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PubMed1997

Memory deficits in schizophrenia: inadequate assimilation or true amnesia? Findings from the Wechsler Memory Scale--revised.

Researchers disagree about why patients with schizophrenia perform poorly on memory tests. Some argue the presence of a fundamental memory deficit stemming from dysfunction in medial temporal lobe structures, principally the hippocampus. Others, stressing the contributions of impaired attention or executive failings such as a disorganized approach to learning, implicate larger neural networks. We compared data from psychometrically similar procedures, the Wechsler Memory Scale-Revised (WMS-R) and Wechsler Adult Intelligence Scale-Revised (WAIS-R), generated by 17 schizophrenia-spectrum patients and 33 psychiatric controls. We then compared our findings in detail with all published WMS-R/WAIS-R schizophrenia data. Our findings and the literature indicate that the acquisition of new information is disrupted in schizophrenia, but they provide little support for claims that memory deficits are especially pronounced relative to other weaknesses. Since schizophrenia patients exhibit reasonable retention following intervening activity, theories that place primary emphasis upon hippocampal dysfunction are not well supported.

Adult↗

PubMed1998

Event-related potentials of verbal encoding into episodic memory: dissociation between the effects of subsequent memory performance and distinctiveness.

Episodic memory encoding and distinctiveness detection were examined using event-related potentials (ERP) in a single-trial word list learning paradigm with free recall following distraction. To manipulate distinctiveness, encoding of high- and very low-frequency words was contrasted. Amplitudes of the N400 and late positive component (LPC) were larger for low- than for high-frequency words, and ERPs were more positive for subsequently recalled than not recalled words. This subsequent memory effect was dissociated from the correlates of distinctiveness by polarity for the N400 and by time course for the LPC and dissociable into two effects. The data suggest that the first subsequent memory effect, which occurred for both word categories, is more directly related to episodic memory formation, whereas the second effect, which occurred for high-frequency words only, is related to processes influencing episodic encoding success indirectly.

Adult↗

PubMed1998

Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters.

The effects of chronic estrogen treatment on radial arm maze performance and on levels of central monoaminergic and amino acid neurotransmitters were examined in ovariectomized (Ovx) rats. In an eight arms baited paradigm, choice accuracy was enhanced following 12 days but not 3 days of treatment. In addition, performance during acquisition of the eight arms baited maze task was better in estrogen-treated Ovx rats than in Ovx rats. Performance of treated rats was also enhanced in win-shift trials conducted 12 days postestrogen treatment. Working, reference, and working-reference memory was examined when four of the eight arms were baited, and only working memory was improved by estrogen and only after long-term treatment. Activity of Ovx rats on an open field, crossings and rearings, was increased at 5 but not at 35 days following estrogen treatment. In medial prefrontal cortex, levels of NE, DA, and 5-HT were decreased but glutamate and GABA levels were not affected following chronic estrogen treatment. Basal forebrain nuclei also showed changes in monoamines following estrogen. Hippocampal subfields showed no effects of estrogen treatment on monoaminergic or amino acid transmitters. Levels of GABA were increased in the vertical diagonal bands following chronic estrogen. Results show that estrogen enhances learning/memory on a task utilizing spatial memory. Effects in Ovx rats appear to require the chronic (several days) presence of estrogen. Changes in activity of both monoaminergic and amino acid transmitters in the frontal cortex and basal forebrain may contribute to enhancing effects of estrogen on learning/memory.

Animals↗

PubMed1981

Amnesia after transection of the fornix in monkeys: long-term memory impaired, short-term memory intact.

Monkeys in whom the fornix had been transected and controls were trained on two versions of delayed non-matching to sample (DNMS). On DNMS-LSS the stimulus pair for each trial was selected from a large set of junk objects so that the animals saw particular stimuli infrequently. On DNMS-RS the same two stimuli were presented repeatedly. Memory for the sample was assessed with retention intervals of 10, 70 and 130 sec spent either in the dark or with levels of illumination designed to promote interference effects. On DNMS-LSS the lesioned animals were impaired, being more susceptible than controls to increases in the retention interval. However, neither group was particularly sensitive to interference. In contrast, on DNMS-RS the lesioned monkeys were unimpaired, both groups showing a marked decrement in performance with increasing retention interval and a high sensitivity to the effects of interference. These data suggest that monkeys possess a short-term memory which is intact after transection of the fornix and a long-term memory which is not.

Animals↗

PubMed2004

Lack of the metabotropic glutamate receptor subtype 7 selectively impairs short-term working memory but not long-term memory.

Metabotropic glutamate receptors (mGluRs), and in particular the mGluR group III receptors (subtypes 4, 6, 7, 8) are known to play a role in synaptic plasticity and learning. Here, we report the effect of mGluR7 gene ablation in different learning paradigms. In the acoustic startle response (ASR), no differences were seen between knockout (KO) mice and wildtype (WT) littermates in parameters including prepulse inhibition and habituation. In an open field test, no differences were seen between genotypes in motor activity, exploratory behaviour, and fearful behaviour. In a T-maze reinforced alternation working memory (WM) task, again no difference was seen between groups. However, when increasing the demands on working-memory in a 4-arm and 8-arm maze task, KO mice committed more WM errors than WT littermates thereby uncovering a highly significant difference between the two groups that persisted every day for the whole 9 days of the experiment. In a 4-arm maze with 2 arms baited, KO and wildtype mice committed the same number of LTM errors, whereas KOs committed more WM errors. Altogether, these findings suggest that a lack of mGluR7 mainly impairs short-term working but not long-term memory performance while having no effect on sensorimotor processing, non-associative learning, motor activity and spatial orientation. The effects on WM are task-dependent and become apparent in more complex but not simple learning tasks. We discuss how mGluR7 could influence WM.

Animals↗

PubMed2003

N-methyl-D-aspartate receptor in working memory impairments in schizophrenia: event-related potential study of late stage of working memory process.

Working memory (WM) deficit in schizophrenic patients has been well established. Still, underlying biological substrate of the impairment is not clear. Among neurotransmitter hypotheses of schizophrenia, N-methyl-D-aspartate (NMDA) receptor model is mostly supported, considering that NMDA receptor antagonist can elicit both psychosis and cognitive impairment observed in schizophrenic patients. In current study, to test the neuropsychological and the electrophysiological effects of NMDA receptor in WM, event-related potentials (ERPs) of Sternberg's short-term memory scanning task (SMST) were analyzed in 10 healthy subjects under intravenous administration of a subanesthetic dose of ketamine (0.65 mg/kg/h) or placebo (normal saline). Late positive component (LPC) of ERP was hypothesized to reflect later stage of WM. Brief Psychiatric Rating Scale score was significantly increased (t=-5.75, df=9, P<.001) and correct response rate was significantly decreased (t=2.21, df=9, P=.054) after ketamine administration. Neither reaction time nor LPC latency, which reflect memory scanning time, was changed. Amplitude of LPC was significantly reduced after ketamine administration (z=-2.31, number of observations=120, P=.021). In conclusion, NMDA receptor antagonist administration elicited WM deficit both in behavioral and electrophysiological level. Electrophysiological component reflecting later stage of WM was impaired by NMDA antagonist.

Adult↗

PubMed2002

Modulation of working memory and of long- but not short-term memory by cholinergic mechanisms in the basolateral amygdala.

Male Wistar rats were exposed to one-trial step-down inhibitory avoidance training using a 0.5 mA footshock. Through bilaterally implanted indwelling cannulae, they received bilateral 0.5 microl infusions of saline, oxotremorine (0.06 or 0.3 microg) or scopolamine (0.25 or 2.0 microg) into the basolateral complex of the amygdaloid nucleus (BLA). Infusions were either 10 min before training (experiment 1) or 4 min after training (experiment 2). In experiment 1, the animals were tested three times: first for working memory (WM) 2 s after training, then for short-term memory (STM) 1.5 h later, and finally for long-term memory (LTM) 24 h later. Oxotremorine enhanced and scopolamine depressed WM and LTM while leaving STM unaffected. In experiment 2, the treatments were given after WM was presumably over. Again, oxotremorine again enhanced and scopolamine depressed LTM, and neither had any effect on STM. The results fit with the suggestion by Beninger and his co-workers that cholinergic synapses in the BLA regulate WM, generalize that finding to a different task, and show that this mechanism uses muscarinic receptors. In addition, they indicate that the well-known effects of intra-amygdala oxotremorine and scopolamine on LTM are independent of those that the drugs have on WM.

Amygdala↗

PubMed2005

Working memory maintenance contributes to long-term memory formation: neural and behavioral evidence.

Theories of human memory have led to conflicting views regarding the relationship between working memory (WM) maintenance and episodic long-term memory (LTM) formation. Here, we tested the prediction that WM maintenance operates in two stages, and that processing during the initial stage of WM maintenance promotes successful LTM formation. Results from a functional magnetic resonance imaging study showed that activity in the dorsolateral prefrontal cortex and hippocampus during the initial stage of WM maintenance was predictive of subsequent LTM performance. In a behavioral experiment, we demonstrated that interfering with processing during the initial stage of WM maintenance impaired LTM formation. These results demonstrate that processing during the initial stage of WM maintenance directly contributes to successful LTM formation, and that this effect is mediated by a network that includes the dorsolateral prefrontal cortex and the hippocampus.

Adult↗

PubMed2000

Impact of emotion on memory. Controlled study of the influence of emotionally charged material on declarative memory in Alzheimer's disease.

BACKGROUND: In an earlier study we showed that a powerful emotional experience (the Kobe earthquake) reinforced memory retention in patients with Alzheimer's disease, but we could not control factors other than the emotional impact of the earthquake. AIMS: To test our previous findings in a controlled experimental study. METHOD: Recall tests consisting of two short stories were administered to 34 patients with Alzheimer's disease and 10 normal subjects. The two stories were identical except for one passage in each story: one was emotionally charged (arousing story) and the other (neutral story) was not. RESULTS: In both groups, the emotionally charged passage in the arousing story was remembered better than the counterpart in the neutral story. In addition, the extent of the memory improvement was similar in the subjects and in the controls. CONCLUSIONS: The results provide further evidence that emotional arousal enhances declarative memory in patients with Alzheimer's disease, and give a clue to the management of people with dementia.

Aged↗

PubMed2000

Bedside evaluation of learning and memory: descriptive information on a shortened version of the Luria Memory Words Test.

Descriptive information on the shortened version of the Luria Memory Words Test (LMWT-SF), a serial word-learning list of seven items, administered across five trials with a three-minute delay, is presented. The purpose of the investigation was to determine what constituted adequate performance among nondemented elderly inpatients, and to compare the results to traditional bedside memory measures among elders diagnosed with dementia. Results revealed significant group differences on Trials 3, 4, 5, total learning score, and the delay trial among demented and non-demented geriatric inpatients. Sensitivity and specificity ratings for the LMWT-SF delay trial were 80% and 72%, respectively, at a cut-off of 3 / 4, and 71% and 60%, respectively, for the total learning score, at a cut-off of 26 / 27. While this measure cannot take the place of a comprehensive evaluation of memory and learning, LMWT-SF performance can suggest when a more comprehensive evaluation is required, and may provide value as a cost-effective screening tool.

Aged↗

PubMed1999

Hippocampus as a memory map: synaptic plasticity and memory encoding by hippocampal neurons.

Hippocampal cells contribute to memory by rapidly encoding information about the perceptual and behavioral structure of experience. This paper describes two complementary experimental approaches that illustrate two important mechanisms that confer these properties to hippocampal cells: (1) Enduring spatial memory and stable place fields each depend upon synaptic plasticity mechanisms that normally rely on the same NMDA-receptor mediated metabolic events as long-term potentiation (LTP). Thus, hippocampal cells "learn" to encode information about the perceptual and behavioral structure of experiences. (2) Hippocampal cells encode the structure of experience and respond in a manner inconsistent with a spatial representation. Place fields are distributed heterogeneously in space, their locations are determined by non-geometric information, the population of active cells can indicate more than one location in space, and hippocampal cells encode discriminative stimuli independent of their spatial location. To the extent that the hippocampus encodes a map, it is more simply described as a memory map than a spatial map. Rather than computing spatial locations, the space it encodes is better described as a life or a problem space that encodes the history of experience into the relational structure of episodes.

Animals↗

PubMed1980

Immune interferon secretion as an expression of immunological memory to transplantation antigens: in vivo generation of long-lived, recirculating memory cells.

Leukocytes from C57Bl/6 mice immunized against DBA/2 strain antigens by intraperitoneal injection of mastocytoma P 815 cells produced, when stimulated in the mixed leukocyte reaction assay with DBA/2 spleen cells, an earlier and more intense secretion of immune interferon than leukocytes from untreated mice. This secondary-type interferon response was independent of cell proliferation. The memory phenomenon was induced by long-lived, recirculating lymphocytes found in spleen, lymph nodes and thoracic duct, but not in the thymus. Memory cells could be recruited into inflammatory sites. They were shown to be specific for H-2 alloantigens, although some cross-reactivity with stimulating cells bearing unrelated H-2 antigens was observed. The possible anti-tumor, antiviral and immunoregulatory roles of this memory phenomenon, and its significance in transplantation immunity are discussed.

Animals↗

PubMed2003

Hippocampal damage equally impairs memory for single items and memory for conjunctions.

In a prior study of continuous recognition performance, data were reported in support of the hypothesis that the hippocampus is not needed to remember the individual components of a stimulus but is important for remembering associations between its components (Kroll et al. 1996. J Mem Lang 35:176-196). Patients with left hippocampal damage were able to endorse recently encountered words and to reject novel words, as well as disyllabic words in which one of the syllables had been previously encountered. However, they failed to reject words in which both syllables had been encountered independently in different words. We present data from five experiments designed to examine this finding in more detail. In each experiment, five patients with bilateral hippocampal damage and eight controls were tested using the same protocol as Kroll et al. (1996). On each trial, a two-component stimulus was presented. Stimuli could be entirely novel, novel with one previously encountered (repeated) component, novel but with both components repeated, or a true repetition. The first experiment was a direct replication using the same disyllabic words as Kroll et al. (1996). The second experiment used pseudo-words, constructed of two monosyllabic words (e.g., jambark). The third experiment used the same pairs of monosyllabic words, but presented separately on the screen to encourage participants to treat each component independently. The fourth experiment used pairs of objects, and the fifth experiment used face-house pairs. In all five experiments, patients with hippocampal damage exhibited impaired recognition memory. The impairment extended across all trial types with no evidence that hippocampal damage selectively (or disproportionately) impaired the associative or conjunctive component of memory. We discuss our findings in the light of the work by Kroll et al. (1996) and other recent neuropsychological, electrophysiological, and neuroimaging studies of hippocampal function and single-item and associative memory.

Adult↗

PubMed2001

Intact LTP and fear memory but impaired spatial memory in mice lacking Ca(v)2.3 (alpha(IE)) channel.

To investigate the functional roles of the Ca(v)2.3 (alpha(1E)) channel in hippocampal CA1 pyramidal neurons, we studied in vitro synaptic properties and in vivo behaviors of the Ca(v)2.3 gene deficient mice. The Ca(v)2.3 channel mRNA was identified in the hippocampal formation of the wild-type mouse by in situ hybridization. The basic excitatory synaptic transmission and long-term potentiation by theta-burst stimulation were intact in CA1 region of Ca(v)2.3-/- mice. We performed two forms of behavioral tests to examine the hippocampus-dependent function, i.e., emotional and spatial learning tests. The Ca(v)2.3-/- mice were able to establish and maintain fear memories. Although general improvement in the performance of Morris water maze test was seen in Ca(v)2.3-/- mice, they displayed an obvious impairment in the probe test. These results suggest that the Ca(v)2.3 channel plays some role in formation of the accurate spatial memory but not of the fear memory.

Animals↗

PubMed1993

Memory to antigenic challenge of the immune system: synergy of idiotypic interactions and memory B cells.

Memory to antigenic challenge of the immune system is described as a synergy of two components: cycles of interacting B cells in a dynamic equilibrium which store an internal image of an antigen, and long-lived memory B cells which stabilize the cycle that generates them. Small cycles are most relevant to the immune system's memory. The network is globally stable and supports Jerne's idea that suppression is important. Our model allows for exponential increase of antigens during the initial stage of infection. It has a number of stable fixed points, viz the virgin state, the healthy immunized state, and a state of chronic infection, the last occurring if the antigen is virulent enough. Numerical simulations show a difference between primary and secondary response and exhibit both predator-prey and intracycle oscillations. In the case of a chronic infection, the simulations suggest a specific stimulation therapy triggered by repeatedly injecting the antigens, thus making the infection acute. An optimal therapy is indicated.

Antigens↗

PubMed1991

Models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on memory, psychomotor performance and mood.

The effects on memory, psychomotor functions and mood of intramuscular scopolamine (0.3 mg, 0.6 mg) were compared with those of oral lorazepam (2 mg) and placebo. Thirty-six volunteers took part in a double-blind, independent groups design. Subjects completed a battery of tests 1 and 3 h after drug administration. Both doses of scopolamine produced levels of sedation comparable to that produced by lorazepam. The time course of effects of scopolamine and lorazepam differed but the pattern of psychomotor impairments and amnestic effects produced was very similar. In terms of mood, lorazepam had an anxiolytic effect whereas scopolamine increased ratings of anxiety. Levels of sedation, indexed by either subjective ratings or motor retardation (tapping speed), were related more to psychomotor performance than to performance on memory tasks. The results suggest that benzodiazepines and scopolamine have similar amnestic and sedative effects and as such may not offer distinct models of memory dysfunction.

Adult↗

PubMed2004

Methylphenidate restores visual memory, but not working memory function in attention deficit-hyperkinetic disorder.

RATIONALE: Dysfunction of executive neuropsychological performance, mediated by the prefrontal cortex, has been the central focus of recent attention deficit/ hyperkinetic disorder (AD-HKD) research. The role of other potential neuropsychological "risk factors", such as recognition memory, remains understudied. Further, the impact of methylphenidate (MPH) on key neuropsychological processes in AD-HKD remains poorly understood. OBJECTIVES: To compare the performance of boys with AD-HKD on a spatial working memory (SWM) task and on two non-working memory tasks [a simultaneous and delayed matching-to-sample task (DMtS) and a pattern-recognition task] with that of healthy boys, and to investigate the impact of acute and chronic MPH on performance of these tasks. METHODS: Baseline performance of 75 stimulant-naive boys with AD-HKD was compared with that of 70 healthy boys. The AD-HKD boys were then re-tested following the administration of acute and chronic challenges with MPH (0.3 mg/kg and 0.6 mg/kg) under randomised double-blind placebo controlled conditions. RESULTS: Compared with healthy boys, the AD-HKD boys demonstrated performance deficits on all neuropsychological tasks. A single dose of MPH restored performance on the DMtS task but had no impact on the SWM or pattern-recognition tasks. Chronic MPH administration did not alter performance on the SWM task but did improve performance on both the pattern-recognition and DMtS tasks. However, the acute restorative effect of MPH on DMtS diminished with repeated administration. CONCLUSIONS: Our results suggest that current conceptualisations of the neuropsychological basis of AD-HKD and the proposed therapeutic mechanisms of MPH require broadening.

Adolescent↗

PubMed1977

Marijuana and memory impairment: effect on free recall and recognition memory.

The effect of marijuana on memory was evaluated by presenting two groups of 17 male volunteers with lists of repeated or nonrepeated words following administration of a single marijuana cigarette containing 14 mg delta9-THC. An immediate free recall, final free recall and recognition memory test followed. Results indicated that marijuana significantly decreased immediate and final free recall but only slightly influenced recognition memory. Rate of acquisition on the repeated lists was the same for both groups. Long term retention of encoded information was not influenced by marijuana. The shape of the serial position curves departed slightly from those reported by other investigators in that some effects of the drug on the recency portion of the curve were noted. Both internal and external intrusions were elevated under marijuana.

Adult↗