Domain-specific Memory Research Articles

Coronavirus spike protein vaccination history affects SARS-CoV-2 receptor-binding domain-specific memory response in a mouse model

Abstract Background: Previous exposure to human common cold coronaviruses (hCCCoVs) has been shown to affect immune responses to SARS-CoV-2. Since most humans have been infected with different hCCoVs throughout their lives, determining exactly how previous immunity to hCCoVs affects anti-SARS-CoV-2 responses, especially to the Spike (S) protein and its receptor-binding domain (RBD), has proven difficult. We, therefore, used a mouse model to investigate how exposure to different coronavirus S alters the immune response to SARS-CoV-2 S vaccination. Methods: C57BL/6 mice were vaccinated intramuscularly with 30 μg of full-length S from several coronaviruses: hCCCoVs, SARS-CoV, or SARS-CoV-2. All mice were then vaccinated with SARS-CoV-2 full-length S 33 days later. Sera from all mice were collected at multiple timepoints after vaccinations and analyzed by ELISA and microneutralization assays. Results: Initial SARS-CoV S vaccination, surprisingly, led to significantly higher levels of anti-RBD IgG antibodies compared to SARS-CoV-2 vaccination. Boosting with SARS-CoV-2 S increased SARS-CoV-2 S IgG and IgM levels, regardless of previous vaccination, but increased RBD IgG responses more in SARS-CoV and SARS-CoV-2 S mice and only previous SARS-CoV S vaccination increased in anti-RBD IgM levels. Microneutralization assay results of each timepoint significantly correlated with combined anti-RBD IgG and IgM levels. Conclusions: SARS-CoV S vaccination leads to more robust anti-SARS-CoV-2 RBD antibody levels in both naïve and SARS-CoV-2 S-vaccinated mice than other coronaviruses studied. Further investigation will help explore which aspects of this SARS-CoV S vaccination could lead to an increased RBD-focused immune response. David C. Brice was supported through The American Association of Immunologists Intersect Fellowship Program for Computational Scientists and Immunologists.

Longitudinal single-cell analysis of SARS-CoV-2-reactive B cells uncovers persistence of early-formed, antigen-specific clones.

Understanding persistence and evolution of B cell clones after COVID-19 infection and vaccination is crucial for predicting responses against emerging viral variants and optimizing vaccines. Here, we collected longitudinal samples from patients with severe COVID-19 every third to seventh day during hospitalization and every third month after recovery. We profiled their antigen-specific immune cell dynamics by combining single-cell RNA-Seq, Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-Seq), and B cell receptor-Seq (BCR-Seq) with oligo-tagged antigen baits. While the proportion of Spike receptor binding domain-specific memory B cells (MBC) increased from 3 months after infection, the other Spike- and Nucleocapsid-specific B cells remained constant. All patients showed ongoing class switching and sustained affinity maturation of antigen-specific cells, and affinity maturation was not significantly increased early after vaccine. B cell analysis revealed a polyclonal response with limited clonal expansion; nevertheless, some clones detected during hospitalization, as plasmablasts, persisted for up to 1 year, as MBC. Monoclonal antibodies derived from persistent B cell families increased their binding and neutralization breadth and started recognizing viral variants by 3 months after infection. Overall, our findings provide important insights into the clonal evolution and dynamics of antigen-specific B cell responses in longitudinally sampled patients infected with COVID-19.

High activation levels maintained in receptor-binding domain-specific memory B cells in people with severe coronavirus disease 2019.

The long-term health consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are still being understood. The molecular and phenotypic properties of SARS-CoV-2 antigen-specific T cells suggest a dysfunctional profile that persists in convalescence in those who were severely ill. By contrast, the antigen-specific memory B-cell (MBC) population has not yet been analyzed to the same degree, but phenotypic analysis suggests differences following recovery from mild or severe coronavirus disease 2019 (COVID-19). Here, we performed single-cell molecular analysis of the SARS-CoV-2 receptor-binding domain (RBD)-specific MBC population in three patients after severe COVID-19 and four patients after mild/moderate COVID-19. We analyzed the transcriptomic and B-cell receptor repertoire profiles at ~2 months and ~4 months after symptom onset. Transcriptomic analysis revealed a higher level of tumor necrosis factor-alpha (TNF-α) signaling via nuclear factor-kappa B in the severe group, involving CD80, FOS, CD83 and TNFAIP3 genes that was maintained over time. We demonstrated the presence of two distinct activated MBCs subsets based on expression of CD80hi TNFAIP3hi and CD11chi CD95hi at the transcriptome level. Both groups revealed an increase in somatic hypermutation over time, indicating progressive evolution of humoral memory. This study revealed distinct molecular signatures of long-term RBD-specific MBCs in convalescence, indicating that the longevity of these cells may differ depending on acute COVID-19 severity.

The amnestic syndrome of posterior cerebral artery infarction.

Background and purposeLittle is known about the character and underlying lesions of ischaemic amnesia. Episodic memory functions and brain lesions were therefore studied in 84 patients with acute ischaemic infarcts in the supply territory of the posterior cerebral artery. The aim was also to learn how the neural memory systems are organized.MethodsStandard neuropsychological tests were used to assess verbal and figural memory. Patients were split into memory‐impaired and memory‐intact groups. Lesions were demarcated, normalized and anatomically labelled, using standard mapping procedures.ResultsOf the 84 patients more than 80% had an amnestic syndrome, mostly with combined memory impairment, less often with figural or verbal memory impairment. Amnesia in subjects with left hemispheric lesions was more frequent and more severe, with significantly lower scores on the verbal memory test. Normal performance or figural amnesia were prevalent after right hemispheric lesions. However, no amnesia subtype was strictly tied to left‐ or right‐sided brain damage. Hippocampal and thalamic lesions were common, but 30% of lesions were extrahippocampal located in the ventral occipito‐temporal cortex and long occipital white matter tracts. Most amnestic patients lacked awareness for their memory impairment.ConclusionsMemory impairment is a key clinical manifestation of acute posterior cerebral artery stroke. Amnesia is more frequent and more severe after left stroke, suggesting a left hemisphere dominance of the two memory systems. Domain specific memory appears not to be strictly lateralized, since deficits in verbal and figural memory were found after lesions of both sides. Extrahippocampal lesions may also cause memory impairment.

Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have demonstrated strong immunogenicity and protection against severe disease, concerns about the duration and breadth of these responses remain. In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only-immunized animals. Importantly, pADA significantly improved the longevity of these enhanced responses in vivo. This coincided with durable increases in frequencies of plasmablasts, receptor-binding domain-specific memory B cells, and SARS-CoV-2-specific T follicular helper cells. Increased spike-specific T cell polyfunctionality was also observed. Notably, animals coimmunized with pADA had significantly reduced viral loads compared with their nonadjuvanted counterparts in a SARS-CoV-2 infection model. These data suggest that pADA enhances immune memory and durability and supports further translational studies.

Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals

Vaccine-mediated immunity often relies on the generation of protective antibodies and memory B cells, which commonly stem from germinal center (GC) reactions. An in-depth comparison of the GC responses elicited by SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals has not yet been performed due to the challenge of directly probing human lymph nodes. Herein, through a fine-needle aspiration-based approach, we profiled the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant recipients (KTXs). We found that, unlike healthy subjects, KTXs presented deeply blunted SARS-CoV-2-specific GC B cell responses coupled with severely hindered T follicular helper cell, SARS-CoV-2 receptor binding domain-specific memory B cell, and neutralizing antibody responses. KTXs also displayed reduced SARS-CoV-2-specific CD4 and CD8 T cell frequencies. Broadly, these data indicate impaired GC-derived immunity in immunocompromised individuals and suggest a GC origin for certain humoral and memory B cell responses following mRNA vaccination.

A Survey on Domain-Specific Memory Architectures

The never-ending demand for high performance and energy efficiency is pushing designers towards an increasing level of heterogeneity and specialization in modern computing systems. In such systems, creating efficient memory architectures is one of the major opportunities for optimizing modern workloads (e.g., computer vision, machine learning, graph analytics, etc.) that are extremely data-driven. However, designers demand proper design methods to tackle the increasing design complexity and address several new challenges, like the security and privacy of the data to be elaborated.This paper overviews the current trend for the design of domain-specific memory architectures. Domain-specific architectures are tailored for the given application domain, with the introduction of hardware accelerators and custom memory modules while maintaining a certain level of flexibility. We describe the major components, the common challenges, and the state-of-the-art design methodologies for building domain-specific memory architectures. We also discuss the most relevant research projects, providing a classification based on our main topics.

δ scores predict multiple neuropsychiatric symptoms.

Dementia severity is strongly related to Spearman's general intelligence factor "g", via the latent dementia phenotype "δ" and is distinct from domain-specific cognitive impairments arising from disease-specific regional pathologies. It is an empiric question whether behavioral and psychological symptoms of dementia (BPSD) are associated with δ or with domain-specific constructs. A recently developed δ homolog ("dDx") was tested as a predictor of 1 year prospective BPSD in n = 723 Mexican-American and non-Hispanic White participants in the Texas Alzheimer's Research and Care Consortium (TARCC). The informant-rated frequencies of 12 BPSD were rated by the neuropsychiatric inventory (NPI-Q). Baseline BPSD, demographic features, selected biomarkers, and treatment exposure to acetylcholinesterase inhibitors were used as covariates. Composite scores derived from orthogonal latent measures of domain-specific memory (MEM) and executive function (EF) were also tested as predictors. "Functionally salient cognitive impairment (FSCI)" that is, categorical "dementia" as diagnosed by dDx was associated with increased prospective frequency of 11/12 BPSD, independently of baseline behavior and covariates. Age, depressive symptoms, and EF were associated with individual BPSD. MEM was not associated with any. Dementia severity, as measured by dDx, was also associated with a prospective increase in total NPI-Q scores. δ is associated non-specifically with multiple BPSD. This suggests the existence of a dementia-specific behavioral profile, arising from insults to general intelligence, and unrelated to disease-specific regional pathology(ies).

ERPs and oscillations during encoding predict retrieval of digit memory in superior mnemonists

Previous studies have consistently demonstrated that superior mnemonists (SMs) outperform normal individuals in domain-specific memory tasks. However, the neural correlates of memory-related processes remain unclear. In the current EEG study, SMs and control participants performed a digit memory task during which their brain activity was recorded. Chinese SMs used a digit-image mnemonic for encoding digits, in which they associated 2-digit groups with images immediately after the presentation of each even-position digit in sequences. Behaviorally, SMs’ memory of digit sequences was better than the controls’. During encoding in the study phase, SMs showed an increased right central P2 (150–250ms post onset) and a larger right posterior high-alpha (10–14Hz, 500–1720ms) oscillation on digits at even-positions compared with digits at odd-positions. Both P2 and high-alpha oscillations in the study phase co-varied with performance in the recall phase, but only in SMs, indicating that neural dynamics during encoding could predict successful retrieval of digit memory in SMs. Our findings suggest that representation of a digit sequence in SMs using mnemonics may recruit both the early-stage attention allocation process and the sustained information preservation process. This study provides evidence for the role of dynamic and efficient neural encoding processes in mnemonists.

Movement Interferes with Visuospatial Working Memory during the Encoding: An ERP Study.

The present study focuses on the functional interactions of cognition and manual action control. Particularly, we investigated the neurophysiological correlates of the dual-task costs of a manual-motor task (requiring grasping an object, holding it, and subsequently placing it on a target) for working memory (WM) domains (verbal and visuospatial) and processes (encoding and retrieval). Thirty participants were tested in a cognitive-motor dual-task paradigm, in which a single block (a verbal or visuospatial WM task) was compared with a dual block (concurrent performance of a WM task and a motor task). Event-related potentials (ERPs) were analyzed separately for the encoding and retrieval processes of verbal and visuospatial WM domains both in single and dual blocks. The behavioral analyses show that the motor task interfered with WM and decreased the memory performance. The performance decrease was larger for the visuospatial task compared with the verbal task, i.e., domain-specific memory costs were obtained. The ERP analyses show the domain-specific interference also at the neurophysiological level, which is further process-specific to encoding. That is, comparing the patterns of WM-related ERPs in the single block and dual block, we showed that visuospatial ERPs changed only for the encoding process when a motor task was performed at the same time. Generally, the present study provides evidence for domain- and process-specific interactions of a prepared manual-motor movement with WM (visuospatial domain during the encoding process). This study, therefore, provides an initial neurophysiological characterization of functional interactions of WM and manual actions in a cognitive-motor dual-task setting, and contributes to a better understanding of the neuro-cognitive mechanisms of motor action control.

Disruption of mGluR5 in parvalbumin-positive interneurons induces core features of neurodevelopmental disorders.

Alterations in glutamatergic transmission onto developing GABAergic systems, in particular onto parvalbumin-positive (Pv(+)) fast-spiking interneurons, have been proposed as underlying causes of several neurodevelopmental disorders, including schizophrenia and autism. Excitatory glutamatergic transmission, through ionotropic and metabotropic glutamate receptors, is necessary for the correct postnatal development of the Pv(+) GABAergic network. We generated mutant mice in which the metabotropic glutamate receptor 5 (mGluR5) was specifically ablated from Pv(+) interneurons postnatally, and investigated the consequences of such a manipulation at the cellular, network and systems levels. Deletion of mGluR5 from Pv(+) interneurons resulted in reduced numbers of Pv(+) neurons and decreased inhibitory currents, as well as alterations in event-related potentials and brain oscillatory activity. These cellular and sensory changes translated into domain-specific memory deficits and increased compulsive-like behaviors, abnormal sensorimotor gating and altered responsiveness to stimulant agents. Our findings suggest a fundamental role for mGluR5 in the development of Pv(+) neurons and show that alterations in this system can produce broad-spectrum alterations in brain network activity and behavior that are relevant to neurodevelopmental disorders.

Impaired Visual Scanning and Memory for Faces in High-Functioning Autism Spectrum Disorders: It's Not Just the Eyes

Prior studies suggest that autism spectrum disorders (ASD) are associated with a domain-specific memory impairment for faces. The underlying cause of this problem and its relation to impaired visual scanning of faces--particularly of the eyes--remains to be determined. We recorded eye movements while 22 high-functioning ASD and 21 typically developing (TD) adolescents encoded and later recognized faces and objects from a single, nonsocial object category (electric fans). Relative to TD subjects, ASD individuals had poorer memory for faces, but not fans. Correlational analyses showed significant relationships between recognition memory and fixations. Eye tracking during encoding revealed that TD subjects made more fixations to faces than fans, whereas ASD individuals did not differ in number of fixations made to each stimulus type. Moreover, although both the TD and ASD groups showed a strong preference for fixating the eyes more than the mouth, the ASD subjects were less likely than TD subjects to scan regions of the face outside of the primary facial features (i.e., eyes, nose, and mouth). We concluded that ASD individuals have a domain-specific memory impairment for faces relative to mechanical objects and that this impairment may be related to abnormal scanning during encoding.

Identifying the processes underpinning anticipation and decision-making in a dynamic time-constrained task

A novel, representative task was used to examine skill-based differences in the perceptual and cognitive processes underlying performance on a dynamic, externally paced task. Skilled and less skilled soccer players were required to move and interact with life-size, action sequences involving 11 versus 11 soccer situations filmed from the perspective of a central defender in soccer. The ability of participants to anticipate the intentions of their opponents and to make decisions about how they should respond was measured across two separate experiments. In Experiment 1, visual search behaviors were examined using an eye-movement registration system. In Experiment 2, retrospective verbal reports of thinking were gathered from a new sample of skilled and less skilled participants. Skilled participants were more accurate than less skilled participants at anticipating the intentions of opponents and in deciding on an appropriate course of action. The skilled players employed a search strategy involving more fixations of shorter duration in a different sequential order and toward more disparate and informative locations in the display when compared with the less skilled counterparts. The skilled players generated a greater number of verbal report statements with a higher proportion of evaluation, prediction, and planning statements than the less skilled players, suggesting they employed more complex domain-specific memory representations to solve the task. Theoretical, methodological, and practical implications are discussed.

Working memory tasks differ in factor structure across age cohorts: Implications for dedifferentiation

Researchers interested in working memory have debated whether it should be considered a single latent cognitive ability or a set of essentially independent latent abilities distinguished by domain-specific memory and/or processing resources. Simultaneously, researchers interested in cognitive aging have established that there are substantial differences in rates of change in various aspects of cognitive function with age. In general, so-called fluid measures of cognitive function including working memory decline at faster rates in later adulthood than so-called crystallized measures. Using an Internet working and short-term memory test battery completed by over 95,000 people aged 18–90, we used multiple-group confirmatory factor analysis to assess the extent to which working memory could be considered a single latent ability as well as how its common and unique variance components varied with age. Results indicated a single latent factor, but the tests did not reflect this factor consistently across age groups. Both individual test residual variances and factor intercepts showed different patterns of variation with age. We discuss the implications for understanding age differences in working memory function.

A reverse Stroop effect without translation or reading difficulty

It is well known that irrelevant color words affect the time needed to identify the color they are displayed in (the Stroop effect). One major view is that a reverse Stroop effect (RSE)--in which the irrelevant color affects the time needed to identify the word--does not occur unless a translation is needed between domain-specific memory codes. In the present article, we report an experiment in which the reverse Stroop effect was investigated by having subjects identify a colored word at fixation by pointing to a location on the screen containing that word. Although the response was untranslated, an RSE was observed. An account is provided in which the strength of association between a stimulus and a specific response plays a central role.

Gender Differences in Coping and Control with Memory Aging

ABSTRACT This secondary analysis of data from a large study of memory perceptions among the elderly examined gender differences in control, coping, health, and metamemory and explored the influence of these factors on anxiety and depression in the elderly. Adults 55 years of age and older, 128 female and 41 males, were recruited from continuing education programs in two Southern states. Females were older than males and reported that their memories were better overall than males. There were no differences between the groups in depression, health, or memory control variables. Females had significantly greater state anxiety than males but no differences were seen in domain-specific memory anxiety or other metamemory domains. Females scored higher than males on help-seeking, existential growth, religiosity, and total coping strategies. In the two regression models the set of study variables predicted 79% of the variance in depression and 15% of the variance in memory anxiety. The addition of perceived health status to each model substantially changed each of their predictive values.

The Manipulation and Measurement of Task-specific Memory Self-Efficacy in Younger and Older Adults

Task-specific memory self-efficacy (TSMSE) was experimentally manipulated through provision of information about task difficulty, to determine its effect on free recall for 56 older (age 63-86) and 56 younger (age 16-25) adults. The implications of using prediction-based measures of TSMSE were addressed. After completing one recall trial of a list of 20 words, half the participants were told a second list comprised more difficult words; the others were told the second list would be similar to the first they had received. Free recall and TSMSE were measured before and after this manipulation. The manipulation reduced TSMSE for participants expecting a harder list of words, but not differently for younger compared with older adults. Younger and older adults’ recall declined at the second recall trial, but there was no difference between those expecting a harder list and those expecting a similar list. Recall was predicted by domain-specific memory self-efficacy as well as a traditional measure of TSMSE. The study demonstrated the malleability of memory self-efficacy, but called into question assertions about its salience as a mediator of older adults’ poorer memory performance.