Structural and Functional MRI Evidence for Distinct Medial Temporal and Prefrontal Roles in Context-dependent Relational Memory.

Declarative memory is supported by distributed brain networks in which the medial-temporal lobes (MTLs) and pFC serve as important hubs. Identifying the unique and shared contributions of these regions to successful memory performance is an active area of research, and a growing literature suggests that these structures often work together to support declarative memory. Here, we present data from a context-dependent relational memory task in which participants learned that individuals belonged in a single room in each of two buildings. Room assignment was consistent with an underlying contextual rule structure in which male and female participants were assigned to opposite sides of a building and the side assignment switched between buildings. In two experiments, neural correlates of performance on this task were evaluated using multiple neuroimaging tools: diffusion tensor imaging (Experiment 1), magnetic resonance elastography (Experiment 1), and functional MRI (Experiment 2). Structural and functional data from each individual modality provided complementary and consistent evidence that the hippocampus and the adjacent white matter tract (i.e., fornix) supported relational memory, whereas the ventromedial pFC/OFC (vmPFC/OFC) and the white matter tract connecting vmPFC/OFC to MTL (i.e., uncinate fasciculus) supported memory-guided rule use. Together, these data suggest that MTL and pFC structures differentially contribute to and support contextually guided relational memory.

Reconstructing relational information.

Hippocampal involvement in learning and remembering relational information has an extensive history, often focusing specifically on spatial information. In humans, spatial reconstruction (SR) paradigms are a powerful tool for evaluating an individuals' spatial-relational memory. In SR tasks, participants study locations of items in space and subsequently reconstruct the studied display after a short delay. Previous work has revealed that patients with hippocampal damage are impaired both in overall placement accuracy as well as on a specific measure of relational memory efficacy, "swaps" (i.e., when the relative location of two items is reversed). However, the necessity of the hippocampus for other types of spatial-relational information involved in reconstruction behaviors (e.g., where in the environment and relative to which other items an item was located) have not yet been investigated systematically. In this work, three patients with hippocampal damage and nine healthy matched comparison participants performed an SR task. An analysis framework was developed to independently assess three first-order types of relations: (1) memory for the binding of specific item identities to locations, (2) memory for arrangement of items in relation to each other or the environment bounds, regardless of memory for the item identity, and (3) higher-order, compound relational errors (i.e., errors involving multiple pieces of relational information). Reconstruction errors were evaluated to determine the degree to which patients and comparisons differed (or not) on each type of spatial-relational information. Data revealed that the primary group difference in performance was for identity-location information. However, when the locations of items were evaluated without regarding the identities, no group difference was found in the number of item placements to studied locations. The present work provides a principled approach to analysis of SR data and clarifies our understanding of the types of spatial relations impaired in hippocampal damaged.

Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference.

Aging affects the interaction between attentional control and source memory: an fMRI study.

Age-related source memory impairments may be due, at least in part, to deficits in executive processes mediated by the PFC at both study and test. Behavioral work suggests that providing environmental support at encoding, such as directing attention toward item-source associations, may improve source memory and reduce age-related deficits in the recruitment of these executive processes. The present fMRI study investigated the effects of directed attention and aging on source memory encoding and retrieval. At study, participants were shown pictures of objects. They were either asked to attend to the objects and their color (source) or to their size. At test, participants determined if objects were seen before, and if so, whether they were the same color as previously. Behavioral results showed that direction of attention improved source memory for both groups; however, age-related deficits persisted. fMRI results revealed that, across groups, direction of attention facilitated medial temporal lobe-mediated contextual binding processes during study and attenuated right PFC postretrieval monitoring effects at test. However, persistent age-related source memory deficits may be related to increased recruitment of medial anterior PFC during encoding, indicative of self-referential processing, as well as underrecruitment of lateral anterior PFC-mediated relational processes. Taken together, this study suggests that, even when supported, older adults may fail to selectively encode goal-relevant contextual details supporting source memory performance.

The effects of aging on material-independent and material-dependent neural correlates of source memory retrieval.

Age-related declines in source memory have been observed for various stimuli and associated details. These impairments may be related to alterations in brain regions contributing to source memory via material-independent processes and/or regions specialized for processing specific materials. Using event-related functional magnetic resonance imaging, we investigate the effects of aging on source memory and associated neural activity for words and objects. Source accuracy was equally impaired in older adults for both materials. Imaging data revealed both groups recruited similar networks of regions to support source memory accuracy irrespective of material, including parietal and prefrontal cortices (PFC) and the hippocampus. Age-related decreases in material-independent activity linked to postretrieval monitoring were observed in right lateral PFC. Additionally, age-related increases in source accuracy effects were shown in perirhinal cortex, which were positively correlated with performance in older adults, potentially reflecting functional compensation. In addition to group differences in material-independent regions, age-related crossover interactions for material-dependent source memory effects were observed in regions selectively engaged by objects. These results suggest that older adults' source memory impairments reflect alterations in regions making material-independent contributions to source memory retrieval, primarily the lateral PFC, but may be further impacted by changes in regions sensitive to particular materials.

Temporal order memory impairments in individuals with moderate-severe traumatic brain injury.

INTRODUCTION: Temporal order memory is a core cognitive function that underlies much of our behavior. The ability to bind together information within and across events, and to reconstruct that sequence of information, critically relies upon the hippocampal relational memory system. Recent work has suggested traumatic brain injury (TBI) may particularly impact hippocampally mediated relational memory. However, it is currently unclear whether such deficits extend to temporal order memory, and whether deficits only arise at large memory loads. The present study assessed temporal order memory in individuals with chronic, moderate-severe TBI across multiple set sizes. METHOD: Individuals with TBI and Neurotypical Comparison participants studied sequences of three to nine objects, one a time. At test, all items were re-presented in pseudorandom order, and participants indicated the temporal position (i.e., first, second, etc.) in which each object had appeared. Critically, we assessed both the frequency and the magnitude of errors (i.e., how far from its studied position was an item remembered). RESULTS: Individuals with TBI were not impaired for the smallest set size, but showed significant impairments at 5+ items. Group differences in the error frequency did not increase further with larger set sizes, but group differences in error magnitude did increase with larger memory loads. Individuals with TBI showed spared performance for the first object of each list (primacy) but were impaired on the last object (recency), though error frequency was better for last compared to middle items. CONCLUSIONS: Our findings demonstrate that TBI results in impaired temporal order memory for lists as small as five items, and that impairments are exacerbated with increasing memory loads. Assessments that test only small set sizes may be insufficient to detect these deficits. Further, these data highlight the importance of additional, sensitive measures in the assessment of cognitive impairments in TBI.

The effects of aging on material-independent and material-dependent neural correlates of contextual binding.

Previous behavioral research suggests that older adults exhibit impairments in source memory across a multitude of stimuli and associated details, possibly due to a deficit in contextual binding. However, it is unclear whether this binding deficit results from alterations in processes that are material-independent, processes that are specific to particular materials, or some combination of the two. We used event-related fMRI to investigate the effect of aging on contextual binding and associated neural activity for words and objects. Behavioral data showed similar age-related deficits in source memory accuracy for both words and objects. Imaging results revealed that young and older adults recruited similar networks of regions in support of contextual binding, independent of material, including the lateral prefrontal cortex (PFC) and hippocampus. Material-dependent binding effects were also present for both groups in ventrolateral prefrontal and parahippocampal cortices for words and objects, respectively. Older adults showed smaller material-independent contextual binding effects in frontal regions, namely the left dorsolateral PFC, and larger binding effects in the hippocampus. Further, age-related declines in object processing effects in extrastriate regions correlated with poorer source accuracy for objects. Collectively, these results suggest that age-related source memory deficits may be primarily due to changes in material-independent contextual binding processes. However, these impairments may be further impacted by impoverished item representations in material-specific processing regions.

Relational Memory at Short and Long Delays in Individuals With Moderate-Severe Traumatic Brain Injury.

Memory deficits are a common and frequently-cited consequence of moderate-severe traumatic brain injury (TBI). However, we know less about how TBI influences relational memory, which allows the binding of the arbitrary elements of experience and the flexible use and recombination of relational representations in novel situations. Relational memory is of special interest for individuals with TBI, given the vulnerability of the hippocampus to injury mechanisms, as well as a growing body of literature establishing the role of relational memory in flexible and goal-directed behavior. In this study, participants with and without a history of moderate-severe TBI completed a continuous relational memory task for face-scene pairings. Participants with TBI exhibited a disruption in relational memory not only when tested after a delay, but also when tested with no experimenter-imposed delay after stimulus presentation. Further, canonical assessments of working and episodic memory did not correspond with performance on the face-scene task, suggesting that this task may tap into relational memory differently and with greater sensitivity than standardized memory assessments. These results highlight the need for rigorous assessment of relational memory in TBI, which is likely to detect deficits that have specific consequences for community reintegration and long-term functional outcomes.

Dynamic Hippocampal and Prefrontal Contributions to Memory Processes and Representations Blur the Boundaries of Traditional Cognitive Domains.

The hippocampus has long been known to be a critical component of the memory system involved in the formation and use of long-term declarative memory. However, recent findings have revealed that the reach of hippocampal contributions extends to a variety of domains and tasks that require the flexible use of cognitive and social behavior, including domains traditionally linked to prefrontal cortex (PFC), such as decision-making. In addition, the prefrontal cortex (PFC) has gained traction as a necessary part of the memory system. These findings challenge the conventional characterizations of hippocampus and PFC as being circumscribed to traditional cognitive domains. Here, we emphasize that the ability to parsimoniously account for the breadth of hippocampal and PFC contributions to behavior, in terms of memory function and beyond, requires theoretical advances in our understanding of their characteristic processing features and mental representations. Notably, several literatures exist that touch upon this issue, but have remained disjointed because of methodological differences that necessarily limit the scope of inquiry, as well as the somewhat artificial boundaries that have been historically imposed between domains of cognition. In particular, this article focuses on the contribution of relational memory theory as an example of a framework that describes both the representations and processes supported by the hippocampus, and further elucidates the role of the hippocampal-PFC network to a variety of behaviors.

Self-referencing enhances recollection in both young and older adults.

Processing information in relation to the self enhances subsequent item recognition in both young and older adults and further enhances recollection at least in the young. Because older adults experience recollection memory deficits, it is unknown whether self-referencing improves recollection in older adults. We examined recollection benefits from self-referential encoding in older and younger adults and further examined the quality and quantity of episodic details facilitated by self-referencing. We further investigated the influence of valence on recollection, given prior findings of age group differences in emotional memory (i.e., "positivity effects"). Across the two experiments, young and older adults processed positive and negative adjectives either for self-relevance or for semantic meaning. We found that self-referencing, relative to semantic encoding, increased recollection memory in both age groups. In Experiment 1, both groups remembered proportionally more negative than positive items when adjectives were processed semantically; however, when adjectives were processed self-referentially, both groups exhibited evidence of better recollection for the positive items, inconsistent with a positivity effect in aging. In Experiment 2, both groups reported more episodic details associated with recollected items, as measured by a memory characteristic questionnaire, for the self-reference relative to the semantic condition. Overall, these data suggest that self-referencing leads to detail-rich memory representations reflected in higher rates of recollection across age.

The influence of directed attention at encoding on source memory retrieval in the young and old: an ERP study.

Neuroimaging evidence suggests that older adults exhibit deficits in frontally-mediated strategic retrieval processes, such as post-retrieval monitoring. Behavioral research suggests that explicitly directing attention toward source features during encoding may improve source memory for both young and older adults and alleviate age-related source memory impairments, in part, by reducing demands on post-retrieval monitoring. We investigated this hypothesis in the present event-related potential (ERP) study. Young and older adults attended to either objects and their presented color (source) or to the object alone during study and made color source memory decisions at test. We attempted to match performance between groups by halving the memory load for older adults. Behavioral results showed that, while direction of attention to object and color improved source memory for both groups, older adults benefited less than the young. ERPs revealed that demands on late right frontal effects, indicative of post-retrieval monitoring, were similarly reduced by directed attention at encoding for both groups. However, older adults showed reduced ERP correlates of recollection (parietal old-new effect), as well as a sustained widespread negativity, potentially indicative of memory searches for perceptual details in the face of impaired recollection. These results suggest that older adults, like the young, can engage in post-retrieval monitoring when source details are difficult to recover. However, impaired recollection may underlie persistent age-related source memory deficits, even when encoding is supported via directed attention.

The effects of aging on emotion-induced modulations of source retrieval ERPs: evidence for valence biases.

Many behavioral studies have shown that memory is enhanced for emotionally salient events across the lifespan. It has been suggested that this mnemonic boost may be observed for both age groups, particularly the old, in part because emotional information is retrieved with less effort than neutral information. Neuroimaging evidence suggests that inefficient retrieval processing (temporally delayed and attenuated) may contribute to age-related impairments in episodic memory for neutral events. It is not entirely clear whether emotional salience may reduce these age-related changes in neural activity associated with episodic retrieval for neutral events. Here, we investigated these ideas using event-related potentials (ERPs) to assess the neural correlates of successful source memory retrieval ("old-new effects") for neutral and emotional (negative and positive) images. Behavioral results showed that older adults demonstrated source memory impairments compared to the young but that both groups showed reduced source memory accuracy for negative compared to positive and neutral images; most likely due to an arousal-induced memory tradeoff for the negative images, which were subjectively more arousing than both positive and neutral images. ERP results showed that early onsetting old-new effects, between 100 and 300 ms, were observed for emotional but not neutral images in both age groups. Interestingly, these early effects were observed for negative items in the young and for positive items in the old. These ERP findings offer support for the idea that emotional events may be retrieved more automatically than neutral events across the lifespan. Furthermore, we suggest that very early retrieval mechanisms, possibly perceptual priming or familiarity, may underlie the negativity and positivity effects sometimes observed in the young and old, respectively, for various behavioral measures of attention and memory.

The effects of aging on ERP correlates of source memory retrieval for self-referential information.

Numerous behavioral studies have suggested that normal aging negatively affects source memory accuracy for various kinds of associations. Neuroimaging evidence suggests that less efficient retrieval processing (temporally delayed and attenuated) may contribute to these impairments. Previous aging studies have not compared source memory accuracy and corresponding neural activity for different kinds of source details; namely, those that have been encoded via a more or less effective strategy. Thus, it is not yet known whether encoding source details in a self-referential manner, a strategy suggested to promote successful memory in the young and old, may enhance source memory accuracy and reduce the commonly observed age-related changes in neural activity associated with source memory retrieval. Here, we investigated these issues by using event-related potentials (ERPs) to measure the effects of aging on the neural correlates of successful source memory retrieval ("old-new effects") for objects encoded either self-referentially or self-externally. Behavioral results showed that both young and older adults demonstrated better source memory accuracy for objects encoded self-referentially. ERP results showed that old-new effects onsetted earlier for self-referentially encoded items in both groups and that age-related differences in the onset latency of these effects were reduced for self-referentially, compared to self-externally, encoded items. These results suggest that the implementation of an effective encoding strategy, like self-referential processing, may lead to more efficient retrieval, which in turn may improve source memory accuracy in both young and older adults.