG.

Spatiotemporal context plays an important role in episodic memory. While temporal context effects have been frequently studied in the laboratory, ecologically valid spatial context manipulations are difficult to implement in stationary conditions. We investigated whether the neural correlates of successful encoding (subsequent memory effect) can be captured in a real-world environment. An off-the-shelf Android smartphone was used for wireless mobile EEG acquisition and stimulus presentation. Participants encoded single words, each of which was presented at a different location on a university campus. Locations were approximately 10-12m away from each other, half of them with striking features (landmarks) nearby. We predicted landmarks would improve recall performance. After a first free recall task of verbal stimuli indoors, participants performed a subsequent recall outdoors, in which words and locations were recalled. As predicted, significantly more words presented at landmark locations as well as significantly more landmark than nonlandmark locations were recalled. ERP analysis yielded a larger posterior positive deflection during encoding for hits compared to misses in the 400-800ms interval. Likewise, time-frequency analysis revealed a significant difference during encoding for hits compared to misses in the form of stronger alpha (200-300ms) and theta (300-400ms) power increases. Our results confirm that a vibrant spatial context is beneficial in episodic memory processing and that the underlying neural correlates can be captured with unobtrusive smartphone EEG technology. The advent of mobile EEG technology promises to unveil the relevance of natural physical activity and natural environments on memory.

Self-perspective in episodic memory after parietal damage and in healthy ageing

Although there is strong support from functional imaging studies for lateral parietal lobe involvement in episodic memory, patients with damage to these regions do not appear to suffer from severe deficits in this cognitive domain. As such there has been no definitive explanation of this area’s precise involvement. Here, we hypothesised that parietal regions play a crucial role in episodic memory – specifically in recollecting details from an egocentric perspective. In order to test this hypothesis systematically, we designed a novel experimental task utilising a head-mounted camera to record images from the participant’s perspective, enabling us to evaluate the integrity of memory from the individual’s own point of view. In the first study we examined patients with parietal damage and in a second study, using fMRI, we examined young and older healthy participants. Right-hemisphere patients with parietal damage were able to recall information accurately when recollecting what items had been present and where these items had been. However, patients were significantly impaired when attempting to judge from which perspective they had viewed the scenes. Critically, the patient group showed no evidence of impairment on standard tests of episodic and working memory. Examination of healthy participants in the second study utilised multi-voxel pattern analysis on neural activity during the recognition phase of a similar task. This revealed sensitivity to be highest around the angular gyrus of the lateral parietal cortex for our critical comparison - that is, when viewing stimuli that were the same as their egocentric view during encoding versus the identical scene but presented from an alternative angle. Our results provide important evidence that parietal cortex is directly involved in egocentric spatial perspective aspects of episodic memory and demonstrate for the first time a specific deficit in episodic memory in patients with right parietal damage.

The experience of vivid autobiographical reminiscence is supported by subjective content representations in the precuneus

The human posteromedial cortex, which includes core regions of the default mode network (DMN), is thought to play an important role in episodic memory. However, the nature and functional role of representations in these brain regions remain unspecified. Nine participants (all female) wore smartphone devices to record episodes from their daily lives for multiple weeks, each night indicating the personally-salient attributes of each episode. Participants then relived their experiences in an fMRI scanner cued by images from their own lives. Representational Similarity Analysis revealed a broad network, including parts of the DMN, that represented personal semantics during autobiographical reminiscence. Within this network, activity in the right precuneus reflected more detailed representations of subjective contents during vivid relative to non-vivid, recollection. Our results suggest a more specific mechanism underlying the phenomenology of vivid autobiographical reminiscence, supported by rich subjective content representations in the precuneus, a hub of the DMN previously implicated in metacognitive evaluations during memory retrieval.

Hippocampal-targeted Theta-burst Stimulation Enhances Associative Memory Formation.

The hippocampus plays a critical role in episodic memory, among other cognitive functions. However, few tools exist to causally manipulate hippocampal function in healthy human participants. Recent work has targeted hippocampal-cortical networks by performing TMS to a region interconnected with the hippocampus, posterior inferior parietal cortex (pIPC). Such hippocampal-targeted TMS enhances associative memory and influences hippocampal functional connectivity. However, it is currently unknown which stages of mnemonic processing (encoding or retrieval) are affected by hippocampal-targeted TMS. Here, we examined whether hippocampal-targeted TMS influences the initial encoding of associations (vs. items) into memory. To selectively influence encoding and not retrieval, we performed continuous theta-burst TMS before participants encoded object-location associations and assessed memory after the direct effect of stimulation dissipated. Relative to control TMS and baseline memory, pIPC TMS enhanced associative memory success and confidence. Item memory was unaffected, demonstrating a selective influence on associative versus item memory. The strength of hippocampal-pIPC functional connectivity predicted TMS-related memory benefits, which was mediated by parahippocampal and retrosplenial cortices. Our findings indicate that hippocampal-targeted TMS can specifically modulate the encoding of new associations into memory without directly influencing retrieval processes and suggest that the ability to influence associative memory may be related to the fidelity of hippocampal TMS targeting. These results support the notion that pIPC TMS may serve as a potential tool for manipulating hippocampal function in healthy participants. Nonetheless, future work combining hippocampal-targeted continuous theta-burst TMS with neuroimaging is needed to better understand the neural basis of TMS-induced memory changes.

Manipulating Hippocampal Place Cell Activity by Single-Cell Stimulation in Freely Moving Mice

Learning critically depends on the ability to rapidly form and store non-overlapping representations of the external world. In line with their postulated role in episodic memory, hippocampal place cells can undergo a rapid reorganization of their firing fields upon contextual manipulations. To explore the mechanisms underlying such global remapping, we juxtacellularly stimulated 42 hippocampal neurons in freely moving mice during spatial exploration. We found that evoking spike trains in silent neurons was sufficient for creating place fields, while in place cells, juxtacellular stimulation induced a rapid remapping of their place fields to the stimulus location. The occurrence of complex spikes was most predictive of place field plasticity. Our data thus indicate that plasticity-inducing stimuli are able to rapidly bias place cell activity, simultaneously suppressing existing place fields. We propose that such competitive place field dynamics could support the orthogonalization of the hippocampal map during global remapping.

PDE4D regulates Spine Plasticity and Memory in the Retrosplenial Cortex

The retrosplenial cortex (RSC) plays a critical role in episodic memory, but the molecular mechanisms governing plasticity in this structure are poorly understood. Diverse studies have demonstrated a role for RSC in acquisition, early consolidation and retrieval similar to the hippocampus (HC), as well as in systems consolidation similar to the anterior cingulate cortex. Here, we asked whether established molecular and structural substrates of memory consolidation in the HC also engage in RSC shortly after learning. We show striking parallels in training induced gene-activation in HC and RSC following contextual conditioning, which is blocked by systemic administration of an NMDA receptor antagonist. Long-term memory is enhanced by retrosplenial and hippocampal knockdown (KD) of the cAMP specific phosphodiesterase Pde4d. However, while training per se induces lasting spine changes in HC, this does not occur in RSC. Instead, increases in the number of mature dendritic spines are found in the RSC only if cAMP signaling is augmented by Pde4d KD, and spine changes are at least partially independent of training. This research highlights parallels and differences in spine plasticity mechanisms between HC and RSC, and provides evidence for a functional dissociation of the two.

The increase in medial prefrontal glutamate/glutamine concentration during memory encoding is associated with better memory performance and stronger functional connectivity in the human medial prefrontal-thalamus-hippocampus network.

The classical model of the declarative memory system describes the hippocampus and its interactions with representational brain areas in posterior neocortex as being essential for the formation of long‐term episodic memories. However, new evidence suggests an extension of this classical model by assigning the medial prefrontal cortex (mPFC) a specific, yet not fully defined role in episodic memory. In this study, we utilized 1H magnetic resonance spectroscopy (MRS) and psychophysiological interaction (PPI) analysis to lend further support for the idea of a mnemonic role of the mPFC in humans. By using MRS, we measured mPFC γ‐aminobutyric acid (GABA) and glutamate/glutamine (GLx) concentrations before and after volunteers memorized face–name association. We demonstrate that mPFC GLx but not GABA levels increased during the memory task, which appeared to be related to memory performance. Regarding functional connectivity, we used the subsequent memory paradigm and found that the GLx increase was associated with stronger mPFC connectivity to thalamus and hippocampus for associations subsequently recognized with high confidence as opposed to subsequently recognized with low confidence/forgotten. Taken together, we provide new evidence for an mPFC involvement in episodic memory by showing a memory‐related increase in mPFC excitatory neurotransmitter levels that was associated with better memory and stronger memory‐related functional connectivity in a medial prefrontal–thalamus–hippocampus network.

The Primacy of Spatial Context in the Neural Representation of Events.

Some theories of episodic memory hypothesize that spatial context plays a fundamental role in episodic memory, acting as a scaffold on which episodes are constructed. A prediction based on this hypothesis is that spatial context should play a primary role in the neural representation of an event. To test this hypothesis in humans, male and female participants imagined events, composed of familiar locations, people, and objects, during an fMRI scan. We used multivoxel pattern analysis to determine the neural areas in which events could be discriminated based on each feature. We found that events could be discriminated according to their location in areas throughout the autobiographical memory network, including the parahippocampal cortex and posterior hippocampus, retrosplenial cortex, posterior cingulate cortex, precuneus, and medial prefrontal cortex. Events were also discriminable based on person and object features, but in fewer regions. Comparing classifier performance in regions involved in memory for scenes and events demonstrated that the location of an event was more accurately classified than the person or object involved. These results support theories that suggest that spatial context is a prominent defining feature of episodic memory.SIGNIFICANCE STATEMENT Remembered and imagined events are complex, consisting of many elements, including people, objects, and locations. In this study, we sought to determine how these types of elements differentially contribute to how the brain represents an event. Participants imagined events consisting of familiar locations, people, and objects (e.g., kitchen, mom, umbrella) while their brain activity was recorded with fMRI. We found that the neural patterns of activity in brain regions associated with spatial and episodic memory could distinguish events based on their location, and to some extent, based on the people and objects involved. These results suggest that the spatial context of an event plays an important role in how an event is represented in the brain.

Using episodic memory to gauge implicit and/or indeterminate social commitments.

In discussing Mahr & Csibra's (M&C's) observations about the role of episodic memory in grounding social commitments, we propose that episodic memory is especially useful for gauging cases of implicit commitment and cases in which the content of a commitment is indeterminate. We conclude with some thoughts about how commitment may relate to the evolution of episodic memory.

Association of KIBRA polymorphism with risk of Alzheimer's disease: Evidence based on 20 case-control studies.

Kidney and brain expressed protein (KIBRA) has been demonstrated to play an important role in episodic memory by genome-wide association study (GWAS). Since memory impairment is a typical clinical feature of AD, KIBRA has been considered to be a candidate gene for AD. Previous case-control association studies on KIBRA SNP rs17070145 have yielded inconsistent results. Thus, this study aimed to assess the risk of KIBRA polymorphism for sporadic AD via meta-analysis. A total of 7 articles including 20 case-control studies were included in this study. Results showed that rs17070145 had a significant association with AD risk in the homozygote comparison model (OR=1.23; 95%CI=1.07, 1.41), and the dominant model (OR=1.14; 95%CI=1.02, 1.26). In the subgroup analysis by ethnicity, an increased risk was detected in the homozygote comparison model and the dominant model among Caucasians, as well as in the homozygote comparison model and recessive model among Asians. Notably, in the subgroup analysis by age, a borderline increased risk was detected in the Old subgroup under the dominant model (OR=1.19; 95%CI=1.00, 1.43), but not in the Young subgroup. Results of the present meta-analysis indicated that KIBRA polymorphism rs17070145 might increase the risk of sporadic AD, especially among Caucasians, Asians and elders.

Prefrontal–hippocampal interactions in episodic memory

The roles of the hippocampus and prefrontal cortex (PFC) in memory processing - individually or in concert - are a major topic of interest in memory research. These brain areas have distinct and complementary roles in episodic memory, and their interactions are crucial for learning and remembering events. Considerable evidence indicates that the PFC and hippocampus become coupled via oscillatory synchrony that reflects bidirectional flow of information. Furthermore, newer studies have revealed specific mechanisms whereby neural representations in the PFC and hippocampus are mediated through direct connections or through intermediary regions. These findings suggest a model of how the hippocampus and PFC, along with their intermediaries, operate as a system that uses the current context of experience to retrieve relevant memories.

The future is now: the impact of present fluency in judgments about the future

ABSTRACTRecent research has emphasised the role of episodic memory in both remembering past events and in envisaging future events. On the other hand, it has been repeatedly shown that judgments about past events are affected by the fluency with which retrieval cues are processed. In this paper we investigate whether perceptual fluency also plays a role in judgments about future events. For this purpose we conducted four experiments. The first experiment replicated recent findings showing that stimuli that are processed fluently tend to be wrongly recognised as having been encountered in the past outside the laboratory walls [Brown, A. S., & Marsh, E. J. (2009). Creating illusions of past encounter through brief exposure. Psychological Science, 20, 534–538. doi:10.1111/j.1467-9280.2009.02337.x]. Two follow-up experiments using Brown and Marsh’s [(2009). Creating illusions of past encounter through brief exposure. Psychological Science, 20, 534–538. doi:10.1111/j.1467-9280.2009.02337] task tested the influence of perceptual fluency on future judgments. The fourth and last experiment was designed to rule out a potential confounding factor in the two previous experiments. Across experiments, we found that people rely on fluency when making judgments about events that are yet to come. These results suggest that fluency is an equally valid cue for past and future judgments.