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Reactivation of earlier perceptual activity is thought to underlie long-term memory recall. Despite evidence for this view, it is unclear whether mnemonic activity exhibits the same tuning properties as feedforward perceptual activity. Here, we leverage population receptive field models to parameterize fMRI activity in human visual cortex during spatial memory retrieval. Though retinotopic organization is present during both perception and memory, large systematic differences in tuning are also evident. Whereas there is a three-fold decline in spatial precision from early to late visual areas during perception, this pattern is not observed during memory retrieval. This difference cannot be explained by reduced signal-to-noise or poor performance on memory trials. Instead, by simulating top-down activity in a network model of cortex, we demonstrate that this property is well explained by the hierarchical structure of the visual system. Together, modeling and empirical results suggest that computational constraints imposed by visual system architecture limit the fidelity of memory reactivation in sensory cortex.

Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. We tested this idea using high-resolution, pattern-based fMRI analyses. Here we show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. The magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide insight into why remapping occurs., When two memories are similar, their encoding and retrieval can be disrupted by each other. Here the authors show that memory interference is resolved through abrupt remapping of activity patterns in the human hippocampal CA3 and dentate gyrus.

Reactivation refers to the phenomenon wherein patterns of neural activity expressed during perceptual experience are re-expressed at a later time, a putative neural marker of memory. Reactivation of perceptual content has been observed across many cortical areas and correlates with objective and subjective expressions of memory in humans. However, because reactivation emphasizes similarities between perceptual and memory-based representations, it obscures differences in how perceptual events and memories are represented. Here, we highlight recent evidence of systematic differences in how (and where) perceptual events and memories are represented in the brain. We argue that neural representations of memories are best thought of as spatially transformed versions of perceptual representations. We consider why spatial transformations occur and identify critical questions for future research.

Remapping refers to a decorrelation of hippocampal representations of similar spatial environments. While it has been speculated that remapping may contribute to the resolution of episodic memory interference in humans, direct evidence is surprisingly limited. Here, we tested this idea using high-resolution, pattern-based fMRI analyses. We show that activity patterns in human CA3/dentate gyrus exhibit an abrupt, temporally-specific decorrelation of highly similar memory representations that is precisely coupled with behavioral expressions of successful learning. Strikingly, the magnitude of this learning-related decorrelation was predicted by the amount of pattern overlap during initial stages of learning, with greater initial overlap leading to stronger decorrelation. Finally, we show that remapped activity patterns carry relatively more information about learned episodic associations compared to competing associations, further validating the learning-related significance of remapping. Collectively, these findings establish a critical link between hippocampal remapping and episodic memory interference and provide novel insight into why remapping occurs.

The hippocampus (HC) and surrounding medial temporal lobe (MTL) cortical regions play a critical role in spatial navigation and episodic memory. However, it remains unclear how the interaction between the HC’s conjunctive coding and mnemonic differentiation contributes to neural representations of spatial environments. Multivariate functional magnetic resonance imaging (fMRI) analyses enable examination of how human HC and MTL cortical regions encode multidimensional spatial information to support memory-guided navigation. We combined high-resolution fMRI with a virtual navigation paradigm in which participants relied on memory of the environment to navigate to goal locations in two different virtual rooms. Within each room, participants were cued to navigate to four learned locations, each associated with one of two reward values. Pattern similarity analysis revealed that when participants successfully arrived at goal locations, activity patterns in HC and parahippocampal cortex (PHC) represented room-goal location conjunctions and activity patterns in HC subfields represented room-reward-location conjunctions. These results add to an emerging literature revealing hippocampal conjunctive representations during goal-directed behavior.

Mental representation of the future is a fundamental component of goal-directed behavior. Computational and animal models highlight prospective spatial coding in the hippocampus, mediated by interactions with the prefrontal cortex, as a putative mechanism for simulating future events. Using whole-brain high-resolution functional magnetic resonance imaging and multi-voxel pattern classification, we tested whether the human hippocampus and interrelated cortical structures support prospective representation of navigational goals. Results demonstrated that hippocampal activity patterns code for future goals to which participants subsequently navigate, as well as for intervening locations along the route, consistent with trajectory-specific simulation. The strength of hippocampal goal representations covaried with goal-related coding in the prefrontal, medial temporal, and medial parietal cortex. Collectively, these data indicate that a hippocampal-cortical network supports prospective simulation of navigational events during goal-directed planning.

In studies of human episodic memory, the phenomenon of reactivation has traditionally been observed in regions of occipitotemporal cortex (OTC) involved in visual perception. However, reactivation also occurs in lateral parietal cortex (LPC), and recent evidence suggests that stimulus-specific reactivation may be stronger in LPC than in OTC. These observations raise important questions about the nature of memory representations in LPC and their relationship to representations in OTC. Here, we report two fMRI experiments that quantified stimulus feature information (color and object category) within LPC and OTC, separately during perception and memory retrieval, in male and female human subjects. Across both experiments, we observed a clear dissociation between OTC and LPC: while feature information in OTC was relatively stronger during perception than memory, feature information in LPC was relatively stronger during memory than perception. Thus, while OTC and LPC represented common stimulus features in our experiments, they preferentially represented this information during different stages. In LPC, this bias toward mnemonic information co-occurred with stimulus-level reinstatement during memory retrieval. In Experiment 2, we considered whether mnemonic feature information in LPC was flexibly and dynamically shaped by top-down retrieval goals. Indeed, we found that dorsal LPC preferentially represented retrieved feature information that addressed the current goal. In contrast, ventral LPC represented retrieved features independent of the current goal. Collectively, these findings provide insight into the nature and significance of mnemonic representations in LPC and constitute an important bridge between putative mnemonic and control functions of parietal cortex. SIGNIFICANCE STATEMENT When humans remember an event from the past, patterns of sensory activity that were present during the initial event are thought to be reactivated. Here, we investigated the role of lateral parietal cortex (LPC), a high-level region of association cortex, in representing prior visual experiences. We find that LPC contained stronger information about stimulus features during memory retrieval than during perception. We also found that current task goals influenced the strength of stimulus feature information in LPC during memory. These findings suggest that, in addition to early sensory areas, high-level areas of cortex, such as LPC, represent visual information during memory retrieval, and that these areas may play a special role in flexibly aligning memories with current goals.

Older adults experience impairments in episodic memory, ranging from mild to clinically significant. Given the critical role of the medial temporal lobe (MTL) in episodic memory, age-related changes in MTL structure and function may partially account for individual differences in memory. Using ultra-high-field 7T structural MRI and high-resolution 3T functional MRI (hr-fMRI), we evaluated MTL subfield thickness and function in older adults representing a spectrum of cognitive health. Participants performed an associative memory task during hr-fMRI in which they encoded and later retrieved face-name pairs. Motivated by prior research, we hypothesized that differences in performance would be explained by the following: (i) entorhinal cortex (ERC) and CA1 apical neuropil layer [CA1-stratum radiatum lacunosum moleculare (SRLM)] thickness, and (ii) activity in ERC and the dentate gyrus (DG)/CA3 region. Regression analyses revealed that this combination of factors significantly accounted for variability in memory performance. Among these metrics, CA1-SRLM thickness was positively associated with memory, whereas DG/CA3 retrieval activity was negatively associated with memory. Furthermore, including structural and functional metrics in the same model better accounted for performance than did single-modality models. These results advance the understanding of how independent but converging influences of both MTL subfield structure and function contribute to age-related memory impairment, complementing findings in the rodent and human postmortem literatures.

Summary Across the domains of spatial navigation and episodic memory, the hippocampus is thought to play a critical role in disambiguating (pattern separating) representations of overlapping events. However, it is not fully understood how and why hippocampal patterns become separated. Here, we test the idea that event overlap triggers a "repulsion" among hippocampal representations that develops over the course of learning. Using a naturalistic route-learning paradigm and spatiotemporal pattern analysis of human fMRI data, we found that hippocampal representations of overlapping routes gradually diverged with learning to the point that they became less similar than representations of non-overlapping events. In other words, the hippocampus not only disambiguated overlapping events but formed representations that "reversed" the objective similarity among routes. This finding, which was selective to the hippocampus, is not predicted by standard theoretical accounts of pattern separation. Critically, because the overlapping route stimuli that we used ultimately diverged (so that each route contained overlapping and non-overlapping segments), we were able to test whether the reversal effect was selective to the overlapping segments. Indeed, once overlapping routes diverged (eliminating spatial and visual similarity), hippocampal representations paradoxically became relatively more similar . Finally, using a novel analysis approach, we show that the degree to which individual hippocampal voxels were initially shared across route representations was predictive of the magnitude of learning-related separation. Collectively, these findings indicate that event overlap triggers a repulsion of hippocampal representations—a finding that provides critical mechanistic insight into how and why hippocampal representations become separated.

MMSE1⁄428.58) from the Rush Memory and Aging Project, a clinical-pathological cohort study of aging and dementia, were scanned using restingstate functional MRI. Financial literacy was assessed using a series of questions imbedded as part of an ongoing decision making study. A 4 mm radius spherical seed region of interest (ROI) was prescribed in the posterior cingulate cortex (x1⁄40, y1⁄4-53, z1⁄426) after removal of 6 head motion parameters, white matter signal, global mean signal, and cerebrospinal fluid as nuisance variables. Results: After adjusting for age, education, sex, and global cognition, and correcting for multiple comparisons, analyses revealed significant associations (AlphaSim cluster level p

A study in this issue of Nature Neuroscience reports that administering caffeine to humans immediately after memory encoding enhances consolidation, as reflected by improved performance in a memory test a day later.