Specific Memory Research Articles

Call and response: Ethnomusicological methods to awaken specific memories with targeted songs encoded in neuronal populations of a dementia patient

AbstractThis study collaborates with a fellow expert ethnomusicologist Sean Williams to trigger specific contextual memories associated with songs of her mother Julian Williams, born in 1932, and currently struggling with the early stages of dementia. The goal was to ascertain the success rate of a one‐to‐one correspondence type: The use of targeted, known songs of the dementia patient as a means to trigger the patient’s contextual memories.By adopting a methodology in Ethnomusicology involving the autobiography of one’s music history and their corresponding memories of the patient Julian Williams, I set up the experiment for Sean Williams to conduct. Dividing the study into discrete music time periods (infancy, childhood, teenager, young adult, older adult), I asked Sean Williams to choose specific songs with specific memories to the patient to be sung. The memory responses of the patient on video were then recorded.Each of those songs had deep levels of recognition by the Alzheimer’s patient, as evidenced in her singing with some memories (lyrics and contextual environment) stronger than than others. The fact that there is some autobiographical recall, despite a weakened sense of time and space after the onset of Alzheimer’s, suggests there may be use for this technique in dementia care. Of note, is the fun‐filled disposition of the participants during the recording of the singing. That speaks to a higher quality of life one could expect by using music as a memory‐recall and time‐ travel companion.This single case study needs to be broadened into a larger‐scale experiment involving many participants from different cultures to ascertain the use of individualized targeted songs to awaken specific memories of the dementia patients. In the area of dementia care, this approach also makes it possible for families to participate actively since the songs will probably be known to them as well.

Age‐related and AD pathology‐related differences in neural activation and neural specificity in memory

AbstractBackgroundBeta‐amyloid (Aß) and tau deposition is spatially selective in the early stages of Alzheimer’s Disease (AD), with Aß depositing predominately in posterior‐medial (PM) regions and tau accumulating in the medial temporal lobe (MTL) with increasing age before spreading to anterior‐temporal (AT) regions. Functionally, AT and PM are linked to object and scene processing, respectively, and the hippocampus in the MTL is important for integration and forming associations between objects and scenes. Given the differential vulnerability of AT, PM, and MTL to Aß and tau, we examined the behavioral and neural differences in memory for objects, scenes, and object‐in‐scene pairs between young and cognitively normal older adults with and without AD pathologies.MethodTwenty‐three young (19‐34 yrs) and 32 older (60‐91 yrs) participants completed an incidental encoding task on object, scene, and object‐in‐scene pair images during fMRI and a recognition test outside the scanner (Fig.1). Thirty older participants underwent PiB and FTP PET that measured Aß and tau. We conducted univariate whole‐brain analysis and multi‐voxel pattern analysis (MVPA) of AT, PM, and the hippocampus. The MVPA trains a support vector machine to classify the stimulus category (object, scene, pair) based on the ROI’s activation pattern. A higher classification accuracy represents informative neural representation that reflects functional specificity of the region.ResultBehaviorally, older people had worse object (ps<.027) and pair (ps<.017) memory. Greater temporal meta‐ROI tau was related to worse object (p = .032) and pair (p = .022) memory. Whole‐brain analyses showed activations in AT and PM networks for object and scene processing, and additional frontal, temporal, and occipital regions for pair processing (Fig.2A‐C) where older adults, compared to younger adults, showed activation reductions in fusiform, parahippocampal, precuneus, and occipital regions (Fig.2D). The MVPA revealed age‐related reductions in classification accuracy for pairs (Fig.3A) and that greater Aß and tau were related to lower accuracy in the hippocampus (Fig.3B).ConclusionWe found evidence supporting specific vulnerabilities in object and associative memory in older adults correlated with tau pathology. FMRI findings suggest both lower neural activation and lower neural specificity in older adults when processing complex associations. AD pathology appears to contribute to lower neural specificity in the hippocampus.

Memórias femininas da luta armada no Brasil e em Portugal

Abstract Literature and cinema can serve as historical documents, bearing potent testimonial content that aims to transmit the experiences and memories of those who have lived them. This analysis centers on the narrative of women who were active participants in armed organizations during the military dictatorship in Brazil and the Salazar dictatorship in Portugal, between the end of the 1960s and the beginning of the 1970s, and that later chose to make public their memories and experiences. Two works are analyzed: the 1989 documentary Que Bom te ver viva [How Nice to See You Alive] by Brazilian filmmaker Lucia Murat, and the 2012 book Mulheres de Armas: História das Brigadas Revolucionárias [Women in Arms: History of the Revolutionary Brigades], by Portuguese journalist Isabel Lindim. The testimonies presented in these works make explicit the differences in the political processes experienced in the two countries, as well as the specificity of histories and memories narrated by the women who were interviewed. These differences are not only indicative of the distinct political characteristics of the two countries but also reflect the specific contexts of remembrance at stake in the book and film under analysis.

Only reduced specificity of negative memories is associated with reduced goal specificity in depression.

Only reduced specificity of negative memories is associated with reduced goal specificity in depression.

Genetic predisposition to Alzheimer’s disease is differentially associated with joint volumetric variations in the disease continuum

AbstractBackgroundImaging genetics studies commonly assess the individual association between genetic information and brain features without considering joint brain modulations. The aim of this study was to explore the structural variation of the brain at different stages of Alzheimer’s disease (AD), depending on the genetic predisposition to AD.MethodA total of 351 cognitively unimpaired (CU) middle‐age participants from the ALFA (Alzheimer’s and FAmilies) study and 330 cognitively impaired participants from ADNI (Alzheimer’s Disease Neuroimaging Initiative) with magnetic resonance imaging scans, genetic information and CSF‐amyloid status were included. They were classified as CU Aβ‐, CU Aβ+, (mild cognitive impairment) MCI Aβ+ and AD Aβ+[Table 1]. Freesurfer was used to obtain cortical and subcortical parcellations using the Desikan‐Killiany atlas. A polygenic risk score estimating each participant’s genetic predisposition to AD (PRS‐AD) was calculated including genetic variants at the genome‐wide suggestive level (5×10‐6). Individuals were classified into high/low genetic predisposition groups. Statistical analysis was based on compositional data analysis. First, we computed the optimal multivariate brain structural variation signature (elastic net selection). Then, a logistic regression was performed to determine the association between the optimal signature and the PRS‐AD. Models were stratified by disease stage and adjusted for age and sex.ResultIndividuals at different stages on the AD continuum displayed different brain volumetric modulations associated with higher genetic predisposition to AD [Figure 1]. For instance, the optimal signature associated with an increased risk of AD was mainly characterized by increased hippocampal volumes in Aβ‐ individuals, but decreased volumes in MCI individuals along with the modulation of other temporal regions. Moreover, in AD patients at higher genetic predisposition of AD, the optimal signature was characterized by increased and decreased volumes in frontal regions (e.g. pars triangularis, lateral orbitofrontal vs. medial orbitofrontal, respectively) [Figure 2].ConclusionResults showed AD stage‐specific multivariate volumetric variation associated with an increased genetic risk of AD. Main results suggested that regions that modulated together, although differing according to AD stage, were implicated in the structural brain topology of specific memory networks. The analysis of the joint volumetric variation of brain subregions brings an innovative modeling perspective for neurogenetic studies of AD.

Genetic predisposition to Alzheimer’s disease is differentially associated with joint volumetric variations in the disease continuum

AbstractBackgroundImaging genetics studies commonly assess the individual association between genetic information and brain features without considering joint brain modulations. The aim of this study was to explore the structural variation of the brain at different stages of Alzheimer’s disease (AD), depending on the genetic predisposition to AD.MethodA total of 351 cognitively unimpaired (CU) middle‐age participants from the ALFA (Alzheimer’s and FAmilies) study and 330 cognitively impaired participants from ADNI (Alzheimer’s Disease Neuroimaging Initiative) with magnetic resonance imaging scans, genetic information and CSF‐amyloid status were included. They were classified as CU Aβ‐, CU Aβ+, (mild cognitive impairment) MCI Aβ+ and AD Aβ+[Table 1]. Freesurfer was used to obtain cortical and subcortical parcellations using the Desikan‐Killiany atlas. A polygenic risk score estimating each participant’s genetic predisposition to AD (PRS‐AD) was calculated including genetic variants at the genome‐wide suggestive level (5×10‐6). Individuals were classified into high/low genetic predisposition groups. Statistical analysis was based on compositional data analysis. First, we computed the optimal multivariate brain structural variation signature (elastic net selection). Then, a logistic regression was performed to determine the association between the optimal signature and the PRS‐AD. Models were stratified by disease stage and adjusted for age and sex.ResultIndividuals at different stages on the AD continuum displayed different brain volumetric modulations associated with higher genetic predisposition to AD [Figure 1]. For instance, the optimal signature associated with an increased risk of AD was mainly characterized by increased hippocampal volumes in Aβ‐ individuals, but decreased volumes in MCI individuals along with the modulation of other temporal regions. Moreover, in AD patients at higher genetic predisposition of AD, the optimal signature was characterized by increased and decreased volumes in frontal regions (e.g. pars triangularis, lateral orbitofrontal vs. medial orbitofrontal, respectively) [Figure 2].ConclusionResults showed AD stage‐specific multivariate volumetric variation associated with an increased genetic risk of AD. Main results suggested that regions that modulated together, although differing according to AD stage, were implicated in the structural brain topology of specific memory networks. The analysis of the joint volumetric variation of brain subregions brings an innovative modeling perspective for neurogenetic studies of AD.

Specific memory binding indexes and their potential to discriminate between Alzheimer´s disease biomarker‐positive and biomarker‐negative older adults with amnestic mild cognitive impairment

AbstractBackgroundThe Memory Binding Test (MBT) and Face‐Name Associative Memory Exam (FNAME‐12) are challenging tests based on relational memory binding paradigm. Recent studies support their sensitivity to subtle memory changes; however, their specificity to Alzheimer´s disease (AD) related memory deficit has not been studied. This study aimed to explore differences in MBT and FNAME‐12 scores between patients with amnestic mild cognitive impairment (aMCI) due to AD (aMCI‐AD), those with aMCI with non‐Alzheimer´s etiology (aMCI‐nonAD), and cognitively normal older adults (CN) as a control group, and to compare the potential of the challenging tests and the standard Rey Auditory Verbal Learning Test (RAVLT) to discriminate between the aMCI groups.MethodSixty‐seven Czech Brain Aging Study participants (aMCI, n = 37; CN, n = 30) underwent neuropsychological assessment (including the MBT and FNAME‐12), laboratory evaluation, and brain magnetic resonance imaging, and were further classified as aMCI‐AD (n = 18) or aMCI‐nonAD (n = 19) based on the results of amyloid positron emission tomography or AD cerebrospinal fluid biomarkers. The groups were compared using the multivariate analysis of covariance controlling for sex, age, education, and global cognition.ResultIn MBT, aMCI‐AD patients scored the lowest on the paired cued recall scores (CR) (aMCI‐AD<aMCI‐nonAD<CN, ps≤0.003). In FNAME‐12, aMCI‐AD patients scored the lowest on the CR of face‐occupation pairs (aMCI‐AD<aMCI‐nonAD<CN, ps<0.001). On the CR of face‐name pairs, both aMCI groups scored lower than CN (p<0.001); however, they did not differ from each other [p = 0.525; (aMCI‐AD = aMCI‐nonAD)<CN]. In RAVLT, aMCI‐AD patients did not differ from the aMCI‐nonAD patients, except for the delayed free recall (FR) (p<0.001). Adding the RAVLT delayed FR as covariate, the differences in the MBT and FNAME‐12 paired CR scores remained significant. To discriminate aMCI‐AD from aMCI‐nonAD, the MBT paired CR and FNAME‐12 CR of face‐occupation pairs yielded areas under the curve (AUCs) of 88% and 85%, respectively, which was comparable to RAVLT delayed FR (87%). Controlling for RAVLT, the AUCs were 91% for MBT and 88% for FNAME‐12.ConclusionOur findings support excellent discriminative ability of selected MBT and FNAME‐12 scores for AD‐related memory deficit and suggest their potential for differential diagnosis of memory deficit in older adults in addition to the standard RAVLT.

Specific autobiographical memories are a resource for identity strength among mature but not emerging adults

ABSTRACT Four studies, three pre-planned on Open Science Framework, with 2296 participants explored the potential role of recollecting autobiographical memories in enhancing the sense of identity. Among emerging adults (college students under age 25), recollecting important autobiographical memories did not strengthen sense of identity. Autobiographical memories failed to strengthen identity among emerging adults despite inducing low self-clarity first; despite attempts to prime self-consistent memories by having emerging adults report their stable self-aspects first; and despite attempts to inspire self-event connections by asking emerging adults to explain how the memories exemplified something enduring about the self. Among mature adults (age 25 and older), recollecting important autobiographical memories strengthened sense of identity. Identity was strengthened regardless of whether mature adults were asked to explain how the memories exemplified something enduring about the self. Differences in types of memories or motivation did not account for the differential effects of recollecting autobiographical memories in identity. In short, mature adults appear to readily use autobiographical memories as a resource for identity in a way that emerging adults have not yet mastered.

Cross-cultural effects of reminiscence therapy on life satisfaction and autobiographical memory of older adults: a pilot study across Mexico and Spain

BackgroundThere are increasing reports on the cognitive and emotional benefits of positive reminiscence therapy in older people. The objective of this study is to assess the differential improvement of the quality of life for older people in different vital situations (three different types of aging) and from different countries by implementing a positive reminiscence therapy program (REMPOS).MethodsThe participants were 144 older adults above the age of 65, 77 participants from Spain (45 experimental groups, 32 control groups) and 67 from Mexico (34 experimental groups, 33 control groups). The participants were recruited from nursing and retirement homes. A factorial randomized design with pre–post measurement with three independent variables: country (Mexico, Spain), condition (experimental, control), and types of aging (healthy aging, HA., mild cognitive impairment, MCI., Alzheimer’s disease, AD). The experimental groups received REMPOS therapy and control groups received standard cognitive stimulation program. The quality of life was measured with the Life Satisfaction Inventory for adults (LSI-A) and autobiographical memory test (AMT) before and after REMPOS therapy.ResultsThe REMPOS intervention showed significantly higher positive effects than the control condition on the recall of specific positive memories across countries and types of aging, except for the Spanish MCI group. Life satisfaction in the Alzheimer’s and MCI group only improved with REMPOS in the Mexican sample.ConclusionsThe REMPOS effects showed generalizable effects across countries, but the cross-cultural differences shown highlight the necessity of running studies to test those differential effects.

When having photographs of events influences the visual perspective of autobiographical memories

AbstractPhotographs are frequently taken to preserve memories of events from the personal past, but they can also bias how we remember. For example, photographs often capture events from a novel visual perspective (e.g., seeing ourselves in the image). Here, we examined how the presence of the self in photographs influences autobiographical memories. Participants provided subjective ratings for specific autobiographical memories, and then, following the retrieval phase, they were asked to indicate whether they had photographs for these memories and the nature of these images. Across three studies (N = 378), we found that autobiographical memories that participants reported the presence of photographs containing the self were more likely to be remembered from an observer‐like perspective than memories with photographs in which the self was not visible. These findings have important implications for understanding how the growing number of photographs taken in everyday life biases the perspective of our memories.

Item-specific neural representations during human sleep support long-term memory.

Understanding how individual memories are reactivated during sleep is essential in theorizing memory consolidation. Here, we employed the targeted memory reactivation (TMR) paradigm to unobtrusively replaying auditory memory cues during human participants' slow-wave sleep (SWS). Using representational similarity analysis (RSA) on cue-elicited electroencephalogram (EEG), we found temporally segregated and functionally distinct item-specific neural representations: the early post-cue EEG activity (within 0 to 2,000 ms) contained comparable item-specific representations for memory cues and control cues, signifying effective processing of auditory cues. Critically, the later EEG activity (2,500 to 2,960 ms) showed greater item-specific representations for post-sleep remembered items than for forgotten and control cues, indicating memory reprocessing. Moreover, these later item-specific neural representations were supported by concurrently increased spindles, particularly for items that had not been tested prior to sleep. These findings elucidated how external memory cues triggered item-specific neural representations during SWS and how such representations were linked to successful long-term memory. These results will benefit future research aiming to perturb specific memory episodes during sleep.

The neuropsychological mechanism in loci memory using 7T fMRI

Memory has been a preoccupation of human civilization for centuries, and people have been searching for ways to increase its capacity and special memorisation methods tend to get more attention. Though efficient memory methods have always been a goal pursued by humans, the physiological nature still demands proper explanation. In this paper, a memory method called loci memorize is explored in the hope of obtaining a comparison of the level of activity in a particular region. This work utilized a 7T fMRI with a high resolution to unlock the neurological activity during quick memory of unordered numbers in eleven right-handed memory athletes. By designing a specific numerical memory task and initiating the task in two different groups of people, the coordinates of activated brain regions were located by analysing the degree of activity, with reference to the corresponding recall data. Results showed that brain activations associated with the loci memory were found in the middle cingulate, left precuneus, left supramarginal gyrus, left insula, left inferior frontal gyrus, left middle occipital, and right superior parietal lobule. These brain regions were more active in the group using loci memorise compared to that not using loci memorise under the same memory task. The preference for loci memory provides a possibility for the memory improvement. The work can be a reference of studying the memory mechanism in the neuropsychological science.

Divergent brain regional atrophy and associated fiber disruption in amnestic and non-amnestic MCI

BackgroundUnderstanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI).MethodsT1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed.ResultsThe aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language.ConclusionsThe divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.

The effect of donepezil hydrochloride on post-COVID memory impairment: A randomized controlled trial

BackgroundPost-Coronavirus Disease (COVID-19) condition, known as “post-COVID syndrome,” is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment. MethodsA randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis. ResultsThe statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals. ConclusionWhile donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment. Trial registrationThe study was approved by the Research Ethics Committee of Aja University of Medical Sciences (Approval ID: IR.AJAUMS.REC.1400.125) and registered in the Iranian Registry of Clinical Trials (IRCT) (Approval ID: IRCT20210816052203N1).

ApoB-specific CD4+ T cells circulate in human blood and formation of a memory population is driven by coronary artery disease and an elevated cardiovascular risk profile

Abstract Aim Atherosclerosis is a chronic inflammatory disease involving an autoimmune response against Apolioprotein B (ApoB), the core protein of low-density lipoprotein (LDL) cholesterol. Using a translational bench-to-bedside approach, we linked the presence and immuno-phenotype of ApoB-specific CD4+ T cells to clinical risk profiles for cardiovascular disease in humans. Methods Peripheral blood mononuclear cells (PBMCs) from 230 patients that underwent coronary angiography were co-incubated in vitro with a pool of immunodominant peptides from human ApoB for 6h. Reactive ApoB-specific T cells (ApoB+) were defined in flow cytometry by expression of the activation marker CD40L. Partition of ApoBpos into naïve and memory T cells was achieved by extracellular fluorochrome-based staining of CD45RO, CCR7 and CD45RA. Cytokine expression of ApoBpos was determined by intracellular staining. Results We found that a median of 0.69±0.1% of circulating CD4+ T cells were reactive to Apolipoprotein B. We found detectable concentrations of auto reactive ApoB+ T cells in 86,44% of all healthy individuals. However, overall frequencies of ApoB reactive T cells did not correlate with diagnosed coronary artery disease (CAD). Compared to ApoBneg. T cells, we detected a higher fraction of memory T cells in ApoBpos (p<0,0001), suggesting a previously occurred ApoB directed immune response. Accordingly, elevated serum levels of ApoB specific IgG Antibodies associated with high proportions of ApoB specific memory cells. Patients diagnosed with coronary artery disease presented higher percentages of central memory T cells among ApoBpos compared to healthy individuals. Correspondingly, these observations applied to patients with an elevated 10-year risk for cardiovascular events estimated by the ESC-SCORE2. These effects largely grounded on strong associations with the clinical diagnosis of arterial hypertension, elevated levels of Lp(a) and obesity. Interestingly, systolic blood pressure and LDL-serum levels correlated with elevated proportions of memory-status ApoBpos T cells in patients without statin intake, although this was not the case for patients with LDL-lowering medication. Analysis of cytokine expression in ApoBpos CD4+ T cells showed significantly increased expression of anti-inflammatory Il-2 and IL-10 in addition to pro-inflammatory IFNγ. Cytokine secretion was mainly driven by memory-status ApoBpos when compared to naïve ApoBpos T cells. Interestingly, a significant number of patients showed a mixed TH1/Treg phenotype among ApoBpos with simultaneous expression of IL-10 and IFN-γ. Conclusions Our data show for the first time that ApoB-reactive T cells exist even in healthy individuals. Cardiovascular risk factors and clinically relevant atherosclerotic disease drive memory formation and activation of ApoB+ T cells. ApoB+ Memory T cells are prone to secrete pro- and anti-inflammatory cytokines and may modulate systemic inflammation in atherosclerosis.

Advances in Cancer Vaccine Research.

The use of cancer vaccines is considered a promising therapeutic strategy in clinical oncology, which is achieved by stimulating antitumor immunity with tumor antigens delivered in the form of cells, peptides, viruses, and nucleic acids. The ideal cancer vaccine has many advantages, including low toxicity, specificity, and induction of persistent immune memory to overcome tumor heterogeneity and reverse the immunosuppressive microenvironment. Many therapeutic vaccines have entered clinical trials for a variety of cancers, including melanoma, breast cancer, lung cancer, and others. However, many challenges, including single antigen targeting, weak immunogenicity, off-target effects, and impaired immune response, have hindered their broad clinical translation. In this review, we introduce the principle of action, components (including antigens and adjuvants), and classification (according to applicable objects and preparation methods) of cancer vaccines, summarize the delivery methods of cancer vaccines, and review the clinical and theoretical research progress of cancer vaccines. We also present new insights into cancer vaccine technologies, platforms, and applications as well as an understanding of potential next-generation preventive and therapeutic vaccine technologies, providing a broader perspective for future vaccine design.

Virus-Specific CD8+ Stem Memory T Lymphocytes Display Enhanced Anti-Virus Responses

Virus specific memory CD8+ T cells can be divided into three subsets, stem memory (T SCM), central (T CM) and effector (T EM), but their lineage relationships and their ability to persist and confer protective immunity against virus infection are not well understood. Our results show that virus-specific CD8+T SCM have a greater capacity than T CM and T EM to persist in vivo and in vitro and are more efficient in mediating protective immunity against CMV infection and EBV infection because of their increased self-renew potential whether in transcriptome or in epigenome. We firstly expanded virus-specific T cells containing CD8+TSCM and CD8+TCM cells in vitro by stimulating healthy human PBMCs with cytokines and CMV (pp65 and IE1) and EBV (LMP2a and EBNA1) virus peptides. Then we fully evaluated the phenotypic and functional differences of diverse virus-specific memory T subsets and found that CD8+TSCM cells are a subset of low exhaustion, high migration and high secretion of IL-2. However, the expression of IFN-γand TNF-a and CD107a were lower compared with TEM cells, although comparable to CD8+TCM cells. We then evaluated the self-renewal and differentiation capacity of CD8+TSCM cells, compared with TCM or TEM cells. The results showed after stimulated with a-CD3/CD2/CD28 for 5 days, that CD8+TSCM cells possess around 50% of CD45RA+CD62L+ subpopulation cells. Meanwhile, CD8+TSCM cells constantly keep a higher expression of CD45RA+ cells than TCM and TEM cells in different proliferation generations. Notably, around 20% of TCM cells,5% of TEM cells and 10% of TEFF cells were found, suggesting that TSCM cells can reconstitute the whole memory T subsets. By contrast, the TCM cells mainly retained a central memory phenotype or differentiated into effector memory T cells and the TEM cells maintained its original phenotype. We also used the stem cell index to evaluate the stemness of different subgroups, and the results confirmed that the stemness evaluation of TSCM cells were significantly higher than TCM and TEM subsets. In vivo rein-fusion of different virus-specific T cell into irradidated NPG mice also showed that CD8+TSCM cells in vivo can differentiate into all memory T subsets in vivo while TCM cells mainly retained TEM and TCM subgroups at 4W post T cell infusion in mouse liver,lung and spleen(Figure 1A-G). To explore whether the antiviral ability of TSCM cells lasted longer than that of TCM and TEM cells. We first evaluated the apoptosis of different T cell subsets stimulated by AD169 virus and found less apoptosis rate was lower than TCM and TEM cells, suggesting persistent virus infection leads to damage to T cells and CD8+TSCM cells have a strong ability to resist virus damage, which may potentially lead to stronger and longer lasting antiviral effects. Based on this, we also evaluated the apoptosis level of virus-infected MRC-5 cells to evaluate whether CD8+TSCM cells exert a stronger anti-virus effect. The result showed that AD-169 infected MRC-5 cells co-incubated with CD8+TSCM had a higher proportion of apoptotic level than CD8+TCM cells. We also used the 5day-long-term infection model in vitro to evaluate the effect of virus infection on T cell differentiation and evaluated the change of virus copy number after long-term co-culture of different cell subsets. We found that sorted CD8+TSCM system can significantly reduce the virus copy number compared with the control group, while there is no significant difference among TCM and TEM cells (Figure1H,). Further analysis into survival ability of T cell subpopulations found that the proportion of CD3+ T cells in TSCM group were significantly higher and the CD8+TSCM group was dominated by TCM and TEM cells after 5-day stimulation but still kept about 22 percentage of TSCM phenotype. (Figure1I). In summary, CD8+ TSCM cells have a sustainable ability against CMV than TCM and TEM. To examine the in vivo activity of virus-specific CD8+TSCM cells. We used Raji-HLA*A0201-pp65-luciferase cells to construct tumor infiltration mouse model. The result showed that in contrast to control mice, we observed a reduction in bioluminescence over three weeks in mice treated with CD8+TSCM cells. Although mice treated with CD8+TCM and CD8+TEM cells retained a lower tumor size in the early two weeks post adoptive T infusion, they showed a rapid tumor progresses and event lead to shorter survival compared with CD8+TSCM group, indicating a sustained anti-CMV effect of CD8+TSCM cells.

Differential attentional costs of encoding specific and gist episodic memory representations.

Theories of episodic memory posit that more attentional resources are needed for encoding specific compared to gist representations. This position has been challenged by recent findings of similar divided attention (DA) at encoding costs on both specific and gist representations. However, the disrupting effects of DA on specific representations may emerge under less difficult DA conditions than those under which effects on gist representations emerge. The present study addressed this possibility by manipulating the difficulty of a concurrent DA task (low, intermediate, or high difficulty) during encoding among 176 young adult participants, who encoded face-scene pairs under either full attention or one of the three levels of DA. During retrieval, participants discriminated intact pairs from recombined pairs that varied in how similar they were to studied pairs. Results, interpreted using a multinomial-processing-tree model of specific and gist memory, showed that the disrupting effects of DA on specific representations emerged under less difficult attentional loads (intermediate-demanding condition) compared to those under which gist representations were disrupted (high-demanding condition). These findings reinforce the suggestion of differential attentional demands for specific and gist representations and also provide insights into attentional resource theories of adult age-related cognitive decline. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An immune memory-structured SIS epidemiological model for hyperdiverse pathogens.

A hyperdiverse class of pathogens of humans and wildlife, including the malaria parasite Plasmodium falciparum, relies on multigene families to encode antigenic variation. As a result, high (asymptomatic) prevalence is observed despite high immunity in local populations under high-transmission settings. The vast diversity of "strains" and genes encoding this variation challenges the application of established models for the population dynamics of such infectious diseases. Agent-based models have been formulated to address theory on strain coexistence and structure, but their complexity can limit application to gain insights into population dynamics. Motivated by P. falciparum malaria, we develop an alternative formulation in the form of a structured susceptible-infected-susceptible population model in continuous time, where individuals are classified not only by age, as is standard, but also by the diversity of parasites they have been exposed to and retain in their specific immune memory. We analyze the population dynamics and bifurcation structure of this system of partial-differential equations, showing the existence of alternative steady states and an associated tipping point with transmission intensity. We attribute the critical transition to the positive feedback between parasite genetic diversity and force of infection. Basins of attraction show that intervention must drastically reduce diversity to prevent a rebound to high infection levels. Results emphasize the importance of explicitly considering pathogen diversity and associated specific immune memory in the population dynamics of hyperdiverse epidemiological systems. This statement is discussed in a more general context for ecological competition systems with hyperdiverse trait spaces.

4 Preoperative International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) Phenotype is Associated with Postoperative Memory Decline Following Temporal Lobectomy

Objective:The International Classification of Cognitive Disorder in Epilepsy (IC-CoDE) is a new consensus-based taxonomy that classifies patients into one of four cognitive phenotypes (i.e., cognitively intact, single-domain impairment, bi-domain impairment, generalized impairment). The IC-CoDE has been effectively applied to patients with temporal lobe epilepsy (TLE), but little is known about the relationship between pre-operative cognitive phenotype and post-operative cognitive outcome following epilepsy surgery. The purpose of this study was to examine whether the IC-CoDE classifications are related to memory decline following surgery for TLE.Participants and Methods:347 patients (ages 16-66; 57% female) with pharmacoresistant TLE completed comprehensive pre- and post-surgical neuropsychological assessments. Patients were classified into IC-CoDE phenotypes based on pre-surgical pattern of cognitive impairment using a threshold of >1.5 standard deviations (SD) below the normative mean. Change scores were calculated from delay trial scores of the following memory tests: Rey Auditory Verbal Learning Test (RAVLT), and Logical Memory (LM) and Verbal Paired Associates (VPA) subtests from the Wechsler Memory Scale - Third Edition (WMS-III). Cutoffs were applied using epilepsy-specific reliable change indices and patients were classified within the ‘decline’ group if they experienced significant decline on any of the three memory measures.Results:The distribution of IC-CoDE phenotypes in our sample were as follows: 57% intact, 29% single-domain, 10% bi-domain, and 5% generalized impairment. 108 patients (31%) demonstrated post-surgical memory decline. Patients who underwent dominant temporal lobectomy were more likely to show post-surgical memory decline compared to non-dominant temporal lobectomy. However, there was no significant difference in phenotype distribution between patients who underwent left versus right-sided resections; thus, analyses were conducted on the entire sample to increase power. Chi-square analyses revealed unique patterns of post-surgical memory decline across phenotypes, X2 = 8.79, p = .032. There was a significantly higher proportion of patients with memory decline in the single-domain phenotype (39%) and this was followed by the bi-domain phenotype (33%) and the intact phenotype (29%). In contrast, patients with generalized impairment were unlikely to show memory decline (.06%). Within the single domain impaired phenotype, there were no differences between the specific domains impaired and memory decline. Logistic regression model was also significant; after controlling for surgery side, the IC-CoDE phenotypes significantly predicted the likelihood of a patient experiencing post-surgical memory decline; X2 = 8.18, p = .043.Conclusions:In addition to the IC-CoDE providing a useful cognitive classification scheme in epilepsy, the IC-CoDE phenotypes appear helpful in identifying those at risk for post-operative memory decline. Previous literature has suggested that those with better pre-surgical cognition are generally at highest risk for cognitive decline. Our results generally follow this trend, but interestingly, patients with single domain impairment were at the highest risk of memory decline, even above those in the cognitively intact group. Future studies are important to confirm this pattern in other samples and examine additional contributing factors and underlying mechanisms that may influence risk of memory decline across these cognitive phenotypes.