Disruption of Anterior Temporal Lobe Reduces Distortions in Memory From Category Knowledge.

Memory retrieval does not provide a perfect recapitulation of past events, but instead an imperfect reconstruction of event-specific details and general knowledge. However, it remains unclear whether this reconstruction relies on mixtures of signals from different memory systems, including one supporting general knowledge. Here, we investigate whether the anterior temporal lobe (ATL) distorts new memories because of prior category knowledge. In this preregistered experiment (n = 36), participants encoded and retrieved image-location associations. Most images' locations were clustered according to their category, but some were in random locations. With this protocol, we previously demonstrated that randomly located images were retrieved closer to their category cluster relative to their encoded locations, suggesting an influence of category knowledge. We combined this procedure with TMS delivered to the left ATL before retrieval. We separately examined event-specific details (error) and category knowledge (bias) to identify distinct signals attributable to different memory systems. We found that TMS to ATL attenuated bias in location memory, but this effect was limited to exploratory analyses of atypical category members of animal categories. The magnitude of error was not impacted, suggesting that a memory's fidelity can be decoupled from its distortion by category knowledge. This raises the intriguing possibility that retrieval is jointly supported by separable memory systems.

Agency enhances temporal order memory in an interactive exploration game.

Agency has been shown to facilitate episodic memory. However, most paradigms use simple list-learning tasks, which preclude the ability to characterize more associative forms of memory, such as binding of items into spatial and temporal context. Across two studies, we characterize the role of agency on associative memory formation. We delineate agentive from passive memory encoding by allowing agency participants to play an online text-based game meant to simulate free exploration of objects in different rooms and yoking each passive participant's trajectory to an agentive participant, thus equating their exposure to the stimuli. To assess memory differences, we gathered three measures: item descriptions, spatial location, and temporal order. While memory for spatial location and item features did not differ between groups, there was a marked enhancement of temporal order memory in the agentive group across two independent samples. These findings support a model of self-directed learning, in which agency facilitates the binding of items into a temporal context, which allows for the sequential binding of information into continuous narratives.

Tracking the relation between gist and item memory over the course of long-term memory consolidation.

Our experiences in the world support memories not only of specific episodes but also of the generalities (the 'gist') across related experiences. It remains unclear how these two types of memories evolve and influence one another over time. In two experiments, 173 human participants encoded spatial locations from a distribution and reported both item memory (specific locations) and gist memory (center for the locations) across 1-2 months. Experiment 1 demonstrated that after 1 month, gist memory was preserved relative to item memory, despite a persistent positive correlation between them. Critically, item memories were biased toward the gist over time. Experiment 2 showed that a spatial outlier item changed this relationship and that the extraction of gist is sensitive to the regularities of items. Our results suggest that the gist starts to guide item memories over longer durations as their relative strengths change.

Semantic influences on episodic memory distortions.

Prior knowledge has long been known to shape new episodic memories. However, it is less clear how prior knowledge can scaffold the learning of a new class of information, and how this can bias memory for the episodes that contributed to its acquisition. We aimed to quantify distortions in episodic memories resulting from the use of prior category knowledge to facilitate learning new information. Across 4 experiments, participants encoded and retrieved image-location associations. Most members of a category (e.g., birds) were located near each other, such that participants could leverage their prior category knowledge to learn the spatial locations of categories as they encoded specific image locations. Critically, some typical and atypical category members were in random locations. We decomposed location memory into 2 measures: error, a measure of episodic specificity; and bias toward other category members, a measure of the influence of newly-learned information about category locations. First, we found that location memory was more accurate for images whose locations were spatially consistent with their category membership. Second, when images were spatially inconsistent (i.e., in random locations), retrieval of typical category members was more biased toward their category's location relative to atypical ones. These effects replicated across 3 experiments, disappeared when images were not arranged by category, and were stronger than effects observed with images arranged by visual similarity rather than category membership. Our observations provide compelling evidence that memory is a reconstruction of multiple sources of prior knowledge, new learning, and memory for specific events. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Age-Related Increases in Posterior Hippocampal Granularity Are Associated with Remote Detailed Episodic Memory in Development.

Episodic memory is critical to human functioning. In adults, episodic memory involves a distributed neural circuit in which the hippocampus plays a central role. As episodic memory abilities continue to develop across childhood and into adolescence, studying episodic memory maturation can provide insight into the development and construction of these hippocampal networks, and ultimately clues to their function in adulthood. While past developmental studies have shown that the hippocampus helps to support memory in middle childhood and adolescence, the extent to which ongoing maturation within the hippocampus contributes to developmental change in episodic memory abilities remains unclear. In contrast, slower maturing regions, such as the PFC, have been suggested to be the neurobiological locus of memory improvements into adolescence. However, it is also possible that the methods used to detect hippocampal development during middle childhood and adolescence are not sensitive enough. Here, we examine how temporal covariance (or differentiation) in voxel representations within anterior and posterior hippocampus change with age to support the development of detailed recollection in male and female developing humans. We find age-related increases in the distinctiveness of temporal activation profiles in the posterior, but not anterior, hippocampus. Second, we show that this measure of granularity, when present during postencoding rest periods, correlates with the recall of detailed memories of preceding stimuli several weeks postencoding, suggesting that granularity may promote memory stabilization.SIGNIFICANCE STATEMENT Studying hippocampal maturation can provide insight into episodic memory development, as well as clues to episodic functioning in adulthood. Past work has shown evidence both for and against hippocampal contributions to age-related improvements in memory performance, but has relied heavily on univariate approaches (averaging activity across hippocampal voxels), which may not be sensitive to nuanced developmental change. Here we use a novel approach, examining time signatures in individual hippocampal voxels to reveal regionally specific (anterior vs posterior hippocampus) differences in the distinctiveness (granularity) of temporal activation profiles across development. Importantly, posterior hippocampus granularity during windows of putative memory stabilization was associated with long-term memory specificity. This suggests that the posterior hippocampus gradually builds the capacity to support detailed episodic recall.

Schematic memories develop quickly, but are not expressed unless necessary.

Episodic memory retrieval is increasingly influenced by schematic information as memories mature, but it is unclear whether this is due to the slow formation of schemas over time, or the slow forgetting of the episodes. To address this, we separately probed memory for newly learned schemas as well as their influence on episodic memory decisions. In this experiment, participants encoded images from two categories, with the location of images in each category drawn from a different spatial distribution. They could thus learn schemas of category locations by encoding specific episodes. We found that images that were more consistent with these distributions were more precisely retrieved, and this schematic influence increased over time. However, memory for the schema distribution, measured using generalization to novel images, also became less precise over time. This incongruity suggests that schemas form rapidly, but their influence on episodic retrieval is dictated by the need to bolster fading memory representations.

Acute stress throughout the memory cycle: Diverging effects on associative and item memory.

Acute stress can modulate memory for individual parts of an event (items), but whether it similarly influences memory for associations between items remains unclear. We used a within-subjects design to explore the influence of acute stress on item and associative memory in humans. Participants associated negative words with neutral objects, rated their subjective arousal for each pair, and completed delayed item and paired associative recognition tasks. We found strikingly different patterns of acute stress effects on item and associative memory: for high-arousal pairs, preencoding stress enhanced associative memory, whereas postencoding stress enhanced item memory. Preretrieval stress consistently impaired both forms of memory. We found that the influence of stress-induced cortisol also varied, with a linear relationship between cortisol and item memory but a quadratic relationship between cortisol and associative memory. These findings reveal key differences in how stress, throughout the memory cycle, shapes our memories for items and associations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Attending to What and Where: Background Connectivity Integrates Categorical and Spatial Attention.

Top-down attention prioritizes the processing of goal-relevant information throughout visual cortex based on where that information is found in space and what it looks like. Whereas attentional goals often have both spatial and featural components, most research on the neural basis of attention has examined these components separately. Here we investigated how these attentional components are integrated by examining the attentional modulation of functional connectivity between visual areas with different selectivity. Specifically, we used fMRI to measure temporal correlations between spatially selective regions of early visual cortex and category-selective regions in ventral temporal cortex while participants performed a task that benefitted from both spatial and categorical attention. We found that categorical attention modulated the connectivity of category-selective areas, but only with retinotopic areas that coded for the spatially attended location. Similarly, spatial attention modulated the connectivity of retinotopic areas only with the areas coding for the attended category. This pattern of results suggests that attentional modulation of connectivity is driven both by spatial selection and featural biases. Combined with exploratory analyses of frontoparietal areas that track these changes in connectivity among visual areas, this study begins to shed light on how different components of attention are integrated in support of more complex behavioral goals.

Stimulus generalization as a mechanism for learning to trust.

How do humans learn to trust unfamiliar others? Decisions in the absence of direct knowledge rely on our ability to generalize from past experiences and are often shaped by the degree of similarity between prior experience and novel situations. Here, we leverage a stimulus generalization framework to examine how perceptual similarity between known individuals and unfamiliar strangers shapes social learning. In a behavioral study, subjects play an iterative trust game with three partners who exhibit highly trustworthy, somewhat trustworthy, or highly untrustworthy behavior. After learning who can be trusted, subjects select new partners for a second game. Unbeknownst to subjects, each potential new partner was parametrically morphed with one of the three original players. Results reveal that subjects prefer to play with strangers who implicitly resemble the original player they previously learned was trustworthy and avoid playing with strangers resembling the untrustworthy player. These decisions to trust or distrust strangers formed a generalization gradient that converged toward baseline as perceptual similarity to the original player diminished. In a second imaging experiment we replicate these behavioral gradients and leverage multivariate pattern similarity analyses to reveal that a tuning profile of activation patterns in the amygdala selectively captures increasing perceptions of untrustworthiness. We additionally observe that within the caudate adaptive choices to trust rely on neural activation patterns similar to those elicited when learning about unrelated, but perceptually familiar, individuals. Together, these findings suggest an associative learning mechanism efficiently deploys moral information encoded from past experiences to guide future choice.

Consolidation Promotes the Emergence of Representational Overlap in the Hippocampus and Medial Prefrontal Cortex.

Structured knowledge is thought to form, in part, through the extraction and representation of regularities across overlapping experiences. However, little is known about how consolidation processes may transform novel episodic memories to reflect such regularities. In a multi-day fMRI study, participants encoded trial-unique associations that shared features with other trials. Multi-variate pattern analyses were used to measure neural similarity across overlapping and non-overlapping memories during immediate and 1-week retrieval of these associations. We found that neural patterns in the hippocampus and medial prefrontal cortex represented the featural overlap across memories, but only after a week. Furthermore, after a week, the strength of a memory's unique episodic reinstatement during retrieval was inversely related to its representation of overlap, suggesting a trade-off between the integration of related memories and recovery of episodic details. These findings suggest that consolidation-related changes in neural representations support the gradual organization of discrete episodes into structured knowledge.

Selectivity in Postencoding Connectivity with High-Level Visual Cortex Is Associated with Reward-Motivated Memory.

Reward motivation has been demonstrated to enhance declarative memory by facilitating systems-level consolidation. Although high-reward information is often intermixed with lower reward information during an experience, memory for high value information is prioritized. How is this selectivity achieved? One possibility is that postencoding consolidation processes bias memory strengthening to those representations associated with higher reward. To test this hypothesis, we investigated the influence of differential reward motivation on the selectivity of postencoding markers of systems-level memory consolidation. Human participants encoded intermixed, trial-unique memoranda that were associated with either high or low-value during fMRI acquisition. Encoding was interleaved with periods of rest, allowing us to investigate experience-dependent changes in connectivity as they related to later memory. Behaviorally, we found that reward motivation enhanced 24 h associative memory. Analysis of patterns of postencoding connectivity showed that, even though learning trials were intermixed, there was significantly greater connectivity with regions of high-level, category-selective visual cortex associated with high-reward trials. Specifically, increased connectivity of category-selective visual cortex with both the VTA and the anterior hippocampus predicted associative memory for high- but not low-reward memories. Critically, these results were independent of encoding-related connectivity and univariate activity measures. Thus, these findings support a model by which the selective stabilization of memories for salient events is supported by postencoding interactions with sensory cortex associated with reward. SIGNIFICANCE STATEMENT: Reward motivation is thought to promote memory by supporting memory consolidation. Yet, little is known as to how brain selects relevant information for subsequent consolidation based on reward. We show that experience-dependent changes in connectivity of both the anterior hippocampus and the VTA with high-level visual cortex selectively predicts memory for high-reward memoranda at a 24 h delay. These findings provide evidence for a novel mechanism guiding the consolidation of memories for valuable events, namely, postencoding interactions between neural systems supporting mesolimbic dopamine activation, episodic memory, and perception.

Trial-by-Trial Hippocampal Encoding Activation Predicts the Fidelity of Cortical Reinstatement During Subsequent Retrieval.

According to current models of episodic memory, the hippocampus binds together the neural representation of an experience during encoding such that it can be reinstated in cortex during subsequent retrieval. However, direct evidence linking hippocampal engagement during encoding with subsequent cortical reinstatement during retrieval is lacking. In this study, we aim to directly test the relationship between hippocampal activation during encoding and cortical reinstatement during retrieval. During a scanned encoding session, human participants studied Noun-Sound and Noun-Picture pairs. One day later, during a scanned retrieval session, participants retrieved the sounds and pictures when given the nouns as cues. First, we found that trial-by-trial hippocampal encoding activation was related to trial-by-trial reactivation during retrieval as measured by the univariate BOLD response in several modality-specific cortical regions. Second, using multivariate measures, we found a correlation between encoding-retrieval pattern similarity computed for each trial and hippocampal encoding activation on the corresponding encoding event, suggesting that the magnitude of hippocampal activation during an experience is related to the fidelity of subsequent reinstatement of cortical activity patterns during retrieval. Consistent with current theories of episodic memory, our findings demonstrate a critical link between initial hippocampal activation during an experience and subsequent cortical reinstatement.

Attentional modulation of background connectivity between ventral visual cortex and the medial temporal lobe.

Attention prioritizes information that is most relevant to current behavioral goals. This prioritization can be accomplished by amplifying neural responses to goal-relevant information and by strengthening coupling between regions involved in processing this information. Such modulation occurs within and between areas of visual cortex, and relates to behavioral effects of attention on perception. However, attention also has powerful effects on learning and memory behavior, suggesting that similar modulation may occur for memory systems. We used fMRI to investigate this possibility, examining how visual information is prioritized for processing in the medial temporal lobe (MTL). We hypothesized that the way in which ventral visual cortex couples with MTL input structures will depend on the kind of information being attended. Indeed, visual cortex was more coupled with parahippocampal cortex when scenes were attended and more coupled with perirhinal cortex when faces were attended. This switching of MTL connectivity was more pronounced for visual voxels with weak selectivity, suggesting that connectivity might help disambiguate sensory signals. These findings provide an initial window into an attentional mechanism that could have consequences for learning and memory.

High-resolution investigation of memory-specific reinstatement in the hippocampus and perirhinal cortex.

Episodic memory involves remembering the details that characterize a prior experience. Successful memory recovery has been associated with the reinstatement of brain activity patterns in a number of sensory regions across the cortex. However, how the hippocampus and surrounding medial temporal lobe (MTL) cortex contribute to this process is less clear. Models of episodic memory posit that hippocampal pattern reinstatement, also referred to as pattern completion, may mediate cortical reinstatement during retrieval. Empirical evidence of this process, however, remains elusive. Here, we use high-resolution fMRI and encoding-retrieval multi-voxel pattern similarity analyses to demonstrate for the first time that the hippocampus, particularly right hippocampal subfield CA1, shows evidence of reinstating individual episodic memories. Furthermore, reinstatement in perirhinal cortex (PrC) is also evident. Critically, we identify distinct factors that may mediate the cortical reinstatement in PrC. First, we find that encoding activation in PrC is related to later reinstatement in this region, consistent with the theory that encoding strength in the regions that process the memoranda is important for later reinstatement. Conversely, retrieval activation in right CA1 was correlated with reinstatement in PrC, consistent with models of pattern completion. This dissociation is discussed in the context of the flow of information into and out of the hippocampus during encoding and retrieval, respectively. © 2016 Wiley Periodicals, Inc.

Consolidation of Associative and Item Memory Is Related to Post-Encoding Functional Connectivity between the Ventral Tegmental Area and Different Medial Temporal Lobe Subregions during an Unrelated Task.

It is well established that the hippocampus and perirhinal cortex (PrC) encode associative and item representations, respectively. However, less is known about how item and associative memories are consolidated. We used high-resolution fMRI in humans to measure how functional connectivity between these distinct medial temporal lobe regions with the ventral tegmental area (VTA) after a paired associate encoding task is related to both immediate and 24 h item and associative memory performance. We found that the strength of post-encoding functional connectivity between the VTA and CA1 selectively correlated with long-term associative memory, despite subjects actively engaging in an unrelated task during this period. Conversely, VTA-PrC functional connectivity during the same period correlated with long-term item memory. Critically, connectivity between VTA and these MTL regions were only related to memory tested at a 24 h delay, implicating midbrain connectivity in the consolidation of distinct forms of memory.

Quantitative comparison of 21 protocols for labeling hippocampal subfields and parahippocampal subregions in in vivo MRI: towards a harmonized segmentation protocol.

OBJECTIVE: An increasing number of human in vivo magnetic resonance imaging (MRI) studies have focused on examining the structure and function of the subfields of the hippocampal formation (the dentate gyrus, CA fields 1-3, and the subiculum) and subregions of the parahippocampal gyrus (entorhinal, perirhinal, and parahippocampal cortices). The ability to interpret the results of such studies and to relate them to each other would be improved if a common standard existed for labeling hippocampal subfields and parahippocampal subregions. Currently, research groups label different subsets of structures and use different rules, landmarks, and cues to define their anatomical extents. This paper characterizes, both qualitatively and quantitatively, the variability in the existing manual segmentation protocols for labeling hippocampal and parahippocampal substructures in MRI, with the goal of guiding subsequent work on developing a harmonized substructure segmentation protocol. METHOD: MRI scans of a single healthy adult human subject were acquired both at 3 T and 7 T. Representatives from 21 research groups applied their respective manual segmentation protocols to the MRI modalities of their choice. The resulting set of 21 segmentations was analyzed in a common anatomical space to quantify similarity and identify areas of agreement. RESULTS: The differences between the 21 protocols include the region within which segmentation is performed, the set of anatomical labels used, and the extents of specific anatomical labels. The greatest overall disagreement among the protocols is at the CA1/subiculum boundary, and disagreement across all structures is greatest in the anterior portion of the hippocampal formation relative to the body and tail. CONCLUSIONS: The combined examination of the 21 protocols in the same dataset suggests possible strategies towards developing a harmonized subfield segmentation protocol and facilitates comparison between published studies.

Associative encoding and retrieval are predicted by functional connectivity in distinct hippocampal area CA1 pathways.

Determining how the hippocampus supports the unique demands of memory encoding and retrieval is fundamental for understanding the biological basis of episodic memory. One possibility proposed by theoretical models is that the distinct computational demands of encoding and retrieval are accommodated by shifts in the functional interaction between the hippocampal CA1 subregion and its input structures. However, empirical tests of this hypothesis are lacking. To test this in humans, we used high-resolution fMRI to measure functional connectivity between hippocampal area CA1 and regions of the medial temporal lobe and midbrain during extended blocks of associative encoding and retrieval tasks. We found evidence for a double dissociation between the pathways supporting successful encoding and retrieval. Specifically, during the associative encoding task, but not the retrieval task, functional connectivity only between area CA1 and the ventral tegmental area predicted associative long-term memory. In contrast, connectivity between area CA1 and DG/CA3 was greater, on average, during the retrieval task compared with the encoding task, and, importantly, the strength of this connectivity significantly correlated with retrieval success. Together, these findings serve as an important first step toward understanding how the demands of fundamental memory processes may be met by changes in the relative strength of connectivity within hippocampal pathways.