Medial Temporal Lobe Structures Research Articles

The hippocampus supports precise memory for public events regardless of their remoteness

The necessity of the human hippocampus and surrounding medial temporal lobe structures to semantic memory remains contentious. Impaired semantic memory following hippocampal lesions could arise either due to partially intertwined episodic memories and/or retrograde/anterograde effects. In this study, we tested amnesic individuals with lesions in hippocampus and surrounding medial temporal lobe (n = 7) and age-matched controls (n = 14) on their ability to precisely recall the dates of famous public events that occurred either before (i.e., pre-lifetime) or after participants’ birth date (lifetime). We show that deficits in dating precision are greatest for recent lifetime events, consistent with the notion that recent event memory may be particularly intertwined with episodic memory. At the same time, individuals with medial temporal lobe lesions showed more subtle impairments in their ability to date pre-birth and remote lifetime events precisely. Together, these findings suggest that the hippocampus and surrounding medial temporal lobe structures are important for representational precision of semantic memories regardless of their remoteness.

Gray matter volume in women with the BRCA mutation with and without ovarian removal: evidence for increased risk of late-life Alzheimer's disease or dementia.

Ovarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimer's disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counseled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM showing women without the BRCAm had cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and bilateral salpingo-oophorectomy (BSO) noted changes in cognition. The present, cross-sectional study examined whole-brain differences in gray matter (GM) volume using high-resolution, quantitative magnetic resonance imaging in women with BRCAm and intact ovaries (BRCA-preBSO [study cohort with BRCA mutation prior to oophorectomy]; n = 9) and after surgery with (BSO + estradiol-based therapy [ERT]; n = 10) and without (BSO; n = 10) postsurgical estradiol hormone therapy compared with age-matched women (age-matched controls; n = 10) with their ovaries. The BRCA-preBSO and BSO groups showed significantly lower GM volume in the left medial temporal and frontal lobe structures. BSO + ERT exhibited few areas of lower GM volume compared with age-matched controls. Novel to this study, we also observed that all three BRCAm groups exhibited significantly higher GM volume compared with age-matched controls, suggesting continued plasticity. The present study provides evidence, through lower GM volume, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, postsurgical ERT seems to ameliorate GM losses.

Accelerated epigenetic age is associated with whole-brain functional connectivity and impaired cognitive performance in older adults

While chronological age is a strong predictor for health-related risk factors, it is an incomplete metric that fails to fully characterize the unique aging process of individuals with different genetic makeup, neurodevelopment, and environmental experiences. Recent advances in epigenomic array technologies have made it possible to generate DNA methylation-based biomarkers of biological aging, which may be useful in predicting a myriad of cognitive abilities and functional brain network organization across older individuals. It is currently unclear which cognitive domains are negatively correlated with epigenetic age above and beyond chronological age, and it is unknown if functional brain organization is an important mechanism for explaining these associations. In this study, individuals with accelerated epigenetic age (i.e. AgeAccelGrim) performed worse on tasks that spanned a wide variety of cognitive faculties including both fluid and crystallized intelligence (N = 103, average age = 68.98 years, 73 females, 30 males). Additionally, fMRI connectome-based predictive models suggested a mediating mechanism of functional connectivity on epigenetic age acceleration-cognition associations primarily in medial temporal lobe and limbic structures. This research highlights the important role of epigenetic aging processes on the development and maintenance of healthy cognitive capacities and function of the aging brain.

Impairment of unconscious emotional processing after unilateral medial temporal structure resection

The role of the amygdala in unconscious emotional processing remains a topic of debate. Past lesion studies have indicated that amygdala damage leads to impaired electrodermal activity in response to subliminally presented emotional stimuli. However, electrodermal activity can reflect both emotional and nonemotional processes. To provide behavioral evidence highlighting the critical role of the amygdala in unconscious emotional processing, we examined patients (n = 16) who had undergone unilateral resection of medial temporal lobe structures, including the amygdala. We utilized the subliminal affective priming paradigm in conjunction with unilateral visual presentation. Fearful or happy dynamic facial expressions were presented in unilateral visual fields for 30 ms, serving as negative or positive primes. Subsequently, neutral target faces were displayed, and participants were tasked with rating the valence of these targets. Positive primes, compared to negative ones, enhanced valence ratings of the target to a greater extent when they stimulated the intact hemisphere (i.e., were presented in the contralateral visual field of the intact hemisphere) than when they stimulated the resected hemisphere (i.e., were presented in the contralateral visual field of the resected hemisphere). These results suggest that the amygdala is causally involved in unconscious emotional processing.

Neurofilament light chain concentration mediates the association between regional medial temporal lobe structure and memory in adults with Down syndrome.

Virtually all people with Down syndrome (DS) develop neuropathology associated with Alzheimer's disease (AD). Atrophy of the hippocampus and entorhinal cortex (EC), as well as elevated plasma concentrations of neurofilament light chain (NfL) protein, are markers of neurodegeneration associated with late-onset AD. We hypothesized that hippocampus and EC gray matter loss and increased plasma NfL concentrations are associated with memory in adults with DS. T1-weighted structural magnetic resonance imaging (MRI) data were collected from 101 participants with DS. Hippocampus and EC volume, as well as EC subregional cortical thickness, were derived. In a subset of participants, plasma NfL concentrations and modified Cued Recall Test scores were obtained. Partial correlation and mediation were used to test relationships between medial temporal lobe (MTL) atrophy, plasma NfL, and episodic memory. Hippocampus volume, left anterolateral EC (alEC) thickness, and plasma NfL were correlated with each other and were associated with memory. Plasma NfL mediated the relationship between left alEC thickness and memory as well as hippocampus volume and memory. The relationship between MTL gray matter and memory is mediated by plasma NfL levels, suggesting a link between neurodegenerative processes underlying axonal injury and frank gray matter loss in key structures supporting episodic memory in people with DS.

The Sporadic Early‐Onset Alzheimer’s Disease Signature of Regional Atrophy

AbstractBackgroundIn EOAD, the localization of neurodegeneration is often more prominent in posterior lateral temporal, lateral and medial parietal, frontal, or occipital cortex relative to the medial and ventral temporal cortical localization of typical LOAD. Convergently, neuropathological investigations have identified a “hippocampal‐sparing” form of AD that is often present in younger patients. For these reasons, imaging biomarkers of neurodegeneration in EOAD, such as Magnetic Resonance Imaging (MRI) measures of atrophy, likely need to be different than those of neurodegeneration in typical LOAD. Although prior neuroimaging work has advanced our understanding of anatomical abnormalities in EOAD, these studies have included small samples, most composed of amnestic EOAD dementia and none focused on developing an MRI biomarker specific to EOAD. Such a disease‐signature MRI biomarker has been established and validated in LOAD dementia and has proven to be powerful in predicting progressive decline in people with MCI or who were cognitively unimpaired and in predicting molecular biomarker status. An a priori‐defined regional atrophy signature may also be helpful in constraining the analysis of MRI data in studies of putative disease‐modifying therapies.MethodLEADS is an observational study which includes annual MRI. In this analysis, we used FreeSurfer to define the sporadic EOAD atrophy signature in a small sample of MGH EOAD patients, and investigated its reproducibility in LEADS, as well as the magnitude of atrophy and its relationship to clinical measures.ResultThe EOAD signature is robustly reproducible across the two independent patient cohorts, with prominent atrophy in caudal lateral temporal cortex, inferior parietal lobule, and posterior cingulate and precuneus cortex, with relative sparing of medial temporal lobe structures. Comparing patients to controls, Cohen’s d effect sizes within various regions ranged from 0.99 to 1.98.ConclusionThis study demonstrates the specific cortical regions with most prominent atrophy in patients with sporadic EOAD; this signature of regional atrophy will be used to examine longitudinal change.

Organization of pRF size along the AP axis of the hippocampus and adjacent medial temporal cortex is related to specialization for scenes versus faces.

The hippocampus is largely recognized for its integral contributions to memory processing. By contrast, its role in perceptual processing remains less clear. Hippocampal properties vary along the anterior-posterior (AP) axis. Based on past research suggesting a gradient in the scale of features processed along the AP extent of the hippocampus, the representations have been proposed to vary as a function of granularity along this axis. One way to quantify such granularity is with population receptive field (pRF) size measured during visual processing, which has so far received little attention. In this study, we compare the pRF sizes within the hippocampus to its activation for images of scenes versus faces. We also measure these functional properties in surrounding medial temporal lobe (MTL) structures. Consistent with past research, we find pRFs to be larger in the anterior than in the posterior hippocampus. Critically, our analysis of surrounding MTL regions, the perirhinal cortex, entorhinal cortex, and parahippocampal cortex shows a similar correlation between scene sensitivity and larger pRF size. These findings provide conclusive evidence for a tight relationship between the pRF size and the sensitivity to image content in the hippocampus and adjacent medial temporal cortex.

3 The Relationship Between Apolipoprotein-E4 Genotype, Memory, and the Medial Temporal Lobe and How These Relationships Vary by Race in Middle-Aged Persons with HIV

Objective:Many people with HIV (PWH) are at risk for age-related neurodegenerative disorders such as Alzheimer’s disease (AD). Studies on the association between cognition, neuroimaging outcomes, and the Apolipoprotein E4 (APOE4) genotype, which is associated with greater risk of AD, have yielded mixed results in PWH; however, many of these studies have examined a wide age range of PWH and have not examined APOE by race interactions that are observed in HIV-negative older adults. Thus, we examined how APOE status relates to cognition and medial temporal lobe (MTL) structures (implicated in AD pathogenesis) in mid- to older-aged PWH. In exploratory analyses, we also examined race (African American (AA)/Black and non-Hispanic (NH) White) by APOE status interactions on cognition and MTL structures.Participants and Methods:The analysis included 88 PWH between the ages of 45 and 68 (mean age=51±5.9 years; 86% male; 51% AA/Black, 38% NH-White, 9% Hispanic/Latinx, 2% other) from the CNS HIV Antiretroviral Therapy Effects Research multi-site study. Participants underwent APOE genotyping, neuropsychological testing, and structural MRI; APOE groups were defined as APOE4+ (at least one APOE4 allele) and APOE4- (no APOE4 alleles). Eighty-nine percent of participants were on antiretroviral therapy, 74% had undetectable plasma HIV RNA (<50 copies/ml), and 25% were APOE4+ (32% AA/Black/15% NH-White). Neuropsychological testing assessed seven domains, and demographically-corrected T-scores were calculated. FreeSurfer 7.1.1 was used to measure MTL structures (hippocampal volume, entorhinal cortex thickness, and parahippocampal thickness) and the effect of scanner was regressed out prior to analyses. Multivariable linear regressions tested the association between APOE status and cognitive and imaging outcomes. Models examining cognition covaried for comorbid conditions and HIV disease characteristics related to global cognition (i.e., AIDS status, lifetime methamphetamine use disorder). Models examining the MTL covaried for age, sex, andrelevant imaging covariates (i.e., intracranial volume or mean cortical thickness).Results:APOE4+ carriers had worse learning (ß=-0.27, p=.01) and delayed recall (ß=-0.25, p=.02) compared to the APOE4- group, but APOE status was not significantly associated with any other domain (ps>0.24). APOE4+ status was also associated with thinner entorhinal cortex (ß=-0.24, p=.02). APOE status was not significantly associated with hippocampal volume (ß=-0.08, p=0.32) or parahippocampal thickness (ß=-0.18, p=.08). Lastly, race interacted with APOE status such that the negative association between APOE4+ status and cognition was stronger in NH-White PWH as compared to AA/Black PWH in learning, delayed recall, and verbal fluency (ps<0.05). There were no APOE by race interactions for any MTL structures (ps>0.10).Conclusions:Findings suggest that APOE4 carrier status is associated with worse episodic memory and thinner entorhinal cortex in mid- to older-aged PWH. While APOE4+ groups were small, we found that APOE4 carrier status had a larger association with cognition in NH-White PWH as compared to AA/Black PWH, consistent with studies demonstrating an attenuated effect of APOE4 in older AA/Black HIV-negative older adults. These findings further highlight the importance of recruiting diverse samples and suggest exploring other genetic markers (e.g., ABCA7) that may be more predictive of AD in some races to better understand AD risk in diverse groups of PWH.

Menopause age, reproductive span and hormone therapy duration predict the volume of medial temporal lobe brain structures in postmenopausal women

Medial temporal lobe (MTL) atrophy is correlated with risk and severity of Alzheimer disease (AD) pathology and cognitive decline. Increasing evidence suggest that oestrogens affect the aging of MTL structures. Here we investigate the relationship between reproductive hormone exposure, polygenic scores for AD risk and oestradiol concentration, MTL anatomy and cognitive performance in postmenopausal women. To this end, we used data from 10,924 female participants in the UK Biobank from whom brain MRI and genetic data were available. We fitted linear regression models to test whether the volume of structures comprising the MTL were predicted by a) timing related to menopause, b) the use and timing of hormone replacement therapy (HRT) and c) polygenic scores for AD risk and oestradiol concentration. Results showed that longer use of HRT was associated with larger parahippocampal volumes (2.53 mm3/year, p = 0.042). A later age of natural menopause, and a longer reproductive span, was associated with larger hippocampal (6.08 and 5.72 mm3/year, p = 0.0006 and 0.0005), parahippocampal (4.17 mm3 and 4.19 mm3/year, p = 0.00006 and 0.00001), amygdala (2.10 and 2.22 mm3/year, p = 0.028 and 0.01) and perirhinal cortical (2.56 and 2.95 mm3/year, p = 0.028 and 0.008) volumes. Superior prospective memory performance was associated with later age at natural menopause, and a longer reproductive span (ß = 0.05 and 0.05 respectively, p = 0.019 and 0.019). Polygenic scores for AD risk and for oestradiol concentration were not associated with MTL volume and did not interact with menopause-related factors to affect MTL structure. Our results suggest that HRT use did not have any detrimental effects on cognition or brain structure, whilst greater exposure to reproductive hormones across time is associated both with slightly larger volumes of specific MTL structures and marginally superior memory performance, independent of genetic risk for AD and genetic predisposition for higher oestradiol levels. However, the clinical utility of maintenance of oestrogens post-menopause for brain health and protection against cognitive decline is curtailed by the small effect sizes observed.

Perception and Memory in the Ventral Visual Stream and Medial Temporal Lobe.

Perception and memory are traditionally thought of as separate cognitive functions, supported by distinct brain regions. The canonical perspective is that perceptual processing of visual information is supported by the ventral visual stream, whereas long-term declarative memory is supported by the medial temporal lobe. However, this modular framework cannot account for the increasingly large body of evidence that reveals a role for early visual areas in long-term recognition memory and a role for medial temporal lobe structures in high-level perceptual processing. In this article, we review relevant research conducted in humans, nonhuman primates, and rodents. We conclude that the evidence is largely inconsistent with theoretical proposals that draw sharp functional boundaries between perceptual and memory systems in the brain. Instead, the weight of the empirical findings is best captured by a representational-hierarchical model that emphasizes differences in content, rather than in cognitive processes within the ventral visual stream and medial temporal lobe.

Differential effects of expectancy on memory formation in young and older adults.

Novelty can promote subsequent long-term memory via the mesolimbic system, including the medial temporal lobe and midbrain structures. Importantly, these and other brain regions typically degenerate during healthy aging, which suggests a reduced impact of novelty on learning. However, evidence in favor of such a hypothesis is scarce. Thus, we used functional MRI in combination with an established paradigm in healthy young (19-32 years, n = 30) and older (51-81 years, n = 32) humans. During encoding, colored cues predicted the subsequent presentation of either a novel or previously familiarized image (75% cue validity), and approximately 24 h later, recognition memory for novel images was tested. Behaviorally, expected novel images, as compared to unexpected novel images, were better recognized in young and, to a lesser degree, older subjects. At the neural level, familiar cues activated memory related areas, especially the medial temporal lobe, whereas novelty cues activated the angular gyrus and inferior parietal lobe, which may reflect enhanced attentional processing. During outcome processing, expected novel images activated the medial temporal lobe, angular gyrus and inferior parietal lobe. Importantly, a similar activation pattern was observed for subsequently recognized novel items, which helps to explain the behavioral effect of novelty on long-term memory. Finally, age-effects were pronounced for successfully recognized novel images with relatively stronger activations in attention-related brain regions in older adults; younger adults, on the other hand, showed stronger hippocampal activation. Together, expectancy promotes memory formation for novel items via neural activity in medial temporal lobe structures and this effect appears to be reduced with age.

Evaluation of volumetric asymmetry of the dorsolateral prefrontal cortex and medial temporal lobe in Alzheimer's disease using the atlas-based method.

Brain areas affected during neurodegenerative disease progression are considered anatomically connected to the first affected areas. The dorsolateral prefrontal cortex (DLPFC) has connections with the medial temporal lobe (MTL), which includes regions that become atrophic in Alzheimer's disease. In this study, we aimed to investigate the degree of volumetric asymmetry of DLPFC and MTL structures. This is a cross-sectional volumetric study involving 25 Alzheimer's disease patients and 25 healthy adults who underwent MRI with a 3D turbo spin echo sequence at 1.5 Tesla. The atlas-based method incorporated MRIStudio software to automatically measure the volume of brain structures. We compared the asymmetry index and volumetric changes across study groups and correlated them with Mini-Mental State Examination scores. We observed significant volumetric rightward lateralization in the DLPFC and superior frontal gyrus in Alzheimer's disease patients compared to the healthy controls. There was a significant volume loss in the MTL structures of Alzheimer's disease patients. Atrophy of MTL structures was positively correlated with right DLPFC volume changes in Alzheimer's disease patients. Volumetric asymmetry of the DLPFC may be a characteristic for determining disease progression in Alzheimer's disease patients. Future studies are recommended to evaluate whether these volumetric asymmetrical changes are specific to Alzheimer's disease and whether asymmetry measurements can serve as diagnostic markers.

Male rodent perirhinal cortex, but not ventral hippocampus, inhibition induces approach bias under object-based approach-avoidance conflict.

Neural models of approach-avoidance (AA) conflict behavior and its dysfunction have focused traditionally on the hippocampus, with the assumption that this medial temporal lobe (MTL) structure plays a ubiquitous role in arbitrating AA conflict. We challenge this perspective by using three different AA behavioral tasks in conjunction with optogenetics, to demonstrate that a neighboring region in male rats, perirhinal cortex, is also critically involved but only when conflicting motivational values are associated with objects and not contextual information. The ventral hippocampus, in contrast, was found not to be essential for object-associated AA conflict, suggesting its preferential involvement in context-associated conflict. We propose that stimulus type can impact MTL involvement during AA conflict and that a more nuanced understanding of MTL contributions to impaired AA behavior (e.g., anxiety) is required. These findings serve to expand upon the established functions of the perirhinal cortex while concurrently presenting innovative behavioral paradigms that permit the assessment of different facets of AA conflict behavior.

Inconsistencies between human and macaque lesion data can be resolved with a stimulus-computable model of the ventral visual stream.

Decades of neuroscientific research has sought to understand medial temporal lobe (MTL) involvement in perception. Apparent inconsistencies in the literature have led to competing interpretations of the available evidence; critically, findings from human participants with naturally occurring MTL damage appear to be inconsistent with findings from monkeys with surgical lesions. Here we leverage a 'stimulus-computable' proxy for the primate ventral visual stream (VVS), which enables us to formally evaluate perceptual demands across stimulus sets, experiments, and species. With this approach, we analyze a series of experiments administered to monkeys with surgical, bilateral damage to perirhinal cortex (PRC), a MTL structure implicated in visual object perception. Across experiments, PRC-lesioned subjects showed no impairment on perceptual tasks; this originally led us (Eldridge et al., 2018) to conclude that PRC is not involved in perception. Here we find that a 'VVS-like' model predicts both PRC-intact and -lesioned choice behaviors, suggesting that a linear readout of the VVS should be sufficient for performance on these tasks. Evaluating these data alongside findings from human experiments, we suggest that results from Eldridge et al., 2018 alone can not be used as evidence against PRC involvement in perception. These data suggest that the experimental findings from human and non-human primate literature are consistent, and apparent discrepancies between species was due to reliance on informal accounts of perceptual processing.

Functional brain networks reorganization in the absence of medial temporal lobe structures: an example of neuroplasticity

AbstractBackgroundMedial temporal lobe structures are particularly vulnerable in age‐related neurodegenerative diseases. Here, we investigated the brain reorganization that allows maintaining relatively normal global cognitive functioning in patients with herpes simplex encephalitis (HSE) – an infectious neurological disease ‐ with marked focal atrophy most pronounced in the medial temporal lobes, particularly the hippocampus. Using rs‐fMRI we (i) characterized the patterns of functional network organization, and (ii) compared the intra‐/interhemispheric functional connectivity (FC) within each patient.MethodA total of nine HSE patients were included (see Table 1), four of them were affected mainly in the left (LH) and five in the right (RH) hemisphere. The rs‐fMRI data were acquired after a long‐term follow‐up (median 16 years) of the disease and were preprocessed using the AFNI software. For each patient, using different brain parcellations, we computed the intra‐ and inter‐FC strength for each hemisphere separately, yielding four measures of intra‐FC LH/RH and inter‐FC LH/RH . We grouped the subjects according to their lesion‐side and their performance (low, high) in a memory task.ResultWe observed, regardless of the lesion side, a highly variable pattern of disrupted FC in each patient. Left‐lesioned patients showed high intra‐FCLH/RH particularly in the precuneus/posterior cingulate (PPC) and the angular gyrus while right‐lesioned patients exhibited a high inter‐FCRH in the medial prefrontal cortex (MPFC) and PPC regions. Both left and right‐lesioned showed decreased intra‐FCLH/RH in ventral medial temporal areas, more pronounced in the left‐lesioned patients (Figure1). Right‐lesioned individuals who showed a pattern of inter‐FC within the right MPF and PPC performed consistently higher on the memory task (percentiles > 50) (Figure2).ConclusionThe substantial HSE‐induced medial temporal lobe lesions induce a global network reorganization. However, the side of the lesion seems to determine a specific pattern of network reorganization that is associated with differential cognitive performance. Left‐lesioned patients exhibited high PPC intra‐ and inter‐FCLH/RH and low memory performance while the right‐lesioned exhibited a high inter‐FCRH on the PPC and MPFC and better memory performance. Left lesions may result in nonadaptive brain reorganizations, however, right lesions, when linked to prefrontal brain reorganizations, may result in cognitive benefits and therefore be adaptive.

Verbal memory formation across PET-based Braak stages of tau accumulation in Alzheimer's disease.

A classical early sign of typical Alzheimer's disease is memory decline, which has been linked to the aggregation of tau in the medial temporal lobe. Verbal delayed free recall and recognition tests have consistently probed useful to detect early memory decline, and there is substantial debate on how performance, particularly in recognition tests, is differentially affected through health and disease in older adults. Using in vivo PET-Braak staging, we investigated delayed recall and recognition memory dysfunction across the Alzheimer's disease spectrum. Our cross-sectional study included 144 cognitively unimpaired elderly, 39 amyloid-β+ individuals with mild cognitive impairment and 29 amyloid-β+ Alzheimer's disease patients from the Translational Biomarkers in Aging and Dementia cohort, who underwent [18F]MK6240 tau and [18F]AZD4694 amyloid PET imaging, structural MRI and memory assessments. We applied non-parametric comparisons, correlation analyses, regression models and voxel-wise analyses. In comparison with PET-Braak Stage 0, we found that reduced, but not clinically significant, delayed recall starts at PET-Braak Stage II (adjusted P < 0.0015), and that recognition (adjusted P = 0.011) displayed a significant decline starting at PET-Braak Stage IV. While performance in both delayed recall and recognition related to tau in nearly the same cortical areas, further analyses showed that delayed recall rendered stronger associations in areas of early tau accumulation, whereas recognition displayed stronger correlations in mostly posterior neocortical regions. Our results support the notion that delayed recall and recognition deficits are predominantly associated with tau load in allocortical and neocortical areas, respectively. Overall, delayed recall seems to be more dependent on the integrity of anterior medial temporal lobe structures, while recognition appears to be more affected by tau accumulation in cortices beyond medial temporal regions.

Traumatic brain injury alters the relationship between brain structure and episodic memory.

Focal and diffuse pathology resulting from traumatic brain injury (TBI) often disrupts brain circuitry that is critical for episodic memory, including medial temporal lobe and prefrontal regions. Prior studies have focused on unitary accounts of temporal lobe function, associating verbally learned material and brain morphology. Medial temporal lobe structures, however, are domain-sensitive, preferentially supporting different visual stimuli. There has been little consideration of whether TBI preferentially disrupts the type of visually learned material and its association with cortical morphology following injury. Here, we investigated whether (1) episodic memory deficits differ according to the stimulus type, and (2) the pattern in memory performance can be linked to changes in cortical thickness. Forty-three individuals with moderate-severe TBI and 38 demographically similar healthy controls completed a recognition task in which memory was assessed for three categories of stimuli: faces, scenes, and animals. The association between episodic memory accuracy on this task and cortical thickness was subsequently examined within and between groups. Our behavioral results support the notion of category-specific impairments: the TBI group had significantly impaired accuracy for memory for faces and scenes, but not animals. Moreover, the association between cortical thickness and behavioral performance was only significant for faces between groups. Taken together, these behavioral and structural findings provide support for an emergent memory account, and highlight that cortical thickness differentially affects episodic memory for specific categories of stimuli.

Conscious awareness and memory systems in the brain.

The term "memory" typically refers to conscious retrieval of events and experiences from our past, but experience can also change our behaviour without corresponding awareness of the learning process or the associated outcome. Based primarily on early neuropsychological work, theoretical perspectives have distinguished between conscious memory, said to depend critically on structures in the medial temporal lobe (MTL), and a collection of performance-based memories that do not. The most influential of these memory systems perspectives, the declarative memory theory, continues to be a mainstay of scientific work today despite mounting evidence suggesting that contributions of MTL structures go beyond the kinds or types of memory that can be explicitly reported. Consistent with these reports, more recent perspectives have focused increasingly on the processing operations supported by particular brain regions and the qualities or characteristics of resulting representations whether memory is expressed with or without awareness. These alternatives to the standard model generally converge on two key points. First, the hippocampus is critical for relational memory binding and representation even without awareness and, second, there may be little difference between some types of priming and explicit, familiarity-based recognition. Here, we examine the evolution of memory systems perspectives and critically evaluate scientific evidence that has challenged the status quo. Along the way, we highlight some of the challenges that researchers encounter in the context of this work, which can be contentious, and describe innovative methods that have been used to examine unconscious memory in the lab. This article is categorized under: Psychology > Memory Psychology > Theory and Methods Philosophy > Consciousness.

Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth

BackgroundIncreased expression of the complement component 4A (C4A) gene is associated with a greater lifetime risk of schizophrenia. In the brain, C4A is involved in synaptic pruning; yet, it remains unclear the extent to which upregulation of C4A alters brain development or is associated with the risk for psychotic symptoms in childhood. Here, we perform a multi-ancestry phenome-wide association study in 7789 children aged 9–12 years to examine the relationship between genetically regulated expression (GREx) of C4A, childhood brain structure, cognition, and psychiatric symptoms.ResultsWhile C4A GREx is not related to childhood psychotic experiences, cognition, or global measures of brain structure, it is associated with a localized reduction in regional surface area (SA) of the entorhinal cortex. Furthermore, we show that reduced entorhinal cortex SA at 9–10 years predicts a greater number and severity of psychosis-like events at 1-year and 2-year follow-up time points. We also demonstrate that the effects of C4A on the entorhinal cortex are independent of genome-wide polygenic risk for schizophrenia.ConclusionsOur results suggest neurodevelopmental effects of C4A on childhood medial temporal lobe structure, which may serve as a biomarker for schizophrenia risk prior to symptom onset.

The interaction between first-episode drug-naïve schizophrenia and age based on gray matter volume and its molecular analysis: a multimodal magnetic resonance imaging study.

Schizophrenia is a neurodevelopmental disorder characterized by progressive and widespread gray matter (GM) atrophy. Studies have shown that normal brain development has an impact on schizophrenia-induced GM alterations. However, the neuropathology and underlying molecular mechanisms of interaction between age and schizophrenia are unclear. This study enrolled 66/84 first-episode drug-naïve patients with early-onset/adult-onset schizophrenia ((EOS)/(AOS)) and matched normal controls (NC) (46 adolescents/73 adults), undergoing T1-weighted high-resolution magnetic resonance imaging. Gray matter volume (GMV) in four groups was detected using 2-way analyses of variance with diagnosis and age as factors. Then, factors-related volume maps and neurotransmitter maps were spatially correlated using JuSpace to determine the relationship to molecular structure. Compared to AOS, EOS and adult NC had larger GMV in right middle frontal gyrus. Compared to adolescent NC, EOS and adult NC had smaller GMV in right lingual gyrus, right fusiform gyrus, and right cerebellum_6. Disease-induced GMV reductions were mainly distributed in frontal, parietal, thalamus, visual, motor cortex, and medial temporal lobe structures. Age-induced GMV alterations were mainly distributed in visual and motor cortex. The changed GMV induced by schizophrenia, age, and their interaction was related to dopaminergic and serotonergic receptors. Age is also related to glutamate receptors, and schizophrenia is also associated with GABAaergic and noradrenergic receptors. Our results revealed the multimodal neural mechanism of interaction between disease and age. We emphasized age-related GM abnormalities of ventral stream of visual perceptual pathways and high-level cognitive brain in EOS, which may be affected by imbalance of excitatory and inhibitory neurotransmitters.