Stereotypical Hippocampal Clustering Predicts Navigational Success in Virtualized Real-World Environments.

Structural differences along the hippocampal long axis are believed to underlie meaningful functional differences. Yet, recent data-driven parcellations of the hippocampus subdivide the hippocampus into a 10-cluster map with anterior-medial, anterior-lateral, and posteroanterior-lateral, middle, and posterior components. We tested whether task and experience could modulate this clustering using a spatial learning experiment where male and female participants were trained to virtually navigate a novel neighborhood in a Google Street View-like environment. Participants were scanned while navigating routes early in training and after a 2 week training period. Using the 10-cluster map as the ideal template, we found that participants who eventually learn the neighborhood well have hippocampal cluster maps consistent with the ideal-even on their second day of learning-and their cluster mappings do not deviate over the 2 week training period. However, participants who eventually learn the neighborhood poorly begin with hippocampal cluster maps inconsistent with the ideal template, though their cluster mappings may become more stereotypical after the 2 week training. Interestingly this improvement seems to be route specific: after some early improvement, when a new route is navigated, participants' hippocampal maps revert back to less stereotypical organization. We conclude that hippocampal clustering is not dependent solely on anatomical structure and instead is driven by a combination of anatomy, task, and, importantly, experience. Nonetheless, while hippocampal clustering can change with experience, efficient navigation depends on functional hippocampal activity clustering in a stereotypical manner, highlighting optimal divisions of processing along the hippocampal anterior-posterior and medial-lateral axes.

Hippocampal Signal Complexity and Rate-of-Change Predict Navigational Performance: Evidence from a Two-Week VR Training Program.

The hippocampus is believed to be an important region for spatial navigation, helping to represent the environment and plan routes. Evidence from rodents has suggested that the hippocampus processes information in a graded manner along its long-axis, with anterior regions encoding coarse information and posterior regions encoding fine-grained information. Brunec et al. (2018) demonstrated similar patterns in humans in a navigation paradigm, showing that the anterior-posterior gradient in representational granularity and the rate of signal change exist in the human hippocampus. However, the stability of these signals and their relationship to navigational performance remain unclear. In this study, we conducted a two-week training program where participants learned to navigate through a novel city environment. We investigated inter-voxel similarity (IVS) and temporal auto-correlation hippocampal signals, measures of representational granularity and signal change, respectively. Specifically, we investigated how these signals were influenced by navigational ability (i.e., stronger vs. weaker spatial learners), training session, and navigational dynamics. Our results revealed that stronger learners exhibited a clear anterior-posterior distinction in IVS in the right hippocampus, while weaker learners showed less pronounced distinctions. Additionally, lower general IVS levels in the hippocampus were linked to better early learning. Successful navigation was characterized by faster signal change, particularly in the anterior hippocampus, whereas failed navigation lacked the anterior-posterior distinction in signal change. These findings suggest that signal complexity and signal change in the hippocampus are important factors for successful navigation, with IVS representing information organization and auto-correlation reflecting moment-to-moment updating. These findings support the idea that efficient organization of scales of representation in an environment may be necessary for efficient navigation itself. Understanding the dynamics of these neural signals provides insights into the mechanisms underlying navigational learning in humans.

Stereotypical hippocampal clustering predicts navigational success in virtualized real-world environments.

Structural differences along the long-axis of the hippocampus have long been believed to underlie meaningful functional differences, such as the granularity of information processing. Recent findings show that data-driven parcellations of the hippocampus sub-divide the hippocampus into a 10-cluster map with anterior-medial, anterior-lateral, and posteroanterior-lateral, middle, and posterior components. We tested whether task and experience could modulate this clustering using a spatial learning experiment where subjects were trained to virtually navigate a novel neighborhood in a Google Street View-like environment over a two-week period. Subjects were scanned while navigating routes early in training and at the end of their two-week training. Using the 10-cluster map as the ideal template, we find that subjects who eventually learn the neighborhood well have hippocampal cluster-maps consistent with the ideal-even on their second day of learning-and their cluster mappings do not change over the two week training period. However, subjects who eventually learn the neighborhood poorly begin with hippocampal cluster-maps inconsistent with the ideal, though their cluster mappings become more stereotypical by the end of the two week training. Interestingly this improvement seems to be route specific as even after some early improvement, when a new route is navigated participants' hippocampal maps revert back to less stereotypical organization. We conclude that hippocampal clustering is not dependent solely on anatomical structure, and instead is driven by a combination of anatomy, task, and importantly, experience. Nonetheless, while hippocampal clustering can change with experience, efficient navigation depends on functional hippocampal activity clustering in a stereotypical manner, highlighting optimal divisions of processing along the hippocampal anterior-posterior and medial-lateral-axes.

Characterizing production: the production effect is eliminated for unusual voices unless they are frequent at study.

The production effect refers to the finding that items read aloud are better remembered than items read silently. This is often explained with reference to distinctiveness, arguing that aloud items become associated with distinctive sensorimotor features that facilitate retrieval at test. Based on this framework, more distinctive forms of production should result in larger production effects. The present study tested this theory by having participants study items silently or aloud in either their own voice or as a popular character. Participants were then tested for those items using recognition memory. Relative to silent items, aloud items read in the participants' own voice demonstrated a typical production effect; however, contrary to any predictions, no production effect was observed for the character voices. We next manipulated how frequently the character voice was used relative to the participants' own voice. This revealed a production effect for character voices only when those voices were more common than the participant's own voice. This pattern could not be attributed to cognitive demands or performance anxiety but was predicted by a novel computational account based on the Retrieving Effectively from Memory (REM) model. Our results show that the relation between distinctiveness and memory is not necessarily linear.

The production effect is consistent over material variations: support for the distinctiveness account.

The production effect is the superior memory for items read aloud as opposed to silently at the time of study. The distinctiveness account holds that produced items benefit from the encoding of additional elements associated with the act of production. If so, then that benefit should be consistent regardless of item type. Three experiments, using three different sets of materials and three different methods, tested this hypothesis. Experiment 1, using recognition testing, showed consistent production benefits for high and low frequency words. Experiment 2, using free recall, showed consistent production increments for pictures and words. Experiment 3, using incidental learning, showed consistent production benefits for recognition of nonwords and words. Taken together, these results fit with the distinctiveness account: Production at encoding dependably adds information to the memory record, regardless of item type or method of testing, producing a consistently reliable memory benefit.

Remotely delivered environmental enrichment intervention for traumatic brain injury: Study protocol for a randomised controlled trial.

INTRODUCTION: Individuals with moderate-severe traumatic brain injury (m-sTBI) experience progressive brain and behavioural declines in the chronic stages of injury. Longitudinal studies found that a majority of patients with m-sTBI exhibit significant hippocampal atrophy from 5 to 12 months post-injury, associated with decreased cognitive environmental enrichment (EE). Encouragingly, engaging in EE has been shown to lead to neural improvements, suggesting it is a promising avenue for offsetting hippocampal neurodegeneration in m-sTBI. Allocentric spatial navigation (ie, flexible, bird's eye view approach), is a good candidate for EE in m-sTBI because it is associated with hippocampal activation and reduced ageing-related volume loss. Efficacy of EE requires intensive daily training, prohibitive within most current health delivery systems. The present protocol is a novel, remotely delivered and self-administered intervention designed to harness principles from EE and allocentric spatial navigation to offset hippocampal atrophy and potentially improve hippocampal functions such as navigation and memory for patients with m-sTBI. METHODS AND ANALYSIS: Eighty-four participants with chronic m-sTBI are being recruited from an urban rehabilitation hospital and randomised into a 16-week intervention (5 hours/week; total: 80 hours) of either targeted spatial navigation or an active control group. The spatial navigation group engages in structured exploration of different cities using Google Street View that includes daily navigation challenges. The active control group watches and answers subjective questions about educational videos. Following a brief orientation, participants remotely self-administer the intervention on their home computer. In addition to feasibility and compliance measures, clinical and experimental cognitive measures as well as MRI scan data are collected pre-intervention and post-intervention to determine behavioural and neural efficacy. ETHICS AND DISSEMINATION: Ethics approval has been obtained from ethics boards at the University Health Network and University of Toronto. Findings will be presented at academic conferences and submitted to peer-reviewed journals. TRIAL REGISTRATION NUMBER: Version 3, ClinicalTrials.gov Registry (NCT04331392).

Recallable but not recognizable: The influence of semantic priming in recall paradigms.

When people can successfully recall a studied word, they should be able to recognize it as having been studied. In cued-recall paradigms, however, participants sometimes correctly recall words in the presence of strong semantic cues but then fail to recognize those words as actually having been studied. Although the conditions necessary to produce this unusual effect are known, the underlying neural correlates have not been investigated. Across five experiments, involving both behavioral and electrophysiological methods (EEG), we investigated the cognitive and neural processes that underlie recognition failures. Experiments 1 and 2 showed behaviorally that assuming that recalled items can be recognized in cued-recall paradigms is a flawed assumption, because recognition failures occur in the presence of cues, regardless of whether those failures are measured. With event-related potentials (ERPs), Experiments 3 and 4 revealed that successfully recalled words that are recognized are driven by recollection at recall and then by a combination of recollection and familiarity at ensuing recognition. In contrast, recognition failures did not show that memory signature and may instead be driven by semantic priming at recall and followed at recognition stages by negative-going ERP effects consistent with implicit processes, such as repetition fluency. These results demonstrate that recall - long-characterized as predominantly reflecting recollection-based processing in episodic memory - may at times also be served by a confluence of implicit cognitive processes.

Turns during navigation act as boundaries that enhance spatial memory and expand time estimation.

Ongoing experience unfolds over time. To segment continuous experience into component events, humans rely on physical and conceptual boundaries. Here we explored the subjective representation of turns along travelled routes as boundaries. Across two experiments, turns selectively enhanced participants' subjective recollection of locations immediately preceding them, compared to their recollection of locations in the middle of a route straightaway or immediately following turns. In Experiment 2, we also observed a subjective expansion of the time spent at pre-turn, relative to post-turn, locations. These results highlight the influence of turns on memory for travelled routes and provide further evidence for a link between subjective episodic re-experiencing and temporal memory. Taken together, this evidence suggests that turns during navigation act much as boundaries do for events, enhancing memory and processing of pre-boundary locations.

Distinctive encodings and the production effect: failure to retrieve distinctive encodings decreases recollection of silent items.

Studies have shown that when aloud and silent items are studied together, silent items are remembered more poorly than when they are studied independently. We hypothesise that this cost to silent items emerges because, at test, participants search for memories of having said items aloud and when those memory searches fail, participants become uncertain about whether silent items were studied. This effect should be exaggerated if other unique distinctive encoding conditions are also included at study (e.g., mumbling, writing, typing, etc.). To test this prediction, we examined the impact of introducing mumbled, "important" (i.e., words that participants are told are the most important to remember), and mouthed words to a study list of aloud and silent words. Introducing mumbled and "important" words further impaired the recollection of silent items. Introducing mouthed items did not further impair the memorability of silent items because mouthing and speaking aloud are so similar and hence, are not fully unique from each other. The memorability of aloud items was unaffected in all conditions. These results suggest that participants search for distinctive encoding information at test, and only for items that fail those searches (i.e., silent items) do they lose confidence.

Hippocampal and Retrosplenial Goal Distance Coding After Long-term Consolidation of a Real-World Environment.

Recent research indicates the hippocampus may code the distance to the goal during navigation of newly learned environments. It is unclear however, whether this also pertains to highly familiar environments where extensive systems-level consolidation is thought to have transformed mnemonic representations. Here we recorded fMRI while University College London and Imperial College London students navigated virtual simulations of their own familiar campus (>2 years of exposure) and the other campus learned days before scanning. Posterior hippocampal activity tracked the distance to the goal in the newly learned campus, as well as in familiar environments when the future route contained many turns. By contrast retrosplenial cortex only tracked the distance to the goal in the familiar campus. All of these responses were abolished when participants were guided to their goal by external cues. These results open new avenues of research on navigation and consolidation of spatial information and underscore the notion that the hippocampus continues to play a role in navigation when detailed processing of the environment is needed for navigation.

Cognitive mapping style relates to posterior-anterior hippocampal volume ratio.

As London taxi drivers acquire "the knowledge" and develop a detailed cognitive map of London, their posterior hippocampi (pHPC) gradually increase in volume, reflecting an increasing pHPC/aHPC volume ratio. In the mnemonic domain, greater pHPC/aHPC volume ratios in young adults have been found to relate to better recollection ability, indicating that the balance between pHPC and aHPC volumes might be reflective of cross-domain individual differences. Here, we examined participants' self-reported use of cognitive map-based navigational strategies in relation to their pHPC/aHPC hippocampal volume ratio. We find that greater reported cognitive map use was related to significantly greater posterior, relative to anterior, hippocampal volume in two separate samples of young adults. Further, greater reported cognitive map usage correlated with better performance on a self-initiated navigation task. Together, these data help to advance our understanding of differences between aHPC and pHPC and the greater role of pHPC in spatial mapping.

Multiple Scales of Representation along the Hippocampal Anteroposterior Axis in Humans.

The ability to represent the world accurately relies on simultaneous coarse and fine-grained neural information coding, capturing both gist and detail of an experience. The longitudinal axis of the hippocampus may provide a gradient of representational granularity in spatial and episodic memory in rodents and humans [1-8]. Rodent place cells in the ventral hippocampus exhibit significantly larger place fields and greater autocorrelation than those in the dorsal hippocampus [1, 9-11], which may underlie a coarser and slower changing representation of space [10, 12]. Recent evidence suggests that properties of cellular dynamics in rodents can be captured with fMRI in humans during spatial navigation [13] and conceptual learning [14]. Similarly, mechanisms supporting granularity along the long axis may also be extrapolated to the scale of fMRI signal. Here, we provide the first evidence for separable scales of representation along the human hippocampal anteroposterior axis during navigation and rest by showing (1) greater similarity among voxel time courses and (2) higher temporal autocorrelation in anterior hippocampus (aHPC), relative to posterior hippocampus (pHPC), the human homologs of ventral and dorsal rodent hippocampus. aHPC voxels exhibited more similar activity at each time point and slower signal change over time than voxels in pHPC, consistent with place field organization in rodents. Importantly, similarity between voxels was related to navigational strategy and episodic memory. These findings provide evidence that the human hippocampus supports an anterior-to-posterior gradient of coarse-to-fine spatiotemporal representations, suggesting the existence of a cross-species mechanism, whereby lower neural similarity supports more complex coding of experience.

The influence of recollection and familiarity in the formation and updating of associative representations.

Prior representations affect future learning. Little is known, however, about the effects of recollective or familiarity-based representations on such learning. We investigate the ability to reuse or reassociate elements from recollection- and familiarity-based associations to form new associations. Past neuropsychological research suggests that hippocampal, and presumably recollective, representations are more flexible than extra-hippocampal, presumably familiarity-based, representations. We therefore hypothesize that the elements of recollective associations, as opposed to familiarity-based representations, may be more easily manipulated and decoupled from each other, and facilitate the formation of new associations. To investigate this hypothesis we used the AB/AC learning paradigm. Across two recall studies we observed an advantage in learning AC word pairs if AB word pairs were initially recollected. Furthermore, AB word pairs were more likely to intrude during a final AC test if those AB word pairs were initially familiarity-based. A third experiment using a recognition version of the AB/AC paradigm ruled out the possibility that our findings were due to memory strength. Our results support the idea that elements in recollective associative traces may be more discretely coded, leading to their flexible use, whereas elements in familiarity-based associative traces are less flexible.

Recollection-dependent memory for event duration in large-scale spatial navigation.

Time and space represent two key aspects of episodic memories, forming the spatiotemporal context of events in a sequence. Little is known, however, about how temporal information, such as the duration and the order of particular events, are encoded into memory, and if it matters whether the memory representation is based on recollection or familiarity. To investigate this issue, we used a real world virtual reality navigation paradigm where periods of navigation were interspersed with pauses of different durations. Crucially, participants were able to reliably distinguish the durations of events that were subjectively "reexperienced" (i.e., recollected), but not of those that were familiar. This effect was not found in temporal order (ordinal) judgments. We also show that the active experience of the passage of time (holding down a key while waiting) moderately enhanced duration memory accuracy. Memory for event duration, therefore, appears to rely on the hippocampally supported ability to recollect or reexperience an event enabling the reinstatement of both its duration and its spatial context, to distinguish it from other events in a sequence. In contrast, ordinal memory appears to rely on familiarity and recollection to a similar extent.

Familiarity, but not recollection, supports the between-subject production effect in recognition memory.

Five experiments explored the basis of the between-subjects production effect in recognition memory as represented by differences in the recollection and familiarity of produced (read aloud) and nonproduced (read silently) words. Using remember-know judgments (Experiment 1b) and a dual-process signal-detection approach applied to confidence ratings (Experiments 2b and 3), we observed that production influences familiarity but not recollection when manipulated between-subjects. This is in contrast to within-subject designs, which reveal a clear effect of production on both recollection and familiarity (Experiments 1a and 2a). Our findings resolve contention concerning apparent design effects: Whereas the within-subject production effect is subserved by separable recollective- and familiarity-based components, the between-subjects production effect is subserved by the familiarity-based component alone. Our findings support a role for the relative distinctiveness of production as a means of guiding recognition judgments (at least when manipulated within-subjects), but we also propose that production influences the strength of produced items, explaining the persistence of the effect in between-subjects designs. (PsycINFO Database Record

Forget all that nonsense: The role of meaning during the forgetting of recollective and familiarity-based memories.

Memory can be divided into recollection and familiarity. Recollection is characterized as the ability to vividly re-experience past events, and is believed to be supported by the hippocampus, whereas familiarity is defined as an undifferentiated feeling of knowing or acquaintance, and is believed to be supported by extra-hippocampal regions, such as the perirhinal cortex. Recent evidence suggests that the neural architectures of the hippocampus and neocortex lead information in these regions being susceptible to different forgetting processes. We expand on these accounts and propose that the neocortex may be sensitive to the semantic content of a trace, with more meaningful traces being more easily retained. The hippocampus, in contrast, is not hypothesized to be influenced by semantics in the same way. To test this new account, we use a continuous-recognition paradigm to examine the forgetting rates words and nonwords that are either recollected or familiar. We find that words and nonwords that are recollected are equally likely to be forgotten over time. However, nonwords that are familiar are more likely to be forgotten over time than are words that are familiar. Our results support recent neuropsychologically-based forgetting theories of recollection and familiarity and provide new insight into how and why representations are forgotten over time.

Forgetting Patterns Differentiate Between Two Forms of Memory Representation.

For decades, there has been controversy about whether forgetting is caused by decay over time or by interference from irrelevant information. We suggest that forgetting occurs because of decay or interference, depending on the memory representation. Recollection-based memories, supported by the hippocampus, are represented in orthogonal patterns and are therefore relatively resistant to interference from one another. Decay should be a major source of their forgetting. By contrast, familiarity-based memories, supported by extrahippocampal structures, are not represented in orthogonal patterns and are therefore sensitive to interference. In a study in which we manipulated the postencoding task-interference level and the length of the delay between study and testing, we provide direct evidence in support of our representation theory of forgetting. Recollection and familiarity were measured using the remember/know procedure. We show that the causes of forgetting depend on the nature of the underlying memory representation, which places the century-old puzzle of forgetting in a coherent framework.

Remembered study mode: support for the distinctiveness account of the production effect.

The production effect is the finding that words spoken aloud at study are subsequently remembered better than are words read silently at study. According to the distinctiveness account, aloud words are remembered better because the act of speaking those words aloud is encoded and later recovery of this information can be used to infer that those words were studied. An alternative account (the strength-based account) is that memory strength is simply greater for words read aloud. To discriminate these two accounts, we investigated study mode judgements (i.e., "aloud"/"silent"/"new" ratings): The strength-based account predicts that "aloud" responses should positively correlate with memory strength, whereas the distinctiveness account predicts that accuracy of study mode judgements will be independent of memory strength. Across three experiments, where the strength of some silent words was increased by repetition, study mode was discriminable regardless of strength-even when the strength of aloud and repeated silent items was equivalent. Consistent with the distinctiveness account, we conclude that memory for "aloudness" is independent of memory strength and a likely candidate to explain the production effect.

How we forget may depend on how we remember.

Recent developments reveal that memories relying on the hippocampus are relatively resistant to interference, but sensitive to decay. The hippocampus is vital to recollection, a form of memory involving reinstatement of a studied item within its spatial-temporal context. An additional form of memory known as familiarity does not involve contextual reinstatement, but a feeling of acquaintance with the studied items. Familiarity depends more on extrahippocampal structures that do not have the properties promoting resistance to interference. These notions led to the novel hypothesis that the causes of forgetting depend on the memories' nature: memories depending on recollection are more vulnerable to decay than interference, whereas for memories depending on familiarity, the reverse is true. This review provides comprehensive evidence for this hypothesis.