Medial Temporal Lobe Function Research Articles

Individual Differences in Older Adult Frontal Lobe Function Relate to Memory and Neural Activity for Self-Relevant and Emotional Content.

Older adults show memory benefits for self-relevant and emotional content, but there are individual differences in this effect. It has been debated whether processing of self-relevant and emotional information relies on similar processes to one another. We examined whether variation in frontal lobe (FL) function among older adults related similarly to the processing of self-relevant information as it did to emotional information, or whether these relations diverged. While undergoing fMRI, participants (ages 60-88) viewed positive, negative, and neutral objects, and imagined placing those objects in either their home or a stranger's home. Participants completed a surprise memory test outside of the MRI. In a separate session, a cognitive battery was collected and composite scores measuring FL and medial temporal lobe function were computed and related to the behavioral memory performance and the neural engagement during fMRI. Behaviorally, FL function related to memory for self-relevant, but not emotional content. Older adults with higher FL function demonstrated reduced self-bias in memory performance. During the processing of self-relevant stimuli, independent of emotion, levels of activity in the middle frontal gyrus showed positive associations with FL function. This relationship was not driven by compensatory activity or disruptions to nonself-relevant neutral content. These findings point to divergence in the cognitive functions relating to memory enhancements for self- and emotional-relevance. The results further suggest self-relevance as a mnemonic device for older adults, especially in those with lower FL function.

Individual differences in age-related neurocognitive outcomes: within-subject assessment of memory for odors.

Cognitive decline is a common feature of aging, particularly in memory domains supported by the medial temporal lobe (MTL). The ability to identify intervention strategies to treat or prevent this decline is challenging due to substantial variability between adults in terms of age of onset, rate and severity of decline, and many factors that could influence cognitive reserve. These factors can be somewhat mitigated by use of within-subject designs. Aged outbred Long-Evans rats have proven useful for identifying translationally relevant substrates contributing to age-related decline in MTL-dependent memory. In this population, some animals show reliable impairment on MTL-dependent tasks while others perform within the range of young adult rats. However, currently there are relatively few within-subject behavior protocols for assessing MTL function over time, and most require extensive training and appetitive motivation for associative learning. In the current study, we aimed to test whether water maze learning impairments in aged Long-Evans rats would be predictive of delayed recognition memory impairments and whether these odor memory impairments would be stable within subjects over multiple rounds of testing.

SOCIAL CONNECTIVITY IS ASSOCIATED WITH INCREASED PERFORMANCE ON MEDIAL TEMPORAL LOBE FUNCTION IN OLDER AFRICAN AMERICANS

Abstract Research links social connectivity to cognitive function in older adults. However, many of the studies relating social connectivity to cognitive function focused on global cognition—orientation/attention, memory, verbal fluency, language, and visuospatial ability domains. In this study, we aimed to assess the association of social connectivity with generalization, a domain of cognition which relies on hippocampal function, in a population of older African Americans residing in the Greater Newark area. Specifically, we examined the impact of social connectivity on generalization using sensitive measures that tap into medial temporal lobe (MTL) function. Participants (N = 74; M = 73.84) from an ongoing study, Pathways to Healthy Aging in African Americans—a Rutgers University-Newark community partnership fostered over 16 years of community engagement, health education, and public service—responded to measures of cognitive function, social network, social engagement, mental health, and demographic details. Also, they completed a task-based functional Magnetic Resonance Imaging. Results showed that marital status was negatively associated with MTL function, with those that are either single, divorced, or separated outperforming those that are married. Similarly, depressive symptoms had a negative association with MTL function. Further, the linear combination of social network variables and covariates significantly predicted MTL function. Our findings illuminate the benefits of social connectivity and resources on cognitive skills, and amplify the need to study the brain in the social context.

The medial temporal lobe structure and function support positive affect

Positive affect (PA) is not only associated with individuals' psychological and physical health, but also their cognitive processes. However, whether medial temporal lobe (MTL) and its subfields' volume/functional connectivity can explain individual variability in PA remains understudied. We investigated the morphological (i.e., grey matter volume; GMV) and functional characteristics (i.e., resting-state functional connectivity; rsFC) of PA with a combination of univariate and multivariate pattern analyses (MVPA) using a large sample of participants (n = 321). We simultaneously collected the T1-weighted (n = 321), high-resolution MTL T2-weighted, and resting-state functional imaging data (n = 209). The MTL and its subfields' volumes, including the CA1, CA2+3, DG, and subiculum (SUB), perirhinal cortex (PRC), and parahippocampus (PHC), were extracted using an automatic segmentation of hippocampal subfields (ASHS) software. The morphological results revealed that GMVs in the prefrontal-occipital and limbic (i.e., hippocampus, amygdala, and PHC) systems were associated with variability in PA at the whole-brain level using MVPA but not univariate analysis. Linear regression results further revealed a positive association between the MTL subfields’ GMV, especially for the right PRC, and PA after controlling for several covariates. PRC-seed-based rsFC analyses further revealed that its couplings with the fronto-parietal-occipital system predicted PA in both univariate and MVPA. These findings provide novel insights into the neuroanatomical and functional substrates underlying human PA trait. Findings also suggest critical contributions of the MTL and its subfield of the perirhinal cortex, but not hippocampal subfields, as well as its functional coupling with the fronto-parietal control-system on the formation of PA.

Investigating the impact of healthy aging on memory for temporal duration and order

ABSTRACT Temporal information, including information about temporal order and duration, is a fundamental component of event sequence memory. While previous research has demonstrated that aging can have a detrimental effect on memory for temporal order, there has been limited insight into the effect of aging on memory for durations, particularly within the context of sequences. In the current study, neurologically healthy young and older participants were administered two temporal match-mismatch tasks: one in which they were instructed on each trial to compare the temporal order or duration information of stimulus sequences presented first in a study phase and then, after a short delay, in a test phase (event sequence task); and a second in which participants were required to compare single durations or sequences of durations across study and test phases of each trial (pinwheel task). Consistent with the literature, the older participants were significantly poorer compared to their younger counterparts at making temporal order match-mismatch judgments in the event sequence task. In addition to this, data from both tasks suggested that the older adults were also less accurate at match-mismatch judgments based on duration information, with tentative evidence from the pinwheel task to suggest that this age-related effect was most prominent when the duration information was presented within a sequence. We suggest that age-related changes to medial temporal and frontal lobe function may contribute to changes in memory for temporal information in older adults, given the importance of these regions to event sequence memory.

Training with Odors Impacts Hippocampal Thickness in Patients with Mild Cognitive Impairment.

The olfactory system is affected early in Alzheimer's disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI). Olfactory training is effective for improving olfactory and cognitive function by stimulating the olfactory pathway, but its effect on patients with MCI remains unclear. The aim of this randomized, prospective, controlled, blinded study was to assess whether a 4-month period of olfactory training (frequent short-term sniffing various odors) may have an effect on olfactory function, cognitive function, and morphology of medial temporal lobe (MTL) subregions and olfactory bulb in MCI patients. A total of thirty-seven MCI patients were randomly assigned to the training group or a placebo group, which were performed twice a day for 4 months. Olfactory assessments, cognitive tests and magnetic resonance imaging were performed at the baseline and follow-up period. After the training, there was an increase in odor discrimination, and increased cortical thickness of bilateral hippocampus (CA23DG and CA1) and mean MTL. Additionally, the change of olfactory score was positively associated with change of volume of olfactory bulb and hippocampus; the change of global cognition was positively associated with change of cortical thickness of hippocampus, entorhinal cortex and mean MTL; the change of cortical thickness of entorhinal cortex was positively associated with change of executive function. Olfactory training was associated with an increase in cortical thickness of the hippocampus but not olfactory bulb volume in patients with MCI. Olfactory training may serve as an early intervention of preventing hippocampal atrophy.

Blunted neuroeconomic loss aversion in schizophrenia

BackgroundAbnormal social decision-making is prominent in schizophrenia. Antipsychotic medication often improves interpersonal functioning but this action is poorly understood. Neuroeconomic paradigms are an effective method of investigating social decision-making in psychiatric disorders that can be adapted for use with neuroimaging. Using a neuroeconomic approach, it has been shown that healthy humans reproducibly alter their behavior in different contexts, including exhibiting loss aversion: a higher sensitivity to loss outcomes compared to gains of the same magnitude. MethodsHere, using a novel loss aversion task and fMRI, we tested three hypotheses: controls exhibiting normal behavioral loss aversion show changes in brain activity consistent with previous studies on healthy subjects; behavioral loss aversion is significantly reduced in schizophrenia and associated with abnormal activity in the same brain regions activated in controls during loss aversion behavior; and for the patient group alone, there is a significant correlation between increased psychotic symptoms, blunted loss aversion and abnormal brain activity. These hypotheses were tested in patients with schizophrenia and healthy controls using a loss aversion paradigm and fMRI. ResultsThe results support the hypotheses, with patients exhibiting significantly blunted behavioral loss aversion compared to controls. Controls showed a robust loss aversion brain activation pattern in the medial temporal lobe, insula and dopaminergic-linked areas, which was blunted in schizophrenia. ConclusionsOur results are consistent with blunted loss aversion being a reproducible feature of schizophrenia, likely due to abnormal dopaminergic and medial temporal lobe function, suggesting a route by which antipsychotics could influence interpersonal behavior.

Scene memory and hippocampal volume in middle-aged women with early hormone loss

The present study explored whether early midlife bilateral salpingo-oophorectomy (BSO), a female-specific risk factor for dementia, is associated with reduced medial temporal lobe structure and function. Younger middle-aged women with the BRCA1/2 mutation and a BSO prior to spontaneous menopause (SM) were recruited. We determined the performance of women with BSO not taking estradiol-based hormone therapy (n = 18) on a task measuring object and scene recognition and quantified medial temporal lobe subregion volumes using manually segmented high-resolution T2-weighted MRI scans. Comparisons were made to those with BSO taking estradiol-based hormone therapy (n = 20), age-matched premenopausal controls (n = 28), and older women in SM not taking hormone therapy matched for duration of hormone deprivation (n = 17). Reduced hippocampal integrity specific to the BSO group not taking hormone therapy was observed, reflected by significantly smaller dentate gyrus/CA2/CA3 volumes and lower scene recognition memory performance. These findings show that hippocampal subfield volume may be useful for identifying early midlife changes in women at elevated risk for dementia.

Medial temporal lobe contributions to resting-state networks

The medial temporal lobe (MTL) is a set of interconnected brain regions that have been shown to play a central role in behavior as well as in neurological disease. Recent studies using resting-state functional magnetic resonance imaging (rsfMRI) have attempted to understand the MTL in terms of its functional connectivity with the rest of the brain. However, the exact characterization of the whole-brain networks that co-activate with the MTL as well as how the various sub-regions of the MTL are associated with these networks remains poorly understood. Here, we attempted to advance these issues by exploiting the high spatial resolution 7T rsfMRI dataset from the Human Connectome Project with a data-driven analysis approach that relied on independent component analysis (ICA) restricted to the MTL. We found that four different well-known resting-state networks co-activated with a unique configuration of MTL subcomponents. Specifically, we found that different sections of the parahippocampal cortex were involved in the default mode, visual and dorsal attention networks; sections of the hippocampus in the somatomotor and default mode networks; and the lateral entorhinal cortex in the dorsal attention network. We replicated this set of results in a validation sample. These results provide new insight into how the MTL and its subcomponents contribute to known resting-state networks. The participation of the MTL in an expanded range of resting-state networks is in line with recent proposals on MTL function.

Impact of Alzheimer’s disease and related disorders neuropathology on neuropsychiatric symptoms during life

AbstractBackgroundThere is limited information on the impact of specific neuropathologies on neuropsychiatric symptoms (NPS). We evaluated the impact of neuropathologically defined subtypes of Alzheimer’s Disease and Related Dementias (ADRD) on neuropsychiatric symptoms (NPS) during life.MethodThe study design used a direct and unbiased approach that did not consider clinical diagnoses and included all brains with neuropathological diagnoses in the V.10 collection of the National Alzheimer’s Coordinating Center (NACC) database that also had Neuropsychiatric Interview‐Questionnaire (NPI‐Q) data collected during life. Data from 1,808 patients from 39 sites were examined. We utilized pairwise, ordinal and multiple logistic regression analyses to assess the effects of 8 neuropathological diagnoses on 12 domains in the Neuropsychiatric Inventory Questionnaire (NPI‐Q), correcting for multiple statistical comparisons. For NPS, average NPI‐Q domain scores during annual follow‐ups was the primary measure and NPI‐Q domain ever present/always absent was the secondary measure.ResultThe neuropathological diagnosis of Alzheimer’s disease (AD) using ABC criteria showed moderate associations with increased delusions, agitation/aggression and hallucinations. Cerebral amyloid angiopathy showed associations with NPS that were similar to AD. Lewy Body Disease (LBD) showed increased hallucinations. Infarcts/lacunes and microinfarcts showed weak associations with mood and motivational symptoms. Frontotemporal Dementia (FTD) was associated with marked increase in apathy and significantly decreased psychotic features and agitation. Hippocampal sclerosis was associated with less depression and increased apathy and disinhibition; these associations persisted after controlling for vascular neuropathology and FTD. In multiple regression analyses that controlled for other neuropathologies, the main findings were not altered.ConclusionThe associations of ADRD neuropathologies with specific NPS support current diagnostic criteria for behavioral symptoms in specific disorders. The findings on apathy and disinhibition in hippocampal sclerosis are novel and unique, and may explain inconsistent findings for depression treatment in dementia. Further investigation is needed to clarify the impact of hippocampal sclerosis on medial temporal lobe function and NPS, which may help eventually with diagnosis and clinical management.

Increased dynamic flexibility in the medial temporal lobe network following an exercise intervention mediates generalization of prior learning

Recent work has conceptualized the brain as a network comprised of groups of sub-networks or modules. “Flexibility” of brain network(s) indexes the dynamic reconfiguration of comprising modules. Using novel techniques from dynamic network neuroscience applied to high-resolution resting-state functional magnetic resonance imaging (fMRI), the present study investigated the effects of an aerobic exercise intervention on the dynamic rearrangement of modular community structure—a measure of neural flexibility—within the medial temporal lobe (MTL) network. The MTL is one of the earliest brain regions impacted by Alzheimer’s disease. It is also a major site of neuroplasticity that is sensitive to the effects of exercise. In a two-group non-randomized, repeated measures and matched control design with 34 healthy older adults, we observed an exercise-related increase in flexibility within the MTL network. Furthermore, MTL network flexibility mediated the beneficial effect aerobic exercise had on mnemonic flexibility, as measured by the ability to generalize past learning to novel task demands. Our results suggest that exercise exerts a rehabilitative and protective effect on MTL function, resulting in dynamically evolving networks of regions that interact in complex communication patterns. These reconfigurations may underlie exercise-induced improvements on cognitive measures of generalization, which are sensitive to subtle changes in the MTL.

A-04 The Relationship of ApoE Status and Cognition in Non-demented Older Adults

Abstract Objective Apolipoprotein (ApoE)-e4 is well established as a genetic risk factor for Alzheimer’s disease (AD) as well as a predictor for the rate of cognitive decline in AD. Among older adults without dementia, some research has found that e4 carriers have worse episodic memory compared to e4 non-carriers, whereas others have not found this association. The present study examined differences in cognitive performance between ApoE-e4 carriers and non-carriers. Method 91 non-demented individuals (age range: 55–87) were genotyped for ApoE (41 e4 carriers, 49 e4 non-carriers) and completed neuropsychological testing as a part of a longitudinal study at the Center for Neurodegeneration and Translational Neuroscience. Cognitively normal (CN) and mild cognitive impairment (MCI) participants were included (41 CN, 49 MCI). Group differences between e4 carriers and non-carriers were compared across cognitive measures after controlling for age, gender, and education. Results In the total sample, e4 carriers performed significantly worse across measures of verbal and nonverbal memory, as well as on the Boston Naming Test and Symbol Digit Modalities Test (all p’s < .05). No significant group differences were observed across visuospatial or executive function tasks. When diagnostic subgroups were examined, e4 carriers had worse verbal memory than non-carriers in the MCI group, but there was no effect of e4 status on cognition among CN participants. Conclusion(s) These findings support that ApoE-e4 positivity is associated with worse cognitive performance, especially on tasks related to medial temporal lobe function, among non-demented older adults. In MCI, worse verbal memory in e4 carriers likely reflects increased progression of underlying AD pathology.

Medial temporal lobe regions mediate complex visual discriminations for both objects and scenes: A process-based view.

Debate continues regarding the role of medial temporal lobe regions in object and scene processing. Considerable evidence indicates that the perirhinal cortex (PRC) plays an important role in the perception of objects-namely, in disambiguating complex objects that share conjunctions of features. These findings support a content-specific view of medial temporal lobe functioning in which PRC is critically important for processing complex objects, while the parahippocampal cortex (PHC) and hippocampus (HC) may be selectively engaged during scene processing. However, emerging evidence from both animal and human studies suggest that the PRC is sensitive to spatial configural information as well as object information. In this fMRI study, we observed preliminary evidence for BOLD activation in the PRC during a complex visual discrimination task for objects and scenes, as well as robust activation for both stimulus types in PHC and HC. The results are discussed in light of a recent process-based model of medial temporal lobe functioning.

Interaction of APOE, cerebral blood flow, and cortical thickness in the entorhinal cortex predicts memory decline

The ε4 allele of the apolipoprotein E (APOE)gene, a risk factor for cognitive decline, is associated with alterations in medial temporal lobe (MTL) structure and function, yet little research has been dedicated to understanding how these alterations might interact to negatively impact cognition. To bridge this gap, the present study employed linear regression models to determine the extent to which APOE genotype (ε4+, ε4-) modifies interactive effects of baseline arterial spin labeling MRI-measured cerebral blood flow (CBF) and FreeSurfer-derived cortical thickness/volume (CT/Vo) in two MTL regions of interest (entorhinal cortex, hippocampus) on memory change in 98 older adults who were cognitively normal at baseline. Baseline entorhinal CBF was positively associated with memory change, but only among ε4 carriers with lower entorhinal CT. Similarly, baseline entorhinal CT was positively associated with memory change, but only among ε4 carriers with lower entorhinal CBF. Findings suggest that APOE ε4 carriers may experience concomitant alterations in neurovascular function and morphology in the MTL that interact to negatively affect cognition prior to the onset of overt clinical symptoms. Results also suggest the presence of distinct multimodal neural signatures in the entorhinal cortex that may signal relative risk for cognitive decline among this group, perhaps reflecting different stages of cerebrovascular compensation (early effective vs. later ineffective).

Reactivated Spatial Context Guides Episodic Recall

The medial temporal lobe (MTL) is known as the locus of spatial coding and episodic memory, but the interaction between these cognitive domains as well as the extent to which they rely on common neurophysiological mechanisms is poorly understood. Here, we use intracranial electroencephalography and a hybrid spatial-episodic memory task (29 subjects, 15 female) to determine how spatial information is dynamically reactivated in subregions of the human MTL and how this reactivation guides recall of episodic information. Our results implicate theta oscillations across the MTL as a common neurophysiological substrate for spatial coding in navigation and episodic recall. We further show that our index of retrieved spatial context is high in the hippocampus (HC) in an early time window preceding recall. Closer to recall, it decreases in the HC and increases in the parahippocampal gyrus. Finally, we demonstrate that hippocampal theta phase modulates parahippocampal gamma amplitude during retrieval of spatial context, suggesting a role for cross-frequency coupling in coding and transmitting retrieved spatial information.SIGNIFICANCE STATEMENT By recording from the human medial temporal lobe (MTL) while subjects recall items experienced in a virtual environment, we establish a direct relation between the strength of theta activity during memory search and the extent to which memories are organized by their spatial locations. We thereby pinpoint a role for theta oscillations in accessing the "cognitive map" during episodic retrieval and further highlight the dynamic interplay of hippocampus and extrahippocampal MTL in representing retrieved spatial context. Our results provide an important step toward a unified theory of MTL function encompassing its role in spatial navigation and episodic memory.

Neuropsychological Assessment of Learning and Memory in Rats Following Ketamine Exposure during Late Adolescence

With the prevalent issue of drug abuse in society, research regarding the effects of ketamine, a drug frequently abused by youth in club settings, has increased. Despite its potential for misuse, ketamine has demonstrated potential as a fast-acting antidepressant and seems to work well for relieving treatment-resistant depression. However, previous research has shown ketamine use may cause impairments in frontal and medial temporal lobe functioning, leading to problems with memory. While under the influence of ketamine, individuals also display problems with spatial working memory when compared to individuals not dosed with ketamine. The majority of previous research has examined the short-term impact of ketamine use with studies on neurodevelopment largely confined to postnatal exposure. In the present study, the long-term effects on memory caused by repeated ketamine exposure during late adolescence were examined. Rats were used as nonhuman models in order to investigate the cognitive risks resulting from chronic use of ketamine. The results indicated that low-ketamine dosed rats demonstrated significantly better spatial memory recall compared to high-ketamine dosed rats. In addition, high-ketamine dosed rats appeared to struggle more with working memory than the rats in the low-ketamine and control groups. Similarly, both drug groups showed significantly more working memory and reference memory errors than the control group. This indicates that higher doses of ketamine during late adolescence may cause working and spatial memory impairments later in life.

The relationship between episodic detail generation and anterotemporal, posteromedial, and hippocampal white matter tracts

Episodic details populate autobiographical memories with vivid representations of people, objects, and event happenings, and they link events to a specific time and place. Episodic detail generation is believed to be a function of medial temporal lobe (MTL)-cortical interaction, but much remains unclear about how this retrieval process unfolds. In the present study, we combined an autobiographical interview and diffusion magnetic resonance imaging to investigate the relationships of two types of episodic detail, namely details about entities of an event (people and objects) or “event elements” and details about spatiotemporal context, to the integrity of anterotemporal (uncinate fasciculus; UF) and posteromedial (cingulum bundle; CB) cortical pathways. We also measured the relationships of these detail types to the fornix, and the relationship between non-episodic details and these tracts. We found that only episodic detail generation was significantly related to cortical and hippocampal pathways. Notably, the UF was more strongly related to event element details than it was to spatiotemporal context details. In contrast, CB was significantly and similarly related to the generation of event element and spatiotemporal context details (when not controlling for age and global diffusion). The fornix was also significantly related to both types of episodic detail, although the relationship to spatiotemporal context was particularly robust. These findings support the idea that anterotemporal cortical regions are related to the retrieval of episodic details about the entities that are incorporated into autobiographical events. Our findings also align with the notion that posteromedial and hippocampal-cortical involvement support the retrieval of episodic details.

Episodic simulation and empathy in older adults and patients with unilateral medial temporal lobe excisions

Recent work shows that vividly imagining oneself helping others in situations of need (episodic simulation) increases one’s willingness to help. The mechanisms underlying this effect are unclear, though it is known that the medial temporal lobe (MTL) is critical for supporting episodic simulation in general. Therefore, individuals who have compromised MTL functioning, such as older adults and those who have undergone resection of medial temporal lobe tissue as treatment for epilepsy (mTLE patients), may not show the prosocial effects of episodic simulation. Our lab previously found that older adults and mTLE patients are impaired on a problem-solving task that requires the simulation of hypothetical scenarios. Using similar logic in the present study, we predicted that older adults and mTLE patients would show reduced effects of episodic simulation on their empathic concern for, and willingness to help, people in hypothetical situations of need, compared to young adults and age-matched healthy controls, respectively. We also predicted that the subjective vividness and the amount of context-specific detail in imagined helping events would correlate with willingness to help and empathic concern. Participants read brief stories describing individuals in situations of need, and after each story either imagined themselves helping the person or performed a filler task. We analyzed the details in participants’ oral descriptions of their imagined helping events and also collected subjective ratings of vividness, willingness to help, and empathic concern. Episodic simulation significantly boosted willingness to help in all groups except for mTLE patients, and it increased empathic concern in young adults and healthy controls but not in older adults or mTLE patients. While the level of context-specific detail in participants’ oral descriptions of imaged events was unrelated to willingness to help and empathic concern, the effects of episodic simulation on these measures was completely mediated by subjective vividness, though to a significantly lesser degree among mTLE patients. These results increase our understanding not only of how episodic simulation works in healthy people, but also of the social and emotional consequences of compromised MTL functioning.

The intersection between the oculomotor and hippocampal memory systems: empirical developments and clinical implications.

Decades of cognitive neuroscience research has shown that where we look is intimately connected to what we remember. In this article, we review findings from human and nonhuman animals, using behavioral, neuropsychological, neuroimaging, and computational modeling methods, to show that the oculomotor and hippocampal memory systems interact in a reciprocal manner, on a moment‐to‐moment basis, mediated by a vast structural and functional network. Visual exploration serves to efficiently gather information from the environment for the purpose of creating new memories, updating existing memories, and reconstructing the rich, vivid details from memory. Conversely, memory increases the efficiency of visual exploration. We call for models of oculomotor control to consider the influence of the hippocampal memory system on the cognitive control of eye movements, and for models of hippocampal and broader medial temporal lobe function to consider the influence of the oculomotor system on the development and expression of memory. We describe eye movement–based applications for the detection of neurodegeneration and delivery of therapeutic interventions for mental health disorders for which the hippocampus is implicated and memory dysfunctions are at the forefront.

Examining the representational content of perirhinal cortex and posterior ventral visual pathway regions when maintenance of visual information is interrupted

The perirhinal cortex (PRC) is known to support recognition memory, working memory, and perception for objects. Often, information must be maintained in working memory in the face of ongoing visual perception, raising the question of how PRC and other regions supporting object representation deal with this conflict. Here, we used functional MRI to examine the representational content of human ventral visual pathway (VVP) regions, including perirhinal cortex (PRC), during a visual delayed match-to-sample task. Critically, interfering items from a different stimulus category to the target were presented to participants during the maintenance phase, creating conflict between the contents of working memory and ongoing perception. Using representational similarity analysis, we compared information content across study, interference and test phases to models that differed in the extent to which they predicted that information content would be maintained during the delay period and perturbed by interference. This revealed that lateral occipital and fusiform regions are best fit by models that reflect the stimulus content of the item currently being viewed, whereas PRC reflects the information content of the studied item, even when an interfering stimulus is presented during the delay. This division of labor within the VVP sheds light on the specialized nature of representations in VVP regions, including PRC. Our findings support a representational hierarchical understanding of medial temporal lobe function which posits that representations at the most anterior aspect of the VVP are more robust to ongoing perceptual activity.