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The medial temporal lobe (MTL) cortex, located adjacent to the hippocampus, is crucial for memory and prone to the accumulation of certain neuropathologies such as Alzheimer's disease neurofibrillary tau tangles. The MTL cortex is composed of several subregions which differ in their functional and cytoarchitectonic features. As neuroanatomical schools rely on different cytoarchitectonic definitions of these subregions, it is unclear to what extent their delineations of MTL cortex subregions overlap. Here, we provide an overview of cytoarchitectonic definitions of the entorhinal and parahippocampal cortices as well as Brodmann areas (BA) 35 and 36, as provided by four neuroanatomists from different laboratories, aiming to identify the rationale for overlapping and diverging delineations. Nissl‐stained series were acquired from the temporal lobes of three human specimens (two right and one left hemisphere). Slices (50 μm thick) were prepared perpendicular to the long axis of the hippocampus spanning the entire longitudinal extent of the MTL cortex. Four neuroanatomists annotated MTL cortex subregions on digitized slices spaced 5 mm apart (pixel size 0.4 μm at 20× magnification). Parcellations, terminology, and border placement were compared among neuroanatomists. Cytoarchitectonic features of each subregion are described in detail. Qualitative analysis of the annotations showed higher agreement in the definitions of the entorhinal cortex and BA35, while the definitions of BA36 and the parahippocampal cortex exhibited less overlap among neuroanatomists. The degree of overlap of cytoarchitectonic definitions was partially reflected in the neuroanatomists' agreement on the respective delineations. Lower agreement in annotations was observed in transitional zones between structures where seminal cytoarchitectonic features are expressed less saliently. The results highlight that definitions and parcellations of the MTL cortex differ among neuroanatomical schools and thereby increase understanding of why these differences may arise. This work sets a crucial foundation to further advance anatomically‐informed neuroimaging research on the human MTL cortex. [ABSTRACT FROM AUTHOR]

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding--semantic coding, axisbased feature coding, and region-based feature coding--in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our findings revealed the presence of semantic coding throughout the MTL, with a higher prevalence observed in the parahippocampal cortex (PHC) and perirhinal cortex (PRC), while axis coding and region coding were primarily observed in the earlier regions of the MTL. Moreover, we demonstrated that voxels exhibiting axis coding supported the transition to region coding and contained information relevant to semantic coding. Together, by providing a detailed characterization of neural object coding schemes and offering a comprehensive summary of visual coding information for each MTL subregion, our results not only emphasize a clear role of the MTL in perceptual processing but also shed light on the translation of perceptiondriven representations of visual features into memory-driven representations of semantics along the MTL processing pathway. [ABSTRACT FROM AUTHOR]

Cardiorespiratory fitness has a potent effect on neurocognitive health, especially regarding the hippocampal memory system. However, less is known about the impact of cardiorespiratory fitness on medial temporal lobe extrahippocampal neocortical regions. Specifically, it is unclear how cardiorespiratory fitness modulates these brain regions in young adulthood and if these regions are differentially related to cardiorespiratory fitness in young versus older adults. The primary goal of this study was to investigate if cardiorespiratory fitness predicted medial temporal lobe cortical thickness which, with the hippocampus, are critical for spatial learning and memory. Additionally, given the established role of these cortices in spatial navigation, we sought to determine if cardiorespiratory fitness and medial temporal lobe cortical thickness would predict greater subjective sense of direction in both young and older adults. Cross‐sectional data from 56 young adults (20–35 years) and 44 older adults (55–85 years) were included. FreeSurfer 6.0 was used to automatically segment participants' 3T T1‐weighted images. Using hierarchical multiple regression analyses, we confirmed significant associations between greater cardiorespiratory fitness and greater left entorhinal, left parahippocampal, and left perirhinal cortical thickness in young, but not older, adults. Left parahippocampal cortical thickness interacted with age group to differentially predict subjective sense of direction in young and older adults. Young adults displayed a positive, and older adults a negative, correlation between left parahippocampal cortical thickness and sense of direction. Our findings extend previous work on the association between cardiorespiratory fitness and hippocampal subfield structure in young adults to left medial temporal lobe neocortical regions. [ABSTRACT FROM AUTHOR]

Parahippocampal cortex (PHC) is a vital neural bases in spatial navigation. However, its functional role is still unclear. "Contextual hypothesis," which assumes that the PHC participates in processing the spatial association between the landmark and destination, provides a potential answer to the question. Nevertheless, the hypothesis was previously tested using the picture categorization task, which is indirectly related to spatial navigation. By now, study is still needed for testing the hypothesis with a navigation‐related paradigm. In the current study, we tested the hypothesis by an fMRI experiment in which participants performed a distance estimation task in a virtual environment under three different conditions: landmark free (LF), stable landmark (SL), and ambiguous landmark (AL). By analyzing the behavioral data, we found that the presence of an SL improved the participants' performance in distance estimation. Comparing the brain activity in SL‐versus‐LF contrast as well as AL‐versus‐LF contrast, we found that the PHC was activated by the SL rather than by AL when encoding the distance. This indicates that the PHC is elicited by strongly associated context and encodes the landmark reference for distance perception. Furthermore, accessing the representational similarity with the activity of the PHC across conditions, we observed a high similarity within the same condition but low similarity between conditions. This result indicated that the PHC sustains the contextual information for discriminating between scenes. Our findings provided insights into the neural correlates of the landmark information processing from the perspective of contextual hypothesis. [ABSTRACT FROM AUTHOR]

Words, unlike images, are symbolic representations. The associative details inherent within a word's meaning and the visual imagery it generates, are inextricably connected to the way words are processed and represented. It is well recognised that the hippocampus associatively binds components of a memory to form a lasting representation, and here we show that the hippocampus is especially sensitive to abstract word processing. Using fMRI during recognition, we found that the increased abstractness of words produced increased hippocampal activation regardless of memory outcome. Interestingly, word recollection produced hippocampal activation regardless of word content, while the parahippocampal cortex was sensitive to concreteness of word representations, regardless of memory outcome. We reason that the hippocampus has assumed a critical role in the representation of uncontextualized abstract word meaning, as its information-binding ability allows the retrieval of the semantic and visual associates that, when bound together, generate the abstract concept represented by word symbols. These insights have implications for research on word representation, memory, and hippocampal function, perhaps shedding light on how the human brain has adapted to encode and represent abstract concepts. • Explored how words are represented and recognised while varying their abstractness. • Hippocampal activity tracked the degree of abstractness independent of memory. • Recollection of words engaged the hippocampus, regardless of word content. • Abstractness, rather than familiarity, is predicted by hippocampal activity. • Hippocampus helps form associative representations of abstract words. [ABSTRACT FROM AUTHOR]

Path integration, the updating of position and orientation during movement, often involves tracking a home location. Here, we examine processes that could contribute to successful location tracking in humans. In particular, we investigate a homing vector model of path integration, whereby a navigator continuously tracks a trajectory back to the home location. To examine this model, we developed a loop task for fMRI, in which participants viewed movement that circled back to a home location in a sparse virtual environment. In support of a homing vector system, hippocampus, retrosplenial cortex, and parahippocampal cortex were responsive to Euclidean distance from home. These results provide the first evidence of a constantly maintained homing signal in the human brain. In addition, hippocampus, retrosplenial cortex, and parahippocampal cortex, as well as medial prefrontal cortex, were recruited during successful path integration. These findings suggest that dynamic processes recruit hippocampus, retrosplenial cortex, and parahippocampal cortex in support of path integration, including a homing vector system that tracks movement relative to home.Significance statementPath integration is the continual updating of position and orientation during navigation. Animal studies have identified place cells and grid cells as important for path integration, but underlying models of path integration in humans have rarely been studied. The results of our novel loop closure task are the first to suggest that a homing vector tracks Euclidean distance from the home location, supported by the hippocampus, retrosplenial cortex, and parahippocampal cortex. These findings suggest a potential homing vector mechanism supporting path integration, which recruits hippocampus and retrosplenial cortex to track movement relative to home. These results provide new avenues for computational and animal models by directing attention to homing vector models of path integration, which differ from current movement-tracking models.

Contextual features are integral to episodic memories; yet, we know little about context effects on pattern separation, a hippocampal function promoting orthogonalization of overlapping memory representations. Recent studies suggested that various extrahippocampal brain regions support pattern separation; however, the specific role of the parahippocampal cortex-a region involved in context representation-in pattern separation has not yet been studied. Here, we investigated the contribution of the parahippocampal cortex (specifically, the parahippocampal place area) to context reinstatement effects on mnemonic discrimination, using functional magnetic resonance imaging. During scanning, participants saw object images on unique context scenes, followed by a recognition task involving the repetitions of encoded objects or visually similar lures on either their original context or a lure context. Context reinstatement at retrieval improved item recognition but hindered mnemonic discrimination. Crucially, our region of interest analyses of the parahippocampal place area and an object-selective visual area, the lateral occipital cortex indicated that while during successful mnemonic decisions parahippocampal place area activity decreased for old contexts compared to lure contexts irrespective of object novelty, lateral occipital cortex activity differentiated between old and lure objects exclusively. These results imply that pattern separation of contextual and item-specific memory features may be differentially aided by scene and object-selective cortical areas., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC.

Contemporary theories of the medial temporal lobe (MTL) suggest that there are functional differences between the MTL cortex and the hippocampus. High-resolution functional magnetic resonance imaging and multivariate pattern analysis were utilized to study whether MTL subregions could classify categories of images, with the hypothesis that the hippocampus would be less representationally categorical than the MTL cortex. Results revealed significant classification accuracy for faces versus objects and faces versus scenes in MTL cortical regions-parahippocampal cortex (PHC) and perirhinal cortex (PRC)-with little evidence for category discrimination in the hippocampus. MTL cortical regions showed significantly greater classification accuracy than the hippocampus. The hippocampus showed significant classification accuracy for images compared to a nonmnemonic baseline task, suggesting that it responded to the images. Classification accuracy in a region of interest encompassing retrosplenial cortex (RSC) and the posterior cingulate cortex (PCC) posterior to RSC, showed a similar pattern of results to PHC, supporting the hypothesis that these regions are functionally related. The results suggest that PHC, PRC, and RSC/PCC are representationally categorical and the hippocampus is more representationally agnostic, which is concordant with the hypothesis of the role of the hippocampus in pattern separation.

Spatial navigation is a crucial everyday skill, which when impaired leads to a significant decrease in quality of life. In humans, functional magnetic resonance imaging (fMRI) has provided extensive insights into the neural underpinnings of navigation skills. Whereas the hippocampus has been recognized as the prime region underpinning navigation abilities, by providing a cognitive map of the environment, imaging studies have also implicated a range of other brain regions. In this review, we provide an overview of the fMRI evidence for extrahippocampal contributions to spatial navigation. We show that the parahippocampal cortex, retrosplenial cortex, dorsal striatum, and the posterior parietal cortex provide important complementary functions, and ultimately form part of a functional network that regulates successful way‐finding behavior. [ABSTRACT FROM AUTHOR]

Current evidence strongly supports the central involvement of the human medial temporal lobes (MTL) in storing and retrieving memories for recently experienced events. However, a critical remaining question regards exactly how the hippocampus and surrounding cortex represents spatiotemporal context defining an event in memory. Competing accounts suggest that this process may be accomplished by the following: (1) an overall increase in neural similarity of representations underlying spatial and temporal context, (2) a differentiation of competing spatiotemporal representations, or (3) a combination of the two processes, with different subregions performing these two functions within the MTL. To address these competing proposals, we used high-resolution functional magnetic resonance imaging targeting the MTL along with a multivariate pattern similarity approach with 19 participants. While undergoing imaging, participants performed a task in which they retrieved spatial and temporal contextual representations from a recently learned experience. Results showed that successfully retrieving spatiotemporal context defining an episode involved a decrease in pattern similarity between putative spatial and temporal contextual representations in hippocampal subfields CA2/CA3/DG, whereas the parahippocampal cortex (PHC) showed the opposite pattern. These findings could not be accounted for by differences in univariate activations for complete versus partial retrieval nor differences in correlations for correct or incorrect retrieval. Together, these data suggest that the CA2/CA3/DG serves to differentiate competing contextual representations, whereas the PHC stores a comparatively integrated trace of scene-specific context, both of which likely play important roles in successful episodic memory retrieval.

Episodic memory is the binding of an event with information about the context in which that event (or item) was experienced. The context of an event may include its spatial and temporal location as well as goal-directed, conscious thoughts evoked during the event. We call this latter type of information cognitive context. The binding of items and context (BIC) theory of medial temporal lobe function proposes that the parahippocampal cortex (PHc) plays a key role in processing cognitive context. Therefore, we predicted that activity in the PHc during reactivation of a previously experienced cognitive context would be correlated with item recollection, even when the associated item and its episodic binding had not yet been retrieved. Using a novel paradigm, we measured brain activation with functional magnetic resonance imaging in response to covert reinstatement of a cognitive context, prior to presenting an item memory probe. Contexts were studied with multiple items to ensure that spontaneous item retrieval would not occur prior to the test probe. At test, contexts were reinstated for 8 s before the test probe was presented. We manipulated whether the reinstated context matched the encoding context of the test probe that followed. For such matching contexts, we found that increased PHc activation prior to the test probe predicted recollection following the test probe. If a context unrelated to the eventual test item probe was reinstated, there was no such association between PHc activation during context reinstatement and eventual memory judgments. These findings suggest that PHc activation is correlated with cognitive context retrieval.

The human medial temporal lobe (MTL) plays a crucial role in recognizing visual objects, a key cognitive function that relies on the formation of semantic representations. Nonetheless, it remains unknown how visual information of general objects is translated into semantic representations in the MTL. Furthermore, the debate about whether the human MTL is involved in perception has endured for a long time. To address these questions, we investigated three distinct models of neural object coding-semantic coding, axis-based feature coding, and region-based feature coding-in each subregion of the human MTL, using high-resolution fMRI in two male and six female participants. Our findings revealed the presence of semantic coding throughout the MTL, with a higher prevalence observed in the parahippocampal cortex (PHC) and perirhinal cortex (PRC), while axis coding and region coding were primarily observed in the earlier regions of the MTL. Moreover, we demonstrated that voxels exhibiting axis coding supported the transition to region coding and contained information relevant to semantic coding. Together, by providing a detailed characterization of neural object coding schemes and offering a comprehensive summary of visual coding information for each MTL subregion, our results not only emphasize a clear role of the MTL in perceptual processing but also shed light on the translation of perception-driven representations of visual features into memory-driven representations of semantics along the MTL processing pathway., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

In addition to tissues such as liver, the plasma membrane sodium-dependent citrate transporter, NaCT (SLC13A5), is highly expressed in brain neurons, but its function is not understood. Loss-of-function mutations in the human SLC13A5 gene have been associated with severe neonatal encephalopathy and pharmacoresistant seizures. The molecular mechanisms of these neurological alterations are not clear. We performed a detailed examination of a Slc13a5 deletion mouse model including video-EEG monitoring, behavioral tests, and electrophysiologic, proteomic, and metabolomic analyses of brain and cerebrospinal fluid. The experiments revealed an increased propensity for epileptic seizures, proepileptogenic neuronal excitability changes in the hippocampus, and significant citrate alterations in the CSF and brain tissue of Slc13a5 deficient mice, which may underlie the neurological abnormalities. These data demonstrate that SLC13A5 is involved in brain citrate regulation and suggest that abnormalities in this regulation can induce seizures. The present study is the first to (i) establish the Slc13a5-knockout mouse model as a helpful tool to study the neuronal functions of NaCT and characterize the molecular mechanisms by which functional deficiency of this citrate transporter causes epilepsy and impairs neuronal function; (ii) evaluate all hypotheses that have previously been suggested on theoretical grounds to explain the neurological phenotype of SLC13A5 mutations; and (iii) indicate that alterations in brain citrate levels result in neuronal network excitability and increased seizure propensity.

Ictal visual hallucinations may have occipital as well as temporal lobe origin. We report a patient with clustering of focal aware seizures with visual hallucinations. Ictal EEG findings and seizure semiology with alternating contralateral elementary visual phenomena and non-lateralizing experiential hallucinations (visual scenes, memory flashbacks, spatial distortion) corresponded to a lesion in the posterior part of the right parahippocampal gyrus. This area is part of the hippocampal-parahippocampal system for mapping allocentric space. Within this system, the parahippocampal cortex encodes information about visual environmental scenes in concert with functionally defined neurons relevant for episodic memory and spatial cognitive processes (place, grid, border and head direction cells, as well as neurons tracking the passage of time). These functions are tightly linked to visual exploration.We suggest that the hippocampal-parahippocampal spatial navigation system is a crucial part of the networks responsible for the semiology of experiential seizures with complex visual hallucinations and elements of recall.

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. [ABSTRACT FROM AUTHOR]

• Object and spatial pattern separation are differently affected by sleep loss. • Sleep deprivation impaired object pattern separation. • Loss of sleep did not affect spatial pattern separation. • Study supports processing context v. spatial information via different neuronal pathways. • The discrimination projections represent separate but complimentary hippocampal processes. Pattern separation allows us to form discrete representations of information in memory. Pattern separation can be measured in several domains including spatial and object-based discrimination. The brain area largely involved in this process is the dentate gyrus of the hippocampus, which has been shown to be particularly sensitive to the effects of sleep loss. However, methodology in rodent and human studies varies greatly making translational conclusions difficult. Therefore, the aim of the current study was to measure the effects of sleep deprivation on human hippocampal function, using well-validated spatial and object-based pattern separation tests. The effects of acute sleep loss were examined, as this method is frequently used in rodent research but not human studies. Results show that sleep loss impaired performance on the object-based version of the test, but not spatial pattern separation. The findings support the notion that these discrimination projections represent separate but complimentary hippocampal processes, and further elucidates how they may be discretely affected by acute sleep loss. [ABSTRACT FROM AUTHOR]

Future‐oriented coping is a strategy for coping with events that may happen in the future, including efforts to ensure positive outcome and protection from potential threats. Appropriate future‐oriented coping is essential for well‐being and influences mental health and life satisfaction. However, little is known about the neural mechanism of future‐oriented coping. We examined the neural basis of this coping strategy using resting‐state functional connectivity analysis. Thirty healthy volunteers underwent resting‐state functional magnetic resonance imaging scanning and completed the Future‐Oriented Coping Inventory. Seed‐based functional connectivity analysis was used to investigate potentially correlated regions, with 11 nodes in the default mode network defined as regions of interest. Multiple regression analysis was performed to measure the correlation between coping behavior and functional connectivity. We found that proactive coping was significantly correlated with the functional connectivity strength between the parahippocampal cortex (PHC) and the claustrum/insula. These novel findings suggest that cooperation between the PHC and the claustrum/insula plays an important role in proactive coping. Moreover, cognitive components, such as future thinking (the PHC) and sensory judgment (the claustrum/insula) could be important process factors in proactive coping. [ABSTRACT FROM AUTHOR]

Motivation enhances memory by increasing hippocampal engagement during encoding. However, whether such increased hippocampal activation reflects encoding of the value of highly rewarding events per se is less understood. Here, using a monetary incentive encoding task with a novel manipulation, we tested in humans whether the hippocampus represents abstract reward value, independent of perceptual content. During functional MRI scanning, men and women studied object pairs, each preceded by a monetary reward cue indicating the amount of money they would receive if they successfully remembered the object pair at test. Reward cues varied on both the level of reward (penny, dime, and dollar) and visual form (picture or word) across trials to dissociate hippocampal responses to reward value from those reflecting the perceptual properties of the cues. Behaviorally, participants remembered pairs associated with the high reward (dollar) more often than pairs associated with lower rewards. Neural pattern-similarity analysis revealed that hippocampal and parahippocampal cortex activation patterns discriminated between cues of different value regardless of their visual form, and that hippocampal discrimination of value was most pronounced in participants who showed the greatest behavioral sensitivity to reward. Strikingly, hippocampal patterns were most distinct for reward cues that differed in value but had similar visual appearance, consistent with theoretical proposals of hippocampal-pattern differentiation of competing representations. Our data illustrate how contextual representations within the hippocampus go beyond space and time to include information about the motivational salience of events, with hippocampal reward coding tracking the motivational impact on later memory. [ABSTRACT FROM AUTHOR]

Highlights • We examined the frontal and prefrontal connections of perirhinal and postrhinal cortex. • Perirhinal is preferentially connected with medial prefrontal areas. • Postrhinal cortex is preferentially connected with secondary motor cortex, which may be the rodent. homolog of the primate dorsolateral prefrontal cortex. Abstract Knowing how prefrontal regions interact with medial temporal lobe structures is important for understanding memory and cognition. Using anterograde and retrograde tract tracing methods in the rat, we report a detailed study of the perirhinal (PER) and postrhinal (POR) connections with the lateral, ventrolateral, and medial orbitofrontal cortices (ORBl, ORBvl, ORBm), infralimbic and prelimbic cortices (IL, PL), ventral and dorsal anterior cingulate cortices (ACAv, ACAd), and secondary motor cortex (MOs). Our analyses included the topography and laminar patterns of these connections. The PER and POR showed reciprocal connectivity with all prefrontal regions examined, but the patterns of connections differed. In general, PER areas 36 and 35 showed patterns of connectivity that were more similar to each other than to those of the POR. Analysis of anterograde tracers showed that PER areas 36 and 35 provide the strongest projections to prefrontal regions. The heaviest fiber labeling was in IL and PL, closely followed by orbital regions. Fiber labeling arising from injections in POR was weaker overall. The strongest POR efferents targeted MOs, ACAv, and ORBvl. For return projections, analysis of retrograde tracers showed that PER areas 36 and 35 receive strong inputs from orbitofrontal and medial prefrontal regions. Interestingly, PER also received substantial inputs from MOs and ACAd. The POR receives a very strong input from MOs, followed by ACAd, and ORBvl. Based on comparison of our findings with those obtained in monkeys, we argue that the rodent ACAd and MOs may be a functional homolog of the primate dorsolateral prefrontal cortex. [ABSTRACT FROM AUTHOR]

The very different anatomical designs of the adjacent circuitries of the cortico-hippocampal pathway, along with their somewhat different synaptic plasticity mechanisms, suggest a nearly serial pathway of distinct memory circuits each contributing its own specialized processing operation to overall hippocampal function. Modeling and formal theoretical analysis of the prominent anatomical design features of particular circuits (piriform/entorhinal cortex; hippocampal field CA3; hippocampal field CA1) are found to identify potential emergent function not readily arrived at in the absence of these formal models, and yet which once derived can be seen potentially to confer unique capabilities to an integrated hippocampal mechanism for processing memories during behavior.

Context sometimes helps make objects more recognizable. Previous studies using functional magnetic resonance imaging (fMRI) have examined regional neural activity when objects have strong or weak associations with their contexts. Such studies have demonstrated that activity in the parahippocampal cortex (PHC) generally corresponds with strong associations between objects and their spatial contexts while retrosplenial cortex (RSC) activity is linked with episodic memory. However these studies investigated objects viewed in associated contexts, but the direct influence of scene on the perception of visual objects has not been widely investigated. We hypothesized that the PHC and RSC may only be engaged for congruent contexts in which the object could typically be found but not for neutral contexts. While in an fMRI scanner, 15 participants rated the recognizability of 152 photographic images of objects, presented within congruent and incongruent contexts. Regions of interest were created to examine PHC and RSC activity using a hypothesis-driven approach. Exploratory analyses were also performed to identify other regional activity. In line with previous studies, PHC and RSC activity emerged when objects were viewed in congruent contexts. Activity in the RSC, inferior parietal lobe (IPL) and fusiform gyrus also emerged. These findings indicate that different brain regions are employed when objects are meaningfully contextualized.

ObjectiveMesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) may involve extrahippocampal areas of structural damage and dysfunction. The accuracy of medium-term spatial memory can be tested by memory-guided saccades (MGS) to evaluate a functional impairment of the parahippocampal cortex (PHC), while voxel-based morphometry (VBM) analysis can be used to detect a structural damage of the latter region.MethodsMGS with 3- and 30-s memorization delays were compared between 7 patients affected by right MTLE-HS (r-MTLE-HS), 6 patients affected by left MTLE-HS, and 13 healthy controls. The same subjects underwent brain MRI for a VBM analysis. Correlation analysis was performed between the results of VBM and MGS and with patients’ clinical data.ResultsRight MTLE-HS patients showed impaired accuracy of leftward MGS with a 30-s memorization delay; their gray-matter volume was reduced in the right hippocampus and inferior temporal gyrus, and bilaterally in the cerebellum. Left MTLE-HS patients had normal MGS accuracy; their gray-matter volume was reduced in the left hippocampus, in the right-inferior temporal gyrus and corpus callosus, and bilaterally in the insular cortex and in the cerebellum. The difference between right and left parahippocampal volumes correlated with MGS accuracy, while right and left hippocampal volumes did not. Hippocampal and parahippocampal volume did not correlate with clinical variables such as febrile seizures, age at disease onset, disease duration, and seizure frequency.ConclusionMGS abnormalities suggested the functional involvement of the right PHC in patients with r-MTLE-HS, supporting a right lateralization of spatial memory control and showing a relation between functional impairment and degree of atrophy.

Tract-tracing studies in primates indicate that different subregions of the medial temporal lobe (MTL) are connected with multiple brain regions. However, no clear framework defining the distributed anatomy associated with the human MTL exists. This gap in knowledge originates in notoriously low MRI data quality in the anterior human MTL and in group-level blurring of idiosyncratic anatomy between adjacent brain regions, such as entorhinal and perirhinal cortices, and parahippocampal areas TH/TF. Using MRI, we intensively scanned four human individuals and collected whole-brain data with unprecedented MTL signal quality. Following detailed exploration of cortical networks associated with MTL subregions within each individual, we discovered three biologically meaningful networks associated with the entorhinal cortex, perirhinal cortex, and parahippocampal area TH, respectively. Our findings define the anatomical constraints within which human mnemonic functions must operate and are insightful for examining the evolutionary trajectory of the MTL connectivity across species., Competing Interests: Declaration of interests The Max Planck Institute for Human Cognitive Sciences has an institutional research agreement with Siemens Healthcare. N.W. holds a patent on acquisition of MRI data during spoiler gradients (US 10,401,453 B2). N.W. was a speaker at an event organized by Siemens Healthcare and was reimbursed for the travel expenses., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Abstract: Identifying what an object is, and whether an object has been encountered before, is a crucial aspect of human behavior. Despite this importance, we do not yet have a complete understanding of the neural basis of these abilities. Investigations into the neural organization of human object representations have revealed category specific organization in the ventral visual stream in perceptual tasks. Interestingly, these categories fall within broader domains of organization, with reported distinctions between animate, inanimate large, and inanimate small objects. While there is some evidence for category specific effects in the medial temporal lobe (MTL), in particular in perirhinal and parahippocampal cortex, it is currently unclear whether domain level organization is also present across these structures. To this end, we used fMRI with a continuous recognition memory task. Stimuli were images of objects from several different categories, which were either animate or inanimate, or large or small within the inanimate domain. We employed representational similarity analysis (RSA) to test the hypothesis that object‐evoked responses in MTL structures during recognition‐memory judgments also show evidence for domain‐level organization along both dimensions. Our data support this hypothesis. Specifically, object representations were shaped by either animacy, real‐world size, or both, in perirhinal and parahippocampal cortex, and the hippocampus. While sensitivity to these dimensions differed across structures when probed individually, hinting at interesting links to functional differentiation, similarities in organization across MTL structures were more prominent overall. These results argue for continuity in the organization of object representations in the ventral visual stream and the MTL. [ABSTRACT FROM AUTHOR]

A role of perirhinal cortex (PrC) in recognition memory for objects has been well established. Contributions of parahippocampal cortex (PhC) to this function, while documented, remain less well understood. Here, we used fMRI to examine whether the organization of item-based recognition memory signals across these two structures is shaped by object category, independent of any difference in representing episodic context. Guided by research suggesting that PhC plays a critical role in processing landmarks, we focused on three categories of objects that differ from each other in their landmark suitability as confirmed with behavioral ratings (buildings > trees > aircraft). Participants made item-based recognition-memory decisions for novel and previously studied objects from these categories, which were matched in accuracy. Multi-voxel pattern classification revealed category-specific item-recognition memory signals along the long axis of PrC and PhC, with no sharp functional boundaries between these structures. Memory signals for buildings were observed in the mid to posterior extent of PhC, signals for trees in anterior to posterior segments of PhC, and signals for aircraft in mid to posterior aspects of PrC and the anterior extent of PhC. Notably, item-based memory signals for the category with highest landmark suitability ratings were observed only in those posterior segments of PhC that also allowed for classification of landmark suitability of objects when memory status was held constant. These findings provide new evidence in support of the notion that item-based memory signals for objects are not limited to PrC, and that the organization of these signals along the longitudinal axis that crosses PrC and PhC can be captured with reference to landmark suitability. [ABSTRACT FROM AUTHOR]

Context sometimes helps make objects more recognizable. Previous studies using functional magnetic resonance imaging (fMRI) have examined regional neural activity when objects have strong or weak associations with their contexts. Such studies have demonstrated that activity in the parahippocampal cortex (PHC) generally corresponds with strong associations between objects and their spatial contexts while retrosplenial cortex (RSC) activity is linked with episodic memory. However these studies investigated objects viewed in associated contexts, but the direct influence of scene on the perception of visual objects has not been widely investigated. We hypothesized that the PHC and RSC may only be engaged for congruent contexts in which the object could typically be found but not for neutral contexts. While in an fMRI scanner, 15 participants rated the recognizability of 152 photographic images of objects, presented within congruent and incongruent contexts. Regions of interest were created to examine PHC and RSC activity using a hypothesis-driven approach. Exploratory analyses were also performed to identify other regional activity. In line with previous studies, PHC and RSC activity emerged when objects were viewed in congruent contexts. Activity in the RSC, inferior parietal lobe (IPL) and fusiform gyrus also emerged. These findings indicate that different brain regions are employed when objects are meaningfully contextualized. [ABSTRACT FROM AUTHOR]

Objective: Mesial temporal lobe epilepsy with hippocampal sclerosis (MTLE-HS) may involve extrahippocampal areas of structural damage and dysfunction. The accuracy of medium-term spatial memory can be tested by memory-guided saccades (MGS) to evaluate a functional impairment of the parahippocampal cortex (PHC), while voxelbased morphometry (VBM) analysis can be used to detect a structural damage of the latter region. Methods: MGS with 3- and 30-s memorization delays were compared between 7 patients affected by right MTLE-HS (r-MTLE-HS), 6 patients affected by left MTLE-HS, and 13 healthy controls. The same subjects underwent brain MRI for a VBM analysis. Correlation analysis was performed between the results of VBM and MGS and with patients' clinical data. Results: Right MTLE-HS patients showed impaired accuracy of leftward MGS with a 30-s memorization delay; their gray-matter volume was reduced in the right hippocampus and inferior temporal gyrus, and bilaterally in the cerebellum. Left MTLE-HS patients had normal MGS accuracy; their gray-matter volume was reduced in the left hippocampus, in the right-inferior temporal gyrus and corpus callosus, and bilaterally in the insular cortex and in the cerebellum. The difference between right and left parahippocampal volumes correlated with MGS accuracy, while right and left hippocampal volumes did not. Hippocampal and parahippocampal volume did not correlate with clinical variables such as febrile seizures, age at disease onset, disease duration, and seizure frequency. Conclusion: MGS abnormalities suggested the functional involvement of the right PHC in patients with r-MTLE-HS, supporting a right lateralization of spatial memory control and showing a relation between functional impairment and degree of atrophy. [ABSTRACT FROM AUTHOR]

Introduction: Although diet has a substantial influence on the aging brain, the relationship between dietary nutrients and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between a carotenoid important for brain health across the lifespan, lutein, and crystallized intelligence in cognitively intact older adults. We hypothesized that higher serum levels of lutein are associated with better performance on a task of crystallized intelligence, and that this relationship is mediated by gray matter structure of regions within the temporal cortex. This investigation aims to contribute to a growing line of evidence, which suggests that particular nutrients may slow or prevent aspects of cognitive decline by targeting specific features of brain aging.Methods: We examined 75 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between serum lutein, tests of crystallized intelligence (measured by the Wechsler Abbreviated Scale of Intelligence), and gray matter volume of regions within the temporal cortex. A three-step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index.Results: The mediation analysis revealed that gray matter thickness of one region within the temporal cortex, the right parahippocampal cortex (Brodmann’s Area 34), partially mediates the relationship between serum lutein and crystallized intelligence. Conclusion: These results suggest that the parahippocampal cortex acts as a mediator of the relationship between serum lutein and crystallized intelligence in cognitively intact older adults. Prior findings substantiate the individual relationships reported within the mediation, specifically the links between (i) serum lutein and temporal cortex structure, (ii) serum lutein and crystallized intelligence, and (iii) parahippocampal cortex structure and crystallized intelligence. This report is the first to demonstrate a specific structural mediation between lutein status and crystallized intelligence, and therefore provides further evidence that specific nutrients may slow or prevent features of cognitive decline by hindering particular aspects of brain aging. Future work should examine the potential mechanisms underlying this mediation, including the antioxidant, anti-inflammatory, and membrane modulating properties of lutein.

Impaired olfaction is associated with a volume decrease in the olfactory bulb as well as in the gray matter of cortical olfactory areas. On the other hand, restitution of an impaired olfaction results in a regain of volume in these regions. Studies investigating similar changes in the cerebral white matter are virtually not existent. The aim of this prospective study therefore was to investigate cerebral white matter using magnetic resonance diffusion tensor imaging (DTI). 31 patients (54 ± 13 years) with olfactory impairment (chronic rhinosinusitis) and planned functional endoscopic sinus surgery (FESS) were included. Magnetic resonance imaging (MRI) data sets were acquired pre-operatively and 3 months after surgery. Pre- and postoperative olfactory testing was performed to assess the olfactory threshold, discrimination, and identification (TDI) score. A significant postoperative TDI improvement by 9.06 ± 8.81 points was observed. Two groups were subsequently formed – one with relevant postoperative olfactory gain (ΔTDI ≥ 10 points, 12 patients) and one without gain (ΔTDI < 10 points, 19 patients). DTI parameter showed a significant correlation with the TDI score in the left anterior cingulate cortex and the right amygdala. In the group with relevant olfactory improvement higher values of fractional anisotropy and apparent diffusion coefficient were found in the right parahippocampal area and in the white matter below the left inferior temporal sulcus. Tract-specific diffusion property analysis revealed significant group differences in the cingulate cortex in spatial relationship to the perisplenial cortex. Overall, this prospective study indicates structural changes in white matter after postoperative restoration of olfaction. [ABSTRACT FROM AUTHOR]

The hippocampus is famous for mapping locations in spatially organized environments, and several recent studies have shown that hippocampal networks also map moments in temporally organized experiences. Here I consider how space and time are integrated in the representation of memories. The brain pathways for spatial and temporal cognition involve overlapping and interacting systems that converge on the hippocampal region. There is evidence that spatial and temporal aspects of memory are processed somewhat differently in the circuitry of hippocampal subregions but become fully integrated within CA1 neuronal networks as independent, multiplexed representations of space and time. Hippocampal networks also map memories across a broad range of abstract relations among events, suggesting that the findings on spatial and temporal organization reflect a generalized mechanism for organizing memories. [ABSTRACT FROM AUTHOR]

ABSTRACT The specific role of the perirhinal (PRC), entorhinal (ERC) and parahippocampal cortices (PHC) in supporting familiarity-based recognition remains unknown. An fMRI study explored whether these medial temporal lobe (MTL) structures responded in the same way or differentially to familiarity as a function of stimulus type at recognition. A secondary aim was to explore whether the hippocampus responds in the same way to equally strong familiarity and recollection and whether this is influenced by the kind of stimulus involved. Univariate and multivariate analyses revealed that familiarity responses in the PRC, ERC, PHC and the amygdala are material-specific. Specifically, the PRC and ERC selectively responded to object familiarity, while the PHC responded to both object and scene familiarity. The amygdala only responded to familiarity memory for faces. The hippocampus did not respond to stimulus familiarity for any of the three types of stimuli, but it did respond to recollection for all three types of stimuli. This was true even when recollection was contrasted to equally accurate familiarity. Overall, the findings suggest that the role of the MTL neocortices and the amygdala in familiarity-based recognition depends on the kind of stimulus in memory, whereas the role of the hippocampus in recollection is independent of the type of cuing stimulus. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

It is argued that during ongoing visual perception, the brain is generating top-down predictions to facilitate, guide and constrain the processing of incoming sensory input. Here we demonstrate that these predictions are drawn from a diverse range of cognitive processes, in order to generate the richest and most informative prediction signals. This is consistent with a central role for cognitive penetrability in visual perception. We review behavioural and mechanistic evidence that indicate a wide spectrum of domains—including object recognition, contextual associations, cognitive biases and affective state—that can directly influence visual perception. We combine these insights from the healthy brain with novel observations from neuropsychiatric disorders involving visual hallucinations, which highlight the consequences of imbalance between top-down signals and incoming sensory information. Together, these lines of evidence converge to indicate that predictive penetration, be it cognitive, social or emotional, should be considered a fundamental framework that supports visual perception. [ABSTRACT FROM AUTHOR]

Prominent theories posit that associative memory structures, known as cognitive maps, support flexible generalization of knowledge across cognitive domains. Here, we evince a representational account of cognitive map flexibility by quantifying how spatial knowledge formed one day was used predictively in a temporal sequence task 24 hours later, biasing both behavior and neural response. Participants learned novel object locations in distinct virtual environments. After learning, hippocampus and ventromedial prefrontal cortex (vmPFC) represented a cognitive map, wherein neural patterns became more similar for same-environment objects and more discriminable for different-environment objects. Twenty-four hours later, participants rated their preference for objects from spatial learning; objects were presented in sequential triplets from either the same or different environments. We found that preference response times were slower when participants transitioned between same- and different-environment triplets. Furthermore, hippocampal spatial map coherence tracked behavioral slowing at the implicit sequence transitions. At transitions, predictive reinstatement of virtual environments decreased in anterior parahippocampal cortex. In the absence of such predictive reinstatement after sequence transitions, hippocampus and vmPFC responses increased, accompanied by hippocampal-vmPFC functional decoupling that predicted individuals' behavioral slowing after a transition. Collectively, these findings reveal how expectations derived from spatial experience generalize to support temporal prediction., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Although, diet has a substantial influence on the aging brain, the relationship between dietary nutrients and aspects of brain health remains unclear. This study examines the neural mechanisms that mediate the relationship between a carotenoid important for brain health across the lifespan, lutein, and crystallized intelligence in cognitively intact older adults. We hypothesized that higher serum levels of lutein are associated with better performance on a task of crystallized intelligence, and that this relationship is mediated by gray matter structure of regions within the temporal cortex. This investigation aims to contribute to a growing line of evidence, which suggests that particular nutrients may slow or prevent aspects of cognitive decline by targeting specific features of brain aging. Methods: We examined 76 cognitively intact adults between the ages of 65 and 75 to investigate the relationship between serum lutein, tests of crystallized intelligence (measured by the Wechsler Abbreviated Scale of Intelligence), and gray matter volume of regions within the temporal cortex. A three-step mediation analysis was implemented using multivariate linear regressions to control for age, sex, education, income, depression status, and body mass index. Results: The mediation analysis revealed that gray matter thickness of one region within the temporal cortex, the right parahippocampal cortex (Brodmann's Area 34), partially mediates the relationship between serum lutein and crystallized intelligence. Conclusion: These results suggest that the parahippocampal cortex acts as a mediator of the relationship between serum lutein and crystallized intelligence in cognitively intact older adults. Prior findings substantiate the individual relationships reported within the mediation, specifically the links between (i) serum lutein and temporal cortex structure, (ii) serum lutein and crystallized intelligence, and (iii) parahippocampal cortex structure and crystallized intelligence. This report demonstrates a novel structural mediation between lutein status and crystallized intelligence, and therefore provides further evidence that specific nutrients may slow or prevent features of cognitive decline by hindering particular aspects of brain aging. Future work should examine the potential mechanisms underlying this mediation, including the antioxidant, anti-inflammatory, and membrane modulating properties of lutein. [ABSTRACT FROM AUTHOR]

Connectivity studies in animals form the basis for a representational view of medial temporal lobe (MTL) subregions. In this view, distinct subfields of the entorhinal cortex (EC) relay object-related and spatial information from the perirhinal and parahippocampal cortices (PRC, PHC) to the hippocampus. Relatively recent advances in fMRI methodology allow examining properties of human EC subregions directly. Antero-lateral and posterior-medial EC subfields show remarkable consistency to their putative rodent and nonhuman primate homologues with regard to intra- and extra-MTL functional connectivity. Accordingly, there is now evidence for a dissociation of object-related vs. spatial processing in human EC subfields. Here, variance in localization may be integrated in the antero-lateral vs. posterior-medial distinction, but may additionally reflect process differences. Functional results in rodents further suggest material-specific representations may be more integrated in EC compared to PRC/PHC. In humans, however, evidence for such a dissociation between EC and PRC/PHC is lacking. Future research may elucidate on the unique contributions of human EC to memory, especially in light of its high degree of intrinsic and extrinsic connectivity. A thorough characterization of EC subfield function may not only advance our understanding of human memory, but also have important clinical implications.

The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC.