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Working memory deficit as a core neuropsychological dysfunction in schizophrenia.

OBJECTIVE: This study tested the hypothesis that impaired working memory is a core deficit underlying multiple neuropsychological deficits in schizophrenia patients. METHOD: The subjects were 27 men with stable chronic schizophrenia treated with atypical antipsychotics and 38 normal participants. They were assessed with a battery of neuropsychological tests. Verbal working memory was measured with the WAIS digit span tests, and the Dot Test was used to test spatial working memory. RESULTS: In the patients, verbal working memory showed significant correlations with visual retention, visual orientation, simple motor function, visuomotor coordination, and executive function but not with memory for objects, memory for faces, recognition of facial emotions, or attention. Spatial working memory showed significant correlations with visual retention, visual orientation, memory for objects, memory for faces, and simple motor function but not attention, executive function, or visuomotor coordination. In the comparison group, no correlations between working memory and other neuropsychological functions were found. CONCLUSIONS: These findings support the hypothesis that working memory is a core deficit in schizophrenia. The authors postulate that the lower capacity for verbal and spatial "on-line storage" is rate limiting in the performance of other cognitive functions. Executive functions rely critically on the phonetic loop, complex visual functions such as object and face memory rely on the spatial on-line storage system (visuospatial scratch pad), while other functions such as visual orientation depend critically on both capacities.

Adult↗

Selective effects of zolpidem on human memory functions.

Zolpidem is an imidazopyridine hypnotic with preferential binding affinity for the omega1-benzodiazepine (BZD) receptor. The present double-blind, placebo-controlled study evaluated the effects of orally administered zolpidem (15mg/70kg) on specific memory functions in 16 healthy volunteers using a battery of word and picture memory tasks. Relative to placebo, zolpidem significantly impaired memory for material presented after drug administration when memory was assessed directly by referring subjects back to the prior study episode (explicit memory: recall and recognition) but not when memory was assessed indirectly by evaluating subjects' ability to identify degraded versions of studied stimuli (implicit memory: fragment completion). Zolpidem did not impair explicit memory for material presented before drug administration or memory for previously acquired knowledge (semantic memory: categorization). There was evidence suggesting that zolpidem enhanced explicit and implicit memory for material presented before drug administration and that zolpidem produced a specific deficit in the acquisition of contextual information about material presented after drug administration. Despite zolpidem's unique pharmacological profile, the observed selectivity of zolpidem's memory-impairing effects for particular functions appears qualitatively similar to the selectivity observed with classic BZDs in previous studies.

Adult↗

Factor analysis of three standardized tests of memory in a clinical population.

OBJECTIVES: The aim of this study was to determine the factor structure of three standardized memory tests: Wechsler Memory Scale-Revised (WMS-R), Warrington Recognition Memory Test (WRMT), Doors and People Test (D&P). We investigated whether these different standardized tests of memory are consistent in their evaluation of memory function, and the extent to which these tests discriminate between different memory functions (e.g. recall/recognition and verbal/non-verbal memory). DESIGN: Fifty patients with selective memory impairment were tested on the WMS-R, WRMT and D&P. METHODS: Age-scaled scores from selective measures of these tests (WMS-R-verbal, WMS-R-visual, WMS-R-delay, WRMT-words, WRMT-faces, D&P-people, D&P-doors, D&P-shapes, D&P-names) were used as input to a factor analysis. RESULTS: Maximum likelihood factor analysis yielded a three-factor solution consistent with a theoretically motivated fractionation of memory function into recall and recognition components. Recognition performance, but not recall performance, showed dissociation into visual and verbal components. CONCLUSIONS: The WMS-R, WRMT and D&P are highly consistent in their assessment of memory function. The results of the factor analysis are consistent with a theoretically motivated fractionation of recall and recognition memory. They are also partially consistent with a dissociation between visual and verbal memory function.

Adolescent↗

Dissecting the complexity of the memory T cell response.

Memory immune responses are classically attributed to the reactivation of long-lived, antigen-specific T lymphocytes that persist in a quiescent state. Determining mechanisms for the generation of memory T cells and dissecting the functional nature of the memory T cell pool has been encumbered by an inability to distinguish recently activated effector T cells from memory T cells. We have established new activation and biochemical criteria that distinguish effector and memory T cells and have applied these criteria to follow memory generation from activated cells in vivo. We found that the resultant memory T cell pool is heterogeneous and consists of effector-like and resting memory-like subsets that differ in expression of the homing receptor, CD62L. We discuss these findings in the context of memory T cell heterogeneity identified in human and mouse systems. These results suggest that more than one type of previously activated T cell can mediate recall or memory immune responses and that elucidating the fundamental phenotypic and functional features of memory T cell subsets is therefore critical to deciphering the complex nature of the memory immune response.

Animals↗

An evaluation of the effectiveness of group therapy for memory problems.

OBJECTIVE: To investigate the effectiveness of group treatment for memory problems. DESIGN: A cross-over design was employed to compare the memory improvement of subjects while attending a weekly memory therapy session with a waiting period. SETTING: Outpatients. TREATMENT: A variety of memory strategies were taught, and practical advice was provided in the use of external aids. RESULTS: No improvement in memory function was detected on the Behavioural Memory Test or Subjective Memory Questionnaire. There was an increase in the number of memory aids reported as being used after attending the group (p less than 0.05). The number of items reported on the Subjective Memory Questionnaire as 'bothering' the patient decreased in frequency (p less than 0.05) after group treatment. CONCLUSIONS: Attendance at a memory group increased the use of memory aids but did not affect memory impairment.

Adult↗

Smell your way back to childhood: autobiographical odor memory.

This study addressed age distributions and experiential qualities of autobiographical memories evoked by different sensory cues. Ninety-three older adults were presented with one of three cue types (word, picture, or odor) and were asked to relate any autobiographical event for the given cue. The main aims were to explore whether (1) the age distribution of olfactory-evoked memories differs from memories cued by words and pictures and (2) the experiential qualities of the evoked memories vary over the different cues. The results showed that autobiographical memories triggered by olfactory information were older than memories associated with verbal and visual information. Specifically, most odor-cued memories were located to the first decade of life (<10 years), whereas memories associated with verbal and visual cues peaked in early adulthood (11-20 years). Also, odor-evoked memories were associated with stronger feelings of being brought back in time and had been thought of less often than memories evoked by verbal and visual information. This pattern of findings suggests that odor-evoked memories may be different from other memory experiences.

Age Factors↗

Protracted protection to Plasmodium berghei malaria is linked to functionally and phenotypically heterogeneous liver memory CD8+ T cells.

We previously demonstrated that protection induced by radiation-attenuated (gamma) Plasmodium berghei sporozoites is linked to MHC class I-restricted CD8(+) T cells specific for exoerythrocytic-stage Ags, and that activated intrahepatic memory CD8(+) T cells are associated with protracted protection. In this study, we further investigated intrahepatic memory CD8(+) T cells to elucidate mechanisms required for their maintenance. Using phenotypic markers indicative of activation (CD44, CD45RB), migration (CD62L), and IFN-gamma production, we identified two subsets of intrahepatic memory CD8(+) T cells: the CD44(high)CD45RB(low)CD62L(low)CD122(low) phenotype, representing the dominant effector memory set, and the CD44(high)CD45RB(high)CD62L(low/high)CD122(high) phenotype, representing the central memory set. Only the effector memory CD8(+) T cells responded swiftly to sporozoite challenge by producing sustained IFN-gamma; the central memory T cells responded with delay, and the IFN-gamma reactivity was short-lived. In addition, the subsets of liver memory CD8(+) T cells segregated according to the expression of CD122 (IL-15R) in that only the central memory CD8(+) T cells were CD122(high), whereas the effector memory CD8(+) T cells were CD122(low). Moreover, the effector memory CD8(+) T cells declined as protection waned in mice treated with primaquine, a drug that interferes with the formation of liver-stage Ags. We propose that protracted protection induced by P. berghei radiation-attenuated sporozoites depends in part on a network of interactive liver memory CD8(+) T cell subsets, each representing a different phase of activation or differentiation, and the balance of which is profoundly affected by the repository of liver-stage Ag and IL-15.

Animals↗

Discrete event modeling of CD4+ memory T cell generation.

Studies of memory T cell differentiation are hampered by a lack of quantitative models to test hypotheses in silico before in vivo experimentation. We created a stochastic computer model of CD4+ memory T cell generation that can simulate and track 10(1)-10(8) individual lymphocytes over time. Parameters for the model were derived from experimental data using naive human CD4+ T cells stimulated in vitro. Using discrete event computer simulation, we identified two key variables that heavily influence effector burst size and the persistent memory pool size: the cell cycle dependent probability of apoptosis, and the postactivation mitosis at which memory T cells emerge. Multiple simulations were performed and varying critical parameters permitted estimates of how sensitive the model was to changes in all of the model parameters. We then compared two hypotheses of CD4+ memory T cell generation: maturation from activated naive to effector to memory cells (model I) vs direct progression from activated naive to memory cells (model II). We find that direct progression of naive to memory T cells does not explain published measurements of the memory cell mass unless postactivation expansion of the memory cell cohort occurs. We conclude that current models suggesting direct progression of activated naive cells to the persistent memory phenotype (model II) do not account for the experimentally measured size of the postactivation CD4+, Ag-specific, memory T cell cohort.

Apoptosis↗

Memory sources associated with REM and NREM dream reports throughout the night: a new look at the data.

The data from three previously published studies on the memory sources of dreams, representing nine different moments of awakening throughout the night, are re-examined. In the original studies, elicited reports were recorded and segmented online into thematic units. The segmented reports were played back to Ss who were asked to identify memory sources or to associate to each segment. Memory sources were classified as episodic, semantic, or abstract self-references. In the meta-analysis and re-analyses reported here, the mean percentages of episodic memory sources are plotted separately for NREM and REM awakenings throughout the night. Within stages, neither NREM nor REM mean percentages differ significantly from each other, whereas between stages the mean percentage of episodic memory sources is significantly greater for NREM than for REM. Even when the correlation between report length and sleep stage is controlled by computing memory source density, the stage effect throughout the night persists for episodic memory sources. The relatively flat episodic memory curves for both NREM and REM indicate a rather constant recruitment of episodic memory sources throughout the night. No stage effect was found for strictly semantic memory sources. When semantic memory was defined generically, however, to include all non-spatio-temporal, "unmarked," information of self as well as of world, significantly more generic semantic memory sources derived from REM than from NREM reports, though not when corrected for the length of dream reports.

Brain↗

Ethanol-induced impairments in spatial working memory are not due to deficits in learning.

BACKGROUND: Acute ethanol administration impairs spatial reference memory and spatial working memory. However, the experimental designs previously used to test spatial working memory fail to make a distinction between the acquisition, or learning, of spatial information and the retention of this information. This study demonstrates that acute ethanol administration impairs spatial working memory, by using a novel experimental design that eliminates the confound between the learning of new spatial information and the testing of this information. METHODS: Long-Evans male rats received three forced trials to the same place for food reward on an elevated radial arm maze. Subjects were then given six free-choice trials in the first acquisition session, followed by a 30-min consolidation period before an additional six free-choice trials were administered-the retention session. Animals were trained to a criterion of five of six correct in both the acquisition and retention over 2 consecutive days. Once criteria were obtained, subjects received either saline or one of three ethanol doses immediately after the acquisition session to investigate whether ethanol alters retention of the learned spatial information. RESULTS: Acute ethanol administration impaired spatial working memory. Rats tested under saline and low-dose ethanol (1.0 g/kg) made significantly more place choices than rats tested under moderate- or high-dose ethanol (1.5 and 2.0 g/kg, respectively). Ethanol produced a temporary impairment in that no significant differences were found when subjects were retrained and retested 24 hr after initial testing. CONCLUSIONS: These results demonstrate that acute ethanol administration impairs spatial working memory and that such a deficit is not contingent on a learning impairment. These results support earlier findings that acute ethanol administration impairs spatial working memory but provide a significant advance by validating a novel training procedure that allows for direct investigation of working memory. Ethanol's impairment of both spatial working memory and spatial reference memory strengthens the similarities between memory impairments due to ethanol administration and memory impairments due to hippocampal lesions.

Animals↗

[Amnesic presentations of the compulsive obsessional confusions (about 3 patients appearing in a consultation of memory)].

Disorders or complaints of memory are a frequent cause of consultation in depression, major anxiety and psychiatry disease with personality disorders. We report 3 patients with obsessive compulsive disorder (OCD), without diagnosis and treatment, examined in a specialized memory consultation. They always had OCD with cognitive checking. Diagnosis of transient global amnesia and temporal complex seizure were discussed in 2 cases. Psychometric impairment only was observed in first free recall of a verbal memory task and was no specific. Behavioural during testing seemed to be very important to analyse. First, a 49-year-old man consulted because he had stereotyped transient amnesia lasted one minute, 2 or 3 times a week, since 6 months. He was a teacher. Transient amnesia always occurred during lessons. Suddenly he didn't know where he was or what he was speaking about. Episodes lasted one minute. After them, he had no confusion and no difficulty in concentration but intense anxiety. In an another hand, when he was in his car, after lessons, he could forget where he was during some minutes. CT scan and EEG were normal. Neuropsychological tests only objectived impairment in first free recall of Grober and Buschke's words. Patient explained that he could not prevent to check responses. He told us checking obsessive compulsive disorder during since long time ago. We discussed clear differences which existed between seizure and ruminations or preoccupations. Secondly, a 55-year-old woman was afraid of her memory performances. She was medical secretary and had no problem in her work but she would like a memory consultation to reassure herself. She was neither depressed nor anxious. She presented curious production in fluency task. She had to produce as many animals's names as possible: she could say 35 names which was an excellent performance but only in alphabetic order! Neuropsychological tests objectived impairment in her first free recall of Grober and Buschke's words. She tried in her first free recall to remember words in alphabetic order. She explained how she was bound to range everything in alphabetic order! She had a lot of rituals. She thought that she had an obsessive compulsive disorder but never consulted about this. The observation illustrated suspiscions about memory operations which could be observed in patients group with obsessive compulsive disorders. Finally, a 62-year-old man told us that he had presented a transient global amnesia during 4 hours. He had an important appointment and was upset about that. He didn't go to it and wandered in his flat. He always asked the same questions and forgot everything. He had no neurological deficit. He was anxious, sad and cried several times. He perfectly remembered the episod and thought that he had a panic attack! Verbal memory tests only objectived difficulties in his first free recall of Grober and Buschke words as the two others patients. He had a story of obsessive compulsive disorder with checking and rituals. In this observation, we discussed clear differences which existed between panic attacks and global transient amnesia. We analyzed patterns of neuropsychological performances which illustrated clinical features of obsessive compulsive disorder. These three patients impaired in their first free recall of verbal memory task. It is not a specific result. We observed during psychometric evaluation, strategic processing which impaired episodic memory: patients tried to check their performances. Memory complaints only were observed in checking obsessive compulsive disorder. It is a difficulty or a doubt about memory capacities. Difficulties could be due to particular cognitive processes who pertubate normal memory capacities.

Female↗

Self-reported memory symptoms with coronary artery disease: a prospective study of CABG patients and nonsurgical controls.

OBJECTIVE: Subjective memory complaints are common after coronary artery bypass grafting (CABG), but previous studies have concluded that such symptoms are more closely associated with depressed mood than objective cognitive dysfunction. We compared the incidence of self-reported memory symptoms at 3 and 12 months after CABG with that of a control group of patients with comparable risk factors for coronary artery disease but without surgery. METHODS: Patients undergoing CABG (n = 140) and a demographically similar nonsurgical control group with coronary artery disease (n = 92) were followed prospectively at 3 and 12 months. At each follow-up time, participants were asked about changes since the previous evaluation in areas of memory, calculations, reading, and personality. A Functional Status Questionnaire (FSQ) and self-report measure of symptoms of depression (CES-D) were also completed. RESULTS: The frequency of self-reported changes in memory, personality, and reading at 3 months was significantly higher among CABG patients than among nonsurgical controls. By contrast, there were no differences in the frequency of self-reported symptoms relating to calculations or overall rating of functional status. After adjustment for a measure of depression (CES-D rating score), the risk for self-reported memory changes remained nearly 5 times higher among the CABG patients than among control subjects. The relative risk of developing new self-reported memory symptoms between 3 and 12 months was 2.5 times higher among CABG patients than among nonsurgical controls (CI 1.24-5.02), and the overall prevalence of memory symptoms at 12 months was also higher among CABG patients (39%) than controls (14%). CONCLUSIONS: The frequency of self-reported memory symptoms 3 and 12 months after baseline is significantly higher among CABG patients than control patients with comparable risk factors for coronary and cerebrovascular disease. These differences could not be accounted for by symptoms of depression. The self-reported cognitive symptoms appear to be relatively specific for memory and may reflect aspects of memory functioning that are not captured by traditional measures of new verbal learning and memory. The etiology of these self-reported memory symptoms remains unclear, but our findings, as well as those of others, may implicate factors other than cardiopulmonary bypass itself.

Aged↗

Consolidation-like effects in flashbulb memories: evidence from September 11, 2001.

After September 11, 2001, we distributed flashbulb memory questionnaires at 5 different dates: within 48 hr (T1) and at 1 week (T2), 1 month (T3), 3 months (T4), and 1 year (T5). We scored responses for self-reported memory (veracity unverified), memory accuracy (recollection-matched T1 response), and memory consistency (recollection-matched prior responses other than T1). Self-reported memory and subjective confidence remained near ceiling, although the accuracy declined. However, memories given a week or more after September 11 were consistent throughout. We hypothesize that flashbulb memories follow a consolidation-like process: Some details learned later are incorporated into the initial memory, and many others are discarded. After this process, memories stabilize. Therefore, the best predictor of flashbulb memories at long intervals is not the memory as initially reported but memories reported a week or more after the event.

Adolescent↗

[The neurobiology of sleep and its influence on memory].

OBJECTIVE: Recent developments in neuroscience have increased our knowledge of the physiology of sleep and dreaming, and thus the number of studies about the influence of sleep on learning and memory have increased rapidly. In this review the objective is to assess the relationship between sleep and memory considering the evidence regarding the neurobiology of sleep and dreaming. METHOD: This is a retrospective literature review and the relevant studies from the last 10 years are included. For this purpose the PubMed search engine and the key words "sleep, neurobiology, synaptic plasticity, memory" were used. RESULTS: Sleep-wake and NREM-REM cycles are accompanied by neuromodulatory influences on forebrain structures that affect behavior, consciousness and cognition. Animal and human studies in which learning paradigms are used to assess the influence of sleep deprivation on memory show the influence of sleep on memory consolidation. Different sleep stages have different effects on memory processes. Some investigators claim that NREM improves declarative memory while REM improves procedural and implicit memory. Other investigators suggest that NREM and REM affect memory in a complementary and sequential way. Molecular and electrophysiological evidence suggests that the influence of sleep on memory is through synaptic plasticity. CONCLUSION: Studies about the physiology of sleep and dreaming will help us to understand consciousness and memory better. The reverse is also true: understanding the contribution of sleep stages to memory will help us to determine the advantages of sleep and dreaming in an evolutionary perspective.

Humans↗

Can bispectral index or auditory evoked potential index predict implicit memory during propofol-induced sedation?

BACKGROUND: Some patients still suffer from implicit memory of intraoperative events under adequate depth of anaesthesia. The elimination of implicit memory should be a necessary aim of clinical general anaesthesia. However, implicit memory cannot be tested during anaesthesia yet. We propose bispectral index (BIS) and auditory evoked potential index (AEPI), as predictors of implicit memory during anaesthesia. METHODS: Thirty-six patients were equally divided into 3 groups according to the Observer's Assessment of Alertness/Sedation Score: A, level 3; B, level 2; and C, level 1. Every patient was given the first auditory stimulus before sedation. Then every patient received the second auditory stimulus after the target level of sedation had been reached. BIS and AEPI were monitored before and after the second auditory stimulus presentation. Four hours later, the inclusion test and exclusion test were performed on the ward using process dissociation procedure and the scores of implicit memory estimated. RESULTS: In groups A and B but not C, implicit memory estimates were statistically greater than zero (P < 0.05). The implicit memory scores in group A did not differ significantly from those in group B (P > 0.05). Implicit memory scores correlated with BIS and AEPI (P < 0.01). The area under ROC curve is BIS > AEPI. The 95% cutoff points of BIS and AEPI for predicting implicit memory are 47 and 28, respectively. CONCLUSIONS: Implicit memory does not disappear until the depth of sedation increases to level 1 of OAA/S score. Implicit memory scores correlate well with BIS and AEPI during sedation. BIS is a better index for predicting implicit memory than AEPI during propofol induced sedation.

Adolescent↗

[Memory, aging and Alzheimer's disease].

Memory disorders in elderly can be related to various conditions. The concept of "Age-Associated Memory Impairement" is grounded on a age-related memory deficit in memory testing associated with a memory complaint which is considered as the subjective manifestation of the memory deficit. Actually, memory deficit in objective testing and memory complaints do not appear correlated. Impairment in memory performance is mostly related to neurobiologic brain changes associated with aging or Alzheimer's disease. Conversely, memory complaints are more related to psychosocial factors. However, clinical data and qualitative analysis of the memory disturbances are requested to understand the precise significance of memory deficits in objective testing.

Adult↗

Memory functioning in Lyme borreliosis.

BACKGROUND: To objectively measure memory functioning in patients with Lyme borreliosis and examine the relationship between subjective reports of memory dysfunction and actual impairment. METHOD: A prospective pretreatment study of patients with Lyme borreliosis (N = 21), a patient control group (osteomyelitis, N = 21), and healthy controls (N = 21) was conducted by using tests of verbal memory functioning (California Verbal Learning Test) and self-reported depression (Beck Depression Inventory-Cognitive Index), fatigue (Fatigue Severity Scale), and subjective ratings of memory abilities (Self-Rating Scale of Memory Functions). RESULTS: Patients with Lyme borreliosis performed worse than healthy controls on verbal memory testing, but did not perform significantly differently from patient controls. Lyme borreliosis patients reported increased fatigue, which was correlated with poorer memory performance. Although the Lyme borreliosis patients rated their memory as more impaired, subjective complaints were not correlated with objective memory scores. CONCLUSION: These findings suggest impaired memory performance is not specific to Lyme borreliosis and may be a result of evaluating cognitive functioning in patients with physical illness and somatic complaints. Fatigue is a prominent presenting complaint in patients with Lyme borreliosis and needs to be controlled for since it is known to influence neuropsychological performance. Subjective complaints are not correlated with objective memory assessment, so self-report of memory impairment should not be the criterion for inclusion in studies investigating cognitive manifestations of Lyme borreliosis.

Adult↗

[Memory: clinico-pathologic data].

Synaptic modifications are probably the basis of the memory processes that take place in the central nervous system. They have been studied in Aplysia or in hippocampal slices. How these minute alterations of the synaptic strength are integrated in larger neural systems is still poorly understood. In man, hippocampal lesions, when bilateral, cause a deficit in anterograde episodic memory. The loss of previously acquired memories (retrograde amnesia) is limited. Procedural memory is spared. Young patients with hippocampal lesions remain able to learn how to read or to write (abilities that belong to semantic memories). Recordings obtained with intracerebral electrodes have shown that some neurons of the hippocampus act as "place cells". They fire when the animal is in a specific place of the experimental maze, an observation that suggests that the hippocampus acts as a map that may also be viewed as a context indicator (a "cognitive map"). Computer models have been devised to test the hypothesis that the hippocampus recorded the map of the activated synapses at a particular moment in time. This pattern of activity could secondarily be transferred to the isocortex during a process known as consolidation. The frontal lobe plays a role in attention, which greatly influences the memory process. It also plays a role in the various strategies that are used to recall a memory and in the analysis of the quality of the recall (metamemory). An asymmetry has been shown by the PET-scan: the left frontal lobe is activated during acquisition, and the right one during recall. The ability to integrate one's own memories in one's own history and consciousness (self-awareness or "autonoesis") also depends on the activity of the prefrontal region. The loss of acquired memories (retrograde amnesia) is most often observed in cases of large lesions of the anterior part of the temporal lobe. Partial amnesias are difficult to separate from possibly localized deficits of a cognitive function (some types of aphasia may be considered as an amnesia of words). Subcortical amnesias are caused by diencephalic lesions; the topography of the critical structures is still discussed: mamillary bodies and mamillo-thalamic tract or dorsomedial nucleus of the thalamus. The amygdaloid nucleus, the frontal lobe and the dorsomedial nucleus of the thalamus belong to a network of connections that could be involved in emotions. It could be responsible for the emotional flavor of a memory. Basal ganglia could play a role in procedural memory, but experimental or clinicopathological confirmations are still scarce. Finally, the involvement of the cholinergic innervation in the memory processes has been discussed: it could be direct, or according to more recent data, related to its role in attention.

Amnesia↗