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Even partly consolidated memories can be forgotten given sufficient time, but the brain activity associated with durability of episodic memory at different time scales remains unclear. Here, we aimed to identify brain activity associated with retrieval of partly consolidated episodic memories that continued to be remembered in the future. Forty-nine younger (20 to 38 years; 25 females) and 43 older adults (60 to 80 years, 25 females) were scanned with functional magnetic resonance imaging during associative memory retrieval 12 h post-encoding. Twelve hours is sufficient to allow short-term synaptic consolidation as well as early post-encoding replay to initiate memory consolidation. Successful memory trials were classified into durable and transient source memories based on responses from a memory test ~6 d post-encoding. Results demonstrated that successful retrieval of future durable vs. transient memories was supported by increased activity in a medial prefrontal and ventral parietal area. Individual differences in activation as well as the subjective vividness of memories during encoding were positively related to individual differences in memory performance after 6 d. The results point to a unique and novel aspect of brain activity supporting long-term memory, in that activity during retrieval of memories even after 12 h of consolidation contains information about potential for long-term durability., (© The Author(s) 2024. Published by Oxford University Press.)

Memory encoding and retrieval are critical sub-processes of episodic memory. While the hippocampus is involved in both, less is known about its connectivity with the neocortex during memory processing in humans. This is partially due to variations in demands in common memory tasks, which inevitably recruit cognitive processes other than episodic memory. Conjunctive analysis of data from different tasks with the same core elements of encoding and retrieval can reduce the intrusion of patterns related to subsidiary perceptual and cognitive processing. Leveraging data from two large-scale functional resonance imaging studies with different episodic memory tasks (514 and 237 participants), we identified hippocampal-cortical networks active during memory tasks. Whole-brain functional connectivity maps were similar during resting state, encoding, and retrieval. Anterior and posterior hippocampus had distinct connectivity profiles, which were also stable across resting state and memory tasks. When contrasting encoding and retrieval connectivity, conjunctive encoding-related connectivity was sparse. During retrieval hippocampal connectivity was increased with areas known to be active during recollection, including medial prefrontal, inferior parietal, and parahippocampal cortices. This indicates that the stable functional connectivity of the hippocampus along its longitudinal axis is superposed by increased functional connectivity with the recollection network during retrieval, while auxiliary encoding connectivity likely reflects contextual factors., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Systems consolidation of new experiences into lasting episodic memories involves hippocampal-neocortical interactions. Evidence of this process is already observed during early post-encoding rest periods, both as increased hippocampal coupling with task-relevant perceptual regions and reactivation of stimulus-specific patterns following intensive encoding tasks. We investigate the spatial and temporal characteristics of these hippocampally anchored post-encoding neocortical modulations. Eighty-nine adults participated in an experiment consisting of interleaved memory task- and resting-state periods. We observed increased post-encoding functional connectivity between hippocampus and individually localized neocortical regions responsive to stimuli encountered during memory encoding. Post-encoding modulations were manifested as a nearly system-wide upregulation in hippocampal coupling with all major functional networks. The configuration of these extensive modulations resembled hippocampal-neocortical interaction patterns estimated from active encoding operations, suggesting hippocampal post-encoding involvement exceeds perceptual aspects. Reinstatement of encoding patterns was not observed in resting-state scans collected 12 h later, nor when using other candidate seed regions. The similarity in hippocampal functional coupling between online memory encoding and offline post-encoding rest suggests reactivation in humans involves a spectrum of cognitive processes engaged during the experience of an event. There were no age effects, suggesting that upregulation of hippocampal-neocortical connectivity represents a general phenomenon seen across the adult lifespan., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Encoding of durable episodic memories requires cross-talk between the hippocampus and multiple brain regions. Changes in these hippocampal interactions could contribute to age-related declines in the ability to form memories that can be retrieved after extended time intervals. Here we tested whether hippocampal-neocortical- and subcortical functional connectivity (FC) observed during encoding of durable episodic memories differed between younger and older adults. About 48 younger (20-38 years; 25 females) and 43 older (60-80 years; 25 females) adults were scanned with fMRI while performing an associative memory encoding task. Source memory was tested ~20 min and ~6 days postencoding. Associations recalled after 20 min but later forgotten were classified as transient, whereas memories retained after long delays were classified as durable. Results demonstrated that older adults showed a reduced ability to form durable memories and reduced hippocampal-caudate FC during encoding of durable memories. There was also a positive relationship between hippocampal-caudate FC and higher memory performance among the older adults. No reliable age group differences in durable memory-encoding activity or hippocampal-neocortical connectivity were observed. These results support the classic theory of striatal alterations as one cause of cognitive decline in aging and highlight that age-related changes in episodic memory extend beyond hippocampal-neocortical connections., (© The Author(s) 2021. Published by Oxford University Press.)

It has been suggested that specific forms of cognition in older age rely largely on late-life specific mechanisms. Here instead, we tested using task-fMRI (n = 540, age 6-82 years) whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural, and evolutionary influences. We clustered regions of the cerebral cortex according to the shape of the lifespan trajectory of memory activity in each region so that regions showing the same pattern were clustered together. The results revealed that lifespan trajectories of memory encoding function showed a continuity through life but no evidence of age-specific mechanisms such as compensatory patterns. Encoding activity was related to general cognitive abilities and variations of grey matter as captured by a multi-modal independent component analysis, variables reflecting core aspects of cognitive and structural change throughout the lifespan. Furthermore, memory encoding activity aligned to fundamental aspects of brain organization, such as large-scale connectivity and evolutionary cortical expansion gradients. Altogether, we provide novel support for a perspective on memory aging in which maintenance and decay of episodic memory in older age needs to be understood from a comprehensive life-long perspective rather than as a late-life phenomenon only., (© The Author(s) 2020. Published by Oxford University Press.)

Change in hippocampal function is a major factor in life span development and decline of episodic memory. Evidence indicates a long-axis specialization where anterior hippocampus is more engaged during encoding than during retrieval, and posterior more engaged during retrieval than during encoding. We tested the life span trajectory of hippocampal long-axis episodic memory-related activity and functional connectivity (FC) in 496 participants (6.8-80.8 years) encoding and retrieving associative memories. We found evidence for a long-axis encoding-retrieval specialization that declined linearly during development and aging, eventually vanishing in the older adults. This was mainly driven by age effects on retrieval, which was associated with gradually lower activity from childhood to adulthood, followed by positive age relationships until 70 years. This pattern of age effects characterized task engagement regardless of memory success or failure. Especially for retrieval, children engaged posterior hippocampus more than anterior, while anterior was relatively more activated already in teenagers. Significant intrahippocampal connectivity was found during task, which declined with age. The results suggest that hippocampal long-axis differentiation and communication during episodic memory tasks develop rapidly during childhood, are different in older compared with younger adults, and that the age effects are related to task engagement, not the successful retrieval of episodic memories specifically., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Aging is characterized by substantial average decline in memory performance. Yet contradictory explanations have been given for how the brains of high-performing older adults work: either by engagement of compensatory processes such as recruitment of additional networks or by maintaining young adults' patterns of activity. Distinguishing these components requires large experimental samples and longitudinal follow-up. Here, we investigate which features are key to high memory in aging, directly testing these hypotheses by studying a large sample of adult participants (n > 300) with fMRI during an episodic memory experiment where item-context relationships were implicitly encoded. The analyses revealed that low levels of activity in frontal networks-known to be involved in memory encoding-were associated with low memory performance in the older adults only. Importantly, older participants with low memory performance and low frontal activity exhibited a strong longitudinal memory decline in an independent verbal episodic memory task spanning 8 years back (n = 52). These participants were also characterized by lower hippocampal volumes and steeper rates of cortical atrophy. Altogether, maintenance of frontal brain function during encoding seems to be a primary characteristic of preservation of memory function in aging, likely reflecting intact ability to integrate information., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Variations in levels of processing affect memory encoding and subsequent retrieval performance, but it is unknown how processing depth affects communication patterns within the network of interconnected brain regions involved in episodic memory encoding. In 113 healthy adults scanned with functional MRI, we used graph theory to calculate centrality indices representing the brain regions' relative importance in the memory network. We tested how communication patterns in 42 brain regions involved in episodic memory encoding changed as a function of processing depth, and how these changes were related to episodic memory ability. Centrality changes in right middle frontal gyrus, right inferior parietal lobule and left superior frontal gyrus were positively related to semantic elaboration during encoding. In the same regions, centrality during successful episodic memory encoding was related to performance on the episodic memory task, indicating that these centrality changes reflect processes that support memory encoding through deep elaborative processing. Similar analyses were performed for congruent trials, i.e. events that fit into existing knowledge structures, but no relationship between centrality changes and congruity were found. The results demonstrate that while elaboration and congruity have similar beneficial effects on source memory performance, the cortical signatures of these processes are probably not identical.

Episodic memory can be trained in both early and late adulthood, but there is considerable variation in cognitive improvement across individuals. Which brain characteristics make some individuals benefit more than others? We used a multimodal approach to investigate whether volumetric magnetic resonance imaging (MRI) and resting-state functional MRI characteristics of the cortex and hippocampus, brain regions involved in episodic-memory function, were predictive of cognitive improvement after memory training. We hypothesized that these brain characteristics would differentially predict memory improvement in young and older adults, given the vulnerability of cortical regions as well as the hippocampus to healthy aging. Following structural and resting-state activity magnetic resonance scans, 50 young and 76 older participants completed 10 weeks of strategic episodic-memory training. Both age groups improved their memory performance, but the young adults more so than the older. Vertex-wise analyses of cortical volume showed no significant relation to memory benefit. When analyzing the two age groups separately, hippocampal volume was predictive of memory improvement in the group of older participants only. In this age group, the lower resting-state activity of the hippocampus was also predictive of memory improvement. Both volumetric and resting-state characteristics of the hippocampus explained unique variance of the improvement in the older participants suggesting that a multimodal imaging approach is valuable for the understanding of mechanisms underlying memory plasticity in aging., (© 2018 Wiley Periodicals, Inc.)

The formation of episodic memories is associated with deactivation during encoding and activation during retrieval in the posteromedial cortex (PMC). We hypothesized that the encoding/retrieval (E/R) flip is a critical component of episodic memory across the lifespan because structural and metabolic changes in the PMC coincide with the fine tuning of the episodic memory system in development and the reductions of memory performance in aging. The aims of the present study were, first, to describe lifespan trajectories of PMC encoding and retrieval activity in 270 human participants (167 females) from 6 to 80 years of age. Our second goal was to construct a model for episodic memory development in which contributions from brain activity, cortical thickness (CT), and structural connectivity are accounted for. We found that modulation of neural activity in response to memory encoding and retrieval demands was not fully developed until adolescence and decreased from adulthood through old age. The magnitude of the E/R flip was related to source memory and 55% of the age-related variance in source memory performance during childhood and adolescence could be accounted for by the E/R flip, CT, and mean diffusivity together. However, only CT and the E/R flip provided unique contributions with which to explain memory performance. The results suggest that neural dynamics in the PMC is related to the development of episodic memory during childhood and adolescence. The similar trajectories of the E/R flip and episodic memory emergence and decline through development and aging further suggests that a lifelong relationship exists. SIGNIFICANCE STATEMENT Modulation of neural activity in the posteromedial cortex (PMC) in response to memory encoding/retrieval (E/R) demands (E/R flip) does not reach its peak until adolescence and decreases from adulthood through old age. The magnitude of the E/R flip is related to source memory and 55% of the age-related variance in source memory performance during childhood and adolescence can be accounted for by the E/R flip and brain structure together. The results suggest that neural dynamics in the PMC is related to the development of episodic memory function during childhood and adolescence and the similar trajectories of the E/R flip and episodic memory performance through development and aging suggests that a lifelong relationship exists., (Copyright © 2018 the authors 0270-6474/18/388666-14$15.00/0.)

At a large scale, the human brain is organized into modules of interconnected regions, some of which play opposing roles in supporting cognition. In particular, the Default-Mode Network (DMN) has been linked to operations on internal representations, while task-positive networks are recruited during interactions with the external world. Here, we test the hypothesis that the generation of durable long-term memories depends on optimal recruitment of such antagonistic large-scale networks. As long-term memory consolidation is a process ongoing for days and weeks after an experience, we propose that individuals characterized by strong decoupling of the DMN and task-positive networks at rest operate in a mode beneficial for the long-term stabilization of episodic memories. To capture network connectivity unaffected by transient task demands and representative of brain behavior outside an experimental setting, 87 participants were scanned during rest before performing an associative encoding task. To link individual resting-state functional connectivity patterns to time-dependent memory consolidation processes, participants were given an unannounced memory test, either after a brief interval or after a retention period of ~6 weeks. We found that participants with a resting state characterized by high synchronicity in a DMN-centered network system and low synchronicity between task-positive networks showed superior recollection weeks after encoding. These relationships were not observed for information probed only hours after encoding. Furthermore, the two network systems were found to be anticorrelated. Our results suggest that this memory-relevant antagonism between DMN and task-positive networks is maintained through complex regulatory interactions between the systems., (Copyright © 2017. Published by Elsevier Inc.)

Episodic memories are established and maintained by close interplay between hippocampus and other cortical regions, but degradation of a fronto-striatal network has been suggested to be a driving force of memory decline in aging. We wanted to directly address how changes in hippocampal-cortical versus striatal-cortical networks over time impact episodic memory with age. We followed 119 healthy participants (20-83 years) for 3.5 years with repeated tests of episodic verbal memory and magnetic resonance imaging for quantification of functional and structural connectivity and regional brain atrophy. While hippocampal-cortical functional connectivity predicted memory change in young, changes in cortico-striatal functional connectivity were related to change in recall in older adults. Within each age group, effects of functional and structural connectivity were anatomically closely aligned. Interestingly, the relationship between functional connectivity and memory was strongest in the age ranges where the rate of reduction of the relevant brain structure was lowest, implying selective impacts of the different brain events on memory. Together, these findings suggest a partly sequential and partly simultaneous model of brain events underlying cognitive changes in aging, where different functional and structural events are more or less important in various time windows, dismissing a simple uni-factorial view on neurocognitive aging., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

A major task of contemporary cognitive neuroscience of aging is to explain why episodic memory declines. Change in resting-state functional connectivity (rsFC) could be a mechanism accounting for reduced function. We addressed this through 3 studies. In study 1, 119 healthy participants (20-83 years) were followed for 3.5 years with verbal recall testing and magnetic resonance imaging. Independent of atrophy, recall change was related to change in rsFC in anatomically widespread areas. Striking age-effects were observed in that a positive relationship between rsFC and memory characterized older participants while a negative relationship was seen among the younger and middle-aged. This suggests that cognitive consequences of rsFC change are not stable across age. In study 2 and 3, the age-dependent differences in rsFC-memory relationship were replicated by use of a simulation model (study 2) and by a cross-sectional experimental recognition memory task (study 3). In conclusion, memory changes were related to altered rsFC in an age-dependent manner, and future research needs to detail the mechanisms behind age-varying relationships., (Copyright © 2015 Elsevier Inc. All rights reserved.)

We continuously encounter and process novel events in the surrounding world, but only some episodes will leave detailed memory traces that can be recollected after weeks and months. Here, our aim was to monitor brain activity during encoding of events that eventually transforms into long-term stable memories. Previous functional magnetic resonance imaging (fMRI) studies have shown that the degree of activation of different brain regions during encoding is predictive of later recollection success. However, most of these studies tested participants' memories the same day as encoding occurred, whereas several lines of research suggest that extended post-encoding processing is of crucial importance for long-term consolidation. Using fMRI, we tested whether the same encoding mechanisms are predictive of recollection success after hours as after a retention interval of several weeks. Seventy-eight participants were scanned during an associative encoding task and given a source memory test the same day or after ∼6 weeks. We found a strong link between regional activity levels during encoding and recollection success over short time intervals. However, results further showed that durable source memories, i.e., events recollected after several weeks, were not simply the events associated with the highest activity levels at encoding. Rather, strong levels of connectivity between the right hippocampus and perceptual areas, as well as with parts of the self-referential default-mode network, seemed instrumental in establishing durable source memories. Thus, we argue that an initial intensity-based encoding is necessary for short-term encoding of events, whereas additional processes involving hippocampal-cortical communication aid transformation into stable long-term memories., (Copyright © 2015 the authors 0270-6474/15/355202-11$15.00/0.)