Subsequent Memory Retrieval Research Articles

Non-competitive NMDA antagonist MK-801 prevents memory reconsolidation impairment caused by protein synthesis inhibitors in young chicks.

Introduction: Reactivation of already consolidated memory can initiate its destabilization, making the memory trace labile. Normally, this destabilization is followed by reconsolidation of the memory trace, enriched by newly acquired experience. Disrupting the reconsolidation process, for example, by inhibiting protein synthesis, impairs subsequent memory retrieval, leading to reminder-related amnesia. Previous studies in various species have shown that this impairment can be prevented by using NMDA receptor antagonists, which interfere with memory destabilization. Methods: In the present study we examined this phenomenon using a one-trial passive avoidance learning model in newborn chicks, the hypothesis being that inactivation of the NMDA-mediated transmission during memory reactivation would inhibit the memory trace labilization and thus prevent the reminder-related amnesia. Results: We found that reminder-associated administration of the NMDA receptor antagonist MK-801 or one of the protein synthesis inhibitors (anisomycin, cycloheximide, 2-deoxygalactose) each alone produced amnesia. However, when combined, injection of MK-801 before the reminder prevented amnesia induced by protein synthesis inhibitors. Discussion: We suggest that the observed paradoxical effect implicates the involvement of NMDA receptors in both protein synthesis-independent engram destabilization upon its retrieval and protein synthesismediated engram stabilization after its updating. This puzzling dual role of NMDA receptors in memory destabilization/restabilization requires further investigation.

Does Expecting Matter? The Impact of Experimentally Established Expectations on Subsequent Memory Retrieval of Emotional Words.

Previous studies have confirmed that different degrees of expectation, including the bipolarity of the expected and unexpected, as well as an intermediate level (no expectation), can affect memory. However, only a few investigations have manipulated expectation through experimentally established schema, with no consideration of how expectation impacts both item and source memory. Furthermore, stimulus emotionality may also impact memory. Therefore, we conducted a study to investigate the effects of three levels of expectation on item and source memory while considering the impact of stimulus emotionality. The experiment began with a phase dedicated to learning the rules. In the subsequent study phase, negative and neutral words were manipulated as expected, no expectation, and unexpected, based on these rules. This was followed by tasks focused on item and source memory. The study found that there was a "U-shape" relationship between expectation and item memory. Additionally, the study revealed the distinct impacts of expectation on item and source memory. When it came to item memory, both expected and unexpected words were better remembered than those with no expectations. In source memory, expected words showed memory inferiority for expectation-irrelevant source information, but an advantage for expectation-relevant source information. Stimulus emotionality modulated the effect of expectation on both item and source memory. Our findings provide behavioral evidence for the schema-linked interactions between medial prefrontal and medial temporal regions (SLIMM) theory, which proposes that congruent and incongruent events enhance memory through different brain regions. The different patterns between item and source memory also support dual-process models. Moreover, we speculate that processing events with varying levels of emotionality may undermine the impact of expectation, as implied by other neural investigations.

Cognitive tasks affect the relationship between representational pattern similarity and subsequent item memory in the hippocampus

Episodic memories are records of personally experienced events, coded neurally via the hippocampus and surrounding medial temporal lobe cortex. Information about the neural signal corresponding to a memory representation can be measured in fMRI data when the pattern across voxels is examined. Prior studies have found that similarity in the voxel patterns across repetition of a to-be-remembered stimulus predicts later memory retrieval, but the results are inconsistent across studies. The current study investigates the possibility that cognitive goals (defined here via the task instructions given to participants) during encoding affect the voxel pattern that will later support memory retrieval, and therefore that neural representations cannot be interpreted based on the stimulus alone. The behavioral results showed that exposure to variable cognitive tasks across repetition of events benefited subsequent memory retrieval. Voxel patterns in the hippocampus indicated a significant interaction between cognitive tasks (variable vs. consistent) and memory (remembered vs. forgotten) such that reduced voxel pattern similarity for repeated events with variable cognitive tasks, but not consistent cognitive tasks, supported later memory success. There was no significant interaction in neural pattern similarity between cognitive tasks and memory success in medial temporal cortices or lateral occipital cortex. Instead, higher similarity in voxel patterns in right medial temporal cortices was associated with later memory retrieval, regardless of cognitive task. In conclusion, we found that the relationship between pattern similarity across repeated encoding and memory success in the hippocampus (but not medial temporal lobe cortex) changes when the cognitive task during encoding does or does not vary across repetitions of the event.

Piquing Curiosity: Déjà vu-Like States Are Associated with Feelings of Curiosity and Information-Seeking Behaviors.

Curiosity during learning increases information-seeking behaviors and subsequent memory retrieval success, yet the mechanisms that drive curiosity and its accompanying information-seeking behaviors remain elusive. Hints throughout the literature suggest that curiosity may result from a metacognitive signal-possibly of closeness to a not yet accessible piece of information-that in turn leads the experiencer to seek out additional information that will resolve a perceptibly small knowledge gap. We examined whether metacognition sensations thought to signal the likely presence of an as yet unretrieved relevant memory (such as familiarity or déjà vu) might be involved. Across two experiments, when cued recall failed, participants gave higher curiosity ratings during reported déjà vu (Experiment 1) or déjà entendu (Experiment 2), and these states were associated with increased expenditure of limited experimental resources to discover the answer. Participants also spent more time attempting to retrieve information and generated more incorrect information when experiencing these déjà vu-like states than when not. We propose that metacognition signaling of the possible presence of an as yet unretrieved but relevant memory may drive curiosity and prompt information-seeking that includes further search efforts.

Working Memory Constrains Long-Term Memory in Children and Adults: Memory of Objects and Bindings

We explored how individual and age-related differences in working memory (WM) capacity affected subsequent long-term memory (LTM) retrieval. Unlike past studies, we tested WM and LTM not only for items, but also for item-color bindings. Our sample included 82 elementary school children and 42 young adults. The participants performed a WM task with images of unique everyday items presented sequentially at varying set sizes in different colors. Later, we tested LTM for items and item-color bindings from the WM task. The WM load during encoding constrained LTM, and participants with a higher WM capacity retrieved more items in the LTM test. Even when accounting for young children's poor item memory by considering only the items that they did remember, they exhibited an exacerbated difficulty with remembering item-color bindings in WM. Their LTM binding performance, however, as a proportion of remembered objects, was comparable to that of older children and adults. The WM binding performance was better during sub-span encoding loads, but with no clear transfer of this benefit to LTM. Overall, LTM item memory performance was constrained by individual and age-related WM limitations, but with mixed consequences for binding. We discuss the theoretical, practical, and developmental implications of this WM-to-LTM bottleneck.

Episodic memory and self-reference in a naturalistic context: New insights based on a virtual walk in the Latin Quarter of Paris

Although it is now well-known that self-reference processing benefits the episodic memory of laboratory material, studies have rarely investigated its influence on memory for specific episodes in a naturalistic context. We immersed 64 healthy young participants who were personally either very familiar or unfamiliar with the Latin Quarter of Paris in a virtual environment resembling it. They all navigated using a joystick and memorized as many specific events as possible encountered in this environment, together with their perceptual details and spatial and temporal context. However, one group was assigned to a self-perspective condition (i.e., centered on their own interaction with the environment) and another to a condition requiring the mental simulation of an other-perspective (i.e., centered on the interaction of an avatar with the environment) during the period of navigation and the subsequent memory retrieval tasks. The main results showed that both high personal familiarity (irrespective of the perspective) and a self-perspective (irrespective of the familiarity) improved the recall and recognition of specific events and their spatiotemporal contexts and the sense of remembering. Specifically, high personal familiarity was the most efficient condition for improving the memory of allocentric spatial context while, conversely, self-perspective was the most efficient for enhancing temporal context memory. An additive effect of self-perspective and high familiarity was observed regarding the memory of perceptual details and egocentric spatial context. These findings highlight the benefits of self-reference in episodic memory for specific events. They might help pave the way for the development of new perspectives for cognitive remediation of episodic memory encoding in daily life.

Hippocampal-Cortical Encoding Activity Predicts the Precision of Episodic Memory.

Our recollections of past experiences can vary in both the number of specific event details accessible from memory and the precision with which such details are reconstructed. Prior neuroimaging evidence suggests the success and precision of episodic recollection to rely on distinct neural substrates during memory retrieval. In contrast, the specific encoding mechanisms supporting later memory precision, and whether they differ from those underlying successful memory formation in general, are currently unknown. Here, we combined continuous measures of memory retrieval with model-based analyses of behavioral and neuroimaging data to tease apart the encoding correlates of successful memory formation and mnemonic precision. In the MRI scanner, participants encoded object-scene displays and later reconstructed features of studied objects using a continuous scale. We observed overlapping encoding activity in inferior prefrontal and posterior perceptual regions to predict both which object features were later remembered versus forgotten and the precision with which they were reconstructed from memory. In contrast, hippocampal encoding activity significantly predicted the precision, but not overall success, of subsequent memory retrieval. The current results align with theoretical accounts proposing the hippocampus to be critical for representation of high-fidelity associative information and suggest a contribution of shared cortical encoding mechanisms to the formation of both accessible and precise memory representations.

Abnormal Brain Activation During Verbal Memory Encoding in Postacute Anti-N-Methyl-d-Aspartate Receptor Encephalitis.

Background:Patients with postacute anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis are often left with permanent memory impairments. Given that NMDA receptors are essential to memory encoding, and encoding processes have been suggested to contribute to the success of memory retrieval, we investigate whether postacute anti-NMDA receptor encephalitis leads to abnormal brain activation during verbal memory encoding and its potential effects on subsequent memory retrieval performance.Methods:To address this issue, this study recruited 21 adult patients with anti-NMDA receptor encephalitis past the acute stage and 22 healthy controls (HCs). Functional magnetic resonance imaging (fMRI) data were collected when they completed an episodic memory task.Results:At the neural level, the patients showed higher brain activation than the HCs in the bilateral hippocampus/parahippocampus (HG/PHG), right superior temporal gyrus (STG), and right thalamus during memory encoding. At the behavioral level, the patients showed worse memory retrieval performance than the HCs. Importantly, greater brain activation in the left HG/PHG during memory encoding was significantly associated with worse memory retrieval performance among the patients.Conclusion:Our findings indicate that postacute anti-NMDA receptor encephalitis is likely related to altered brain activation during memory encoding. Particularly, less memory retrieval performance often observed in patients with postacute anti-NMDA receptor encephalitis may result from abnormal activation in HG during encoding. These observations may enhance our understanding of NMDA receptor dysfunction in the human brain.Impact statementPatients with anti-N-methyl-D-aspartate (anti-NMDA) receptor encephalitis are often left with permanent memory impairments. In this study, brain activation during verbal memory encoding and its potential effects on subsequent memory retrieval performance are addressed using 21 adult patients with postacute anti-NMDA receptor encephalitis and 22 healthy controls. Greater brain activation in the left hippocampus/parahippocampus during memory encoding was significantly associated with worse memory retrieval performance among the patients. These observations enhance our understanding of NMDA receptor dysfunction in the human brain.

Third-person perspectives in photographs influence visual and spatial perspectives during subsequent memory retrieval

ABSTRACT Reviewing photographs of the past influences our memories, but there is minimal research examining the influence of the viewpoint during photographic review of memories. In the current study, we examined how reviewing photographs from first-person versus third-person perspectives influences visual and spatial perspective in subsequent memories. Participants formed memories for mini-events performed in the lab, reviewed photographs of these events one week later from first-person and third-person perspectives, and then two days later memories for these events were tested against no photographic review. We found that third-person photographs increased observer-like perspectives during subsequent remembering, suggesting that photographic review of novel viewpoints changes the location from which the rememberer views the past event. Reviewing third-person photographs also reduced the accuracy of the spatial location of objects, indicating that photographic review can also update spatial perspective. In sum, these findings show that the viewpoint of photographs can powerfully influence memories.

An emergent neural coactivity code for dynamic memory.

Neural correlates of external variables provide potential internal codes that guide an animal’s behaviour. Notably, first-order features of neural activity, such as single-neuron firing rates, have been implicated in encoding information. However, the extent to which higher-order features, such as multi-neuron coactivity, play primary roles in encoding information or secondary roles in supporting single-neuron codes remains unclear. Here we show that millisecond-timescale coactivity amongst hippocampal CA1 neurons discriminates distinct millisecond-lived behavioural contingencies. This contingency discrimination was unrelated to the tuning of individual neurons but instead an emergent property of their coactivity. Contingency discriminating patterns were reactivated offline after learning and their reinstatement predicted trial-by-trial memory performance. Moreover, optogenetic suppression of inputs from the upstream CA3 region selectively during learning impaired coactivity-based contingency information in CA1 and subsequent dynamic memory retrieval. These findings identify coactivity as a primary feature of neural firing that discriminates distinct behaviourally-relevant variables and supports memory retrieval.

Abnormal dorsal attention network activation in memory impairment after traumatic brain injury.

Memory impairment is a common, disabling effect of traumatic brain injury. In healthy individuals, successful memory encoding is associated with activation of the dorsal attention network as well as suppression of the default mode network. Here, in traumatic brain injury patients we examined whether: (i) impairments in memory encoding are associated with abnormal brain activation in these networks; (ii) whether changes in this brain activity predict subsequent memory retrieval; and (iii) whether abnormal white matter integrity underpinning functional networks is associated with impaired subsequent memory. Thirty-five patients with moderate-severe traumatic brain injury aged 23-65 years (74% males) in the post-acute/chronic phase after injury and 16 healthy control subjects underwent functional MRI during performance of an abstract image memory encoding task. Diffusion tensor imaging was used to assess structural abnormalities across patient groups compared to 28 age-matched healthy controls. Successful memory encoding across all participants was associated with activation of the dorsal attention network, the ventral visual stream and medial temporal lobes. Decreased activation was seen in the default mode network. Patients with preserved episodic memory demonstrated increased activation in areas of the dorsal attention network. Patients with impaired memory showed increased left anterior prefrontal activity. White matter microstructure underpinning connectivity between core nodes of the encoding networks was significantly reduced in patients with memory impairment. Our results show for the first time that patients with impaired episodic memory show abnormal activation of key nodes within the dorsal attention network and regions regulating default mode network activity during encoding. Successful encoding was associated with an opposite direction of signal change between patients with and without memory impairment, suggesting that memory encoding mechanisms could be fundamentally altered in this population. We demonstrate a clear relationship between functional networks activated during encoding and underlying abnormalities within the structural connectome in patients with memory impairment. We suggest that encoding failures in this group are likely due to failed control of goal-directed attentional resources.

Frontal ERP slow waves during memory encoding are associated with affective attitude formation

A neutral stimulus can acquire valence by being paired with a valenced stimulus, leading to a new attitude towards the previously neutral stimulus. There is, however, considerable debate about the mechanisms that underlie this process of affective attitude formation. Therefore, in the present study we employed a single-trial, intentional learning procedure that paired neutral with valenced words while recording ERP activity, and measured subsequent memory and subsequent attitudes for the pre-experimentally neutral words immediately following learning. Using traditional as well as single-trial ERP analyses, we found that frontal slow wave (FSW) activity, elicited while stimuli were being paired, was associated with both subsequent memory for the word pairs and subsequent attitudes towards the pre-experimentally neutral words. Specifically, FSW activity during the pairing of neutral with positive words was related to more positive subsequent attitudes, while during the pairing of neutral with negative words, it was associated with more negative subsequent attitudes, towards the pre-experimentally neutral words. Given that this FSW activity was also related to successful subsequent episodic memory retrieval for the word pairs, these findings provide evidence that the transfer of valence may depend on a process that supports associative episodic encoding during word paring. Further, a single-trial, mixed-effects model indicated that the relationship between encoding FSW activity and subsequent attitudes depended on the strength of the episodic memory trace. Thus, the present study provides novel evidence that a common mechanism contributes to both episodic memory encoding and affective attitude formation.

Structuring Memory Through Inference-Based Event Segmentation.

Although the stream of information we encounter is continuous, our experiences tend to be discretized into meaningful clusters, altering how we represent our past. Event segmentation theory proposes that clustering ongoing experience in this way is adaptive in that it promotes efficient online processing as well as later reconstruction of relevant information. A growing literature supports this theory by demonstrating its important behavioral consequences. Yet the exact mechanisms of segmentation remain elusive. Here, we provide a brief overview of how event segmentation influences ongoing processing, subsequent memory retrieval, and decision making as well as some proposed underlying mechanisms. We then explore how beliefs, or inferences, about what generates our experience may be the foundation of event cognition. In this inference-based framework, experiences are grouped together according to what is inferred to have generated them. Segmentation then occurs when the inference changes, creating an event boundary. This offers an alternative to dominant theories of event segmentation, allowing boundaries to occur independent of perceptual change and even when transitions are predictable. We describe how this framework can reconcile seemingly contradictory empirical findings (e.g., memory can be biased toward both extreme episodes and the average of episodes). Finally, we discuss open questions regarding how time is incorporated into the inference process.

A time-dependent role for the transcription factor CREB in neuronal allocation to an engram underlying a fear memory revealed using a novel in vivo optogenetic tool to modulate CREB function.

The internal representation of an experience is thought to be encoded by long-lasting physical changes to the brain ("engrams") . Previously, we and others showed within the lateral amygdala (LA), a region critical for auditory conditioned fear, eligible neurons compete against one other for allocation to an engram. Neurons with relatively higher function of the transcription factor CREB were more likely to be allocated to the engram. In these studies, though, CREB function was artificially increased for several days before training. Precisely when increased CREB function is important for allocation remains an unanswered question. Here, we took advantage of a novel optogenetic tool (opto-DN-CREB) to gain spatial and temporal control of CREB function in freely behaving mice. We found increasing CREB function in a small, random population of LA principal neurons in the minutes, but not 24 h, before training was sufficient to enhance memory, likely because these neurons were preferentially allocated to the underlying engram. However, similarly increasing CREB activity in a small population of random LA neurons immediately after training disrupted subsequent memory retrieval, likely by disrupting the precise spatial and temporal patterns of offline post-training neuronal activity and/or function required for consolidation. These findings reveal the importance of the timing of CREB activity in regulating allocation and subsequent memory retrieval, and further, highlight the potential of optogenetic approaches to control protein function with temporal specificity in behaving animals.

Hippocampal signatures of awaketargeted memory reactivation.

Dominant theories of episodic memory propose that a key mechanism of memory consolidation is replay-a process, whereby neural patterns of activation during learning are reinstated during offline post-learning periods. Here, we tested whether key signatures of replay defined by studies in rodents, such as recapitulation of specific memory traces, as well as sequences, are apparent in humans during post-encoding memory reactivation. Thirty participants underwent functional imaging that consisted of interleaved encoding and rest periods. During an offline period of wakeful rest, we biased reactivation towards some memories by presenting sound cues that had previously been associated with particular stimulus sequences. Results showed that targeted hippocampal reactivation was biased towards cued memory sequences and that reactivation signatures preserved the temporal order of particular sequences. Importantly, the biased reactivation was related to differences in subsequent memory, suggesting that preferential reactivation may be a mechanism by which specific memory traces can be strengthened for enhanced subsequent memory retrieval.

Should I trust you? Learning and memory of social interactions in dementia.

Social relevance has an enhancing effect on learning and subsequent memory retrieval. The ability to learn from and remember social interactions may impact on susceptibility to financial exploitation, which is elevated in individuals with dementia. The current study aimed to investigate learning and memory of social interactions, the relationship between performance and financial vulnerability and the neural substrates underpinning performance in 14 Alzheimer's disease (AD) and 20 behavioural-variant frontotemporal dementia (bvFTD) patients and 20 age-matched healthy controls. On a "trust game" task, participants invested virtual money with counterparts who acted either in a trustworthy or untrustworthy manner over repeated interactions. A non-social "lottery" condition was also included. Participants' learning of trust/distrust responses and subsequent memory for the counterparts and nature of the interactions was assessed. Carer-rated profiles of financial vulnerability were also collected. Relative to controls, both patient groups showed attenuated learning of trust/distrust responses, and lower overall memory for social interactions. Despite poor learning performance, both AD and bvFTD patients showed better memory of social compared to non-social interactions. Importantly, better memory for social interactions was associated with lower financial vulnerability in AD, but not bvFTD. Learning and memory of social interactions was associated with medial temporal and temporoparietal atrophy in AD, whereas a wider network of frontostriatal, insular, fusiform and medial temporal regions was implicated in bvFTD. Our findings suggest that although social relevance influences memory to an extent in both AD and bvFTD, this is associated with vulnerability to financial exploitation in AD only, and is underpinned by changes to different neural substrates. Theoretically, these findings provide novel insights into potential mechanisms that give rise to vulnerability in people with dementia, and open avenues for possible interventions.

0246 STRESS PRIOR TO ENCODING AFFECTS RESTING STATE FUNCTIONAL CONNECTIVITY AND EMOTIONAL MEMORY RETRIEVAL FOLLOWING SLEEP

Previous work has illustrated that sleep and stress enhance long-term emotional memory. Although memory for emotionally arousing items is strengthened following stress exposure, it is unclear how consolidation-related neural processes are affected. The purpose of this project was to examine whether a psychosocial stressor administered before encoding would influence subsequent emotional memory retrieval following a night of sleep through changes in the functional coupling of the ventral medial prefrontal cortex (vmPFC) and the amygdala. Participants underwent either the Trier Social Stress Test or a control task before encoding a series of negative, positive and neutral scenes while we collected functional magnetic resonance imaging (fMRI) data. Overnight sleep was recorded using polysomnography. The following day, participants returned to the MRI to complete an incidental recognition task. Change in functional connectivity was examined by comparing the resting state fMRI scans following the stress manipulation and shortly before the recognition task. Resting state fMRI data collected shortly before the recognition task revealed that greater functional coupling between the amygdala and the vmPFC post-sleep was associated with negative memory enhancement (negative d’ minus neutral d’) in participants who underwent the psychosocial stressor, β = .51, p = .02 (n = 18). Furthermore, negative memory enhancement was associated with a greater increase in coupling between the amygdala and vmPFC from the encoding to retrieval sessions, β = .46, p = .05. The participants in the stress condition who remembered more negative scenes compared to neutral scenes showed greater functional coupling between the amygdala and the vmPFC post-sleep. These preliminary results suggest that stress prior to encoding affects consolidation-related brain networks important for emotional memory function. National Science Foundation Grant Reward Number: BCS1539361.

Organization of the Claustrum-to-Entorhinal Cortical Connection in Mice.

The claustrum is a poorly understood subcortical structure reciprocally connected with widespread neocortical regions. We investigated the organization and function of identified claustro-cortical projections in mice using pathway-specific approaches. Anatomical tracing showed that the density of anterior claustrum-to-cortical projection is dependent on the target cortical areas and that the medial entorhinal cortex (MEC) is one of the major projection targets. Novel context exposure activated multiple claustro-cortical pathways and a large fraction of the activated neurons projected to the MEC. Optogenetic silencing of the claustro-MEC pathway during contextual fear learning suppressed subsequent memory retrieval. These results suggest that the dense claustro-MEC pathway is activated by novel context and modulates MEC function in contextual memory.

Impact of Sex and Menopausal Status on Episodic Memory Circuitry in Early Midlife.

Cognitive neuroscience of aging studies traditionally target participants age 65 and older. However, epidemiological surveys show that many women report increased forgetfulness earlier in the aging process, as they transition to menopause. In this population-based fMRI study, we stepped back by over a decade to characterize the changes in memory circuitry that occur in early midlife, as a function of sex and women's reproductive stage. Participants (N = 200; age range, 45-55) performed a verbal encoding task during fMRI scanning. Reproductive histories and serologic evaluations were used to determine menopausal status. Results revealed a pronounced impact of reproductive stage on task-evoked hippocampal responses, despite minimal difference in chronological age. Next, we examined the impact of sex and reproductive stage on functional connectivity across task-related brain regions. Postmenopausal women showed enhanced bilateral hippocampal connectivity relative to premenopausal and perimenopausal women. Across women, lower 17β-estradiol concentrations were related to more pronounced alterations in hippocampal connectivity and poorer performance on a subsequent memory retrieval task, strongly implicating sex steroids in the regulation of this circuitry. Finally, subgroup analyses revealed that high-performing postmenopausal women (relative to low and middle performers) exhibited a pattern of brain activity akin to premenopausal women. Together, these findings underscore the importance of considering reproductive stage, not simply chronological age, to identify neuronal and cognitive changes that unfold in the middle decades of life. In keeping with preclinical studies, these human findings suggest that the decline in ovarian estradiol production during menopause plays a significant role in shaping memory circuitry. Maintaining intact memory function with age is one of the greatest public health challenges of our time, and women have an increased risk for memory disorders relative to men later in life. We studied adults early in the aging process, as women transition into menopause, to identify neuronal and cognitive changes that unfold in the middle decades of life. Results demonstrate regional and network-level differences in memory encoding-related activity as a function of women's reproductive stage, independent of chronological age. Analyzing data without regard to sex or menopausal status obscured group differences in circuit-level neural strategies associated with successful memory retrieval. These findings suggest that early changes in memory circuitry are evident decades before the age range traditionally targeted by cognitive neuroscience of aging studies.

Episodic memory and self-reference via semantic autobiographical memory: insights from an fMRI study in younger and older adults.

Self-referential processing relies mainly on the medial prefrontal cortex (MPFC) and enhances memory encoding (i.e., Self-Reference Effect, SRE) as it improves the accuracy and richness of remembering in both young and older adults. However, studies on age-related changes in the neural correlates of the SRE on the subjective (i.e., autonoetic consciousness) and the objective (i.e., source memory) qualitative features of episodic memory are lacking. In the present fMRI study, we compared the effects of a self-related (semantic autobiographical memory task) and a non self-related (general semantic memory task) encoding condition on subsequent episodic memory retrieval. We investigated encoding-related activity during each condition in two groups of 19 younger and 16 older adults. Behaviorally, the SRE improved subjective memory performance in both groups but objective memory only in young adults. At the neural level, a direct comparison between self-related and non self-related conditions revealed that SRE mainly activated the cortical midline system, especially the MPFC, in both groups. Additionally, in older adults and regardless of the condition, greater activity was found in a fronto-parietal network. Overall, correlations were noted between source memory performance and activity in the MPFC (irrespective of age) and visual areas (mediated by age). Thus, the present findings expand evidence of the role of the MPFC in self-referential processing in the context of source memory benefit in both young and older adults using incidental encoding via semantic autobiographical memory. However, our finding suggests that its role is less effective in aging.