Spatial context scaffolds long-term episodic richness of weaker real-world autobiographical memories in both older and younger adults.

Remembering life experiences involves recalling not only what occurred (episodic details), but also where an event took place (spatial context), both of which decline with age. Although spatial context can cue episodic detail recollection, it is unknown whether initially recalling an event alongside greater reinstatement of spatial context protects memory for episodic details in the long term, and whether this is affected by age. Here, we analysed 1079 personally-experienced, real-world events from 29 older adults and 12 younger adults. Events were recalled first on average 6 weeks after they occurred and then again on average 24 weeks after they occurred. We developed a novel scoring protocol to quantify spatial contextual details and used the established Autobiographical Interview to quantify episodic details. We found improved recall of episodic details after a delay if those details had initially been recalled situated in greater spatial context. Notably, for both older and younger adults, this preservation was observed for memories initially recalled with low, but not high, numbers of episodic details, suggesting that spatial context aided episodic retrieval for memories that required more support. This work supports the notion that spatial context scaffolds detail-rich event recollection and inspires memory interventions that leverage this spatial scaffold.

Experience transforms crossmodal object representations in the anterior temporal lobes.

Combining information from multiple senses is essential to object recognition, core to the ability to learn concepts, make new inferences, and generalize across distinct entities. Yet how the mind combines sensory input into coherent crossmodal representations - the crossmodal binding problem - remains poorly understood. Here, we applied multi-echo fMRI across a 4-day paradigm, in which participants learned three-dimensional crossmodal representations created from well-characterized unimodal visual shape and sound features. Our novel paradigm decoupled the learned crossmodal object representations from their baseline unimodal shapes and sounds, thus allowing us to track the emergence of crossmodal object representations as they were learned by healthy adults. Critically, we found that two anterior temporal lobe structures - temporal pole and perirhinal cortex - differentiated learned from non-learned crossmodal objects, even when controlling for the unimodal features that composed those objects. These results provide evidence for integrated crossmodal object representations in the anterior temporal lobes that were different from the representations for the unimodal features. Furthermore, we found that perirhinal cortex representations were by default biased toward visual shape, but this initial visual bias was attenuated by crossmodal learning. Thus, crossmodal learning transformed perirhinal representations such that they were no longer predominantly grounded in the visual modality, which may be a mechanism by which object concepts gain their abstraction.

Impaired perceptual discrimination of complex objects in older adults at risk for dementia.

Tau pathology accumulates in the perirhinal cortex (PRC) of the medial temporal lobe (MTL) during the earliest stages of the Alzheimer's disease (AD), appearing decades before clinical diagnosis. Here, we leveraged perceptual discrimination tasks that target PRC function to detect subtle cognitive impairment even in nominally healthy older adults. Older adults who did not have a clinical diagnosis or subjective memory complaints were categorized into "at-risk" (score <26; n = 15) and "healthy" (score ≥26; n = 23) groups based on their performance on the Montreal Cognitive Assessment. The task included two conditions known to recruit the PRC: faces and complex objects (greebles). A scene condition, known to recruit the hippocampus, and a size control condition that does not rely on the MTL were also included. Individuals in the at-risk group were less accurate than those in the healthy group for discriminating greebles. Performance on either the face or size control condition did not predict group status above and beyond that of the greeble condition. Visual discrimination tasks that are sensitive to PRC function may detect early cognitive decline associated with AD.

Older adults can use memory for distinctive objects, but not distinctive scenes, to rescue associative memory deficits.

Associative memory deficits in aging are frequently characterized by false recognition of novel stimulus associations, particularly when stimuli are similar. Introducing distinctive stimuli, therefore, can help guide item differentiation in memory and can further our understanding of how age-related brain changes impact behavior. How older adults use different types of distinctive information to distinguish overlapping events in memory and to avoid false associative recognition is still unknown. To test this, we manipulated the distinctiveness of items from two stimulus categories, scenes and objects, across three conditions: (1) distinct scenes paired with similar objects, (2) similar scenes paired with distinct objects, and (3) similar scenes paired with similar objects. Young and older adults studied scene-object pairs and then made both remember/know judgments toward single items as well as associative memory judgments to old and novel scene-object pairs ("Were these paired together?"). Older adults showed intact single item recognition of scenes and objects, regardless of whether those objects and scenes were similar or distinct. In contrast, relative to younger adults, older adults showed elevated false recognition for scene-object pairs, even when the scenes were distinct. These age-related associative memory deficits, however, disappeared if the pair contained an object that was visually distinct. In line with neural evidence that hippocampal functioning and scene processing decline with age, these results suggest that older adults can rely on memory for distinct objects, but not for distinct scenes, to distinguish between memories with overlapping features.

Sleep Differentially and Profoundly Impairs Recall Memory in a Patient with Fornix Damage.

In March 2020, C.T., a kind, bright, and friendly young woman underwent surgery for a midline tumor involving her septum pellucidum and extending down into her fornices bilaterally. Following tumor diagnosis and surgery, C.T. experienced significant memory deficits: C.T.'s family reported that she could remember things throughout the day, but when she woke up in the morning or following a nap, she would expect to be in the hospital, forgetting all the information that she had learned before sleep. The current study aimed to empirically validate C.T.'s pattern of memory loss and explore its neurological underpinnings. On two successive days, C.T. and age-matched controls watched an episode of a TV show and took a nap or stayed awake before completing a memory test. Although C.T. performed numerically worse than controls in both conditions, sleep profoundly exacerbated her memory impairment, such that she could not recall any details following a nap. This effect was replicated in a second testing session. High-resolution MRI scans showed evidence of the trans-callosal surgical approach's impact on the mid-anterior corpus callosum, indicated that C.T. had perturbed white matter particularly in the right fornix column, and demonstrated that C.T.'s hippocampal volumes did not differ from controls. These findings suggest that the fornix is important for processing episodic memories during sleep. As a key output pathway of the hippocampus, the fornix may ensure that specific memories are replayed during sleep, maintain the balance of sleep stages, or allow for the retrieval of memories following sleep.

Perception and Memory in the Ventral Visual Stream and Medial Temporal Lobe.

Perception and memory are traditionally thought of as separate cognitive functions, supported by distinct brain regions. The canonical perspective is that perceptual processing of visual information is supported by the ventral visual stream, whereas long-term declarative memory is supported by the medial temporal lobe. However, this modular framework cannot account for the increasingly large body of evidence that reveals a role for early visual areas in long-term recognition memory and a role for medial temporal lobe structures in high-level perceptual processing. In this article, we review relevant research conducted in humans, nonhuman primates, and rodents. We conclude that the evidence is largely inconsistent with theoretical proposals that draw sharp functional boundaries between perceptual and memory systems in the brain. Instead, the weight of the empirical findings is best captured by a representational-hierarchical model that emphasizes differences in content, rather than in cognitive processes within the ventral visual stream and medial temporal lobe.

Resolving Cross-modal Semantic Interference among Object Concepts Requires Medial Temporal Lobe Cortex.

The ability to flexibly categorize object concepts is essential to semantic cognition because the features that make two objects similar in one context may be irrelevant and even constitute interference in another. Thus, adaptive behavior in complex and dynamic environments requires the resolution of feature-based interference. In the current case study, we placed visual and functional semantic features in opposition across object concepts in two categorization tasks. Successful performance required the resolution of functional interference in a visual categorization task and the resolution of visual interference in a functional categorization task. In Experiment 1, we found that patient D. A., an individual with bilateral temporal lobe lesions, was unable to categorize object concepts in a context-dependent manner. His impairment was characterized by an increased tendency to incorrectly group objects that were similar on the task-irrelevant dimension, revealing an inability to resolve cross-modal semantic interference. In Experiment 2, D. A.'s categorization accuracy was comparable to controls when lures were removed, indicating that his impairment is unique to contexts that involve cross-modal interference. In Experiment 3, he again performed as well as controls when categorizing simple concepts, suggesting that his impairment is specific to categorization of complex object concepts. These results advance our understanding of the anterior temporal lobe as a system that represents object concepts in a manner that enables flexible semantic cognition. Specifically, they reveal a dissociation between semantic representations that contribute to the resolution of cross-modal interference and those that contribute to the resolution of interference within a given modality.

The effect of memory load on object reconstruction: Insights from an online mouse-tracking task.

Why can't we remember everything that we experience? Previous work in the domain of object memory has suggested that our ability to resolve interference between relevant and irrelevant object features may limit how much we can remember at any given moment. Here, we developed an online mouse-tracking task to study how memory load influences object reconstruction, testing participants synchronously over virtual conference calls. We first tested up to 18 participants concurrently, replicating memory findings from a condition where participants were tested individually. Next, we examined how memory load influenced mouse trajectories as participants reconstructed target objects. We found interference between the contents of working memory and what was perceived during object reconstruction, an effect that interacted with visual similarity and memory load. Furthermore, we found interference from previously studied but currently irrelevant objects, providing evidence of object-to-location binding errors. At the greatest memory load, participants were nearly three times more likely to move their mouse cursor over previously studied nontarget objects, an effect observed primarily during object reconstruction rather than in the period before the final response. As evidence of the dynamic interplay between working memory and perception, these results show that object reconstruction behavior may be altered by (i) interference between what is represented in mind and what is currently being viewed, and (ii) interference from previously studied but currently irrelevant information. Finally, we discuss how mouse tracking can provide a rich characterization of participant behavior at millisecond temporal resolution, enormously increasing power in cognitive psychology experiments.

Single voxel autocorrelation uncovers gradients of temporal dynamics in the hippocampus and entorhinal cortex during rest and navigation.

During navigation, information at multiple scales needs to be integrated. Single-unit recordings in rodents suggest that gradients of temporal dynamics in the hippocampus and entorhinal cortex support this integration. In humans, gradients of representation are observed, such that granularity of information represented increases along the long axis of the hippocampus. The neural underpinnings of this gradient in humans, however, are still unknown. Current research is limited by coarse fMRI analysis techniques that obscure the activity of individual voxels, preventing investigation of how moment-to-moment changes in brain signal are organized and how they are related to behavior. Here, we measured the signal stability of single voxels over time to uncover previously unappreciated gradients of temporal dynamics in the hippocampus and entorhinal cortex. Using our novel, single voxel autocorrelation technique, we show a medial-lateral hippocampal gradient, as well as a continuous autocorrelation gradient along the anterolateral-posteromedial entorhinal extent. Importantly, we show that autocorrelation in the anterior-medial hippocampus was modulated by navigational difficulty, providing the first evidence that changes in signal stability in single voxels are relevant for behavior. This work opens the door for future research on how temporal gradients within these structures support the integration of information for goal-directed behavior.

The impact of aging and repetition on eye movements and recognition memory.

The modulation of gaze fixations on neural activity in the hippocampus, a region critical for memory, has been shown to be weaker in older adults compared to younger adults. However, as such research has relied on indirect measures of memory, it remains unclear whether the relationship between visual exploration and direct measures of memory is similarly disrupted in aging. The current study tested older and younger adults on a face memory eye-tracking task previously used by our group that showed that recognition memory for faces presented across variable, but not fixed, viewpoints relies on a hippocampal-dependent binding function. Here, we examined how aging influences eye movement measures that reveal the amount (cumulative sampling) and extent (distribution of gaze fixations) of visual exploration. We also examined how aging influences direct (subsequent conscious recognition) and indirect (eye movement repetition effect) expressions of memory. No age differences were found in direct recognition regardless of facial viewpoint. However, the eye movement measures revealed key group differences. Compared to younger adults, older adults exhibited more cumulative sampling, a different distribution of fixations, and a larger repetition effect. Moreover, there was a positive relationship between cumulative sampling and direct recognition in younger adults, but not older adults. Neither age group showed a relationship between the repetition effect and direct recognition. Thus, despite similar direct recognition, age-related differences were observed in visual exploration and in an indirect eye-movement memory measure, suggesting that the two groups may acquire, retain, and use different facial information to guide recognition.

A smartphone intervention that enhances real-world memory and promotes differentiation of hippocampal activity in older adults.

The act of remembering an everyday experience influences how we interpret the world, how we think about the future, and how we perceive ourselves. It also enhances long-term retention of the recalled content, increasing the likelihood that it will be recalled again. Unfortunately, the ability to recollect event-specific details and reexperience the past tends to decline with age. This decline in recollection may reflect a corresponding decrease in the distinctiveness of hippocampal memory representations. Despite these well-established changes, there are few effective cognitive behavioral interventions that target real-world episodic memory. We addressed this gap by developing a smartphone-based application called HippoCamera that allows participants to record labeled videos of everyday events and subsequently replay, high-fidelity autobiographical memory cues. In two experiments, we found that older adults were able to easily integrate this noninvasive intervention into their daily lives. Using HippoCamera to repeatedly reactivate memories for real-world events improved episodic recollection and it evoked more positive autobiographical sentiment at the time of retrieval. In both experiments, these benefits were observed shortly after the intervention and again after a 3-mo delay. Moreover, more detailed recollection was associated with more differentiated memory signals in the hippocampus. Thus, using this smartphone application to systematically reactivate memories for recent real-world experiences can help to maintain a bridge between the present and past in older adults.

Independent features form integrated objects: Using a novel shape-color "conjunction task" to reconstruct memory resolution for multiple object features simultaneously.

Though much progress has been made to understand feature integration, debate remains regarding how objects are represented in mind based on their constituent features. Here, we advance this debate by introducing a novel shape-color "conjunction task" to reconstruct memory resolution for multiple object features simultaneously. In a first experiment, we replicate and extend a classic paradigm originally tested using a change detection task. Replicating previous work, memory resolution for individual features was reduced when the number of objects increased, regardless of the number of to-be-remembered features. Extending previous work, we found that high resolution memory near perfect in resemblance to the target was selectively impacted by the number of to-be-remembered features. Applying a data-driven statistical model of stochastic dependence, we found robust evidence of integration for lower-resolution feature memories, but less evidence for integration of high-resolution feature memories. These results suggest that memory resolution for individual features can be higher than memory resolution for their integration. In a second experiment which manipulated the nature of distracting information, we examined whether object features were directly bound to each other or by virtue of shared spatial location. Feature integration was disrupted by distractors sharing visual features of target objects but not when distractors shared spatial location - suggesting that feature integration can be driven by direct binding between shape and color features in memory. Our results constrain theoretical models of object representation, providing empirical support for hierarchical representations of both integrated and independent features.

Prediction errors disrupt hippocampal representations and update episodic memories.

The brain supports adaptive behavior by generating predictions, learning from errors, and updating memories to incorporate new information. Prediction error, or surprise, triggers learning when reality contradicts expectations. Prior studies have shown that the hippocampus signals prediction errors, but the hypothesized link to memory updating has not been demonstrated. In a human functional MRI study, we elicited mnemonic prediction errors by interrupting familiar narrative videos immediately before the expected endings. We found that prediction errors reversed the relationship between univariate hippocampal activation and memory: greater hippocampal activation predicted memory preservation after expected endings, but memory updating after surprising endings. In contrast to previous studies, we show that univariate activation was insufficient for understanding hippocampal prediction error signals. We explain this surprising finding by tracking both the evolution of hippocampal activation patterns and the connectivity between the hippocampus and neuromodulatory regions. We found that hippocampal activation patterns stabilized as each narrative episode unfolded, suggesting sustained episodic representations. Prediction errors disrupted these sustained representations and the degree of disruption predicted memory updating. The relationship between hippocampal activation and subsequent memory depended on concurrent basal forebrain activation, supporting the idea that cholinergic modulation regulates attention and memory. We conclude that prediction errors create conditions that favor memory updating, prompting the hippocampus to abandon ongoing predictions and make memories malleable.

Flexible Use of Spatial Frames of Reference for Object-Location Memory in Older Adults.

In memory, representations of spatial features are stored in different reference frames; features relative to our position are stored egocentrically and features relative to each other are stored allocentrically. Accessing these representations engages many cognitive and neural resources, and so is susceptible to age-related breakdown. Yet, recent findings on the heterogeneity of cognitive function and spatial ability in healthy older adults suggest that aging may not uniformly impact the flexible use of spatial representations. These factors have yet to be explored in a precisely controlled task that explicitly manipulates spatial frames of reference across learning and retrieval. We used a lab-based virtual reality task to investigate the relationship between object-location memory across frames of reference, cognitive status, and self-reported spatial ability. Memory error was measured using Euclidean distance from studied object locations to participants' responses at testing. Older adults recalled object locations less accurately when they switched between frames of reference from learning to testing, compared with when they remained in the same frame of reference. They also showed an allocentric learning advantage, producing less error when switching from an allocentric to an egocentric frame of reference, compared with the reverse direction of switching. Higher MoCA scores and better self-assessed spatial ability predicted less memory error, especially when learning occurred egocentrically. We suggest that egocentric learning deficits are driven by difficulty in binding multiple viewpoints into a coherent representation. Finally, we highlight the heterogeneity of spatial memory performance in healthy older adults as a potential cognitive marker for neurodegeneration, beyond normal aging.

Perception and memory in the medial temporal lobe: Deep learning offers a new lens on an old debate.

In this issue of Neuron, Bonnen et al. (2021) use artificial neural networks to resolve a long-standing controversy surrounding the neurocognitive dichotomy between memory and perception. They show that the perirhinal cortex supports performance on tasks that cannot be solved by the ventral visual stream.

Visual working memory and sensory processing in autistic children.

While atypical sensory processing is one of the more ubiquitous symptoms in autism spectrum disorder, the exact nature of these sensory issues remains unclear, with different studies showing either enhanced or deficient sensory processing. Using a well-established continuous cued-recall task that assesses visual working memory, the current study provides novel evidence reconciling these apparently discrepant findings. Autistic children exhibited perceptual advantages in both likelihood of recall and recall precision relative to their typically-developed peers. When autistic children did make errors, however, they showed a higher probability of erroneously binding a given colour with the incorrect spatial location. These data align with neural-architecture models for feature binding in visual working memory, suggesting that atypical population-level neural noise in the report dimension (colour) and cue dimension (spatial location) may drive both the increase in probability of recall and precision of colour recall as well as the increase in proportion of binding errors when making an error, respectively. These changes are likely to impact core symptomatology associated with autism, as perceptual binding and working memory play significant roles in higher-order tasks, such as communication.

Reframing spatial frames of reference: What can aging tell us about egocentric and allocentric navigation?

Representations of space in mind are crucial for navigation, facilitating processes such as remembering landmark locations, understanding spatial relationships between objects, and integrating routes. A significant problem, however, is the lack of consensus on how these representations are encoded and stored in memory. Specifically, the nature of egocentric and allocentric frames of reference in human memory is widely debated. Yet, in recent investigations of the spatial domain across the lifespan, these distinctions in mnemonic spatial frames of reference have identified age-related impairments. In this review, we survey the ways in which different terms related to spatial representations in memory have been operationalized in past aging research and suggest a taxonomy to provide a common language for future investigations and theoretical discussion. This article is categorized under: Psychology > Memory Neuroscience > Cognition Psychology > Development and Aging.

Integration and differentiation of hippocampal memory traces.

Prevailing theories of hippocampal function argue that memories are rapidly encoded by non-overlapping memory traces. Concurrently, the hippocampus has been argued to integrate across related experiences, enabling generalization. The cognitive neuroscience of memory has been transformed by the recent proliferation of studies using pattern similarity analyses to investigate the neural substrates of memory in humans, marking an exciting and significant advance in our understanding of population-level neural representations. We provide an overview of hippocampal pattern similarity studies published to date. By considering the effects of stimulus type, time-scale, and hippocampal subregions, we account for both increases and decreases in representational similarity. We argue that hippocampal representations for related memories are not fixed. Instead, the evoked representations are flexibly modulated, depending on whether the current goal is to extract generalities or to reinstate specific experiences. In the first comprehensive review of hippocampal pattern similarity analyses, we provide insight into the mechanisms of memory representation and implications for the interpretation of pattern similarity more generally.

Experience Transforms Conjunctive Object Representations: Neural Evidence for Unitization After Visual Expertise.

Certain transformations must occur within the brain to allow rapid processing of familiar experiences. Complex objects are thought to become unitized, whereby multifeature conjunctions are retrieved as rapidly as a single feature. Behavioral studies strongly support unitization theory, but a compelling neural mechanism is lacking. Here, we examined how unitization transforms conjunctive representations to become more "feature-like" by recruiting posterior regions of the ventral visual stream (VVS) whose architecture is specialized for processing single features. We used functional magnetic resonance imaging to scan humans before and after visual training with novel objects. We implemented a novel multivoxel pattern analysis to measure a conjunctive code, which represented a conjunction of object features above and beyond the sum of the parts. Importantly, a multivoxel searchlight showed that the strength of conjunctive coding in posterior VVS increased posttraining. Furthermore, multidimensional scaling revealed representational separation at the level of individual features in parallel to the changes at the level of feature conjunctions. Finally, functional connectivity between anterior and posterior VVS was higher for novel objects than for trained objects, consistent with early involvement of anterior VVS in unitizing feature conjunctions in response to novelty. These data demonstrate that the brain implements unitization as a mechanism to refine complex object representations over the course of multiple learning experiences.

Resting State BOLD Variability of the Posterior Medial Temporal Lobe Correlates with Cognitive Performance in Older Adults with and without Risk for Cognitive Decline.

Local brain signal variability [SD of the BOLD signal (SDBOLD]] correlates with age and cognitive performance, and recently differentiated Alzheimer's disease (AD) patients from healthy controls. However, it is unknown whether changes to SDBOLD precede diagnosis of AD or mild cognitive impairment. We compared ostensibly healthy older adult humans who scored below the recommended threshold on the Montreal cognitive assessment (MoCA) and who showed reduced medial temporal lobe (MTL) volume in a previous study ("at-risk" group, n = 20), with healthy older adults who scored within the normal range on the MoCA ("control" group, n = 20). Using multivariate partial least-squares analysis we assessed the correlations between SDBOLD and age, MoCA score, global fractional anisotropy, global mean diffusivity, and four cognitive factors. Greater SDBOLD in the MTL and occipital cortex positively correlated with performance on cognitive control/speed tasks but negatively correlated with memory scores in the control group. These relations were weaker in the at-risk group. A post hoc analysis assessed associations between MTL volumes and SDBOLD in both groups. This revealed a negative correlation, most robust in the at-risk group, between MTL SDBOLD and MTL subregion volumetry, particularly the entorhinal and parahippocampal regions. Together, these results suggest that the association between SDBOLD and cognition differs between the at-risk and control groups, which may be because of lower MTL volumes in the at-risk group. Our data indicate relations between MTL SDBOLD and cognition may be helpful in understanding brain differences in individuals who may be at risk for further cognitive decline.