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The perirhinal (PER) and postrhinal (POR) cortices, structures in the medial temporal lobe, are implicated in learning and memory. The PER is understood to process object information and the POR to process spatial or contextual information. Whether the medial temporal lobe is dedicated to memory, however, is under debate. In this study, we addressed the hypothesis that the PER and POR are also involved in non-mnemonic cognitive functions. Rats with PER or POR damage and SHAM surgical controls were shaped, trained, and tested on the five-choice serial reaction time (5CSRT) task, which assesses attention and executive function. Rats with PER damage were impaired in acquiring the task and at asymptote, although processing information about objects was not relevant to the task. When confronted with attentional challenges, rats with PER damage showed a pattern consistent with decreased attentional capacity, increased response errors, and increased impulsive behavior. Rats with POR damage showed intact acquisition and normal asymptotic performance. They also exhibited faster latencies in the absence of speed accuracy trade-off suggesting enhanced response readiness. We suggest this increased response readiness results from decreased automatic monitoring of the local environment, which might normally compete with response readiness. Our findings are consistent with a role for PER in controlled attention and a role for POR in stimulus-driven attention providing evidence that the PER and POR cortices have functions that go beyond memory for objects and memory for scenes and contexts, respectively. These findings provide new evidence for functional specialization in the medial temporal lobe., (Copyright © 2021 Trettel et al.)

Have you ever been to Krakow? If so, then you may recognize the Wawel Royal Castle from a picture due to your personal semantic memory, which stores all autobiographically significant concepts and repeated events of your past. If not, then you might still recognize the Wawel Royal Castle and be able to locate it on a map due to your spatial semantic memory. When recognizing a familiar landmark, how does neural activity depend on your memory related to that place? To address this question, we combined a novel task - the Krakow paradigm - with fMRI. In this task, participants are presented with a set of pictures showing various Krakow landmarks, each followed by two questions - one about its location, and the other about seeing the place in real-life, to trigger spatial and/or personal semantic memory, respectively. Group independent component analysis of fMRI data revealed several brain networks sensitive to the task conditions. Most sensitive was the medial temporal lobe network comprising bilateral hippocampus, parahippocampal, retrosplenial, and angular gyri, as well as distinct frontal areas. In agreement with the contextual continuum perspective, this network exhibited robust stimulus-related activity when the two memory types were combined, medium for spatial memory, and the weakest for baseline condition. The medial prefrontal network showed the same, pronounced deactivation for spatial memory and baseline conditions, yet far less deactivation for places seen in real-life. This effect was interpreted as self-referential processes counterbalancing the suppression of the brain's 'default mode.' In contrast, the motor, frontoparietal, and cingulo-opercular networks exhibited the strongest response-related activity for the spatial condition. These findings indicate that recognizing places based solely on general semantic knowledge requires more evidence accumulation, additional verbal semantics, and greater top-down control. Thus, the study imparts a novel insight into the neural mechanisms of place recognition. The Krakow paradigm has the potential to become a useful tool in future longitudinal or clinical studies., (Copyright © 2020 Elsevier B.V. All rights reserved.)

It is well known that the perirhinal (Prh) and insular (IC) cortices are reciprocally connected, mainly through ipsilateral projections. Although some studies have demonstrated that excitotoxic lesions to these regions, each separately, disrupt taste neophobia, it is not yet known whether the two regions have functional interactions with one another. To find out if they form a functional unit, we examined the effects of crossed excitotoxic lesions to the Prh and the contralateral IC (contralateral group). This group's performance was compared to that of rats with ipsilateral Prh and IC lesions (ipsilateral group) and to that of control-operated rats. All the animals received a 0.3% saccharin solution for fifteen minutes on five consecutive days. Rats with contralateral Prh-IC lesions drank significantly higher amounts of saccharin than the other groups during the first encounter with the novel taste, indicating a disruption in neophobia. However, the lesions did not disrupt attenuation of neophobia, with the contralateral group reaching asymptote in trial 2 and the rest of the groups after 3-5 days of exposure to the saccharin. These findings suggest that both Prh and IC play a necessary role in taste neophobia. Additionally, the two cortices function interdependently and their interaction is critical for normal expression of taste neophobia., (Copyright © 2020 Elsevier Inc. All rights reserved.)

When searching for an object in a familiar environment, we may automatically orient to locations where this object was often placed previously. Contextual cueing refers to the guidance of attention by repeated search context. As an implicit mechanism with high capacity, contextual cueing may be important for people whose cognitive function is compromised, immature, or in decline. Here we review and synthesize the last two decades of research on contextual cueing, focusing on neuropsychological and developmental evidence. Contextual cueing is largely preserved in young children, older adults, and individuals with autism spectrum disorders or mild intellectual impairment. Some, though not all, studies find a deficit in contextual cueing in amnesic patients, patients with basal ganglia damage, children with ADHD, and individuals with psychiatric disorders. Although the medial temporal lobe, the basal ganglia, and the posterior parietal cortex are implicated in contextual cueing, definitive evidence for their necessity is lacking. These findings suggest that contextual cueing is an evolutionarily conserved mechanism that is exceptionally robust to damages to single brain sites., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Synaptic dysfunction or loss in early stages of Alzheimer's disease (AD) is thought to be a major structural correlate of cognitive dysfunction. Early loss of episodic memory, which occurs at the early stage of AD, is closely associated with the progressive degeneration of medial temporal lobe (MTL) structures of which the transentorhinal cortex (TEC) is the first affected area. However, no ultrastructural studies have been performed in this region in human brain samples from AD patients. In the present study, we have performed a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM) to investigate possible synaptic alterations in the TEC of patients with AD. Surprisingly, the analysis of the density, morphological features and spatial distribution of synapses in the neuropil showed no significant differences between AD and control samples. However, light microscopy studies showed that cortical thickness of the TEC was severely reduced in AD samples, but there were no changes in the volume occupied by neuronal and glial cell bodies, blood vessels, and neuropil. Thus, the present results indicate that there is a dramatic loss of absolute number of synapses, while the morphology of synaptic junctions and synaptic spatial distribution are maintained. How these changes affect cognitive impairment in AD remains to be elucidated.

The biological mechanisms that link Beta-amyloid (Aβ) plaque deposition, neurodegeneration, and clinical decline in Alzheimer's disease (AD) dementia, have not been completely elucidated. Here we studied whether amyloid accumulation and neurodegeneration, independently or interactively, predict clinical decline over time in a group of memory impaired older individuals [diagnosed with either amnestic mild cognitive impairment (MCI), or mild AD dementia]. We found that baseline Aβ-associated cortical thinning across clusters encompassing lateral and medial temporal and parietal cortices was related to higher baseline Clinical Dementia Rating Sum-of-Boxes (CDR-SB). Baseline Aβ-associated cortical thinning also predicted CDR-SB over time. Notably, the association between CDR-SB change and cortical thickness values from the right lateral temporo-parietal cortex and right precuneus was driven by individuals with high Aβ burden. In contrast, the association between cortical thickness in the medial temporal lobe (MTL) and clinical decline was similar for individuals with high or low Aβ burden. Furthermore, amyloid pathology was a stronger predictor for clinical decline than MTL thickness. While this study validates previous findings relating AD biomarkers of neurodegeneration to clinical impairment, here we show that regions outside the MTL may be more vulnerable and specific to AD dementia. Additionally, excluding mild AD individuals revealed that these relationships remained, suggesting that lower cortical thickness values in specific regions, vulnerable to amyloid pathology, predict clinical decline already at the prodromal stage.

Introduction: The objective of this study was to distinguish the functional neuroanatomy of verbal learning and recognition in Alzheimer's disease (AD) using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning task., Method: In 81 Veterans diagnosed with dementia due to AD, we conducted a cluster-based correlation analysis to assess the relationships between recency and recognition memory scores from the CERAD Word Learning Task and cortical metabolic activity measured using [ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)., Results: AD patients (Mini-Mental State Examination, MMSE mean = 20.2) performed significantly better on the recall of recency items during learning trials than of primacy and middle items. Recency memory was associated with cerebral metabolism in the left middle and inferior temporal gyri and left fusiform gyrus (p < .05 at the corrected cluster level). In contrast, recognition memory was correlated with metabolic activity in two clusters: (a) a large cluster that included the left hippocampus, parahippocampal gyrus, entorhinal cortex, anterior temporal lobe, and inferior and middle temporal gyri; (b) the bilateral orbitofrontal cortices (OFC)., Conclusions: The present study further informs our understanding of the disparate functional neuroanatomy of recency memory and recognition memory in AD. We anticipated that the recency effect would be relatively preserved and associated with temporoparietal brain regions implicated in short-term verbal memory, while recognition memory would be associated with the medial temporal lobe and possibly the OFC. Consistent with our a priori hypotheses, list learning in our AD sample was characterized by a reduced primacy effect and a relatively spared recency effect; however, recency memory was associated with cerebral metabolism in inferior and lateral temporal regions associated with the semantic memory network, rather than regions associated with short-term verbal memory. The correlates of recognition memory included the medial temporal lobe and OFC, replicating prior studies.

Background: Anti-NMDA-receptor encephalitis is an immune-mediated inflammatory disorder of the central nervous system. Brain MRI is unremarkable in at least 50% of patients and highly variable in the remaining patients with signal abnormalities in different brain regions. Only scarce reports exist on other imaging modalities., Case Presentation: A 31-year-old woman sub-acutely developed psychosis, behavioural changes, amnesia, alternating states of agitation and mutism, fever and epileptic seizures. Clinically suspected diagnosis of anti-NMDA-receptor encephalitis was confirmed by the detection of anti-NMDA receptor antibodies in CSF and serum. During the acute phase, brain MRI abnormalities were found in both insular cortices and hippocampi, whereas F(18)-FDG-PET showed hypermetabolism bilaterally in insular and prefrontal cortex. After resection of the underlying ovarian teratoma and with multimodal immunotherapy the patient substantially improved reaching a modified Rankin Scale score of 2 after 3 months. At follow-up, both hippocampi were still affected on MRI, whereas insular cortex appeared normal; however, both regions showed prominent glucose hypometabolism., Conclusions: Here, we report bi-insular cortical abnormalities on MRI and F(18)-FDG-PET in a patient with anti-NMDA-receptor encephalitis during the acute phase and after clinical improvement.

Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.

To investigate the role of the perirhinal cortex on the development of recognition measured by the visual paired-comparison (VPC) task, infant monkeys with neonatal perirhinal lesions and sham-operated controls were tested at 1.5, 6, 18, and 48 months of age on the VPC task with color stimuli and intermixed delays of 10 s, 30 s, 60 s, and 120 s. Monkeys with neonatal perirhinal lesions showed an increase in novelty preference between 1.5 and 6 months of age similar to controls, although at these two ages, performance remained significantly poorer than that of control animals. With age, performance in animals with neonatal perirhinal lesions deteriorated as compared to that of controls. In contrast to the lack of novelty preference in monkeys with perirhinal lesions acquired in adulthood, novelty preference in the neonatally operated animals remained above chance at all delays and all ages. The data suggest that, although incidental recognition memory processes can be supported by the perirhinal cortex in early infancy, other temporal cortical areas may support these processes in the absence of a functional perirhinal cortex early in development. The neural substrates mediating incidental recognition memory processes appear to be more widespread in early infancy than in adulthood., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Anatomically, the perirhinal cortex sits at the boundary between the medial temporal lobe and the ventral visual pathway. It has prominent interconnections not only with both these systems, but also with a wide range of unimodal and polymodal association areas. Consistent with these diverse projections, neurophysiological studies reveal a multidimensional set of mnemonic signals that include stimulus familiarity, within- and between-domain associations, associative recall, and delay-based persistence. This wide range of perirhinal memory signals not only includes signals that are largely unique to the perirhinal cortex (i.e., object familiarity), consistent with dual-process theories, but also includes a range of signals (i.e., associative flexibility and recall) that are strongly associated with the hippocampus, consistent with single-process theories. These neurophysiological findings have important implications for bridging the gap between single-process and dual-process models of medial temporal lobe function.

Learning is widely believed to involve synaptic plasticity, employing mechanisms such as those used in long-term potentiation (LTP) and long-term depression (LTD). In this chapter, we will review work on mechanisms of synaptic plasticity in perirhinal cortex in vitro and relate these findings to studies underlying recognition memory in vivo. We describe how antagonism of different glutamate and acetylcholine receptors, inhibition of nitric oxide synthase, inhibition of CREB phosphorylation, and interfering with glutamate AMPA receptor internalization can produce deficits in synaptic plasticity in vitro. Inhibition of each of these different mechanisms in vivo also results in recognition memory deficits. Therefore, we provide strong evidence that synaptic plastic mechanisms are necessary for the information processing and storage that underlies object recognition memory., (© 2014 Elsevier Inc. All rights reserved.)

Healthy aging is marked by declines in a variety of cognitive and motor abilities. A better understanding of the aging brain may aid in elucidating the neural substrates of these behavioral effects. Investigations of resting state functional brain connectivity have provided insights into pathology, and to some degree, healthy aging. Given the role of the cerebellum in both motor and cognitive behaviors, as well as its known volumetric declines with age, investigating cerebellar networks may shed light on the neural bases of age-related functional declines. We mapped the resting state networks of the lobules of the right hemisphere and the vermis of the cerebellum in a group of healthy older adults and compared them to those of young adults. We report disrupted cortico-cerebellar resting state network connectivity in older adults. These results remain even when controlling for cerebellar volume, signal-to-noise ratio, and signal-to-fluctuation noise ratio. Specifically, there was consistent disruption of cerebellar connectivity with both the striatum and the medial temporal lobe. Associations between connectivity strength and both sensorimotor and cognitive task performances indicate that cerebellar engagement with the default mode network and striatal pathways is associated with better performance for older adults. These results extend our understanding of the resting state networks of the aging brain to include cortico-cerebellar networks, and indicate that age differences in network connectivity strength are important for behavior., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The wide array of cognitive functions associated with the hippocampus is supported through interactions with the cerebral cortex. However, most of the direct cortical input to the hippocampus originates in the entorhinal cortex, forming the hippocampal-entorhinal system. In humans, the role of the entorhinal cortex in mediating hippocampal-cortical interactions remains unknown. In this study, we used precision neuroimaging to examine the distributed cortical anatomy associated with the human hippocampal-entorhinal system. Consistent with animal anatomy, our results associate different subregions of the entorhinal cortex with different parts of the hippocampus long axis. Furthermore, we find that the entorhinal cortex comprises three band-like zones that are associated with functionally distinct cortical networks. Importantly, the entorhinal cortex bands traverse the proposed human homologs of rodent lateral and medial entorhinal cortices. Finally, we show that the entorhinal cortex is a major convergence area of distributed cortical processing and that the topography of cortical networks associated with the anterior medial temporal lobe mirrors the macroscale structure of high-order cortical processing. • Human entorhinal cortex (ERC) is organized into three parallel band-like zones • Functionally distinct cortical networks associate with distinct ERC bands • Different longitudinal parts of the hippocampus associate with distinct ERC bands • Human ERC is a major convergence hub of distributed cortical processing Using precision neuroimaging, Reznik et al. discover that the human entorhinal cortex is organized into three band-like zones running in parallel to the collateral sulcus. Consistent with animal anatomy, these entorhinal cortex bands associate with functionally distinct cortical networks and different parts of the hippocampus long axis. [ABSTRACT FROM AUTHOR]

Attention influences what is later remembered, but little is known about how this occurs in the brain. We hypothesized that behavioral goals modulate the attentional state of the hippocampus to prioritize goal-relevant aspects of experience for encoding. Participants viewed rooms with paintings, attending to room layouts or painting styles on different trials during high-resolution functional MRI. We identified template activity patterns in each hippocampal subfield that corresponded to the attentional state induced by each task. Participants then incidentally encoded new rooms with art while attending to the layout or painting style, and memory was subsequently tested. We found that when task-relevant information was better remembered, the hippocampus was more likely to have been in the correct attentional state during encoding. This effect was specific to the hippocampus, and not found in medial temporal lobe cortex, category-selective areas of the visual system, or elsewhere in the brain. These findings provide mechanistic insight into how attention transforms percepts into memories.

The perirhinal cortex (PER), which is critical for associative memory and stimulus discrimination, has been described as a wall of inhibition between the neocortex and hippocampus. With advanced age, rats show deficits on PER-dependent behavioral tasks and fewer PER principal neurons are activated by stimuli, but the role of PER interneurons in these altered circuit properties in old age has not been characterized. In the present study, PER neurons were recorded while rats traversed a circular track bidirectionally in which the track was either empty or contained eight novel objects evenly spaced around the track. Putative interneurons were discriminated from principal cells based on the autocorrelogram, waveform parameters, and firing rate. While object modulation of interneuron firing was observed in both young and aged rats, PER interneurons recorded from old animals had lower firing rates compared with those from young animals. This difference could not be accounted for by differences in running speed, as the firing rates of PER interneurons did not show significant velocity modulation. Finally, in the aged rats, relative to young rats, there was a significant reduction in detected excitatory and inhibitory monosynaptic connections. Together these data suggest that with advanced age there may be reduced afferent drive from excitatory cells onto interneurons that may compromise the wall of inhibition between the hippocampus and cortex. This circuit dysfunction could erode the function of temporal lobe networks and ultimately contribute to cognitive aging. [ABSTRACT FROM AUTHOR]

Recent studies have suggested that the perirhinal cortex (Prh) supports representations of feature conjunctions in the visual modality during the acquisition/encoding of complex discriminations. To extend this idea to other sensory modalities and to another stage of the discrimination process, we studied the effect of Prh lesions on the expression of a series of tactual discrimination tasks learned preoperatively. These tasks differed from one another in the degree of feature overlap of the stimuli and in the difficulty of the task. During pre- and post-operative testing phases, rats had to discriminate among 3 stimuli simultaneously exposed in 3 arms of a 4-arm plus-shaped maze. Prh-damaged rats showed a profound impairment in the expression of tactual discrimination tasks when the stimuli had a high or intermediate degree of feature ambiguity, but not when they had a low degree of ambiguity (experiments 1a–1c). In order to experimentally dissociate between subregions within the medial temporal lobe, experiment 2 was conducted to show that hippocampal lesions did not cause any impairment in task expression even when the stimuli had a high degree of feature ambiguity. When the tactual discrimination tasks used simple/individual nonoverlapping features of the stimuli (size), Prh lesions did not affect the expression of these discriminations despite the high level of difficulty of these tasks (experiments 3a and 3b). These findings suggest that, in the somatosensory modality, the Prh plays an essential role in the processing of complex stimuli with overlapping features but not in simple tactual discriminations. Furthermore, the Prh is necessary not just during acquisition but also during expression/performance of the discrimination task. [ABSTRACT FROM AUTHOR]

When faced with a new challenge, we often reflect on related past experiences to guide our behavior. The ability to retrieve memories that overlap with current experience, a process known as pattern completion, is theorized as a critical function of the hippocampus. Although this view has influenced research for decades, there is little empirical support for hippocampal pattern completion to individual memory elements and its influence on behavior. We used pattern analysis of brain activity measured with functional magnetic resonance imaging to demonstrate that specific elements of past experiences are reinstated in the hippocampus, as well as perirhinal cortex (PRC), when making decisions about those experiences. Linking neural measures of specific memory reinstatement in the hippocampus and PRC to behavior with computational modeling revealed that reinstatement predicts the speed of memory-based decisions. Moreover, hippocampal activation during retrieval was selectively coupled to regions of occipito-temporal cortex that showed content-specific item reinstatement. These results provide evidence for hippocampal pattern completion and its role in the mechanisms of decision making. [ABSTRACT FROM AUTHOR]

The article discusses a study which examines a hypothesis regarding the involvement of perirhinal cortex (PrC) and hippocampus (HC) in face and scene perception using diffusion tensor imaging.

Based on the notion that the brain is equipped with a hierarchical organization, which embodies environmental contingencies across many time scales, this paper suggests that the medial temporal lobe (MTL)--located deep in the hierarchy--serves as a bridge connecting supra- to infra--MTL levels. Bridging the upper and lower regions of the hierarchy provides a parallel architecture that optimizes information flow between upper and lower regions to aid attention, encoding, and processing of quick complex visual phenomenon. Bypassing intermediate hierarchy levels, information conveyed through the MTL "bridge" allows upper levels to make educated predictions about the prevailing context and accordingly select lower representations to increase the efficiency of predictive coding throughout the hierarchy. This selection or activation/deactivation is associated with endogenous attention. In the event that these "bridge" predictions are inaccurate, this architecture enables the rapid encoding of novel contingencies. A review of hierarchical models in relation to memory is provided along with a new theory, Medialtemporal- lobe Conduit for Parallel Connectivity (MCPC). In this scheme, consolidation is considered as a secondary process, occurring after a MTL-bridged connection, which eventually allows upper and lower levels to access each other directly. With repeated reactivations, as contingencies become consolidated, less MTL activity is predicted. Finally, MTL bridging may aid processing transient but structured perceptual events, by allowing communication between upper and lower levels without calling on intermediate levels of representation. [ABSTRACT FROM AUTHOR]

Aging is associated with a decline in episodic memory function. This is accompanied by degradation of and functional changes in the medial temporal lobe (MTL) which subserves mnemonic processing. To date no study has investigated age-related functional change in MTL substructures during specific episodic memory processes such as intra-item associative memory. The aim of this study was to characterize age-related change in the neural correlates of intra-item associative memory processing. Sixteen young and 10 older subjects participated in a compound word intra-item associative memory task comprising a measure of associative recognition memory and a measure of recognition memory. There was no difference in performance between groups on the associative memory measure but each group recruited different MTL regions while performing the task. The young group recruited the left anterior hippocampus and posterior parahippocampal gyrus whereas the older participants recruited the hippocampus bilaterally. In contrast, recognition memory was significantly worse in the older subjects. The left anterior hippocampus was recruited in the young group during successful recognition memory whereas the older group recruited a more posterior region of the left hippocampus and showed a more bilateral activation of frontal brain regions than was observed in the young group. Our results suggest a reorganization of the neural correlates of intra-item associative memory in the aging brain. [ABSTRACT FROM AUTHOR]

Highlights: [•] Hippocampus, perirhinal cortex and postrhinal cortex are dissociable in spatial memory. [•] Hippocampal lesions produce a profound deficit in acquisition and retention. [•] Postrhinal lesions affect retention profoundly but acquisition only midly. [•] Perirhinal lesions do not affect acquisition or retention. [•] Inflexible behavior and motor perseveration are observed only in hippocampal rats. [ABSTRACT FROM AUTHOR]

Abstract: Studies of people with memory impairments have shown that a specific set of brain structures in the medial temporal lobe (MTL) is vital for memory function. However, whether these structures have a role outside of memory remains contentious. Recent studies of amnesic patients with damage to two structures within the MTL, the hippocampus and the perirhinal cortex, indicated that these patients also performed poorly on perceptual tasks. More specifically, they performed worse than controls when discriminating between objects, faces and scenes with overlapping features. In order to investigate whether these perceptual deficits are reflected in their viewing strategies, we tested a group of amnesic patients with MTL damage that included the hippocampus and perirhinal cortex on a series of oddity discrimination tasks in which they had to select an odd item from a visual array. Participants'' eye movements were monitored throughout the experiment. Results revealed that patients were impaired on tasks that required them to discriminate between items that shared many features, and tasks that required processing items from different viewpoints. An analysis of their eye movements revealed that they exhibited a similar viewing pattern as controls: they fixated more on the target item on trials answered correctly, but not on trials answered incorrectly. In addition, their impaired performance was not explained by an abnormal viewing-strategy that assessed their use of working memory. These results suggest that the perceptual deficits in the MTL patients are not a consequence of abnormal viewing patterns of the objects and scenes, but instead, could involve an inability to bind information gathered from several fixations into a cohesive percept. These data also support the view that MTL structures are important not only for long-term memory, but are also involved in perceptual tasks. [Copyright &y& Elsevier]

Volume losses in the medial temporal lobe, posterior cingulated, and orbitofrontal region have been observed in Alzheimer's disease (AD). Smaller reductions in similar regions have also been reported in amnestic mild cognitive impairment (aMCI), a canonical precursor to AD. We previously demonstrated that volume loss in bilateral anteromedial temporal lobe is present at baseline in longitudinally followed normal subjects who later developed MCI or AD. In this study we compared grey matter volumes within this predefined anteromedial temporal region (AMTR) at baseline between: 1) normal subjects enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who subsequently developed cognitive complaints as reflected in a CDR memory box score of 0.5; and 2) normal subjects who remained normal over a median of 48 months of follow-up (CDR sum of boxes 0). We found significantly decreased volume within AMTR in the ADNI memory complainers. To relate AMTR results to those from conventional anatomy, we demonstrate that volumes extracted with the ICBM amygdala region had the best correspondence with AMTR volumes. In contrast, regions that have demonstrated volume loss in frank MCI and AD in ADNI, e.g., the posterior cingulate, did not show volume loss. These findings provide independent confirmation that volume changes preceding MCI occur in AMTR, a region of overlap between amygdala and anterior hippocampus. [ABSTRACT FROM AUTHOR]

Abstract: In déjà vu, a phenomenological impression of familiarity for the current visual environment is experienced with a sense that it should in fact not feel familiar. The fleeting nature of this phenomenon in daily life, and the difficulty in developing experimental paradigms to elicit it, has hindered progress in understanding déjà vu. Some neurological patients with temporal-lobe epilepsy (TLE) consistently experience déjà vu at the onset of their seizures. An investigation of such patients offers a unique opportunity to shed light on its possible underlying mechanisms. In the present study, we sought to determine whether unilateral TLE patients with déjà vu (TLE+) show a unique pattern of interictal memory deficits that selectively affect familiarity assessment. In Experiment 1, we employed a Remember-Know paradigm for categorized visual scenes and found evidence for impairments that were limited to familiarity-based responses. In Experiment 2, we administered an exclusion task for highly similar categorized visual scenes that placed both recognition processes in opposition. TLE+ patients again displayed recognition impairments, and these impairments spared their ability to engage recollective processes so as to counteract familiarity. The selective deficits we observed in TLE+ patients contrasted with the broader pattern of recognition-memory impairments that was present in a control group of unilateral patients without déjà vu (TLE−). MRI volumetry revealed that ipsilateral medial temporal structures were less broadly affected in TLE+ than in TLE− patients, with a trend for more focal volume reductions in the rhinal cortices of the TLE+ group. The current findings establish a first empirical link between déjà vu in TLE and processes of familiarity assessment, as defined and measured in current cognitive models. They also reveal a pattern of selectivity in recognition impairments that is rarely observed and, thus, of significant theoretical interest to the memory literature at large. [Copyright &y& Elsevier]

The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course. (JINS, 2012, 18, 1–12) [ABSTRACT FROM PUBLISHER]

Abstract: The axons in the parahippocampal white matter (PWM) region that includes the perforant pathway relay multimodal sensory information, important for memory function, from the entorhinal cortex to the hippocampus. Previous work suggests that the integrity of the PWM shows changes in individuals with amnestic mild cognitive impairment and is further compromised as Alzheimer''s disease progresses. The present study was undertaken to determine the effects of healthy aging on macro- and micro-structural alterations in the PWM. The study characterized in vivo white matter changes in the parahippocampal region that includes the perforant pathway in cognitively healthy young (YNG, n=21) compared to cognitively healthy older (OLD, n=21) individuals using volumetry, diffusion tensor imaging (DTI) and tractography. Results demonstrated a significant reduction in PWM volume in old participants, with further indications of reduced integrity of remaining white matter fibers. In logistic regressions, PWM volume, memory performance and DTI indices of PWM integrity were significant indicator variables for differentiating the young and old participants. Taken together, these findings suggest that age-related alterations do occur in the PWM region and may contribute to the normal decline in memory function seen in healthy aging by degrading information flow to the hippocampus. [Copyright &y& Elsevier]