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PubMed1992

Neuronal activity in the hippocampus during delayed non-match to sample performance in rats: evidence for hippocampal processing in recognition memory.

Neuronal activity in the CA1 of rats was explored with regard to functional correlates of performance in an odor-guided continuous delayed non-match to sample task. Although different CA1 cells fired in association with each identifiable trial event, these analyses focused on cells that fired selectively during the period of odor cue sampling and response generation. The firing patterns of many of these cells reflected the match or non-match comparison between current and previous odor cues independent of the particular stimuli that composed those comparisons. Such cells were more prevalent in sessions when performance was highly accurate. Hippocampal cells did not demonstrate stimulus-evoked firing that persisted through the memory delay, nor did they fire differentially to session-novel vs. repeated odor presentations. These results suggest that the hippocampus contributes to recognition memory by processing comparisons between current information and representations of previous stimuli stored in parahippocampal and neocortical structures.

Animals↗
PubMed2003

Verbal memory impairment in congestive heart failure.

Cognitive dysfunction, mainly memory impairment, characterizes congestive heart failure (CHF). Aim of this study was to verify whether: (1) CHF has differential effects on primary and secondary memory; (2) memory dysfunction can be diagnosed by a screening instrument. In a multicenter study we enrolled 369 patients with stable CHF who underwent a structured assessment of verbal memory mechanisms and selected cognitive functions. Performance on some verbal memory indexes (Recency, Rey's immediate and delayed recall, Learning efficiency) progressively decreased from II to IV New York Heart Association (NYHA) class. Rate of forgetting was uniformly high across NYHA classes II-IV. Verbal memory indexes were highly correlated with most nonverbal scores. The Mini Mental State Examination (MMSE) had poor sensitivity and specificity versus primary or secondary verbal memory dysfunction. Therefore, a deficit of both primary and secondary memory is relatively common in CHF but cannot be accurately recognized by a screening neuropsychological test.

Activities of Daily Living↗
PubMed2002

Errors produced on the mini-mental state examination and neuropsychological test performance in Alzheimer's disease, ischemic vascular dementia, and Parkinson's disease.

The authors investigated whether MMSE indices designed to measure temporal and physical orientation, declarative memory, language, working memory, and motor/constructional function could differentiate patients with different dementia diagnoses: Alzheimer's disease (AD), ischemic vascular dementia (IVD), or Parkinson's disease (PD). MMSE summary scores did not differ (AD, 21.4; IVD, 21.1; PD, 22.3). The AD group scored lower than IVD or PD on temporal orientation and declarative memory, IVD lower than AD on motor/ constructional and working memory. The IVD and PD groups made more errors in writing a sentence and copying intersecting pentagons. Significant correlations were found between the orientation indices and neuropsychological tests of naming and memory, and between the working memory and motor/constructional indices and tests of executive control. Such analyses of MMSE performance could assist in formulating referral questions for cognitive assessment and in tracking the course of dementing illnesses.

Aged↗
PubMed1986

Signal-detection analysis of recognition memory of obese subjects.

Obese and normal-weight subjects were run on a series of recognition-memory tasks with low and high meaningful CVC trigrams. Subjects received feedback or no feedback regarding the appropriateness of their answers during testing for recognition memory. A signal-detection analysis was used to examine a relatively pure index of memory (d') as compared to response-bias factors [Ln (beta)]. No significant main effect on memory of obese and control subjects was noted although a significant interaction indicated that obese subjects' memory increases over trials in a differential fashion from normal-weight individuals with poorer performance among the obese after 3 trials. Feedback facilitated memory for both groups. Analysis of response criteria [Ln (beta)] showed no significant difference between groups. Highly meaningful trigrams had a significantly lower response criterion than low meaningful trigrams and there was a significant interaction of meaningfulness by trials. An interaction of feedback by meaningfulness was also present. Advantages of using a signal-detection analysis in memory studies comparing obese and normal weight subjects are discussed. Ramifications of the present data for the internality/externality hypothesis of obesity are also discussed.

Adolescent↗
PubMed2002

Effects of stress hormones on traumatic memory formation and the development of posttraumatic stress disorder in critically ill patients.

A majority of patients after intensive care treatment report traumatic memories from their stay in the intensive care unit (ICU). Traumatic memories can be associated with the development of posttraumatic stress disorder (PTSD) in a subpopulation of these patients. In contrast to other patient populations at risk for PTSD, patients in the ICU often receive exogenously administered stress hormones like epinephrine, norepinephrine, or cortisol for medical reasons and are extensively monitored. ICU patients therefore represent a suitable population for studying the relationship between stress hormones, traumatic memories, and the development of PTSD. Studies in long-term survivors of ICU treatment demonstrated a clear and vivid recall of different categories of traumatic memory such as nightmares, anxiety, respiratory distress, or pain with little or no recall of factual events. The number of categories of traumatic memory recalled increased with the total administered dosages of stress hormones (both catecholamines and cortisol), and the evaluation of these categories at different time points after discharge from the ICU showed better memory consolidation with higher dosages of stress hormones administered. However, the administration of stress doses of cortisol to critically ill patients resulted in more complex findings as it caused a significant reduction in PTSD symptoms measured after recovery. This effect can possibly be explained by a differential influence of cortisol on memory. Increased serum cortisol levels not only result in consolidation of emotional memory but are also known to cause a temporary impairment in memory retrieval which appears to be independent of glucocorticoid effects on memory formation. Disrupting retrieval mechanisms with glucocorticoids during critical illness may therefore act protectively against the development of PTSD by preventing recall of traumatic memories. Our findings indicate that stress hormones influence the development of PTSD through complex and simultaneous interactions on memory formation and retrieval. Our studies also demonstrate that animal models of aversive learning are useful in analyzing and predicting clinical findings in critically ill humans.

Affect↗
PubMed1998

OX-40: life beyond the effector T cell stage.

The OX-40 receptor (OX-40R) is a transmembrane protein found on the surface of activated CD4(+) T cells. When engaged by an agonist such as anti-OX-40 antibody or the OX-40 ligand (OX-40L) during antigen presentation to T cell lines, the OX-40R generates a costimulatory signal that is as potent as CD28 costimulation. Engagement of OX-40R enhances effector and memory-effector T cell function by up-regulating IL-2 production and increasing the life-span of effector T cells. We hypothesize that the signal generated by the OX-40R inhibits activation-induced T cell death (AICD) and thereby increases the number of cells differentiating from the effector to memory T cell stage. In experimental autoimmune encephalomyelitis (EAE) OX-40R+ T cells are found only within the inflammatory site [central nervous system (CNS)]. Sorting OX-40R+ T cells from the CNS of animals with EAE revealed that they are autoantigen-specific T cells. Therefore, OX-40R-specific therapies were devised to eliminate or inhibit autoreactive T cells, while sparing the remainder of the T cell repertoire. In contrast, in vivo costimulation through the OX-40R in animals with cancer generated enhanced tumor-specific immunity leading to improved tumor-free survival. Thus, manipulation of the OX-40R during inflammatory responses can alter effector CD4(+) T cell function by enhancing or limiting T cell activation and survival.

Animals↗
PubMed2005

IELs: enforcing law and order in the court of the intestinal epithelium.

The intestinal intraepithelial lymphocytes (IELs) are mostly T cells dispersed as single cells within the epithelial cell layer that surrounds the intestinal lumen. IELs are, therefore, strategically located at the interface between the antigen-rich outside world and the sterile core of the body. The intestine of higher vertebrates has further evolved to harbor numerous commensal bacteria that carry out important functions for the host, and while defensive immunity can effectively protect against the invasion of pathogens, similar immune reactions against food-derived antigens or harmless colonizing bacteria can result in unnecessary and sometimes damaging immune responses. Probably as a result of this unique dilemma imposed by the gut environment, multiple subsets of IEL have differentiated, which all display characteristics of 'activated yet resting' immune cells. Despite this common feature, IELs are heterogeneous with regard to their phenotype, ontogeny, and function. In this review, we discuss the different subtypes of IELs and highlight the distinct pathways they took that led to their unique differentiation into highly specialized effector memory T cells, which provide the most effective immune protection yet in a strictly regulated fashion to preserve the integrity and vital functions of the intestinal mucosal epithelium.

Animals↗
PubMed1989

Differentiating Alzheimer's patients from the normal elderly and stroke patients with aphasia.

The performance of individuals with mild and moderate Alzheimer's disease (AD), normal age-matched elderly individuals, and stroke patients with fluent and nonfluent aphasia were compared on a group of neuropsychological tasks. The unique performance profiles associated with each subject group are discussed, and the best tasks for intergroup differentiation specified. Whereas the tasks employed were efficacious for discriminating early- and middle-stage AD patients from normal subjects and aphasic stroke patients, and early- from middle-stage AD patients, they were not efficacious for subtyping aphasia patients according to fluency. Generally, memory measures were best for intergroup differentiation.

Aged↗
PubMed2004

Double dissociation of social and environmental stimulation on spatial learning and reversal learning in rats.

Environmental enrichment induces structural and biochemical changes in the brains of mammals that correlate with improved learning and memory. Research in rats suggests that social compared to inanimate stimulation might affect behavior differently, by acting upon dissociable neural substrates. Here we tested this hypothesis at the behavioral level by examining whether social and inanimate stimulation affect spatial memory formation and non-spatial discrimination reversal learning selectively. Spatial memory formation is known to depend on hippocampal-neocortical pathways, whereas reversal learning depends primarily on prefrontal cortico-striatal pathways. Male Lister hooded rats were housed singly or in groups of three in either small barren or large enriched cages, from weaning onwards. After 10 weeks of differential housing, spatial learning and memory were examined in the Morris water maze, followed by a series of tactile and odour discriminations, including discrimination reversal, in a two-choice discrimination task. Regardless of inanimate stimulation, social deprivation affected neither the acquisition of simple or complex discriminations, nor spatial memory formation, but was associated with impaired reversal learning in the two-choice discrimination task. By contrast, inanimate deprivation, regardless of social stimulation, affected neither acquisition nor reversal of two-choice discriminations, but selectively delayed the acquisition of spatial memory in the Morris water maze. This is the first demonstration of a double dissociation of early social and inanimate stimulation on two distinct behavioural functions that are mediated by dissociable underlying neural pathways. These findings strengthen the view that social and inanimate stimulation act, at least in part, upon dissociable neural substrates.

Animals↗
PubMed2005

Interaction of sensory and cognitive processes during visual recognition: the role of the associative areas of the cerebral cortex.

The first part of the present study used a model of Alzheimer's disease in two groups of animals (three monkeys in each), given injections of neurotoxins (monkeys of group I) and physiological saline (monkeys of group II). Before injections, all monkeys were trained to discriminate stimuli containing different types of information (spatial frequency grids and geometrical figures of different colors and with different spatial relationships between objects) and to perform spatial selection. The dynamics of impairments in the characteristics of working memory were identified using delayed differentiation tasks in monkeys of both groups before injections and every two months after injections. Quantitative measures of impairments were made using the entropy of visual recognition, which characterizes uncertainty in decision-taking. The development of Alzheimer's disease in rhesus macaques was characterized by a deficit of working memory, resulting from lesions to the two component processes of memory. Impairments of the first of these in monkeys of group I were manifest as a significant increase in entropy, which is associated with correct decision-taking. The magnitude of the increase depended on the type of visual information. Impairments of the second component were characterized by increases in entropy associated with refusals to take decisions and were independent of the delay duration and the type of visual information. Monkeys given injections of physiological saline showed no significant changes in these characteristics. The features of working memory were also studied in the second part of the investigation, using four groups of Rhesus macaques: intact, those with bilateral extirpation of the sulcus principalis or field 7 or both: degradation again identified two components. Entropy associated with this was increased significantly for most of the stimuli tested on monkeys of all extirpation groups as compared with intact animals. Significant differences were found in these characteristics for a number of stimuli, which depended on the location of the structures removed. The characteristics of impairments of the components of working memory resulting in the development of Alzheimer's disease showed that the cholinergic mechanisms responsible for sensory processing differ from those involved in decision-taking. The structural-functional organization of the interaction of sensory and cognitive processes controlled by the motivation and attention systems is discussed, as is the role of the associative areas of the cortex.

Animals↗
PubMed1980

Tactile recognition memory in infants.

This experiment was conducted to determine whether infants can recognize the shapes of objects by touch alone. 25 1-year-olds were administered 2 tasks, each of which consisted of a familiarization stage followed by a recognition test stage. The familiarization stage of both tasks was identical in that infants manipulated objects in the light. The test stages differed with respect to the lighting conditions. In the first task infants manipulated familiar and novel objects in the light, and in the second task, in darkness. Behavior in darkness was videotaped by infrared recording. Recognition memory was determined by infants' differential manipulatory responsiveness to novel and familiar objects. In both the lighted and darkness tests infants engaged in significantly more manipulation, exhibited more mouthing, and displayed more hand-to-hand transfers with novel compared to familiar objects. These data provide initial evidence that infants are capable of tactile recognition memory.

Discrimination Learning↗
PubMed1998

Simulating a memory impairment: can amnesics implicitly outperform simulators?

OBJECTIVES: The purpose of this study was to examine the effectiveness of a variety of tests in differentiating simulating test performances from genuine memory-impaired and normal (control) test performances. DESIGN: A simulation design was implemented, based on an analogue design in which normal participants were given experimental instructions to feign a mental impairment and are compared to (a) other normal participants with instructions to perform honestly, and (b) a comparison group, for example, acquired brain-injured persons, with similar instructions. METHOD: Forty individuals comprised the simulating and control group and all participants were randomly assigned to the simulating and control groups. Twenty memory-impaired patients, all of whom had been diagnosed as suffering from a memory impairment following acquired brain damage, participated as the memory-impaired control group. The simulation group was directed to imitate a person with a memory impairment. The primary outcome measure involved identifying those tests, if any, where simulators were significantly different from normal and memory-impaired participants. RESULTS: On 5 of the 15 tasks administered, simulators performed significantly differently from normal and memory-impaired participants. Of these 5 tasks, the coin-in-the-hand, when administered in conjunction with the autobiographical interview, identified 95 per cent of the simulators without misclassifying any of the memory-impaired or normal participants. CONCLUSION: It is suggested that these two tests, when administered jointly, might be of use in clinical settings to assist in the detection of malingerers.

Adult↗
PubMed1999

The functional neuroanatomy of comprehension and memory: the importance of prior knowledge.

Stories are a common way in which humans convey and acquire new information. Their effectiveness and memorability require that they be understood which, in turn, depends on two factors-whether the story makes sense and the prior knowledge that the listener brings to bear. Comprehension requires the linking of related pieces of information, some provided within the story and some by the listener, in a process establishing coherence. In this study, we examined brain activations associated with story processing. During PET scanning, passages of prose were read twice to subjects during successive scans with the requirement to remember them. These were either standard stories that were readily comprehensible, or unusual stories for which the global theme was very difficult to extract without prior knowledge of the mental framework. This was manipulated by the provision of relevant, irrelevant or no visual cues shortly before the story. Ratings of comprehension provided by the subjects just after each scan confirmed that standard stories were more comprehensible than the unusual stories, as were unusual stories with a mental framework compared with those without. PET results showed activation of anterior and ventral parts of the medial parietal/posterior cingulate cortex in association with hearing unusual stories when subjects were given prior knowledge of what it might be about. Medial ventral orbitofrontal cortex and left temporal pole activations were found to be associated with more general aspects of comprehension. Medial parietal cortex (precuneus) and left prefrontal cortex were associated with story repetition. We suggest that while the temporal pole is involved in the linking of propositions to build a narrative, the anterior medial parietal/posterior cingulate cortex is concerned with linking this information with prior knowledge. All of this occurs in the context of a general memory processing/retrieval system that includes the posterior parietal (precuneus) and prefrontal cortex. Knowledge of how distinct brain regions contribute differentially to aspects of comprehension and memory has implications for understanding how these processes break down in conditions of brain injury or disease.

Acoustic Stimulation↗
PubMed2005

Memory T cells have gene expression patterns intermediate between naive and effector.

The biological basis underlying differentiation of naive (NAI) T cells into effector (EFFE) and memory (MEM) cells is incompletely understood. Furthermore, whether NAI T cells serially differentiate into EFFE and then MEM cells (linear differentiation) or whether they concurrently differentiate into either EFFE or MEM cells (parallel differentiation) remains unresolved. We isolated NAI, EFFE, and MEM CD8(+) T cell subsets from human peripheral blood and analyzed their gene expression by using microarrays. We identified 156 genes that strongly differentiate NAI, EFFE, and MEM CD8(+) T cells; these genes provide previously unrecognized markers to help identify each cell type. Using several statistical approaches to analyze and group the data (standard heat-map and hierarchical clustering, a unique circular representation, multivariate analyses based on principal components, and a clustering method based on phylogenetic parsimony analysis), we assessed the lineage relationships between these subsets and showed that MEM cells have gene expression patterns intermediate between NAI and EFFE T cells. Our analysis suggests a common differentiation pathway to an intermediate state followed by a split into EFFE or MEM cells, hence supporting the parallel differentiation model. As such, conditions under which NAI T cells are activated may determine the magnitude of both EFFE and MEM cells, which arise subsequently. A better understanding of these conditions may be very useful in the design of future vaccine strategies to maximize MEM cell generation.

CD8-Positive T-Lymphocytes↗
PubMed1999

The Alzheimer's plaques, tangles and memory deficits may have a common origin. Part V: why is Ca2+ signal lower in the disease?

The state of intracellular Ca2+ in aging and in Alzheimer's disease (AD) is a key but highly controversial issue and direct measurement of the Ca2+ fluctuations in the living human brain has not been possible thus far. We therefore further considered this issue from a theoretical perspective. Ca2+ signaling mediates many life processes including: fertilization, gene expression, cell division, growth and differentiation, muscle contraction, neurotransmission and memory formation. It is common observation that these Ca2+-mediated activities in human life are highest in young adulthood but diminish during aging, indicating that Ca2+ signaling potency (or intracellular Ca2+ levels) must be decreased in aging and AD. A potential explanation for this phenomenon could be that the Ca2+-mediated processes are also energy-dependent processes, because they all utilize the free energy reserve of the body for "useful" work, and it is known that Ca2+ gradient formation and Ca2+ movement across cell membrane are driven by energy-dependent systems. This intimate relationship between energy and Ca2+ signaling implies that the potency of Ca2+ signaling would be affected by changes of energy levels, which would necessarily decline in aging. These may underlie the deficit of Ca2+ signaling in the presymptomatic stage of AD. These considerations also support our view that Abeta and tau accumulation in AD is the result of inactivation of calcium-dependent enzymes, rather than overactivation of beta/(-secretases and some tau kinases. This is because most enzyme activities should be diminished, rather than overactivated, during aging. Furthermore, since energy/Ca2+ deficit is a natural event in aging, it follows that the accumulation of Abeta and tau would be initiated "spontaneously" as a result of "natural" aging, not necessarily by a "pathological" factor. Based on the analyses, we propose that intracellular Ca2+ deficit is most likely the primary and common cause (among the many contributing, secondary or individualized factors) for the plaque and tangle accumulation underlying sporadic AD. And we predict that this contention, though in contrast to many competing models, will be confirmed by the proposed experimentation in the future.

Aging↗
PubMed1994

Efficient induction of immunoglobulin production in neonatal naive B cells by memory CD4+ T cell subset expressing homing receptor L-selectin.

The humoral response in newborns is mainly restricted to IgM production, which may be attributable to the naive nature of both B and T cells at birth. In light of the current evidence that memory (CD45RO+) CD4+ T cells help B cell differentiation, the present study was undertaken to examine whether a specified population within memory CD4+ T cells could induce the maturation of neonatal naive B cells. In the conventional PWM-stimulated cultures, the generation of IgG- and IgA-producing cells in addition to IgM production by neonatal B cells was significantly enhanced by co-cultures with memory, but not naive, CD4+ T cells. Memory CD4+ T cells were further divided into two populations based on expression of homing receptor L-selectin. These memory CD4+ T cell subpopulations appeared to behave in different fashions concerning help for Ig production by naive (sIgD+) and mature (sIgD-) B cells. L-selectin-negative memory CD4+ T cells exhibited helper function for Ig secretion by mature B cells. Intriguingly, Ig production by neonatal B cells as well as adult naive B cells, although less than that by mature B cells, was efficiently promoted by L-selectin-positive memory CD4+ T cells rather than L-selectin-negative ones. The results suggest that the capability of neonatal naive B cells to secrete IgG and IgA can be elicited by appropriate T-cell signals, especially from the L-selectin-positive population within memory CD4+ T cells, seemingly indicating its possible role for isotype switching in B cells.

Adult↗