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PubMed2004

Differences between recognition memory and remote memory for olfactory and visual stimuli in nondemented elderly individuals genetically at risk for Alzheimer's disease.

Recognition and remote memory for olfactory and visual stimuli were assessed in nondemented elderly individuals positive for the apolipoprotein E 4 allele and in 4 negative controls to examine whether the 4 allele differentially affects recognition and/or remote memory depending on the modality of stimulus to be remembered. Compared to controls, 4 positive individuals committed more false positive recognition memory errors for olfactory but not visual stimuli suggesting that 4 positive individuals may show false positive errors for olfactory stimuli before deficits for other stimuli are detectable. There were no significant differences in familiarity ratings (a proposed measure of remote memory) suggesting that brain areas involved in remote memory are not affected in nondemented 4 positive individuals. The results suggest that neuropathological changes in nondemented individuals genetically at risk for Alzheimer's disease may differentially affect memory processes.

Aged↗
PubMed2002

Visual imagery of famous faces: effects of memory and attention revealed by fMRI.

Complex pictorial information can be represented and retrieved from memory as mental visual images. Functional brain imaging studies have shown that visual perception and visual imagery share common neural substrates. The type of memory (short- or long-term) that mediates the generation of mental images, however, has not been addressed previously. The purpose of this study was to investigate the neural correlates underlying imagery generated from short- and long-term memory (STM and LTM). We used famous faces to localize the visual response during perception and to compare the responses during visual imagery generated from STM (subjects memorized specific pictures of celebrities before the imagery task) and imagery from LTM (subjects imagined famous faces without seeing specific pictures during the experimental session). We found that visual perception of famous faces activated the inferior occipital gyri, lateral fusiform gyri, the superior temporal sulcus, and the amygdala. Small subsets of these face-selective regions were activated during imagery. Additionally, visual imagery of famous faces activated a network of regions composed of bilateral calcarine, hippocampus, precuneus, intraparietal sulcus (IPS), and the inferior frontal gyrus (IFG). In all these regions, imagery generated from STM evoked more activation than imagery from LTM. Regardless of memory type, focusing attention on features of the imagined faces (e.g., eyes, lips, or nose) resulted in increased activation in the right IPS and right IFG. Our results suggest differential effects of memory and attention during the generation and maintenance of mental images of faces.

Adult↗
PubMed1999

Infusion of neurosteroids into the rat nucleus basalis affects paradoxical sleep in accordance with their memory modulating properties.

The neurosteroids pregnenolone sulfate and allopregnanolone affect memory processes in an opposite manner, pregnenolone sulfate acts as a potent memory-enhancer whereas allopregnanolone impairs memory performance. The mechanisms underlying these memory modulating properties have yet to be elucidated. We have previously reported that infusions of either neurosteroid into the nucleus basalis magnocellularis, one of the main forebrain cholinergic nuclei, differentially affect spatial memory in rats. The relationships between memory performance and paradoxical sleep are well documented, therefore we investigated whether neurosteroids infused into the nucleus basalis magnocellularis affected the sleep-wakefulness cycle in rats, measured by electroencephalographic recordings. Results show that pregnenolone sulfate (5 ng) increased by 12%, whereas allopregnanolone (2 ng) decreased by 24%, the duration of paradoxical sleep in the 24 h interval following injection compared to control recordings. Pregnenolone sulfate inhibits GABA(A) receptors whereas allopregnanolone stimulates them. Since cholinergic neurons of the nucleus basalis magnocellularis are GABA-modulated, it may be postulated that these neurosteroids modify paradoxical sleep by acting on the cholinergic transmission. This may account, at least in part, for the memory modulating properties of these compounds.

Animals↗
PubMed1997

Differential involvement of left temporolateral and temporomesial structures in verbal declarative learning and memory: evidence from temporal lobe epilepsy.

A wealth of animal and human research has pointed to a significant involvement of the temporal lobes in memory processing, and yet the different functional roles of temporal cortical vs. mesial structures remain unclear. We studied verbal declarative memory, by using a word list paradigm that differentiates among learning (immediate recall), memory (delayed recall), and recognition, in epilepsy patients being considered for surgical resection of the left temporal lobe. Verbal memory was evaluated preoperatively and during the recording of intracranial event related potentials and postoperatively after selective hippocampectomy, temporal cortical lesionectomy, or anterior two-thirds en bloc temporal lobe resection procedures. Preoperative differences in verbal memory performance as a function of differences in underlying neuropathology, concurrent event-related potentials, and specific patterns of postoperative memory impairments lead to converging evidence that verbal declarative memory relies on a synergistic interaction of at least two functionally distinct brain systems. Material-specific data acquisition, or working memory, is mediated by neocortical temporal structures, whereas long-term consolidation/retrieval is particularly mediated by temporomesial structures. In contrast to the left temporal neocortex, the function of the temporomesial system appears to be material nonspecific. Apparently, its preferential involvement in verbal memory is due to its close interaction with overlying neocortical structures that are specialized for language processing.

Adult↗
PubMed2006

Longitudinal assessment of cognitive performance in Holocaust survivors with and without PTSD.

BACKGROUND: There are currently no longitudinal studies of cognitive performance in older patients with Posttraumatic Stress Disorder (PTSD). It is therefore unclear whether relationships between memory and symptoms differ over time among older persons with and without PTSD. METHODS: Twenty-eight Holocaust survivors and nineteen comparison subjects were evaluated 5 years after they had received a memory assessment including paired-associates learning and the California Verbal Learning Test (CVLT). RESULTS: While Holocaust survivors with PTSD showed a diminution in symptom severity (t = 2.99, df = 12, p = .011), they still manifested a decline in paired associates learning, suggesting an acceleration in age-related memory impairment (related word pairs: t = 2.87, df = 13, p = .013; unrelated word pairs: t = 2.06, df = 13, p = .060). The survivors with PTSD showed improvements on several CVLT measures over time. These improvements correlated with symptom improvements, such that group differences at the follow-up were no longer detected. CONCLUSIONS: The discrepancy in the pattern of performance on these two tests of memory following symptom improvement suggests possible differentiation between of aspects of memory functions associated with aging and trauma exposure and those associated with the severity of PTSD symptoms. Performance on the CVLT appeared related to clinical symptom severity while paired associate learning worsened over time in Holocaust survivors with PTSD, consistent with earlier cross-sectional findings.

Aged↗
PubMed2000

Separate roles for beta2- and beta3-adrenoceptors in memory consolidation.

Consolidation of a labile memory which would not normally be stored can be achieved by intracerebral administration of noradrenaline. In a series of experiments using discriminated, one trial passive avoidance learning with the day-old chick, the effect of noradrenaline has been shown to be due to actions at different subtypes of adrenoceptors. The effect of noradrenaline is dose-dependent, with a moderate dose producing memory consolidation. However, higher doses of noradrenaline (0.3-10 nmol/hemisphere) prevent consolidation, an effect not seen with isoprenaline suggesting that these doses stimulate alpha-adrenoceptors. The promotion of memory consolidation by noradrenaline or isoprenaline at low doses was attributable to beta3-adrenoceptors and at medium doses to beta2-adrenoceptors. At higher doses of noradrenaline, there was alpha1-adrenoceptor-mediated inhibition of memory consolidation. Consolidation can also be achieved by administration of either beta2- or beta3-adrenoceptor agonists at specific times after training. Although these two adrenoceptors both promoted memory consolidation, there was a differential action on the stages of memory formation. The dose-response curve to the beta3- and the beta2-agonists was shifted by the appropriate antagonist but not by the antagonist at the other beta-adrenoceptor. Although beta1-adrenoceptors are present in chick brain, they do not seem to have a role in memory formation. These results explain why noradrenaline, acting at different adrenoceptors, can have different effects on memory formation with memory being either consolidated or inhibited depending on the dose. The findings also demonstrate a role in memory formation for beta3-adrenoceptors found in the brain. Agonists acting specifically at beta2- or beta3-adrenoceptors may be of value in diseases involving cognitive impairment.

Adrenergic beta-Agonists↗
PubMed2005

Increased central memory T cells in patients with chronic pancreatitis.

BACKGROUND/AIMS: A dysregulated immune response has been suggested to be important for the pathogenesis of chronic pancreatitis (CP). Formation of immunological memory is based on the differentiation of naive T lymphocytes to memory T lymphocytes after exposure to antigens and specific cytokines. The aim of this study was to analyze peripheral blood mononuclear cells (PBMCs) in patients with CP for different T lymphocyte subsets including naive and memory T cells. METHODS: PBMCs from 9 patients who had undergone pancreatic resection due to CP, 9 CP patients who had not been resected and 9 healthy controls were analyzed by flow cytometry. RESULTS: Patients with CP had a skewed distribution of T lymphocytes, with an increased level of CCR7+/CD45RA- central memory T lymphocytes compared to healthy controls. Nonresected CP patients and subjects who had undergone pancreatic resection due to CP had similar levels of central memory T lymphocytes. CONCLUSION: Our results indicate that the dysregulation of the immune system in chronic pancreatitis seems to persist even after removal of large parts of the local inflammatory site. We suggest that the increase of central memory T lymphocytes may be important for maintaining the inflammatory process in chronic pancreatitis.

Adult↗
PubMed1993

Differential rates of forgetting from long-term memory in Alzheimer's and multi-infarct dementia.

In this study we explored the rate of forgetting from long-term memory in Alzheimer's (AD) and multi-infarct (MID) dementia. For this purpose, we administered to 15 AD, 15 MID, and 22 control subjects two tasks exploring, respectively, long-term verbal and long-term visuo-spatial memory. The absolute rate of forgetting in both tasks was computed as the difference between immediate and delayed recall of memorandum. Since level of immediate recall was significantly different between groups, a proportional rate of forgetting (percentage of memorandum lost passing from immediate to delayed recall) was computed for each patient. In the verbal task (Rey's 15 words) AD patients displayed significantly larger absolute and proportional rates of forgetting than MID and control subjects. In the spatial task (Corsi block supraspan), the absolute rate of forgetting was only marginally different between groups. Nevertheless, AD patients demonstrated a larger proportional rate of forgetting than MID and normal subjects. These results point out an exalted decay of information from long-term memory store in AD patients. In the light of previous data (Corkin et al., 1984; Kopelman, 1985) we propose that long-term memory deficits in AD is due, at least in part, to an abnormal forgetting of information within the first few minutes following acquisition. Information still present in the subsequent period (10 min to several days) is retained normally. The normal rate of forgetting in MID patients, further, suggests different mechanisms underlying memory disorders in vascular and degenerative dementias.

Aged↗
PubMed2002

Role of 4-1BB (CD137) in the functional activation of cord blood CD28(-)CD8(+) T cells.

The CD28(-) subset of CD8(+) T cells is associated with cytotoxic T lymphocyte (CTL) effector function. We investigated a potential role for 4-1BB, a costimulatory molecule structurally related to members of the tumor necrosis factor (TNF) receptor family, in the generation and functional activation of CD28(-) CTLs by using human cord blood (CB) cells composed exclusively of naive CD8(+) T cells with few or no CD28(-) CTLs. The 4-1BB was induced preferentially on the CB CD28(-)CD8(+) T cells when CD28 down-regulation was induced by interleukin 15 (IL-15) and IL-12 stimulation. Anti-4-1BB costimulation induced dramatic phenotypic changes in the CD28(-) CTLs, including restoration of CD28 expression as well as that of memory markers such as CD45RO and CC chemokine receptor 6 (CCR6). Anti-4-1BB costimulation also promoted long-term survival of CD28(-) CTLs, which were sensitive to activation-induced cell death upon anti-CD3 stimulation. The memory-type CD28(+) CTLs induced by anti-4-1BB costimulation acquired a greatly enhanced content of granzyme B, a cytolytic mediator, and enhanced cytotoxic activity as compared with CD28(-) CTLs. Strong cytotoxicity of memory-type CTLs to a 4-1BB ligand-expressing Epstein-Barr virus (EBV)-transformed B-cell line was almost completely abrogated by 4-1BB-Fc, a soluble form of 4-1BB, suggesting involvement of 4-1BB in cytolytic processes. Taken all together, our results suggest that 4-1BB plays a role in the differentiation of effector memory CTLs.

Antigens, CD↗
PubMed1980

Age differences in memory as a function of depth of processing.

It has been proposed that the old do not process information as deeply as the young and therefore show poorer memory. This study manipulated level of processing via type of instruction given to subjects prior to the memory tasks (recall followed by recognition). Five types of instructions were employed: non-semantic, non-semantic + intentional, intentional, semantic, and semantic + intentional. Type of instruction affected the two age groups differentially on recall memory but not on recognition memory. The young and old recalled at the same level following a non-semantic (shallow) instruction, but parted ways thereafter; the young became disproportionately superior with semantic instructions. The addition of an intentional component to the non-semantic instruction benefited the recalll performance of the young to a greater extent than the old. The addition of an intentional component to a semantic component benefited the recal performance of the young, but not the old. It was concluded that the old have more difficulty than the young in dealing with two instructional components simultaneously when recall performance is under consideration.

Adolescent↗
PubMed2006

Do CD8 effector cells need IL-7R expression to become resting memory cells?

The role for IL-7R expression in the differentiation of effector T cells into resting memory remains controversial. Here, using a conditional IL-7R transgenic model, we were able to test directly whether CD8 effector T cells require IL-7R expression for their differentiation into resting memory cells. In the absence of IL-7R expression, effector cells transferred into "full" hosts underwent a protracted and unremitting contraction compared with IL-7R-expressing control cells and were unable to develop into long-term resting memory cells. Surprisingly, when the same effector cells were transferred into empty T-cell-deficient hosts, they could generate long-lived fully functional resting memory cells independently of IL-7R expression. Formation of these latter cells was found to be dependent on IL-15, because the same IL-7R-deficient effector cells were rapidly lost from IL-15-deficient hosts, having a half-life of less than 40 hours. Therefore, our data suggest that, under physiological conditions, both IL-7 and IL-15 synergize to promote the formation of memory cells directly by limiting the contraction of effectors that occurs following an immune response and that reexpression of IL-7R is a key checkpoint in the regulation of this process.

Adoptive Transfer↗
PubMed2005

Cortisol, contingency learning, and memory in preterm and full-term infants.

Cortisol plays an important role in learning and memory. An inverted-U shaped function has been proposed to account for the positive and negative effects of cortisol on cognitive performance and memory in adults, such that too little or too much impair but moderate amounts facilitate performance. Whether such relationships between cortisol and mental function apply to early infancy, when cortisol secretion, learning, and memory undergo rapid developmental changes, is unknown. We compared relationships between learning/memory and cortisol in preterm and full-term infants and examined whether a greater risk for adrenal insufficiency associated with prematurity produces differential cortisol-memory relationships. Learning in three-month old (corrected for gestational age) preterm and full-term infants was evaluated using a conjugate reinforcement mobile task. Memory was tested by repeating the same task 24h later. Salivary cortisol samples were collected before and 20 min after the presentation of the mobile. We found that preterm infants had lower cortisol levels and smaller cortisol responses than full-term infants. This is consistent with relative adrenal insufficiency reported in the neonatal period. Infants who showed increased cortisol levels from 0 to 20 min on Day 1 had significantly better memory, regardless of prematurity, than infants who showed decreased cortisol levels.

Female↗
PubMed2004

The molecular program induced in T cells undergoing homeostatic proliferation.

Naïve T cells proliferate independently of cognate antigen when introduced into lymphopenic hosts. Lymphopenia-induced proliferation depends on low-affinity MHC/self-peptide complexes and on IL-7. To elucidate the intracellular signals mediating this proliferation, we analyzed changes in gene expression in naive CD8+ T cells at different times after their transfer into a lymphopenic environment. The genes induced in response to lymphopenia were largely an attenuated subset of those turned up by full antigenic stimulation, including genes related to cell cycling, whereas excluding genes specifically associated with effector activity. After the initial phase of proliferation in an empty compartment, the naive T cells adopted a stable pattern of gene expression similar to that of antigen-experienced memory cells. Thus, T cells proliferating in lymphopenic hosts do not exhibit a unique gene-expression profile, instead relying on "traditional" signals for this antigen-independent proliferation; this process ultimately results in differentiation to "authentic" memory cells.

Animals↗
PubMed2004

Enhanced expression of cell cycle regulatory genes in virus-specific memory CD8+ T cells.

Unlike naive CD8+ T cells, antigen-experienced memory CD8+ T cells persist over time due to their unique ability to homeostatically proliferate. It was hypothesized that memory cells might differentially regulate the expression of genes that control the cell cycle to facilitate homeostatic proliferation. To test this, the expression levels of 96 different cell cycle regulatory genes were compared between transgenic naive and memory CD8+ T cells that specifically recognize the GP33-41 epitope of lymphocytic choriomeningitis virus (LCMV). It was discovered that relative to naive cells, memory cells overexpress several important genes that control the transition between G(1) and S phase. Some of these genes include those encoding cyclins D3, D2, B1, C, and H, cyclin-dependent kinases (cdk's) 4 and 6, the cdk inhibitors p16, p15, and p18, and other genes involved in protein degradation and DNA replication. Importantly, these differences were observed both in total populations of LCMV-specific naive and memory CD8+ cells and in LCMV-specific CD8+ T-cell populations that were in the G(1) phase of the cell cycle only. In addition, the expression differences between naive and memory cells were exaggerated following antigenic stimulation. The fact that memory cells are precharged with several of the major factors that are necessary for the G(1)- to-S-phase transition suggests they may require a lower threshold of stimulation to enter the cell cycle.

Animals↗
PubMed2006

Nodal peripheral T-cell lymphomas correspond to distinct mature T-cell populations.

Peripheral T-cell lymphomas (PTCL) have not been successfully correlated with specific developmental stages of reactive T-cells. Mature T-cells pass through distinct stages upon antigen encounter. Naïve T-cells are CD45RA(+)/CD45R0(-)/CD27(+)/CCR7(+). After antigen contact they replace CD45RA expression with CD45R0. The mature T-cells differentiate to central memory cells, which retain CD27 and CCR7, or to effector memory cells, which lose expression of both molecules depending on the strength of the antigen interaction. In this study, we evaluated lymph node biopsies from eight PTCL-not otherwise specified (PTCL-NOS), seven angioimmunoblastic T-cell lymphomas (AILT), and 15 anaplastic large cell lymphomas (ALCL). Detection of tumour cells with antibodies that recognize specific rearranged T-cell receptor Vbeta segments allowed us to investigate the expression of various differentiation-associated molecules. Results were analysed by hierarchical cluster analysis. All AILT and ALCL showed a homogeneous effector cell phenotype (CD45RA(-)/CD45R0(+)/CD27(-)), but differed in the cytotoxic and activation markers expressed. Several (5/8) PTCL-NOS clustered together; these cases all exhibited a CD4(+) central memory cell phenotype (CD45RA(-)/CD45R0(+)/CD27(+)) and four expressed the lymph node homing receptor CCR7. In conclusion, AILT and ALCL tumour cells correspond to different subsets of effector cells, while a subset of PTCL-NOS correlates with a non-effector T-cell population.

CD4-Positive T-Lymphocytes↗
PubMed2006

Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling.

BACKGROUND AND OBJECTIVES: In early and polymorphic post-transplant lymphoproliferative disorders (PTLD) Epstein-Barr virus (EBV), through its latency proteins, drives the proliferation of B lymphocytes, a process which in immunocompetent individuals leads to the establishment of latently infected memory B cells. DESIGN AND METHODS: We analyzed 11 cases, which included early and polymorphic PTLD, and 12 controls for latency of EBV infection and their antigenic profile. RESULTS: We identified a minority of terminally differentiated EBER+ IRTA1+ memory B cells and EBER+ CD138+ PRDM1+ plasma cells in these samples. These elements were identified both in PTLD and in tumor-free tonsils from post-transplant patients but not in EBV- control tonsils. The expression of EBV latency proteins is heterogeneous, and is associated with activation of the NF-kB pathway. EBV signaling (through EBNA2, LMP1 and LMP2A) and NF-kB activation correlated with upregulation of target proteins: cMYC, JunB, CCL22, TRAF1 and IRF4. EBV-infected lymphocytes in early and polymorphic PTLDs represent a mixture of latencies II, III and, in at least 1/3 of infected cells, of latency 0. INTERPRETATION AND CONCLUSIONS: EBV infection correlates with NF-kB activation, with EBV-dependent cell signaling, and lastly, with the presence of EBV-infected plasma cells and memory cells.

Adolescent↗
PubMed1993

The diagnostic utility of savings scores: differentiating Alzheimer's and Huntington's diseases with the logical memory and visual reproduction tests.

Recent research has demonstrated that patients with dementia of the Alzheimer type (DAT) evidence more rapid forgetting than do patients with Huntington's disease (HD). The present study focused on whether such group differences translated into measures with adequate sensitivity and specificity at different stages of these disorders. It was found that measures of forgetting (i.e., savings scores) based upon the Logical Memory and Visual Reproduction tests of the Wechsler Memory Scale--Revised had satisfactory to excellent sensitivity and specificity in differentiating DAT and HD patients from healthy control subjects. Savings scores also had good sensitivity and specificity in differentiating DAT from HD in the early stages of the diseases. However, unsatisfactory specificity may limit the utility of savings scores in differentiating among patients with moderate DAT and HD.

Aged↗