Face recognition is an important component of successful social interactions in humans. A large literature in social psychology has focused on the phenomenon termed the "other race" (ORE) effect, the tendency to be more proficient with face recognition within one's own ethnic group compared with other ethnic groups. Several potential hypotheses have been proposed for this effect, including perceptual expertise, social grouping, and holistic face processing. Recent work on mnemonic discrimination (i.e., the ability to resolve mnemonic interference among similar experiences) may provide a mechanistic account for the ORE. In the current study, we examined how discrimination and generalization in the presence of mnemonic interference may contribute to the ORE. We developed a database of computerized faces divided evenly among ethnic origins (Black, Caucasian, East Asian, South Asian), as well as morphed face stimuli that varied in the amount of similarity to the original stimuli (30%, 40%, 50%, and 60% morphs). Participants first examined the original unmorphed stimuli during study, then during test were asked to judge the prior occurrence of repetitions (targets), morphed stimuli (lures), and new stimuli (foils). We examined participants' ability to correctly reject similar morphed lures and found that it increased linearly as a function of face dissimilarity. We additionally found that Caucasian participants' mnemonic discrimination-generalization functions were sharply tuned for Caucasian faces but considerably less tuned for East Asian and Black faces. These results suggest that expertise plays an important role in resolving mnemonic interference, which may offer a mechanistic account for the ORE.

The extent to which current information is consistent with past experiences and our capacity to recognize or discriminate accordingly are key factors in flexible memory-guided behavior. Despite a wealth of evidence linking hippocampal and neocortical computations to these phenomena, many important factors remain poorly understood. One such factor is repeated encoding of learned information. In this experiment, participants completed a task in which study stimuli were incidentally encoded either once or three separate times during high-resolution fMRI scanning. We asked how repetition influenced recognition and discrimination memory judgments, and how this affects engagement of hippocampal and neocortical regions. Repetition revealed shifts in engagement in an anterior (ventral) CA1-thalamic-medial prefrontal network related to true and false recognition. Conversely, repetition revealed shifts in a posterior (dorsal) dentate/CA3-parahippocampal-restrosplenial network related to accurate discrimination. These differences in engagement were accompanied by task-related correlations in respective anterior and posterior networks. In particular, the anterior thalamic region observed during recognition judgments is functionally and anatomically consistent with nucleus reuniens in humans, and was found to mediate correlations between the anterior CA1 and medial prefrontal cortex. These findings offer new insights into how repeated experience affects memory and its neural substrates in hippocampal-neocortical networks. © 2016 Wiley Periodicals, Inc.

A vital component of episodic memory is the ability to determine the temporal order of remembered events. Although it has been demonstrated that the hippocampus plays a crucial role in this ability, the details of its contributions are not yet fully understood. One proposed contribution of the hippocampus is the reduction of mnemonic interference through pattern separation. Prior studies have used behavioral paradigms designed to assess this function in the temporal domain by evaluating the ability to determine the order of remembered events as a function of proximity in time. Results from these paradigms in older adults (OA) have been mixed, possibly due to limitations in controlling elapsed time and narrow range of temporal lags. Here, we introduce a novel behavioral paradigm designed to overcome these limitations. We report that OAs are impaired relative to younger adults at moderate and high temporal lags but not at low lags (where performance approached floor). We evaluated OAs' ability to benefit from primacy (enhanced order judgment on the first few items of any given sequence) and found two distinct subgroups: one group was on par with young adults [aged-unimpaired (AU)] and the other group was two standard deviations below the mean of young adults [aged-impaired (AI)]. Temporal discrimination performance in AU adults was consistent with a pattern separation deficit, while performance in AI adults was consistent with a generalized temporal processing deficit. We propose that the task introduced is a sensitive marker for episodic memory deficits with age, and may have diagnostic value for early detection of age-related pathology.

While aging is generally associated with episodic memory decline, not all older adults exhibit memory loss. Furthermore, emotional memories are not subject to the same extent of forgetting and appear preserved in aging. We conducted high-resolution fMRI during a task involving pattern separation of emotional information in older adults with and without age-related memory impairment (characterized by performance on a word-list learning task: low performers: LP vs. high performers: HP). We found signals consistent with emotional pattern separation in hippocampal dentate (DG)/CA3 in HP but not in LP individuals, suggesting a deficit in emotional pattern separation. During false recognition, we found increased DG/CA3 activity in LP individuals, suggesting that hyperactivity may be associated with overgeneralization. We additionally observed a selective deficit in basolateral amygdala-lateral entorhinal cortex-DG/CA3 functional connectivity in LP individuals during pattern separation of negative information. During negative false recognition, LP individuals showed increased medial temporal lobe functional connectivity, consistent with overgeneralization. Overall, these results suggest a novel mechanistic account of individual differences in emotional memory alterations exhibited in aging.

Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc.

Numerous studies have suggested that older adults preferentially remember positive information ("positivity effect"), however others have reported mixed results. One potential source of conflict is that aging is not a unitary phenomenon and individual differences exist. We modified a standard neuropsychological test to vary emotional content and tested memory at three time points (immediate/20 min/1 wk). Cognitively normal older adults were stratified into those with and without subclinical memory impairment. We found that the positivity effect was limited to those with subclinical memory impairment, suggesting that consideration of subclinical memory impairment is necessary for understanding age-related emotional memory alterations.

Detailed representations of past events rely on the ability to form associations between items and their contextual features (i.e., source memory), as well as the ability to distinctly represent a new event from a similar one stored in memory (i.e., pattern separation). These processes are both known to engage the hippocampus, although whether they share similar mechanisms remains unclear. It is also unknown if, and in which region(s), activity related to these processes overlaps and/or interacts. Here, we used high-resolution fMRI to examine the contributions of hippocampal subfields and neocortical areas to pattern separation and source memory with an experimental paradigm that concurrently tested both. During encoding, male and female human subjects incidentally studied items in one of four quadrants on the screen. During test, they viewed repeated items (targets), similar items (lures), and new items (foils) and were asked to indicate whether each item was old, similar, or new. Following each item judgment, subjects were asked to indicate the quadrant in which the original stimulus was presented. Thus, each lure trial had a lure discrimination component (taxing pattern separation) and a location judgment (source memory). We found two main response profiles: (1) pattern separation-related signals in DG/CA3 and perirhinal cortex and (2) source memory signals in posterior CA1, parahippocampal cortex, and angular gyrus. Whole-brain voxelwise analysis revealed that activity related to lure discrimination and source memory was largely nonoverlapping. These findings suggest that distinct processes underlie the retrieval of pattern separated item representations and recollection of source information.SIGNIFICANCE STATEMENT Recalling past events with detail and accuracy depends on the ability to remember the contextual features of an event (i.e., source memory) as well as the ability to distinguish among similar events in memory (i.e., pattern separation). Previous work has shown that these processes are behaviorally dissociable (e.g., people can have clear memory for context but misidentify people or items). However, both processes engage the hippocampus, and it is unclear whether they rely on shared or distinct neural mechanisms. Here, we used high-resolution fMRI to concurrently assess hippocampal and neocortical activity related to source memory and pattern separation. We found that activity related to these processes was largely nonoverlapping, shedding light on two complementary but distinct mechanisms supporting episodic memory.

It is well established that aging is associated with declines in episodic memory. In recent years, an emphasis has emerged on the development of behavioral tasks and the identification of biomarkers that are predictive of cognitive decline in healthy as well as pathological aging. Here, we describe a memory task designed to assess the accuracy of discrimination ability for the locations of objects. Object locations were initially encoded incidentally, and appeared in a single space against a 5 × 7 grid. During retrieval, subjects viewed repeated object-location pairings, displacements of 1, 2, 3, or 4 grid spaces, and maximal corner-to-opposite-corner displacements. Subjects were tasked with judging objects in this second viewing as having retained their original location, or having moved. Performance on a task such as this is thought to rely on the capacity of the individual to perform hippocampus-mediated pattern separation. We report a performance deficit associated with a physically healthy aged group compared to young adults specific to trials with low mnemonic interference. Additionally, for aged adults, performance on the task was correlated with performance on the delayed recall portion of the Rey Auditory Verbal Learning Test (RAVLT), a neuropsychological test sensitive to hippocampal dysfunction. In line with prior work, dividing the aged group into unimpaired and impaired subgroups based on RAVLT Delayed Recall scores yielded clearly distinguishable patterns of performance, with the former subgroup performing comparably to young adults, and the latter subgroup showing generally impaired memory performance even with minimal interference. This study builds on existing tasks used in the field, and contributes a novel paradigm for differentiation of healthy from possible pathological aging, and may thus provide an avenue for early detection of age-related cognitive decline.

A wealth of evidence has implicated the hippocampus and surrounding medial temporal lobe cortices in support of recognition memory. However, the roles of the various subfields of the hippocampus are poorly understood. In this study, we concurrently varied stimulus familiarization and repetition to engage different facets of recognition memory. Using high-resolution fMRI (1.5 mm isotropic), we observed distinct familiarity and repetition-related recognition signal profiles in the dentate gyrus (DG)/CA3 subfield in human subjects. The DG/CA3 demonstrated robust response suppression with repetition and familiarity-related facilitation. Both of these discrete responses were predictive of different aspects of behavioral performance. Consistent with previous work, we observed novelty responses in CA1 consistent with "match/mismatch detection," as well as mixed recognition signaling distributed across medial temporal lobe cortices. Additional analyses indicated that the repetition and familiarity-related signals in the DG/CA3 were strikingly dissociated along the hippocampal longitudinal axis and that activity in the posterior hippocampus was strongly correlated with the retrosplenial cortex. These data provide novel insight into the roles of hippocampal subfields in support of recognition memory and further provide evidence of a functional heterogeneity in the human DG/CA3, particularly along the longitudinal axis.