The Relationship between Neurobiological Function and Inflammation in Depressed Children and Adolescents: A Scoping Review.

INTRODUCTION: Neurobiological dysfunction is associated with depression in children and adolescents. While research in adult depression suggests that inflammation may underlie the association between depression and brain alterations, it is unclear if altered levels of inflammatory markers provoke neurobiological dysfunction in early-onset depression. The aim of this scoping review was to provide an overview of existing literature investigating the potential interaction between neurobiological function and inflammation in depressed children and adolescents. METHODS: Systematic searches were conducted in six databases. Primary research studies that included measures of both neurobiological functioning and inflammation among children (≤18 years) with a diagnosis of depression were included. RESULTS: Four studies (240 participants; mean age 16.0 ± 0.6 years, 62% female) meeting inclusion criteria were identified. Studies primarily examined the inflammatory markers interleukin 6, tumor necrosis factor alpha, C-reactive protein, and interleukin 1 beta. Exploratory whole brain imaging and analysis as well as region of interest approaches focused on the anterior cingulate cortex, basal ganglia, and white matter tracts were conducted. Most studies found correlations between neurobiological function and inflammatory markers; however, depressive symptoms were not observed to moderate these effects. CONCLUSIONS: A small number of highly heterogeneous studies indicate that depression may not modulate the association between altered inflammation and neurobiological dysfunction in children and adolescents. Replication in larger samples using consistent methodological approaches (focus on specific inflammatory markers, examine certain brain areas) is needed to advance the knowledge of potential neuro-immune interactions early in the course of depression.

Elucidating medial temporal and frontal lobe contributions to approach-avoidance conflict decision-making using functional MRI and the hierarchical drift diffusion model.

The prefrontal cortex (PFC) has long been associated with arbitrating between approach and avoidance in the face of conflicting and uncertain motivational information, but recent work has also highlighted medial temporal lobe (MTL) involvement. It remains unclear, however, how the contributions of these regions differ in their resolution of conflict information and uncertainty. We designed an fMRI paradigm in which participants approached or avoided object pairs that differed by motivational conflict and outcome uncertainty (complete certainty vs. complete uncertainty). Behavioral data and decision-making parameters estimated using the hierarchical drift diffusion model revealed that participants' responding was driven by conflict rather than uncertainty. Our neural data suggest that PFC areas contribute to cognitive control during approach-avoidance conflict by potentially adjusting response caution and the strength of evidence generated towards either choice, with differential involvement of anterior cingulate cortex and dorsolateral prefrontal cortex. The MTL, on the other hand, appears to contribute to evidence generation, with the hippocampus linked to evidence accumulation for stimuli. Although findings within perirhinal cortex were comparatively equivocal, some evidence suggests contributions to perceptual representations, particularly under conditions of threat. Our findings provide evidence that MTL and PFC regions may contribute uniquely to arbitrating approach-avoidance conflict.

Perirhinal Cortex is Involved in the Resolution of Learned Approach-Avoidance Conflict Associated with Discrete Objects.

The rodent ventral and primate anterior hippocampus have been implicated in approach-avoidance (AA) conflict processing. It is unclear, however, whether this structure contributes to AA conflict detection and/or resolution, and if its involvement extends to conditions of AA conflict devoid of spatial/contextual information. To investigate this, neurologically healthy human participants first learned to approach or avoid single novel visual objects with the goal of maximizing earned points. Approaching led to point gain and loss for positive and negative objects, respectively, whereas avoidance had no impact on score. Pairs of these objects, each possessing nonconflicting (positive-positive/negative-negative) or conflicting (positive-negative) valences, were then presented during functional magnetic resonance imaging. Participants either made an AA decision to score points (Decision task), indicated whether the objects had identical or differing valences (Memory task), or followed a visual instruction to approach or avoid (Action task). Converging multivariate and univariate results revealed that within the medial temporal lobe, perirhinal cortex, rather than the anterior hippocampus, was predominantly associated with object-based AA conflict resolution. We suggest the anterior hippocampus may not contribute equally to all learned AA conflict scenarios and that stimulus information type may be a critical and overlooked determinant of the neural mechanisms underlying AA conflict behavior.

Evidence for the incorporation of temporal duration information in human hippocampal long-term memory sequence representations.

There has been much interest in how the hippocampus codes time in support of episodic memory. Notably, while rodent hippocampal neurons, including populations in subfield CA1, have been shown to represent the passage of time in the order of seconds between events, there is limited support for a similar mechanism in humans. Specifically, there is no clear evidence that human hippocampal activity during long-term memory processing is sensitive to temporal duration information that spans seconds. To address this gap, we asked participants to first learn short event sequences that varied in image content and interval durations. During fMRI, participants then completed a recognition memory task, as well as a recall phase in which they were required to mentally replay each sequence in as much detail as possible. We found that individual sequences could be classified using activity patterns in the anterior hippocampus during recognition memory. Critically, successful classification was dependent on the conjunction of event content and temporal structure information (with unsuccessful classification of image content or interval duration alone), and further analyses suggested that the most informative voxels resided in the anterior CA1. Additionally, a classifier trained on anterior CA1 recognition data could successfully identify individual sequences from the mental replay data, suggesting that similar activity patterns supported participants' recognition and recall memory. Our findings complement recent rodent hippocampal research, and provide evidence that long-term sequence memory representations in the human hippocampus can reflect duration information in the order of seconds.

Corticocortical and Thalamocortical Changes in Functional Connectivity and White Matter Structural Integrity after Reward-Guided Learning of Visuospatial Discriminations in Rhesus Monkeys.

The frontal cortex and temporal lobes together regulate complex learning and memory capabilities. Here, we collected resting-state functional and diffusion-weighted MRI data before and after male rhesus macaque monkeys received extensive training to learn novel visuospatial discriminations (reward-guided learning). We found functional connectivity changes in orbitofrontal, ventromedial prefrontal, inferotemporal, entorhinal, retrosplenial, and anterior cingulate cortices, the subicular complex, and the dorsal, medial thalamus. These corticocortical and thalamocortical changes in functional connectivity were accompanied by related white matter structural alterations in the uncinate fasciculus, fornix, and ventral prefrontal tract: tracts that connect (sub)cortical networks and are implicated in learning and memory processes in monkeys and humans. After the well-trained monkeys received fornix transection, they were impaired in learning new visuospatial discriminations. In addition, the functional connectivity profile that was observed after the training was altered. These changes were accompanied by white matter changes in the ventral prefrontal tract, although the integrity of the uncinate fasciculus remained unchanged. Our experiments highlight the importance of different communication relayed among corticocortical and thalamocortical circuitry for the ability to learn new visuospatial associations (learning-to-learn) and to make reward-guided decisions.SIGNIFICANCE STATEMENT Frontal neural networks and the temporal lobes contribute to reward-guided learning in mammals. Here, we provide novel insight by showing that specific corticocortical and thalamocortical functional connectivity is altered after rhesus monkeys received extensive training to learn novel visuospatial discriminations. Contiguous white matter fiber pathways linking these gray matter structures, namely, the uncinate fasciculus, fornix, and ventral prefrontal tract, showed structural changes after completing training in the visuospatial task. Additionally, different patterns of functional and structural connectivity are reported after removal of subcortical connections within the extended hippocampal system, via fornix transection. These results highlight the importance of both corticocortical and thalamocortical interactions in reward-guided learning in the normal brain and identify brain structures important for memory capabilities after injury.

The Human Medial Temporal Lobe Is Necessary for Remembering Durations within a Sequence of Events but Not Durations of Individual Events.

Recent interest in the role of the hippocampus in temporal aspects of cognition has been fueled, in part, by the observation of "time" cells in the rodent hippocampus-that is, cells that have differential firing patterns depending on how long ago an event occurred. Such cells are thought to provide an internal representation of elapsed time. Yet, the hippocampus is not needed for processing temporal duration information per se, at least on the order of seconds, as evidenced by intact duration judgments in rodents and humans with hippocampal damage. Rather, it has been proposed that the hippocampus may be essential for coding higher order aspects of temporal mnemonic processing, such as those needed to temporally organize a sequence of events that form an episode. To examine whether (1) the hippocampus uses duration information in the service of establishing temporal relations among events and (2) its role in memory for duration is unique to sequences, we tested amnesic patients with medial-temporal lobe damage (including the hippocampus). We hypothesized that medial-temporal lobe damage should impair the ability to remember sequential duration information but leave intact judgments about duration devoid of a sequential demand. We found that amnesics were impaired in making judgments about durations within a sequence but not in judging single durations. This impairment was not due to higher cognitive load associated with duration judgments about sequences. In convergence with rodent and human fMRI work, these findings shed light on how time coding in the hippocampus may contribute to temporal cognition.

Mapping the anatomy of perceptual pseudoneglect. A multivariate approach.

Fundamental to the understanding of the functions of spatial cognition and attention is to clarify the underlying neural mechanisms. It is clear that relatively right-dominant activity in ventral and dorsal parieto-frontal cortex is associated with attentional reorienting, certain forms of mental imagery and spatial working memory for higher loads, while lesions mostly to right ventral areas cause spatial neglect with pathological attentional biases to the right side. In contrast, complementary leftward biases in healthy people, called pseudoneglect, have been associated with varying patterns of cortical activity. Notably, this inconsistency may be explained, at least in part, by the fact that pseudoneglect studies have often employed experimental paradigms that do not control sufficiently for cognitive processes unrelated to pseudoneglect. To address this issue, here we administered a carefully designed continuum of pseudoneglect and control tasks in healthy adults while using functional magnetic resonance imaging (fMRI). Data submitted to partial least square (PLS) imaging analysis yielded a significant latent variable that identified a right-dominant network of brain regions along the intra-occipital and -parietal sulci, frontal eye fields and right ventral cortex in association with perceptual pseudoneglect. Our results shed new light on the interplay of attentional and cognitive systems in pseudoneglect.

Double dissociation of learned approach-avoidance conflict processing and spatial pattern separation along the dorsoventral axis of the dentate gyrus.

The ventral portion of the rodent hippocampus (HPC; anterior in primates) has been implicated in the detection and resolution of approach-avoidance conflict, which arises when an organism encounters a stimulus that predicts both positive and negative outcomes. Previous work has found differential regulation of approach-avoidance conflict behavior by the CA3 and CA1 subfields, with inhibition of ventral CA3 increasing approach toward conflicting stimuli and inhibition of the ventral CA1 potentiating avoidance. Here, we sought to extend these findings by investigating the role of the dentate gyrus (DG), the input region of the HPC, in learned approach-avoidance conflict processing in rats. Animals were first trained to acquire three different visuotactile cue-outcome associations in separate arms of a Y-maze (appetitive, aversive, and neutral). Postacquisition, they were administered a "conflict test," in which they were presented with a choice between exploring an arm in which the appetitive and aversive cues were concurrently presented (conflict stimulus), and another arm containing the neutral stimulus. GABAR-mediated inactivation of the ventral DG, but not dorsal DG, potentiated approach behavior toward the conflict stimulus, similar to the effects of ventral CA3 inactivation. In contrast, dorsal DG, but not ventral DG, inactivation was found to impair performance on a metric spatial discrimination task, which is commonly used as a test of pattern separation. The findings of this study demonstrate a robust double dissociation between the ventral and dorsal aspects of the DG, in line with previous reports of functional differences along the longitudinal axis of the HPC.

Therapeutic cooperation between auranofin, a thioredoxin reductase inhibitor and anti-PD-L1 antibody for treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBCs) is a very aggressive and lethal form of breast cancer with no effective targeted therapy. Neoadjuvant chemotherapies and radiotherapy remains a mainstay of treatment with only 25-30% of TNBC patients responding. Thus, there is an unmet clinical need to develop novel therapeutic strategies for TNBCs. TNBC cells have increased intracellular oxidative stress and suppressed glutathione, a major antioxidant system, but still, are protected against higher oxidative stress. We screened a panel of antioxidant genes using the TCGA and METABRIC databases and found that expression of the thioredoxin pathway genes is significantly upregulated in TNBC patients compared to non-TNBC patients and is correlated with adverse survival outcomes. Treatment with auranofin (AF), an FDA-approved thioredoxin reductase inhibitor caused specific cell death and impaired the growth of TNBC cells grown as spheroids. Furthermore, AF treatment exerted a significant in vivo antitumor activity in multiple TNBC models including the syngeneic 4T1.2 model, MDA-MB-231 xenograft and patient-derived tumor xenograft by inhibiting thioredoxin redox activity. We, for the first time, showed that AF increased CD8+Ve T-cell tumor infiltration in vivo and upregulated immune checkpoint PD-L1 expression in an ERK1/2-MYC-dependent manner. Moreover, combination of AF with anti-PD-L1 antibody synergistically impaired the growth of 4T1.2 primary tumors. Our data provide a novel therapeutic strategy using AF in combination with anti-PD-L1 antibody that warrants further clinical investigation for TNBC patients.

Exploring the interaction between approach-avoidance conflict and memory processing.

The medial temporal lobe (MTL) has been implicated in approach-avoidance (AA) conflict processing, which arises when a stimulus is imbued with both positive and negative valences. Notably, since the MTL has been traditionally viewed as a mnemonic brain region, a pertinent question is how AA conflict and memory processing interact with each other behaviourally. We conducted two behavioural experiments to examine whether increased AA conflict processing has a significant impact on incidental mnemonic encoding and inferential reasoning. In Experiment 1, participants first completed a reward and punishment AA task and were subsequently administered a surprise recognition memory test for stimuli that were presented during high and no AA conflict trials. In Experiment 2, participants completed a reward and punishment task in which they learned the valences of objects presented in pairs (AB, BC pairs). Next, we assessed their ability to integrate information across these pairs (infer A-C relationships) and examined whether inferential reasoning was more challenging across objects with conflicting compared to non-conflicting incentive values. We observed that increased motivational conflict did not significantly impact encoding or inferential reasoning. Potential explanations for these findings are considered, including the possibility that AA conflict and memory processing are not necessarily intertwined behaviourally.

How are visual words represented? Insights from EEG-based visual word decoding, feature derivation and image reconstruction.

Investigations into the neural basis of reading have shed light on the cortical locus and the functional role of visual-orthographic processing. Yet, the fine-grained structure of neural representations subserving reading remains to be clarified. Here, we capitalize on the spatiotemporal structure of electroencephalography (EEG) data to examine if and how EEG patterns can serve to decode and reconstruct the internal representation of visually presented words in healthy adults. Our results show that word classification and image reconstruction were accurate well above chance, that their temporal profile exhibited an early onset, soon after 100 ms, and peaked around 170 ms. Further, reconstruction results were well explained by a combination of visual-orthographic word properties. Last, systematic individual differences were detected in orthographic representations across participants. Collectively, our results establish the feasibility of EEG-based word decoding and image reconstruction. More generally, they help to elucidate the specific features, dynamics, and neurocomputational principles underlying word recognition.

Multivoxel pattern similarity suggests the integration of temporal duration in hippocampal event sequence representations.

Recent rodent work suggests the hippocampus may provide a temporal representation of event sequences, in which the order of events and the interval durations between them are encoded. There is, however, limited human evidence for the latter, in particular whether the hippocampus processes duration information pertaining to the passage of time rather than qualitative or quantitative changes in event content. We scanned participants while they made match-mismatch judgements on each trial between a study sequence of events and a subsequent test sequence. Participants explicitly remembered event order or interval duration information (Experiment 1), or monitored order only, with duration being manipulated implicitly (Experiment 2). Hippocampal study-test pattern similarity was significantly reduced by changes to order or duration in mismatch trials, even when duration was processed implicitly. Our findings suggest the human hippocampus processes short intervals within sequences and support the idea that duration information is integrated into hippocampal mnemonic representations.

Does Family History of Alcohol Use Disorder Relate to Differences in Regional Brain Volumes? A Descriptive Review with New Data.

BACKGROUND: Differences in regional brain volumes as a function of family history (FH) of alcohol use disorder (AUD) have been reported, and it has been suggested that these differences might index genetic risk for AUD. However, results have been inconsistent. The aims of the current study were (i) to provide an updated descriptive review of the existing literature and (ii) to examine the association of FH with indices of subcortical volumes and cortical thickness in a sample of youth recruited based on FH status. METHODS: To address aim 1, a literature search located 15 published studies comprising 1,735 participants. Studies were characterized according to population, analytic methods, regions of interest, and primary findings. To address the second aim, we examined volumetric and cortical thickness in a sample of 69 youth (mean age = 19.71 years, SD = 0.79) recruited based on FH status and matched on drinking variables. Associations of sex and alcohol use with volumetric outcomes were also examined. RESULTS: Our descriptive review revealed an inconsistent pattern of results with respect to the presence, direction, and regional specificity of volumetric differences across FH groups. The most consistent finding, significantly smaller amygdala volumes in FH+ participants, was not replicated in all studies. In the current sample of youth, measures of subcortical volumes and cortical thickness did not significantly differ as a function of FH, sex, or their interaction. CONCLUSIONS: Evidence for FH group differences in regional brain volumes is inconsistent, and the current study failed to detect any group differences. Further research is needed to confirm the reproducibility of FH group differences and implications for AUD risk.

Perception of Impossible Scenes Reveals Differential Hippocampal and Parahippocampal Place Area Contributions to Spatial Coherency.

Surprisingly little is known about how the brain combines spatial elements to form a coherent percept. Regions that may underlie this process include the hippocampus (HC) and parahippocampal place area (PPA), regions central to spatial perception but whose role in spatial coherency has not been explored. Participants were scanned with functional MRI while they judged whether Escher-like scenes were possible or impossible. Univariate analyses revealed differential HC and PPA involvement, with greater HC activity during spatial incoherency detection and more PPA activity during spatial coherency detection. Recognition and eye-tracking data ruled out long- or short-term memory confounds. Multivariate statistics demonstrated spatial coherency-dependent functional connectivity for the HC, but not PPA, with greater HC connectivity to various brain regions including lateral occipital complex during spatial incoherency detection. We suggest the PPA is preferentially involved during the perception of spatially coherent scenes, whereas the HC binds distinct features to create coherent representations. © 2016 Wiley Periodicals, Inc.

Examining the Role of the Human Hippocampus in Approach-Avoidance Decision Making Using a Novel Conflict Paradigm and Multivariate Functional Magnetic Resonance Imaging.

Rodent models of anxiety have implicated the ventral hippocampus in approach-avoidance conflict processing. Few studies have, however, examined whether the human hippocampus plays a similar role. We developed a novel decision-making paradigm to examine neural activity when participants made approach/avoidance decisions under conditions of high or absent approach-avoidance conflict. Critically, our task required participants to learn the associated reward/punishment values of previously neutral stimuli and controlled for mnemonic and spatial processing demands, both important issues given approach-avoidance behavior in humans is less tied to predation and foraging compared to rodents. Participants played a points-based game where they first attempted to maximize their score by determining which of a series of previously neutral image pairs should be approached or avoided. During functional magnetic resonance imaging, participants were then presented with novel pairings of these images. These pairings consisted of images of congruent or opposing learned valences, the latter creating conditions of high approach-avoidance conflict. A data-driven partial least squares multivariate analysis revealed two reliable patterns of activity, each revealing differential activity in the anterior hippocampus, the homolog of the rodent ventral hippocampus. The first was associated with greater hippocampal involvement during trials with high as opposed to no approach-avoidance conflict, regardless of approach or avoidance behavior. The second pattern encompassed greater hippocampal activity in a more anterior aspect during approach compared to avoid responses, for conflict and no-conflict conditions. Multivoxel pattern classification analyses yielded converging findings, underlining a role of the anterior hippocampus in approach-avoidance conflict decision making. SIGNIFICANCE STATEMENT: Approach-avoidance conflict has been linked to anxiety and occurs when a stimulus or situation is associated with reward and punishment. Although rodent work has implicated the hippocampus in approach-avoidance conflict processing, there is limited data on whether this role applies to learned, as opposed to innate, incentive values, and whether the human hippocampus plays a similar role. Using functional neuroimaging with a novel decision-making task that controlled for perceptual and mnemonic processing, we found that the human hippocampus was significantly active when approach-avoidance conflict was present for stimuli with learned incentive values. These findings demonstrate a role for the human hippocampus in approach-avoidance decision making that cannot be explained easily by hippocampal-dependent long-term memory or spatial cognition.

Early cognitive decline in older adults better predicts object than scene recognition performance.

There is an ongoing debate regarding the nature of memory deficits that occur in the early stages of mild cognitive impairment (MCI). MCI has been associated with atrophy to regions that process objects, namely perirhinal and lateral entorhinal cortices. However, it is currently unclear whether older adults with early MCI will show memory deficits that are specific to objects, or whether they will also show memory deficits for other stimulus classes, such as scenes. We tested 75 older adults using an object and scene recognition task with stimulus-specific interference (i.e., exposure to irrelevant object or scene stimuli). We found an interaction (P = 0.05) whereby scores on the Montreal Cognitive Assessment, a neuropsychological test with high sensitivity to MCI, shared a stronger relationship with object recognition than with scene recognition performance. Interestingly, this relationship was not modulated by the stimulus category of interfering items. To further explore these findings, we also tested an amnesic patient (DA) with known medial temporal lobe damage. Like older adults with early signs of MCI, DA showed poorer object recognition than scene recognition performance. Additionally, his performance was not modulated by the stimulus category of interfering material. By demonstrating that object memory is more predictive of cognitive decline than scene memory, these findings support the notion of perirhinal and lateral entorhinal cortex dysfunction in the early stages of MCI. © 2016 Wiley Periodicals, Inc.

Medical Student and Primary Care Physician Perception of the Surgical Management of Upper- and Lower-Extremity Peripheral Nerve Entrapment.

BACKGROUND: Upper- and lower-extremity peripheral neuropathies are commonly encountered in the primary care setting and account for 14.3 million specialist referrals in the United States annually. Despite the integral role of plastic surgeons in the development of the field of peripheral nerve surgery, plastic surgeons are not commonly recognized as peripheral nerve specialists. The purpose of this study was to investigate the pattern of diagnosis, treatment, and referral of upper- and lower-extremity peripheral nerve entrapment syndromes by both medical students and primary care providers. METHODS: An online survey including 5 peripheral nerve entrapment clinical scenarios (2 upper extremity and 3 lower extremity) was administered to medical students and primary care providers at a large academic medical center. Respondents were surveyed for level of training, prior clinical exposure, initial diagnostic studies of choice, initial therapeutic modalities of choice, need for subspecialty referral, and appropriate surgical subspecialists for management of the peripheral nerve entrapment. RESULTS: Overall, 248 medical students (38.3% response rate) and 54 primary care providers (13.5% response rate) completed the study. The majority of medical students and primary care providers indicated prior clinical experience with upper-extremity peripheral nerve entrapment in contrast to lower-extremity peripheral nerve entrapment with 26.2% and 39.9% of medical students and primary care physicians reporting prior clinical exposure, respectively. Medical students and primary care providers identified orthopedic surgery as the preferred choice for subspecialty referral for both upper- and lower-extremity peripheral nerve entrapment. Primary care physicians are more inclined to initially manage upper-extremity nerve entrapment without referral to other specialties than for the management of lower-extremity nerve entrapment; 38.0% and 61.1% of the primary care physicians surveyed would refer to another specialty for the initial management of carpal tunnel and cubital tunnel syndromes, in contrast to 83.0%, 90.0%, and 88.2% for the management of common peroneal nerve compression, sural nerve compression, and deep peroneal nerve compression, respectively. CONCLUSIONS: We contend that early education of medical students and primary care providers regarding the role of plastic surgeons as peripheral nerve specialists may improve future referral patterns.

Multivariate fMRI and Eye Tracking Reveal Differential Effects of Visual Interference on Recognition Memory Judgments for Objects and Scenes.

Recent work has demonstrated that the perirhinal cortex (PRC) supports conjunctive object representations that aid object recognition memory following visual object interference. It is unclear, however, how these representations interact with other brain regions implicated in mnemonic retrieval and how congruent and incongruent interference influences the processing of targets and foils during object recognition. To address this, multivariate partial least squares was applied to fMRI data acquired during an interference match-to-sample task, in which participants made object or scene recognition judgments after object or scene interference. This revealed a pattern of activity sensitive to object recognition following congruent (i.e., object) interference that included PRC, prefrontal, and parietal regions. Moreover, functional connectivity analysis revealed a common pattern of PRC connectivity across interference and recognition conditions. Examination of eye movements during the same task in a separate study revealed that participants gazed more at targets than foils during correct object recognition decisions, regardless of interference congruency. By contrast, participants viewed foils more than targets for incorrect object memory judgments, but only after congruent interference. Our findings suggest that congruent interference makes object foils appear familiar and that a network of regions, including PRC, is recruited to overcome the effects of interference.

The perirhinal cortex and recognition memory interference.

There has recently been an increase in interest in the effects of visual interference on memory processing, with the aim of elucidating the role of the perirhinal cortex (PRC) in recognition memory. One view argues that the PRC processes highly complex conjunctions of object features, and recent evidence from rodents suggests that these representations may be vital for buffering against the effects of pre-retrieval interference on object recognition memory. To investigate whether PRC-dependent object representations play a similar role in humans, we used functional magnetic resonance imaging to scan neurologically healthy participants while they performed a novel interference-match-to-sample task. This paradigm was specifically designed to concurrently assess the impact of object versus spatial interference, on recognition memory for objects or scenes, while keeping constant the amount of object and scene information presented across all trials. Activity at retrieval was examined, within an anatomically defined PRC region of interest, according to the demand for object or scene memory, following a period of object compared with spatial interference. Critically, we found greater PRC activity for object memory following object interference, compared with object memory following scene interference, and no difference between object and scene interference for scene recognition. These data demonstrate a role for the human PRC during object recognition memory, following a period of object, but not scene interference, and emphasize the importance of representational content to mnemonic processing.

Older adults can use memory for distinctive objects, but not distinctive scenes, to rescue associative memory deficits.

Associative memory deficits in aging are frequently characterized by false recognition of novel stimulus associations, particularly when stimuli are similar. Introducing distinctive stimuli, therefore, can help guide item differentiation in memory and can further our understanding of how age-related brain changes impact behavior. How older adults use different types of distinctive information to distinguish overlapping events in memory and to avoid false associative recognition is still unknown. To test this, we manipulated the distinctiveness of items from two stimulus categories, scenes and objects, across three conditions: (1) distinct scenes paired with similar objects, (2) similar scenes paired with distinct objects, and (3) similar scenes paired with similar objects. Young and older adults studied scene-object pairs and then made both remember/know judgments toward single items as well as associative memory judgments to old and novel scene-object pairs ("Were these paired together?"). Older adults showed intact single item recognition of scenes and objects, regardless of whether those objects and scenes were similar or distinct. In contrast, relative to younger adults, older adults showed elevated false recognition for scene-object pairs, even when the scenes were distinct. These age-related associative memory deficits, however, disappeared if the pair contained an object that was visually distinct. In line with neural evidence that hippocampal functioning and scene processing decline with age, these results suggest that older adults can rely on memory for distinct objects, but not for distinct scenes, to distinguish between memories with overlapping features.