The effects of age on neural correlates of recognition memory: An fMRI study.

Studies examining the effects of age on the neural correlates of recognition memory have yielded mixed results. In the present study, we employed a modified remember-know paradigm to compare the fMRI correlates of recollection and familiarity in samples of healthy young and older adults. After studying a series of words, participants underwent fMRI scanning during a test phase in which they responded "remember" to a test word if any qualitative information could be recollected about the study event. When recollection failed, participants signaled how confident they were that the test item had been studied. Young and older adults demonstrated statistically equivalent estimates of recollection and familiarity strength, while recognition memory accuracy was significantly lower in the older adults. Robust, age-invariant fMRI effects were evident in two sets of a priori defined brain regions consistently reported in prior studies to be sensitive to recollection and familiarity respectively. In addition, the magnitudes of 'familiarity-attenuation effects' in perirhinal cortex demonstrated age-invariant correlations with estimates of familiarity strength and memory accuracy, replicating prior findings. Together, the present findings add to the evidence that the neural correlates of recognition memory are largely stable across much of the healthy human adult lifespan.

Separation of item and context in item-method directed forgetting.

Contextual information plays a critical role in directed forgetting (DF) of lists of items, whereas DF of individual items has been primarily associated with item-level processing. This study was designed to investigate whether context processing also contributes to the forgetting of individual items. Participants first viewed a series of words, with task-irrelevant scene images (used as "context tags") interspersed between them. Later, these words reappeared without the scenes and were followed by an instruction to remember or forget that word. Multivariate pattern analyses of fMRI data revealed that the reactivation of context information associated with the studied words (i.e., scene-related activity) was greater whereas the item-related information diminished after a forget instruction compared to a remember instruction. Critically, we found the magnitude of the separation between item information and context information predicted successful forgetting. These results suggest that the unbinding of an item from its context may support the intention to forget, and more generally they establish that contextual processing indeed contributes to item-method DF.

More Is Less: Increased Processing of Unwanted Memories Facilitates Forgetting.

The intention to forget can produce long-lasting effects. This ability has been linked to suppression of both rehearsal and retrieval of unwanted memories, processes mediated by the prefrontal cortex and hippocampus. Here, we describe an alternative account in which the intention to forget is associated with increased engagement with the unwanted information. We used pattern classifiers to decode human functional magnetic resonance imaging data from a task in which male and female participants viewed a series of pictures and were instructed to remember or forget each one. Pictures followed by a forget instruction elicited higher levels of processing in the ventral temporal cortex compared with those followed by a remember instruction. This boost in processing led to more forgetting, particularly for items that showed moderate (vs weak or strong) activation. This result is consistent with the nonmonotonic plasticity hypothesis, which predicts weakening and forgetting of memories that are moderately activated.SIGNIFICANCE STATEMENT The human brain cannot remember everything. Forgetting has a critical role in curating memories and discarding unwanted information. Intentional forgetting has traditionally been linked to passive processes, such as the withdrawal of sustained attention or a stoppage of memory rehearsal. It has also been linked to active suppression of memory processes during encoding and retrieval. Using functional magnetic resonance imaging and machine-learning methods, we show new evidence that intentional forgetting involves an enhancement of memory processing in the sensory cortex to achieve desired forgetting of recent visual experiences. This enhancement temporarily boosts the activation of the memory representation and renders it vulnerable to disruption via homeostatic regulation. Contrary to intuition, deliberate forgetting may involve more rather than less attention to unwanted information.

Effects of age on across-participant variability of cortical reinstatement effects.

Using functional magnetic resonance imaging data, we assessed whether across-participant variability of content-selective retrieval-related neural activity differs with age. We addressed this question by employing across-participant multi-voxel pattern analysis (MVPA), predicting that increasing age would be associated with reduced variability of retrieval-related cortical reinstatement across participants. During study, 24 young and 24 older participants viewed objects and concrete words. Test items comprised studied words, names of studied objects, and unstudied words. Participants judged whether the items were recollected, familiar, or new by making 'Remember', 'Know' and 'New' responses, respectively. MVPA was conducted on each region belonging to the 'core recollection network', dorsolateral prefrontal cortex, and a previously identified content-selective voxel set. A leave-one-participant-out classification approach was employed whereby a classifier was trained on a subset of participants and tested on the data from a yoked pair of held-out participants. Classifiers were trained on the study phase data to discriminate the study trials as a function of content (picture or word). The classifiers were then applied to the test phase data to discriminate studied test words according to their study condition. In all of the examined regions, classifier performance demonstrated little or no sensitivity to age and, for the test data, was robustly above chance. Thus, there was little evidence to support the hypothesis that across-participant variability of retrieval-related cortical reinstatement differs with age. The findings extend prior evidence by demonstrating that content-selective cortical reinstatement is sufficiently invariant to support across-participant multi-voxel classification across the healthy adult lifespan.

Dissociation between the neural correlates of recollection and familiarity in the striatum and hippocampus: Across-study convergence.

In tests of recognition memory, neural activity in the striatum has consistently been reported to differ according to the study status of the test item. A full understanding of the functional significance of striatal 'retrieval success' effects is impeded by a paucity of evidence concerning whether the effects differ according to the nature of the memory signal supporting the recognition judgment (recollection vs. familiarity). Here, we address this issue through an analysis of retrieval-related striatal activity in three independent fMRI studies (total N = 88). Recollection and familiarity were operationalized in a different way in each study, allowing the identification of test-independent, generic recollection- and familiarity-related effects. While activity in a bilateral dorsal striatal region, mainly encompassing the caudate nucleus, was enhanced equally by recollected and 'familiar only' test items, activity in bilateral ventral striatum and adjacent subgenual frontal cortex was enhanced only in response to items that elicited successful recollection. By contrast, relative to familiar items, activity in anterior hippocampus was enhanced for both recollected and novel test items. Thus, recollection- and familiarity-driven recognition memory judgments are associated with anatomically distinct patterns of retrieval-related striatal activity, and these patterns are at least partially independent of recollection and novelty effects in the hippocampus.

Independent contributions of fMRI familiarity and novelty effects to recognition memory and their stability across the adult lifespan.

The impact of age on the neural correlates of familiarity-driven recognition memory has received relatively little attention. Here, the relationships between age, the neural correlates of familiarity, and memory performance were investigated using an associative recognition test in young, middle-aged and older participants. Test items comprised studied, rearranged (items studied on different trials) and new word pairs. fMRI 'familiarity effects' were operationalized as greater activity for studied test pairs incorrectly identified as 'rearranged' than for correctly rejected new pairs. The reverse contrast was employed to identify 'novelty' effects. Estimates of familiarity strength were slightly but significantly lower for the older relative to the younger group. With the exception of one region in dorsal medial prefrontal cortex, fMRI familiarity effects (which were identified in medial and lateral parietal cortex, dorsal medial and left lateral prefrontal cortex, and bilateral caudate among other regions) did not differ significantly with age. Age-invariant 'novelty effects' were identified in the anterior hippocampus and the perirhinal cortex. When entered into the same regression model, familiarity and novelty effects independently predicted familiarity strength across participants, suggesting that the two classes of memory effect reflect functionally distinct mnemonic processes. It is concluded that the neural correlates of familiarity-based memory judgments, and their relationship with familiarity strength, are largely stable across much of the healthy adult lifespan.

Decoding the content of recollection within the core recollection network and beyond.

Recollection - retrieval of qualitative information about a past event - is associated with enhanced neural activity in a consistent set of neural regions (the 'core recollection network') seemingly regardless of the nature of the recollected content. Here, we employed multi-voxel pattern analysis (MVPA) to assess whether retrieval-related functional magnetic resonance imaging (fMRI) activity in core recollection regions - including the hippocampus, angular gyrus, medial prefrontal cortex, retrosplenial/posterior cingulate cortex, and middle temporal gyrus - contain information about studied content and thus demonstrate retrieval-related 'reinstatement' effects. During study, participants viewed objects and concrete words that were subjected to different encoding tasks. Test items included studied words, the names of studied objects, or unstudied words. Participants judged whether the items were recollected, familiar, or new by making 'remember', 'know', and 'new' responses, respectively. The study history of remembered test items could be reliably decoded using MVPA in most regions, as well as from the dorsolateral prefrontal cortex, a region where univariate recollection effects could not be detected. The findings add to evidence that members of the core recollection network, as well as at least one neural region where mean signal is insensitive to recollection success, carry information about recollected content. Importantly, the study history of recognized items endorsed with a 'know' response could be decoded with equal accuracy. The results thus demonstrate a striking dissociation between mean signal and multi-voxel indices of recollection. Moreover, they converge with prior findings in suggesting that, as it is operationalized by classification-based MVPA, reinstatement is not uniquely a signature of recollection.

The relationships between age, associative memory performance, and the neural correlates of successful associative memory encoding.

Using functional magnetic resonance imaging, subsequent memory effects (greater activity for later remembered than later forgotten study items) predictive of associative encoding were compared across samples of young, middle-aged, and older adults (total N = 136). During scanning, participants studied visually presented word pairs. In a later test phase, they discriminated between studied pairs, "rearranged" pairs (items studied on different trials), and new pairs. Subsequent memory effects were identified by contrasting activity elicited by study pairs that went on to be correctly judged intact or incorrectly judged rearranged. Effects in the hippocampus were age-invariant and positively correlated across participants with associative memory performance. Subsequent memory effects in the right inferior frontal gyrus (IFG) were greater in the older than the young group. In older participants only, both left and, in contrast to prior reports, right IFG subsequent memory effects correlated positively with memory performance. We suggest that the IFG is especially vulnerable to age-related decline in functional integrity and that the relationship between encoding-related activity in right IFG and memory performance depends on the experimental context.

The neural correlates of recollection and retrieval monitoring: Relationships with age and recollection performance.

The relationships between age, retrieval-related neural activity, and episodic memory performance were investigated in samples of young (18-29yrs), middle-aged (43-55yrs) and older (63-76yrs) healthy adults. Participants underwent fMRI scanning during an associative recognition test that followed a study task performed on visually presented word pairs. Test items comprised pairs of intact (studied pairs), rearranged (items studied on different trials) and new words. fMRI recollection effects were operationalized as greater activity for studied pairs correctly endorsed as intact than for pairs incorrectly endorsed as rearranged. The reverse contrast was employed to identify retrieval monitoring effects. Robust recollection effects were identified in the core recollection network, comprising the hippocampus, along with parahippocampal and posterior cingulate cortex, left angular gyrus and medial prefrontal cortex. Retrieval monitoring effects were identified in the anterior cingulate and right dorsolateral prefrontal cortex. Neither recollection effects within the core network, nor the monitoring effects differed significantly across the age groups after controlling for individual differences in associative recognition performance. Whole brain analyses did however identify three clusters outside of these regions where recollection effects were greater in the young than in the other age groups. Across-participant regression analyses indicated that the magnitude of hippocampal and medial prefrontal cortex recollection effects, and both of the prefrontal monitoring effects, correlated significantly with memory performance. None of these correlations were moderated by age. The findings suggest that the relationships between memory performance and functional activity in regions consistently implicated in successful recollection and retrieval monitoring are stable across much of the healthy adult lifespan.

The Effects of Age on the Neural Correlates of Recollection Success, Recollection-Related Cortical Reinstatement, and Post-Retrieval Monitoring.

Functional magnetic resonance imaging (fMRI) was used to investigate whether age-related differences in episodic memory performance are accompanied by a reduction in the specificity of recollected information. We addressed this question by comparing recollection-related cortical reinstatement in young and older adults. At study, subjects viewed objects and concrete words, making 1 of 2 different semantic judgments depending on the study material. Test items were words that corresponded to studied words or the names of studied objects. Subjects indicated whether each test item was recollected, familiar, or novel. Reinstatement of information differentiating the encoding tasks was quantified both with a univariate analysis of the fMRI signal and with a multivoxel pattern analysis, using a classifier that had been trained to discriminate between the 2 classes of study episode. The results of these analyses converged to suggest that reinstatement did not differ according to age. Thus, there was no evidence that specificity of recollected information was reduced in older individuals. Additionally, there were no age effects in the magnitude of recollection-related modulations in regional activity or in the neural correlates of post-retrieval monitoring. Taken together, the findings suggest that the neural mechanisms engaged during successful episodic retrieval can remain stable with advancing age.

Recollection-related increases in functional connectivity predict individual differences in memory accuracy.

Recollection involves retrieving specific contextual details about a prior event. Functional neuroimaging studies have identified several brain regions that are consistently more active during successful versus failed recollection-the "core recollection network." In the present study, we investigated whether these regions demonstrate recollection-related increases not only in activity but also in functional connectivity in healthy human adults. We used fMRI to compare time-series correlations during successful versus unsuccessful recollection in three separate experiments, each using a different operational definition of recollection. Across experiments, a broadly distributed set of regions consistently exhibited recollection-related increases in connectivity with different members of the core recollection network. Regions that demonstrated this effect included both recollection-sensitive regions and areas where activity did not vary as a function of recollection success. In addition, in all three experiments the magnitude of connectivity increases correlated across individuals with recollection accuracy in areas diffusely distributed throughout the brain. These findings suggest that enhanced functional interactions between distributed brain regions are a signature of successful recollection. In addition, these findings demonstrate that examining dynamic modulations in functional connectivity during episodic retrieval will likely provide valuable insight into neural mechanisms underlying individual differences in memory performance.

Cortical reinstatement and the confidence and accuracy of source memory.

Cortical reinstatement refers to the overlap between neural activity elicited during the encoding and the subsequent retrieval of an episode, and is held to reflect retrieved mnemonic content. Previous findings have demonstrated that reinstatement effects reflect the quality of retrieved episodic information as this is operationalized by the accuracy of source memory judgments. The present functional magnetic resonance imaging (fMRI) study investigated whether reinstatement-related activity also co-varies with the confidence of accurate source judgments. Participants studied pictures of objects along with their visual or spoken names. At test, they first discriminated between studied and unstudied pictures and then, for each picture judged as studied, they also judged whether it had been paired with a visual or auditory name, using a three-point confidence scale. Accuracy of source memory judgments- and hence the quality of the source-specifying information--was greater for high than for low confidence judgments. Modality-selective retrieval-related activity (reinstatement effects) also co-varied with the confidence of the corresponding source memory judgment. The findings indicate that the quality of the information supporting accurate judgments of source memory is indexed by the relative magnitude of content-selective, retrieval-related neural activity.

Sensitivity of negative subsequent memory and task-negative effects to age and associative memory performance.

The present fMRI experiment employed associative recognition to investigate the relationships between age and encoding-related negative subsequent memory effects and task-negative effects. Young, middle-aged and older adults (total n=136) were scanned while they made relational judgments on visually presented word pairs. In a later memory test, the participants made associative recognition judgments on studied, rearranged (items studied on different trials) and new pairs. Several regions, mostly localized to the default mode network, demonstrated negative subsequent memory effects in an across age-group analysis. All but one of these regions also demonstrated task-negative effects, although there was no correlation between the size of the respective effects. Whereas negative subsequent memory effects demonstrated a graded attenuation with age, task-negative effects declined markedly between the young and the middle-aged group, but showed no further reduction in the older group. Negative subsequent memory effects did not correlate with memory performance within any age group. By contrast, in the older group only, task-negative effects predicted later memory performance. The findings demonstrate that negative subsequent memory and task-negative effects depend on dissociable neural mechanisms and likely reflect distinct cognitive processes. The relationship between task-negative effects and memory performance in the older group might reflect the sensitivity of these effects to variations in amount of age-related neuropathology. This article is part of a Special Issue entitled SI: Memory.

Effects of age on negative subsequent memory effects associated with the encoding of item and item-context information.

It has consistently been reported that "negative" subsequent memory effects--lower study activity for later remembered than later forgotten items--are attenuated in older individuals. The present functional magnetic resonance imaging study investigated whether these findings extend to subsequent memory effects associated with successful encoding of item-context information. Older (n = 25) and young (n = 17) subjects were scanned while making 1 of 2 encoding judgments on a series of pictures. Memory was assessed for the study item and, for items judged old, the item's encoding task. Both memory judgments were made using confidence ratings, permitting item and source memory strength to be unconfounded and source confidence to be equated across age groups. Replicating prior findings, negative item effects in regions of the default mode network in young subjects were reversed in older subjects. Negative source effects, however, were invariant with respect to age and, in both age groups, the magnitude of the effects correlated with source memory performance. It is concluded that negative item effects do not reflect processes necessary for the successful encoding of item-context associations in older subjects. Negative source effects, in contrast, appear to reflect the engagement of processes that are equally important for successful episodic encoding in older and younger individuals.

Effects of age on the neural correlates of familiarity as indexed by ERPs.

ERPs were recorded from samples of young (18-29 years) and older (63-77 years) participants while they performed a modified "remember-know" recognition memory test. ERP correlates of familiarity-driven recognition were obtained by contrasting the waveforms elicited by unrecollected test items accorded "confident old" and "confident new" judgments. Correlates of recollection were identified by contrasting the ERPs elicited by items accorded "remember" and confident old judgments. Behavioral analyses revealed lower estimates of both recollection and familiarity in older participants than in young participants. The putative ERP correlate of recollection-the "left parietal old-new effect"-was evident in both age groups, although it was slightly but significantly smaller in the older sample. By contrast, the putative ERP correlate of familiarity-the "midfrontal old-new effect"-could be identified in young participants only. This age-related difference in the sensitivity of ERPs to familiarity was also evident in subgroups of young and older participants, in whom familiarity-based recognition performance was equivalent. Thus, the inability to detect a reliable midfrontal old-new effect in older participants was not a consequence of an age-related decline in the strength of familiarity. These findings raise the possibility that familiarity-based recognition memory depends upon qualitatively different memory signals in older and young adults.

The effects of age, memory performance, and callosal integrity on the neural correlates of successful associative encoding.

This functional magnetic resonance imaging study investigated the relationship between the neural correlates of associative memory encoding, callosal integrity, and memory performance in older adults. Thirty-six older and 18 young subjects were scanned while making relational judgments on word pairs. Neural correlates of successful encoding (subsequent memory effects) were identified by contrasting the activity elicited by study pairs that were correctly identified as having been studied together with the activity elicited by pairs wrongly judged to have come from different study trials. Subsequent memory effects common to the 2 age groups were identified in several regions, including left inferior frontal gyrus and bilateral hippocampus. Negative effects (greater activity for forgotten than for remembered items) in default network regions in young subjects were reversed in the older group, and the amount of reversal correlated negatively with memory performance. Additionally, older subjects' subsequent memory effects in right frontal cortex correlated positively with anterior callosal integrity and negatively with memory performance. It is suggested that recruitment of right frontal cortex during verbal memory encoding may reflect the engagement of processes that compensate only partially for age-related neural degradation.

Effects of advanced aging on the neural correlates of successful recognition memory.

Functional neuroimaging studies have reported that the neural correlates of retrieval success (old>new effects) are larger and more widespread in older than in young adults. In the present study we investigated whether this pattern of age-related 'over-recruitment' continues into advanced age. Using functional magnetic resonance imaging (fMRI), retrieval-related activity from two groups (N=18 per group) of older adults aged 84-96 years ('old-old') and 64-77 years ('young-old') was contrasted. Subjects studied a series of pictures, half of which were presented once, and half twice. At test, subjects indicated whether each presented picture was old or new. Recognition performance of the old-old subjects for twice-studied items was equivalent to that of the young-old subjects for once-studied items. Old>new effects common to the two groups were identified in several cortical regions, including medial and lateral parietal and prefrontal cortex. There were no regions where these effects were of greater magnitude in the old-old group, and thus no evidence of over-recruitment in this group relative to the young-old individuals. In one region of medial parietal cortex, effects were greater (and only significant) in the young-old group. The failure to find evidence of over-recruitment in the old-old subjects relative to the young-old group, despite their markedly poorer cognitive performance, suggests that age-related over-recruitment effects plateau in advanced age. The findings for the medial parietal cortex underscore the sensitivity of this cortical region to increasing age.

Open Access Series of Imaging Studies (OASIS): cross-sectional MRI data in young, middle aged, nondemented, and demented older adults.

The Open Access Series of Imaging Studies is a series of magnetic resonance imaging data sets that is publicly available for study and analysis. The initial data set consists of a cross-sectional collection of 416 subjects aged 18 to 96 years. One hundred of the included subjects older than 60 years have been clinically diagnosed with very mild to moderate Alzheimer's disease. The subjects are all right-handed and include both men and women. For each subject, three or four individual T1-weighted magnetic resonance imaging scans obtained in single imaging sessions are included. Multiple within-session acquisitions provide extremely high contrast-to-noise ratio, making the data amenable to a wide range of analytic approaches including automated computational analysis. Additionally, a reliability data set is included containing 20 subjects without dementia imaged on a subsequent visit within 90 days of their initial session. Automated calculation of whole-brain volume and estimated total intracranial volume are presented to demonstrate use of the data for measuring differences associated with normal aging and Alzheimer's disease.

The effect of a naturalistic stressor on frontal EEG asymmetry, stress, and health.

The aim of the current study was to investigate the effect of a naturalistic stressor, examination stress, on frontal EEG asymmetry, psychological stress, hormonal stress, and negative health. Forty-nine subjects were tested during periods of low and high examination stress. During the high examination stress period, subjects reported higher levels of stress on the Spielberger State Anxiety Inventory and Cohen's Perceived Stress Scale. However, no change in cortisol was detected across the two sessions. Furthermore, a shift from relatively greater left frontal activity during the low examination session to relatively greater right frontal activity during the high examination session was also found. Moreover, the increasing right frontal activity asymmetry associated with the high exam session compared to the low exam session correlated with increasing reports of negative health. No evidence was found for the prediction that cortisol mediated either the relationship between examination stressor and right frontal asymmetry or between right frontal asymmetry and negative health. In conclusion, while the findings from this study are compelling, the mechanism mediating increases in psychological stress, relatively greater right frontal activity, and increases in negative health from naturally occurring stressors is in need of further investigation.