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Influences of intentionality at encoding and retrieval on memory in adulthood and old age.

This research investigated whether different memory functions are differentially affected by the adult aging process. Four groups of normal adults (18-35, 60-68, 69-78, and 79-91 years of age) were presented with a set of pictures of faces with first names and surnames. Subjects were instructed to memorize the faces and the surnames for subsequent memory tests. Memory performance was assessed in four ways: stem completion of surnames; recognition of faces; recognition of surnames and recognition of first names. These memory tests varied in terms of intentionality at encoding and retrieval. The stem completion task involved intention at encoding, but not at retrieval, and thus served as a measure of implicit memory. With respect to the three explicit memory tasks, recognition of faces and surnames involved intention at both encoding and retrieval, whereas recognition of first names involved intention at retrieval, but not at encoding. Results indicated no age-related differences in implicit memory, as assessed by the stem completion test. In addition, there was an age-related deficit in recognition of faces and surnames, although there were no age-related differences in recognition of first names. The overall pattern of results suggests that age-related deficits in memory may be most likely to occur when there are demands of conscious mental activity at encoding and retrieval.

Adolescent↗

Dissociation of mnemonic and perceptual processes during spatial and nonspatial working memory using fMRI.

Neuroimaging studies in humans have consistently found robust activation of frontal, parietal, and temporal regions during working memory tasks. Whether these activations represent functional networks segregated by perceptual domain is still at issue. Two functional magnetic resonance imaging experiments were conducted, both of which used multiple-cycle, alternating task designs. Experiment 1 compared spatial and object working memory tasks to identify cortical regions differentially activated by these perceptual domains. Experiment 2 compared working memory and perceptual control tasks within each of the spatial and object domains to determine whether the regions identified in experiment 1 were driven primarily by the perceptual or mnemonic demands of the tasks, and to identify common brain regions activated by working memory in both perceptual domains. Domain-specific activation occurred in the inferior parietal cortex for spatial tasks, and in the inferior occipitotemporal cortex for object tasks, particularly in the left hemisphere. However, neither area was strongly influenced by task demands, being nearly equally activated by the working memory and perceptual control tasks. In contrast, activation of the dorsolateral prefrontal cortex and the intraparietal sulcus (IPS) was strongly task-related. Spatial working memory primarily activated the right middle frontal gyrus (MFG) and the IPS. Object working memory activated the MFG bilaterally, the left inferior frontal gyrus, and the IPS, particularly in the left hemisphere. Finally, activation of midline posterior regions, including the cingulate gyrus, occurred at the offset of the working memory tasks, particularly the shape task. These results support a prominent role of the prefrontal and parietal cortices in working memory, and indicate that spatial and object working memory tasks recruit differential hemispheric networks. The results also affirm the distinction between spatial and object perceptual processing in dorsal and ventral visual pathways.

Adult↗

Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis.

Cytokines play a crucial role in the maintenance of polyclonal naive and memory T cell populations. It has previously been shown that ex vivo, the IL-7 cytokine induces the proliferation of naive recent thymic emigrants (RTE) isolated from umbilical cord blood but not mature adult-derived naive and memory human CD4(+) T cells. We find that the combination of IL-2 and IL-7 strongly promotes the proliferation of RTE, whereas adult CD4(+) T cells remain relatively unresponsive. Immunological activity is controlled by a balance between proliferation and apoptotic cell death. However, the relative contributions of IL-2 and IL-7 in regulating these processes in the absence of MHC/peptide signals are not known. Following exposure to either IL-2 or IL-7 alone, RTE, as well as mature naive and memory CD4(+) T cells, are rendered only minimally sensitive to Fas-mediated cell death. However, in the presence of the two cytokines, Fas engagement results in a high level of caspase-dependent apoptosis in both RTE as well as naive adult CD4(+) T cells. In contrast, equivalently treated memory CD4(+) T cells are significantly less sensitive to Fas-induced cell death. The increased susceptibility of RTE and naive CD4(+) T cells to Fas-induced apoptosis correlates with a significantly higher IL-2/IL-7-induced Fas expression on these T cell subsets than on memory CD4(+) T cells. Thus, IL-2 and IL-7 regulate homeostasis by modulating the equilibrium between proliferation and apoptotic cell death in RTE and mature naive and memory T cell subsets.

Adult↗

Adult age differences in the effects of goals on self-regulated sentence processing.

The authors examined age differences in adults' allocation of effort when reading text for either high levels of recall accuracy or high levels of efficiency. Participants read a series of sentences, making judgments of learning before recall. Older adults showed less sensitivity than the young to the accuracy goal in both reading time allocation and memory performance. Memory accuracy and differential allocation of effort to unlearned items were age equivalent, so age differences in goal adherence were not attributable to metacognitive factors. However, comparison with data from a control reading task without monitoring showed that learning gains among older adults across trial were reduced relative to those of the young by memory monitoring, suggesting that monitoring may be resource consuming for older learners. Age differences in the responsiveness to (information-acquisition) goals could be accounted for, in part, by independent contributions from working memory and memory self-efficacy. Our data suggest that both processing capacity ("what you have") and beliefs ("knowing you can do it") can contribute to individual differences in engaging resources ("what you do") to effectively learn novel content from text.

Adult↗

Trypanosoma cruzi modulates the profile of memory CD8+ T cells in chronic Chagas' disease patients.

We present a cross-sectional analysis of the maturation and migratory properties of the memory CD8(+) T cell compartment, in relation to the severity of heart disease in individuals with chronic Trypanosoma cruzi infection removed from endemic areas for longer than 20 years. Subjects with none or mild heart involvement were more likely to mount T. cruzi-specific memory IFN-gamma responses than subjects with more advanced cardiac disease, and the T. cruzi-specific CD8(+) T cell population was enriched in early-differentiated (CD27(+)CD28(+)) cells in responding individuals. In contrast, the frequency of CD27(+)CD28(+)CD8(+) T cells in the total memory CD8(+) T cell population decreases, as disease becomes more severe, while the proportion of fully differentiated memory (CD27(-)CD28(-)) CD8(+) T cells increases. The analysis of CCR7 expression revealed a significant increase in total effector/memory CD8(+) T cells (CD45RA(-)CCR7(-)) in subjects with mild heart disease as compared with uninfected controls. Altogether, these results are consistent with the hypothesis of a gradual clonal exhaustion in the CD8(+) T cell population, perhaps as a result of continuous antigenic stimulation by persistent parasites.

Adult↗

Differences in attention, executive functioning, and memory in children with and without ADHD after severe traumatic brain injury.

Although the development of Attention Deficit Hyperactivity Disorder (ADHD) after traumatic brain injury (TBI) has been described, it is unknown whether children with TBI and ADHD have greater neuropsychological impairments than children with TBI alone. This study examines attention, executive functioning, and memory in children with TBI-only and TBI + ADHD. Caregivers of 82 children with severe TBI completed structured psychiatric interviews at enrollment to diagnose premorbid ADHD and one-year after injury to diagnose post-injury ADHD. Children underwent neuropsychological testing one year after injury. One memory measure significantly differentiated children with TBI-only from children with newly developed ADHD [secondary ADHD (S-ADHD)] and those with premorbid ADHD that persisted after injury [persisting ADHD (P-ADHD)]. Compared with the TBI-only group, children with TBI + ADHD had worse performance on measures of attention, executive functioning, and memory. Results reveal that in children with severe TBI, the behavioral diagnosis of ADHD is associated with more difficulty in attention, executive functioning, and memory. Additionally, results suggest greater deficits in memory skills in the S-ADHD group compared with the P-ADHD group. Although findings provide preliminary support for distinguishing P-ADHD from S-ADHD, further research is needed to investigate neuropsychological differences between these subgroups of children with severe TBI.

Attention↗

Alpha-helical CRF blocks differential influence of corticotropin releasing factor (CRF) on appetitive and aversive memory retrieval in rats.

This study examined whether corticotropin releasing factor (CRF), given prior to test, would produce an improved retrieval of aversive memory in the same way as pre-exposure to inescapable footshocks and the CRF antagonist, alpha-helical CRF 9-41 (a-h CRF), blocks this effect in rats. For this purpose animals conditioned in a T-maze with appetitive (10% sucrose) and aversive (2.0mA footshock) events were given intracerebroventricularly (i.c.v.) 20 min before testing, a single dose of 0.05, 0.1, 0.2 or 0.4 microgram/rat of CRF, or 5 micrograms/rat of a-h CRF, or both at 10 min interval. In the retention test conducted with the same training apparatus 72-hr after conditioning, CRF (0.05, 0.1 and 0.2 microgram) treated rats showed a dose-dependent increase in latencies to enter the previously shocked goalarm, with the absence of such a difference in responding to the nonshocked goalarm. The highest dose of CRF (0.4 microgram), however, increased the latencies to enter both the goalboxes. Alpha-helical CRF, administered 10 min before, antagonized the memory-enhancing effect of CRF. Further, CRF (0.1, 0.2 and 0.4 microgram) significantly decreased the total number of center entries in the open field, consistent with the view that i.c.v. administered CRF produces "anxiogenic-like" effect. Alpha-helical CRF reversed this effect. The effect of CRF on memory retrieval was similar to that seen following inescapable footshock in rats. The results thus suggest the possible involvement of central CRF mechanisms in the differential enhancement of memory of helplessness condition.

Animals↗

Activity of concanavalin A-induced suppressor cells in human MLR: differential effects on primary MLR, secondary MLR, and memory cell precursors.

The relative sensitivity of the MLR responses of freshly isolated human lymphocytes to Con A-induced suppressor cells (SC) was compared to that of lymphocytes that had been primed previously in vitro. Fresh and primed cells were suppressed 72 and 17%, respectively, when cultured under similar conditions (p less than 0.0005). Titration of SC indicated that equivalent suppression in the two populations would require greater than a 50-fold excess of SC in the primed cells. Neither preincubation of the primed cells for 24 or 72 hr with the SC before restimulation, addition of fresh autologous cells to the primed cells, nor preincubation of the SC with fresh cells before addition to the primed cells increased suppression of primed cells. SC added at the beginning of a primary MLC were, however, very suppressive for both the primary response (67% suppression) and the subsequent secondary response (81% suppression). These data indicate that although the human primary MLR and the precursor of the memory cell are both sensitive to the suppressors induced by Con A, the memory cell itself possess an intrinsic resistance to such suppressors that is not related to simple kinetic phenomena nor to the loss in vitro of an intermediate regulatory cell. Cell depletion experiments suggest that resistance to nonspecific suppression may occur at the level of the helper cell.

Antibodies, Monoclonal↗

Detection of memory B lymphocytes specific to hepatitis B virus (HBV) surface antigen (HBsAg) from HBsAg-vaccinated or HBV-immunized subjects by ELISPOT assay.

To improve the investigation of the role of human memory B lymphocytes following hepatitis B virus (HBV) infection or vaccination, we developed a method to characterize circulating memory B cells specific to hepatitis B surface antigen (HBsAg). Our approach combined: (1) purification of CD19+ cells, (2) CD40-CD40L polyclonal stimulation, and (3) enumeration of memory B cells differentiated into anti-HBs antibody (Ab)-secreting cells (HBs-SCs) by a HBs-ELISPOT assay. In this way, HBs-SCs were detected in 17 HBsAg-vaccinated and nine HBV-immunized subjects including four individuals with serum anti-HBs Ab levels < 10 mIU/ml, but not in six controls. IgG+, IgA+ plus IgM+ HBs-SCs, representing 5-1736 cells/10(6) circulating B cells and 0.02-0.58% of total immunoglobulin-SCs generated by the B cell polyclonal stimulation, were counted by an Ig two-colour ELISPOT assay. In addition, anti-HBs Abs were found in 8/15 supernatants recovered from B cell cultures which contained HBs-SCs, suggesting that the HBs-ELISPOT assay is more reliable in tracking HBsAg-specific memory B cells than ELISA measurement of anti-HBs Abs secreted in supernatants. This new approach could be useful to explore the presence and the longevity of HBsAg-specific memory B cells in vaccinated and immunized subjects, in chronic HBV infection and after liver transplantation for HBV-related disease.

Antibody-Producing Cells↗

Benzodiazepines alter acquisition and retention of an inhibitory avoidance response in mice.

These experiments were performed to examine the effects of graded doses of diazepam, flurazepam, or lorazepam given to Swiss-Webster mice either 30 min prior to training or immediately after training in a one-trial inhibitory (passive) avoidance task. A 350 MUA footshock was administered following entry into a darkened compartment and retention was tested three days later. Doses of 10.0 mg/kg diazepam and 20.0 mg/kg lorazepam given before training significantly impaired acquisition, while 1.0 mg/kg flurazepam, given immediately after training, produced retrograde amnesia. These results indicate that benzodiazepines affect memory processes and that various drugs of the benzodiazepine family differentially affect acquisition and memory consolidation.

Animals↗

Visual memory processes in high-functioning individuals with autism.

High-functioning autistic individuals were compared with age-matched normal control subjects on a visual recognition memory task. In order to evaluate the effects of "meaning" and "delay" on the visual memory of autistic individuals, meaningful (pictures) and meaningless (nonsense shapes) stimuli were presented visually in no delay and 1-minute delay intervals to both groups. It was concluded that autistic subjects perform particularly poorly on meaningless material, but they are able to utilize meaning to aid their visual memory. Contrary to expectations, 1-minute delay intervals did not differentially affect the visual memory performance of autistic individuals compared to control subjects. The results do not support the idea of a simple parallel between autism and mediotemporal lobe amnesias. The visual memory performance of the autistic subjects was discussed in the light of the possibility of a subtle involvement of the mediotemporal brain structures and inflexible cognitive strategies poorly suited to encode novel information.

Adolescent↗

A quantitative model suggests immune memory involves the colocalization of B and Th cells.

A prominent and essential feature of the humoral immune response of vertebrates is immunologic memory: the ability to recall previous exposure to antigen. We present a mathematical model of the growth and interactions of the major cell populations involved in the humoral immune response. Our analysis of this model predicts that the formation of a dynamic association between small numbers of antigen-specific B and Th cells, "colocalization", is sufficient to account for memory and the kinetics of the secondary response--neither specifically differentiated Th or B memory cells nor networks of antigen and anti-idiotypes are required. The colocalization hypothesis explains a number of existing experimental observations and can be tested by straightforward experiments which we describe.

Animals↗

Interference effects in chronic alcoholism.

This study investigated underlying mechanisms of the verbal memory disorder associated with chronic alcoholism. Previous investigations have suggested that alcoholics are more vulnerable to interference effects on verbal learning and memory tasks, both with respect to retroactive interference (RI) and proactive interference (PI); this was the hypothesis of the current study. Measures of RI and build-up and release from PI were administered to 31 abstinent male chronic alcoholics and 24 healthy male nonalcoholic control subjects. Alcoholics demonstrated more sensitivity to RI than controls. Additionally, alcoholics displayed a more rapid build-up of PI, although they showed normal release. An increased interference effect was found to be a component of chronic alcoholics' verbal memory impairment and may differentiate chronic alcoholism from other disorders affecting verbal learning and memory.

Adult↗

Antigen-specific T cell activation and proliferation during oral tolerance induction.

One of several routes of achieving immunologic tolerance is through functional inactivation of Ag-specific T cells. Oral administration of Ag can allow survival of the Ag-specific T cells that are functionally anergic. The aim of this study was to investigate whether functional inactivation of Ag-specific T cells is directed through an activation process and to further define the differentiative pathways and functional characteristics of anergic T cells. Mice were transplanted with OVA-specific TCR-transgenic T cells and either fed OVA or immunized s.c. with the OVA peptide 323-339 in CFA. OVA-specific T cells from OVA-fed mice were unresponsive to restimulation in vitro within 48-72 h after treatment. In vivo, however, T cell proliferation was detected by 5, 6-carboxy-succinimidyl-fluoresceine-ester intensity changes in OVA-specific T cells. The mesenteric lymph nodes (LNs) from OVA-fed mice more frequently contained OVA-specific dividing cells in vivo than those in the peripheral LNs, and the reciprocal was observed following s.c. immunization of the OVA peptide in CFA. The induction of anergy in OVA-fed mice was accompanied by rapid up-regulation of CD69 and CTLA-4, later down-regulation of CD45RB on OVA-specific T cells, and a marked decrease in T cell secretion of IL-2, IL-10, and IFN-gamma after OVA restimulation in vitro. Results from this study indicate that the inductive phase of oral tolerance is preceded by Ag-specific T cell activation in vivo, proliferation in the regional draining LNs, and differentiation into a memory-like state. These results indicate that Ag-directed differentiation occurs as a part of T cell tolerance through anergy.

Administration, Oral↗

Stability and commitment in T helper cell development.

Specialized effector activities that are required to eliminate various pathogens involve cytokines produced by specialized CD4(+) T cells subsets, dogmatically termed Th1 and Th2 cells. Despite some oversimplifications, this paradigm is useful for organizing the complex pathways that control forward and backward movements along the road of T cell differentiation. Effective immune memory relies, in part, on the maintenance of the T helper phenotype. This review will address basic issues that relate to the maintenance or reversibility of Th1/Th2 states within the CD4(+) T cell lineage.

Animals↗

Knowing which and knowing what: a potential mouse model for age-related human declarative memory decline.

The present study was built on the original report of Eichenbaum et al. [Eichenbaum, H., Fagan, A., Mathews, P. & Cohen, N.J. (1988), Behav. Neurosci., 102, 3531-3542] on the contrasting effects of fornix lesion in different versions of an odour-guided discrimination task in rats, and attempted to extend this into a mouse model for the preferential loss of declarative memory seen in human senescence. Each of the two experiments reported here consisted of a two-stage paradigm, with an initial learning phase followed by a test phase. The information acquired in the first stage was identical in both experiments, i.e. the valence or reward contingency associated with six (three positive and three negative) arms of a radial maze. The only parameter which was varied between Experiment A and B, and also between the two successive stages within each experiment, was the way of presenting the arms to the mice, i.e. either in pairs (simultaneous discriminations) or one at a time (successive go : no-go discrimination). Performance in the first stage demonstrated that our aged mice were impaired in learning concurrent simultaneous discriminations but not successive go/no-go discrimination, thereby resembling that reported in rats with hippocampal damage. Most importantly, our present set of data supports the conclusion that two forms of memory expression for the same piece of acquired experience can be assessed in the same subjects by manipulating the way of presenting two arms that were previously experienced separately. These two forms of memory expressions are differentially affected in aged mice, thereby demonstrating the highly selective and specific deleterious effect of ageing.

Aging↗

Phenotypic and functional analysis of EBV-specific memory CD8 cells in SLE.

T cell dysfunction has been described in systemic lupus erythematosus (SLE). However, the specific phenotype and function of antigen-specific CD8 cells is less clear. Here we determined phenotype and function of Epstein-Barr virus (EBV)-specific CD8 cells at the single-cell level in SLE. HLA-A2-restricted EBV-BMLF-1-specific CD8 cells were enumerated by flow cytometry using tetramers in SLE and healthy control subjects. Antigen-specific CD8 cells were analyzed for expression of differentiation, activation, proliferation, and anti-apoptotic markers. EBV-specific, other virus-specific (specific against a viral peptide pool consisting of cytomegalovirus, EBV and influenza virus peptides), and mitogen-induced CD8 cell function was assessed by INF-gamma ELISPOT assay. Frequencies of EBV-specific CD8 cells tended to be greater in SLE subjects than in healthy control subjects (p=0.07). While over 10% of EBV-specific CD8 cells were capable of producing IFN-gamma in four out of five healthy control subjects, such proportions of EBV-specific CD8 cells capable of IFN-gamma production were observed in only one out of six SLE subjects (p=0.04). In contrast, viral peptide pool-specific and mitogen-induced IFN-gamma-producing T cell function was intact in SLE subjects. Phenotypic analysis revealed EBV-specific CD8 cells to be in an early to intermediate differentiation and resting memory state in both groups. While EBV-specific CD8 cells are similar in phenotype, their frequency tends to be increased, and function appears to be decreased in SLE. Therefore, an impaired EBV-specific CD8 immune response may exist in SLE, potentially contributing to disease pathogenesis.

Adult↗

Taste memory induces brain activation as revealed by functional MRI.

PURPOSE: Our goal was to use functional MRI (fMRI) to measure brain activation in response to imagination of tastes in humans. METHOD: fMR brain scans were obtained in 31 subjects (12 men, 19 women) using multislice FLASH MRI and echo planar imaging (EPI) in response to imagination of tastes of salt and sweet in coronal sections selected from anterior to posterior temporal brain regions. Activation images were derived using correlation analysis, and ratios of areas of brain activated to total brain areas were calculated. Total activated pixel counts were used to quantitate regional brain activation. RESULTS: Activation was present in each section in all subjects after imagination of each tastant. Activation was similar in response to imagination of either salt or sweet and was quantitatively similar to that previously reported in response to imagination of odors of banana and peppermint. Activation was similar in both men and women as opposed to previous results of odor memory in which activation in men was greater than in women. However, subjective responses of intensity of imagined tastes were significantly greater than those previously obtained for odor memory and were consistently, albeit not significantly, greater in women than in men, similar to results previously reported for odor memory. Brain regions activated in response to taste imagination were consistent with regions previously described as involved with actual taste perception in both humans and animals. Regional brain localization for salt and sweet memories could not be differentiated. CONCLUSION: These studies indicate that (a) tastes can be imagined, (b) brain regions activated for taste imagination are consistent with regions previously described for actual taste perception, and (c) similar to odor memory for banana and menthone, regional brain localization for salt or sweet taste memories could not be differentiated.

Adult↗