Constructive Memory and Conscious Experience.

Episodic memory relies on constructive processes that support simulating novel future events by flexibly recombining elements of past experiences, and that can also give rise to memory errors. In recent studies, we have developed methods to characterize the cognitive and neural processes that support conscious experiences linked to this process of episodic recombination, both when people simulate novel future events and commit recombination-related memory errors. In this Perspective, we summarize recent studies that illustrate these phenomena, and discuss broader implications for characterizing the basis of conscious experiences associated with constructive memory from a cognitive neuroscience perspective.

Transcranial magnetic stimulation to the angular gyrus modulates the temporal dynamics of the hippocampus and entorhinal cortex.

Transcranial magnetic stimulation (TMS) delivered to the angular gyrus (AG) affects hippocampal function and associated behaviors (Thakral PP, Madore KP, Kalinowski SE, Schacter DL. Modulation of hippocampal brain networks produces changes in episodic simulation and divergent thinking. 2020a. Proc Natl Acad Sci U S A. 117:12729-12740). Here, we examine if functional magnetic resonance imaging (fMRI)-guided TMS disrupts the gradient organization of temporal signal properties, known as the temporal organization, in the hippocampus (HPC) and entorhinal cortex (ERC). For each of 2 TMS sessions, TMS was applied to either a control site (vertex) or to a left AG target region (N = 18; 14 females). Behavioral measures were then administered, and resting-state scans were acquired. Temporal dynamics were measured by tracking change in the fMRI signal (i) "within" single voxels over time, termed single-voxel autocorrelation and (ii) "between" different voxels over time, termed intervoxel similarity. TMS reduced AG connectivity with the hippocampal target and induced more rapid shifting of activity in single voxels between successive time points, lowering the single-voxel autocorrelation, within the left anteromedial HPC and posteromedial ERC. Intervoxel similarity was only marginally affected by TMS. Our findings suggest that hippocampal-targeted TMS disrupts the functional properties of the target site along the anterior/posterior axis. Further studies should examine the consequences of altering the temporal dynamics of these medial temporal areas to the successful processing of episodic information under task demand.

Impaired cognitive performance in older adults is associated with deficits in item memory and memory for object features.

Amnestic mild cognitive impairment (aMCI) is associated with damage to the perirhinal/entorhinal cortex, and consequently, deficits in item/object memory. However, cognitive assessments commonly used to identify individuals with aMCI require a clinician to administer and interpret the test. We developed a novel self-administered global cognitive assessment, called the Cognitive Assessment via Keyboard (CAKe). To assess the relationship between CAKe performance and perirhinal/entorhinal cortex-dependent memory function, participants completed the CAKe, a feature source memory task, and a context memory task. During the memory tasks, participants studied line drawings with either a green or orange internal color (feature memory runs) or external color (context memory runs) and then classified each item as old and previously presented with a "green" or "orange" color, or "new". CAKe scores were correlated with item memory accuracies and source memory accuracies on both tasks. Participants with 'impaired' CAKe performance had worse item memory and worse feature source memory accuracies than those with 'normal' CAKe performance. These results demonstrate specific deficits in item memory and feature source memory and suggest that our assessments may be a valid predictor of aMCI memory deficits.

Constructive episodic retrieval processes underlying memory distortion contribute to creative thinking and everyday problem solving.

Constructive episodic retrieval processes play an adaptive role in supporting divergent thinking (i.e., creatively combining diverse bits of information) and means-end problem solving (i.e., generating steps to solve a social problem). However, the constructive nature of episodic memory that supports these adaptive functions also leads to memory error. In three experiments we aimed to identify a direct link between divergent thinking and means-end problem solving - as assessed in the Alternative Uses Task (AUT) and Means-End Problem Solving (MEPS) task - with the generation of false memories in the Deese-Roediger-McDermott paradigm. In Experiment 1, we replicated prior findings where false memory was positively correlated with performance on the AUT, and also showed for the first time that increased performance in the MEPS task is associated with increased false recall. In Experiment 2, we demonstrated that the link between false recall and performance on the MEPS task did not extend to other forms of problem solving, as assessed with the Everyday Descriptions Task (EDT). In Experiment 3, we showed that when the EDT was preceded by the MEPS task in an attempt to influence participants to engage in a similar episodic-problem solving strategy, performance in both tasks was correlated with false memory. These findings provide evidence for a direct link between the adaptive benefits of constructive episodic processes, in the form of enhanced divergent creative thinking and problem solving, and costs, in the form of increased memory error.

Modulation of hippocampal brain networks produces changes in episodic simulation and divergent thinking.

Prior functional magnetic resonance imaging (fMRI) studies indicate that a core network of brain regions, including the hippocampus, is jointly recruited during episodic memory, episodic simulation, and divergent creative thinking. Because fMRI data are correlational, it is unknown whether activity increases in the hippocampus, and the core network more broadly, play a causal role in episodic simulation and divergent thinking. Here we employed fMRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of hippocampal brain networks impairs both episodic simulation and divergent thinking. For each of two TMS sessions, continuous θ-burst stimulation (cTBS) was applied to either a control site (vertex) or to a left angular gyrus target region. The target region was identified on the basis of a participant-specific resting-state functional connectivity analysis with a hippocampal seed region previously associated with memory, simulation, and divergent thinking. Following cTBS, participants underwent fMRI and performed a simulation, divergent thinking, and nonepisodic control task. cTBS to the target region reduced the number of episodic details produced for the simulation task and reduced idea production on divergent thinking. Performance in the control task did not statistically differ as a function of cTBS site. fMRI analyses revealed a selective and simultaneous reduction in hippocampal activity during episodic simulation and divergent thinking following cTBS to the angular gyrus versus vertex but not during the nonepisodic control task. Our findings provide evidence that hippocampal-targeted TMS can specifically modulate episodic simulation and divergent thinking, and suggest that the hippocampus is critical for these cognitive functions.

Reinstatement of item-specific contextual details during retrieval supports recombination-related false memories.

Flexible retrieval mechanisms that allow us to infer relationships across events may also lead to memory errors or distortion when details of one event are misattributed to the related event. Here, we tested how making successful inferences alters representation of overlapping events, leading to false memories. Participants encoded overlapping associations ('AB' and 'BC'), each of which was superimposed on different indoor and outdoor scenes that were pre-exposed prior to associative learning. Participants were subsequently tested on both the directly learned pairs ('AB' and 'BC') and inferred relationships across pairs ('AC'). We predicted that when people make a correct inference, features associated with overlapping events may become integrated in memory. To test this hypothesis, participants completed a final detailed retrieval test, in which they had to recall the scene associated with initially learned 'AB' pairs (or 'BC' pairs). We found that the outcome of inference decisions impacted the degree to which neural patterns elicited during detailed 'AB' retrieval reflected reinstatement of the scene associated with the overlapping 'BC' event. After successful inference, neural patterns in the anterior hippocampus, posterior medial prefrontal cortex, and our content-reinstatement region (left inferior temporal gyrus) were more similar to the overlapping, yet incorrect 'BC' context relative to after unsuccessful inference. Further, greater hippocampal activity during inference was associated with greater reinstatement of the incorrect, overlapping context in our content-reinstatement region, which in turn tracked contextual misattributions during detailed retrieval. These results suggest recombining memories during successful inference can lead to misattribution of contextual details across related events, resulting in false memories.

Distinct patterns of hippocampal activity associated with color and spatial source memory.

The hippocampus is known to be involved in source memory across a wide variety of stimuli and source types. Thus, source memory activity in the hippocampus is thought to be domain-general such that different types of source information are similarly processed in the hippocampus. However, there is some evidence of domain-specificity for spatial and temporal source information. The current fMRI study aimed to determine whether patterns of activity in the hippocampus differed for two types of visual source information: spatial location and background color. Participants completed three runs of a spatial memory task and three runs of a color memory task. During the study phase, 32 line drawings of common objects and animals were presented to either the left or right of fixation for the spatial memory task or on either a red or green background for the color memory task. During the test phase of both tasks, 48 object word labels were presented in the center of the screen and participants classified the corresponding item as old and previously on the "left"/on a "green" background, old and previously on the "right"/on a "red" background, or "new." Two analysis methods were employed to assess whether hippocampal activity differed between the two source types: a general linear model analysis and a classification-based searchlight multivoxel pattern analysis (MVPA). The searchlight MVPA revealed that activity associated with spatial memory and color memory could be classified with above-chance accuracy in a region of the right anterior hippocampus, and a follow-up analysis revealed that there was a significant effect of memory accuracy. These results indicate that different types of source memory are represented by distinct patterns of activity in the hippocampus.

Reinstatement of Event Details during Episodic Simulation in the Hippocampus.

According to the constructive episodic simulation hypothesis, episodic simulation (i.e., imagining specific novel future episodes) draws on some of the same neurocognitive processes that support episodic memory (i.e., recalling specific past episodes). Episodic retrieval supports the ability to simulate future experiences by providing access to episodic details (e.g., the people and locations that comprise memories) that can be recombined in new ways. In the current functional neuroimaging study, we test this hypothesis by examining whether the hippocampus, a region implicated in the reinstatement of episodic information during memory, supports reinstatement of episodic information during simulation. Employing a multivoxel pattern similarity analysis, we interrogated the similarity between hippocampal neural patterns during memory and simulation at the level of individual event details. Our findings indicate that the hippocampus supports the reinstatement of detail-specific information from episodic memory during simulation, with the level of reinstatement contributing to the subjective experience of simulated details.

Divergent thinking and constructing future events: dissociating old from new ideas.

Divergent thinking (the ability to generate creative ideas by combining diverse types of information) has been previously linked to the ability to imagine novel and specific future autobiographical events. Here, we examined whether divergent thinking is differentially associated with the ability to construct novel imagined future events and recast future events (i.e., actual past events recast as future events) as opposed to recalled past events. We also examined whether different types of creative ideas (i.e., old ideas from memory or new ideas from imagination) underlie the linkage between divergent thinking and various autobiographical events. Divergent thinking ability was measured using the Alternate Uses Task (AUT). In Experiment 1, the amount of episodic details for both novel and recast future events was associated with divergent thinking (AUT scores), and this relationship was significant with AUT scores for new creative ideas but not old creative ideas. There was no significant relationship between divergent thinking and the amount of episodic detail for recalled past events. We extended these findings in Experiment 2 to a different test of divergent thinking, the Consequences Task. These results demonstrate that individual differences in divergent thinking are associated with the capacity to both imagine and recast future events.

Neural Mechanisms of Episodic Retrieval Support Divergent Creative Thinking.

Prior research has indicated that brain regions and networks that support semantic memory, top-down and bottom-up attention, and cognitive control are all involved in divergent creative thinking. Kernels of evidence suggest that neural processes supporting episodic memory-the retrieval of particular elements of prior experiences-may also be involved in divergent thinking, but such processes have typically been characterized as not very relevant for, or even a hindrance to, creative output. In the present study, we combine functional magnetic resonance imaging with an experimental manipulation to test formally, for the first time, episodic memory's involvement in divergent thinking. Following a manipulation that facilitates detailed episodic retrieval, we observed greater neural activity in the hippocampus and stronger connectivity between a core brain network linked to episodic processing and a frontoparietal brain network linked to cognitive control during divergent thinking relative to an object association control task that requires little divergent thinking. Stronger coupling following the retrieval manipulation extended to a subsequent resting-state scan. Neural effects of the episodic manipulation were consistent with behavioral effects of enhanced idea production on divergent thinking but not object association. The results indicate that conceptual frameworks should accommodate the idea that episodic retrieval can function as a component process of creative idea generation, and highlight how the brain flexibly utilizes the retrieval of episodic details for tasks beyond simple remembering.

Effects of age on across-participant variability of cortical reinstatement effects.

Using functional magnetic resonance imaging data, we assessed whether across-participant variability of content-selective retrieval-related neural activity differs with age. We addressed this question by employing across-participant multi-voxel pattern analysis (MVPA), predicting that increasing age would be associated with reduced variability of retrieval-related cortical reinstatement across participants. During study, 24 young and 24 older participants viewed objects and concrete words. Test items comprised studied words, names of studied objects, and unstudied words. Participants judged whether the items were recollected, familiar, or new by making 'Remember', 'Know' and 'New' responses, respectively. MVPA was conducted on each region belonging to the 'core recollection network', dorsolateral prefrontal cortex, and a previously identified content-selective voxel set. A leave-one-participant-out classification approach was employed whereby a classifier was trained on a subset of participants and tested on the data from a yoked pair of held-out participants. Classifiers were trained on the study phase data to discriminate the study trials as a function of content (picture or word). The classifiers were then applied to the test phase data to discriminate studied test words according to their study condition. In all of the examined regions, classifier performance demonstrated little or no sensitivity to age and, for the test data, was robustly above chance. Thus, there was little evidence to support the hypothesis that across-participant variability of retrieval-related cortical reinstatement differs with age. The findings extend prior evidence by demonstrating that content-selective cortical reinstatement is sufficiently invariant to support across-participant multi-voxel classification across the healthy adult lifespan.

Content-specific phenomenological similarity between episodic memory and simulation.

Numerous studies have indicated that remembering specific past experiences (i.e., episodic memory) and imagining specific novel future experiences (i.e., episodic simulation) are supported by common mental processes. An open question, however, is whether and to what extent the content of specific past episodes is sampled when simulating a specific future episode. The current study aimed to answer this question. Participants recalled past episodes each comprising two episodic details, a personally familiar location and person. Participants also simulated novel future episodes using recombined pairs of person and location details taken from different recalled episodes. Participants rated the vividness of each location and person in their memory and simulation. We conducted a multi-level analysis where the vividness rating during memory was used to predict the vividness rating during simulation at the level of individual shared details (i.e., location or person). The vividness of the memorial detail co-varied with the vividness of the simulated detail; this relationship persisted even after accounting for the underlying familiarity of the details. These findings strongly suggest that simulations of specific future experiences are based upon the contents of specific prior episodes.

A Role for the Left Angular Gyrus in Episodic Simulation and Memory.

Functional magnetic resonance imaging (fMRI) studies indicate that episodic simulation (i.e., imagining specific future experiences) and episodic memory (i.e., remembering specific past experiences) are associated with enhanced activity in a common set of neural regions referred to as the core network. This network comprises the hippocampus, medial prefrontal cortex, and left angular gyrus, among other regions. Because fMRI data are correlational, it is unknown whether activity increases in core network regions are critical for episodic simulation and episodic memory. In the current study, we used MRI-guided transcranial magnetic stimulation (TMS) to assess whether temporary disruption of the left angular gyrus would impair both episodic simulation and memory (16 participants, 10 females). Relative to TMS to a control site (vertex), disruption of the left angular gyrus significantly reduced the number of internal (i.e., episodic) details produced during the simulation and memory tasks, with a concomitant increase in external detail production (i.e., semantic, repetitive, or off-topic information), reflected by a significant detail by TMS site interaction. Difficulty in the simulation and memory tasks also increased after TMS to the left angular gyrus relative to the vertex. In contrast, performance in a nonepisodic control task did not differ statistically as a function of TMS site (i.e., number of free associates produced or difficulty in performing the free associate task). Together, these results are the first to demonstrate that the left angular gyrus is critical for both episodic simulation and episodic memory.SIGNIFICANCE STATEMENT Humans have the ability to imagine future episodes (i.e., episodic simulation) and remember episodes from the past (i.e., episodic memory). A wealth of neuroimaging studies have revealed that these abilities are associated with enhanced activity in a core network of neural regions, including the hippocampus, medial prefrontal cortex, and left angular gyrus. However, neuroimaging data are correlational and do not tell us whether core regions support critical processes for simulation and memory. In the current study, we used transcranial magnetic stimulation and demonstrated that temporary disruption of the left angular gyrus leads to impairments in simulation and memory. The present study provides the first causal evidence to indicate that this region is critical for these fundamental abilities.

Core Network Contributions to Remembering the Past, Imagining the Future, and Thinking Creatively.

The core network refers to a set of neural regions that have been consistently associated with episodic memory retrieval and episodic future simulation. This network is thought to support the constructive thought processes that allow the retrieval and flexible combination of stored information to reconstruct past and construct novel future experiences. Recent behavioral research points to an overlap between these constructive processes and those also engaged during divergent thinking-the ability to think creatively and generate novel ideas-but the extent to which they involve common neural correlates remains unclear. Using fMRI, we sought to address this question by assessing brain activity as participants recalled past experiences, simulated future experiences, or engaged in divergent thinking. Consistent with past work, we found that episodic retrieval and future simulation activated the core network compared with a semantic control condition. Critically, a triple conjunction of episodic retrieval, future simulation, and divergent thinking revealed common engagement of core network regions, including the bilateral hippocampus and parahippocampal gyrus, as well as other regions involved in memory retrieval (inferior frontal gyrus) and mental imagery (middle occipital gyrus). The results provide further insight into the roles of the hippocampus and the core network in episodic memory retrieval, future simulation, and divergent thinking and extend recent work highlighting the involvement of constructive episodic processes in creative cognition.

Increased hippocampus to ventromedial prefrontal connectivity during the construction of episodic future events.

Both the hippocampus and ventromedial prefrontal cortex (vmPFC) appear to be critical for episodic future simulation. Damage to either structure affects one's ability to remember the past and imagine the future, and both structures are commonly activated as part of a wider core network during future simulation. However, the precise role played by each of these structures and, indeed, the direction of information flow between them during episodic simulation, is still not well understood. In this study, we scanned participants using functional magnetic resonance imaging while they imagined future events in response to object cues. We then used dynamic causal modeling to examine effective connectivity between the left anterior hippocampus and vmPFC during the initial mental construction of the events. Our results show that while there is strong bidirectional intrinsic connectivity between these regions (i.e., irrespective of task conditions), only the hippocampus to vmPFC connection increases during the construction of episodic future events, suggesting that the hippocampus initiates event simulation in response to retrieval cues, driving activation in the vmPFC where episodic details may be further integrated.

Characterizing the role of the hippocampus during episodic simulation and encoding.

The hippocampus has been consistently associated with episodic simulation (i.e., the mental construction of a possible future episode). In a recent study, we identified an anterior-posterior temporal dissociation within the hippocampus during simulation. Specifically, transient simulation-related activity occurred in relatively posterior portions of the hippocampus and sustained activity occurred in anterior portions. In line with previous theoretical proposals of hippocampal function during simulation, the posterior hippocampal activity was interpreted as reflecting a transient retrieval process for the episodic details necessary to construct an episode. In contrast, the sustained anterior hippocampal activity was interpreted as reflecting the continual recruitment of encoding and/or relational processing associated with a simulation. In the present study, we provide a direct test of these interpretations by conducting a subsequent memory analysis of our previously published data to assess whether successful encoding during episodic simulation is associated with the anterior hippocampus. Analyses revealed a subsequent memory effect (i.e., later remembered > later forgotten simulations) in the anterior hippocampus. The subsequent memory effect was transient and not sustained. Taken together, the current findings provide further support for a component process model of hippocampal function during simulation. That is, unique regions of the hippocampus support dissociable processes during simulation, which include the transient retrieval of episodic information, the sustained binding of such information into a coherent episode, and the transient encoding of that episode for later retrieval.

An attention account of neural priming.

Repetition priming of familiar stimuli (e.g., objects) produces a decrease in visual cortical activity for repeated versus novel items, which has been attributed to more fluent processing for repeated items. By contrast, priming of unfamiliar stimuli (e.g., abstract shapes) produces an increase in visual cortical activity. The mechanism for priming-related increases in activity for repeated unfamiliar stimuli is unknown. We hypothesised that such increases in activity may reflect attentional allocation to these items. We tested this hypothesis using a priming-spatial attention paradigm. During Phase 1 of Experiment 1, participants viewed unfamiliar abstract shapes and familiar objects. During Phase 2, participants identified target letters (S or H). Each target letter was preceded by a non-informative shape or object cue that was repeated (from Phase 1) or novel in the same (valid) or opposite (invalid) hemifield. In Experiment 2, we manipulated shape familiarity by presenting shapes once or six times during Phase 1. For both experiments, at valid locations, target identification accuracy was higher following repeated versus novel unfamiliar item cues and lower following repeated versus novel familiar item cues. These findings support our hypothesis that priming-related increases in visual cortical activity for repeated unfamiliar items may, in part, reflect attentional allocation.

Cortical reinstatement and the confidence and accuracy of source memory.

Cortical reinstatement refers to the overlap between neural activity elicited during the encoding and the subsequent retrieval of an episode, and is held to reflect retrieved mnemonic content. Previous findings have demonstrated that reinstatement effects reflect the quality of retrieved episodic information as this is operationalized by the accuracy of source memory judgments. The present functional magnetic resonance imaging (fMRI) study investigated whether reinstatement-related activity also co-varies with the confidence of accurate source judgments. Participants studied pictures of objects along with their visual or spoken names. At test, they first discriminated between studied and unstudied pictures and then, for each picture judged as studied, they also judged whether it had been paired with a visual or auditory name, using a three-point confidence scale. Accuracy of source memory judgments- and hence the quality of the source-specifying information--was greater for high than for low confidence judgments. Modality-selective retrieval-related activity (reinstatement effects) also co-varied with the confidence of the corresponding source memory judgment. The findings indicate that the quality of the information supporting accurate judgments of source memory is indexed by the relative magnitude of content-selective, retrieval-related neural activity.

The dead salmon strikes again: Reports of unconscious processing in the hippocampus may reflect Type-I error.

Steinkrauss and Slotnick (2024) reviewed neuroimaging studies linking the hippocampus with implicit memory. They conclude that there is no convincing evidence that the hippocampus is associated with implicit memory because prior studies are confounded by explicit memory (among other factors). Here, we ask a different yet equally important question: do reports of unconscious hippocampal activity reflect a Type-I error (i.e. a false positive)? We find that 39% of studies linking the hippocampus with implicit memory (7 of 18) do not report correcting for multiple comparisons. These results indicate that many unconscious hippocampal effects may reflect a Type-I error.

Prefrontal cortex-mediated inhibition supports face recognition.

Inhibitory processes are thought to be important for memory function. A recent behavioral study that employed a face recognition paradigm reported that participants made fewer "old" responses to highly similar faces than less similar faces, providing evidence that memory for faces may rely on related-item inhibition. However, these results could also be explained by a non-inhibitory recall-to-reject process. The current study sought to use fMRI connectivity analysis to distinguish between these hypotheses. Although both hypotheses predict correct rejection of highly similar faces will produce activity in the prefrontal cortex, the inhibition hypothesis predicts negative connectivity between the prefrontal cortex and regions associated with memory retrieval and face processing, whereas the recall-to-reject hypothesis predicts positive connectivity between these regions. During the study phase, participants were presented with male and female faces. During the test phase, they viewed old faces, related face morphs (20-80% similar to old faces), and new faces, and made "old"-"new" judgements. Correct rejection of highly similar face morphs was associated with increased activity in the right lateral prefrontal cortex and negative connectivity between this region and regions associated with face processing and memory retrieval. These results indicate that prefrontal cortex-mediated memory inhibition supports face recognition.