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PubMed2006

Beta 1-integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory.

Integrins comprise a large family of cell adhesion receptors that mediate diverse biological events through cell-cell and cell-extracellular matrix interactions. Recent studies have shown that several integrins are localized to synapses with suggested roles in synaptic plasticity and memory formation. We generated a postnatal forebrain and excitatory neuron-specific knock-out of beta1-integrin in the mouse. Electrophysiological studies demonstrated that these mutants have impaired synaptic transmission through AMPA receptors and diminished NMDA receptor-dependent long-term potentiation. Despite the impairment in hippocampal synaptic transmission, the mutants displayed normal hippocampal-dependent spatial and contextual memory but were impaired in a hippocampal-dependent, nonmatching-to-place working memory task. These phenotypes parallel those observed in animals carrying knock-outs of the GluR1 (glutamate receptor subunit 1) subunit of the AMPA receptor. These observations suggest a new function of beta1-integrins as regulators of synaptic glutamate receptor function and working memory.

Animals↗
PubMed1996

Examination of the working memory components in normal aging and in dementia of the Alzheimer type.

The verbal and attentional components of working memory were examined in patients with Alzheimer's disease, normal elderlies, and young controls. Patients with Alzheimer's disease, showed a reduced span but were sensitive to word length. This is indicative of a functional rehearsal procedure. However, the effect of phonological similarity on immediate recall was smaller in patients with Alzheimer's disease and these patients showed a depressed performance in tasks of phonological analysis. There was also a significant decrement in a task that assessed the attentional component of working memory. Examination of individual patterns of performance showed that the phonological deficiency was severe in a subgroup of patients while the attentional deficit was more general.

Adolescent↗
PubMed2005

Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans.

Functional abnormalities in muscarinic and nicotinic receptors are associated with a number of disorders including Alzheimer's disease and schizophrenia. While the contribution of muscarinic receptors in modulating cognition is well established in humans, the effects of nicotinic receptors and the interactions and possible synergistic effects between muscarinic and nicotinic receptors have not been well characterized in humans. The current study examined the effects of selective and simultaneous muscarinic and nicotinic receptor antagonism on a range of cognitive processes. The study was a double-blind, placebo-controlled, repeated measures design in which 12 healthy, young volunteers completed cognitive testing under four acute treatment conditions: placebo (P); mecamylamine (15 mg) (M); scopolamine (0.4 mg i.m.) (S); mecamylamine (15 mg)/scopolamine (0.4 mg i.m.) (MS). Muscarinic receptor antagonism with scopolamine resulted in deficits in working memory, declarative memory, sustained visual attention and psychomotor speed. Nicotinic antagonism with mecamylamine had no effect on any of the cognitive processes examined. Simultaneous antagonism of both muscarinic and nicotinic receptors with mecamylamine and scopolamine impaired all cognitive processes impaired by scopolamine and produced greater deficits than either muscarinic or nicotinic blockade alone, particularly on working memory, visual attention and psychomotor speed. These findings suggest that muscarinic and nicotinic receptors may interact functionally to have synergistic effects particularly on working memory and attention and suggests that therapeutic strategies targeting both receptor systems may be useful in improving selective cognitive processes in a number of disorders.

Adult↗
PubMed2005

Neural substrates for verbal working memory in deaf signers: fMRI study and lesion case report.

The nature of the representations maintained in verbal working memory is a topic of debate. Some authors argue for a modality-dependent code, tied to particular sensory or motor systems. Others argue for a modality-neutral code. Sign language affords a unique perspective because it factors out the effects of modality. In an fMRI experiment, deaf participants viewed and covertly rehearsed strings of non-sense signs; analyses focused on regions responsive in both sensory and rehearsal phases. Compared with previous findings in hearing subjects, deaf subjects showed a significantly increased involvement of parietal regions. A lesion case study indicates that this network is left-dominant. The findings support the hypothesis that linguistic working memory is supported by modality-specific neural systems, but some modality-neutral systems may also be involved.

Brain Mapping↗
PubMed2006

Assessment of working memory in children with attention-deficit/hyperactivity disorder.

OBJECTIVE: This research investigated the cognitive abilities and the working memory in children and youngsters with three different types of attention-deficit/hyperactivity disorder (ADHD): (a) mainly with attention-deficit, (b) hyperactive and impulsive, and (c) combined. METHOD: A computerized test called Infant Cognitive Abilities Test, which measures five cognitive abilities based on the Cattell-Horn-Carroll model, was used. Thirty-two children from both sexes, aged 7 to 15 years, from the Hospital das Clínicas, suffering from ADHD and a control group with 30 children from a state elementary school (first through eighth grades) were submitted to the test. RESULTS: The results showed that there were significant differences with regard to the reaction time of the working memory of the different types of ADHD. CONCLUSION: Children suffering from ADHD had high test scores for the visual memory items of the test, when compared with the results in the auditory memory items.

Adolescent↗
PubMedDate not supplied

Adult age differences in the storage of information in working memory.

The performance of 97 young and 91 old persons were compared to determine if a deficiency in working memory resources for processing, storage, or allocation could be detected. Persons simultaneously performed a storage and one of two processing tasks while instructed to allocate resources to processing, storage, or both tasks. The storage task involved remembering the names of one, three, or five persons. Processing tasks involved solving addition problems presented on flashcards or answering common knowledge questions. Results showed increased age differences on the storage task as demands for resources increased but no differences on processing tasks. Individuals seemed unable to allocate resources as instructed. A comparison of young-old and old-old groups showed the same results as those obtained comparing young and old groups and support the hypothesis of a deficiency of storage, but not processing, resources in working memory for old, especially old-old, adults.

Adolescent↗
PubMed2006

Involvement of hippocampal extracellular signal-regulated kinase 1/2 in spatial working memory in rats.

The role of the phosphorylation of hippocampal extracellular signal-regulated kinase 1/2 in spatial working memory in rats was assessed with a delayed spatial win-shift task in a radial arm maze. The task consisted of two phases, a training phase and a test phase, separated by a delay. Phosphorylated extracellular signal-regulated kinase 1/2 levels were significantly and transiently increased in the hippocampus by 60 min, and then returned to the control levels 120 min after the training phase. Bilateral microinjections of the PD98059, an inhibitor of the extracellular signal-regulated kinase 1/2 kinase MEK, into the hippocampus impaired performance in the test phase of the delayed spatial win-shift task at 5-min delay. These results suggest that extracellular signal-regulated kinase 1/2 activation in the hippocampus plays a crucial role in spatial working memory.

Animals↗
PubMed2006

Exploring the temporal dynamics of the spatial working memory n-back task using steady state visual evoked potentials (SSVEP).

The neural networks associated with spatial working memory (SWM) are well established. However, the temporal dynamics of SWM-related brain activity are less clear. This study examined changes in temporal neurophysiology during the spatial n-back task using steady state probe topography (SSPT) to record cortical steady state visual evoked potentials (SSVEPs) at 64 scalp locations. Twenty healthy male volunteers participated in the study. The findings identified three different time periods of significance during the spatial n-back task--an early perceptual/encoding period (approximately 0-500 ms), an early delay period just following the stimulus disappearing from view (approximately 850-1400 ms), and a late period lasting the final second of the delay and anticipation of the new stimulus (approximately 2500-3500 ms). The delay period was associated with increases in frontal and occipital region amplitude, consistent with previous findings in more basic working memory tasks. The two different SSVEP components during the delay appear reflective of the additional "executive" demands associated with the n-back and may suggest variable roles for the PFC during different stages of the delay. All three n-back levels demonstrated a relative consistent electrophysiological profile, indicating that this pattern is specific to the spatial n-back task. Nevertheless, these findings supported the hypothesis that memory load modulates activity within the networks identified, consistent with previous neuroimaging studies. The current findings may offer a framework in which to further investigate the temporal aspects of SWM.

Adult↗
PubMed2006

Effect of clozapine on interval timing and working memory for time in the peak-interval procedure with gaps.

Previous research indicates that dopamine controls both the speed of an internal clock [Maricq, A.V., Church, R.M., 1983. The differential effects of haloperidol and methamphetamine on time estimation in the rat. Psychopharmacology 79, 10-15] and sharing of resources between the timer and other cognitive processes [Buhusi, C.V., 2003. Dopaminergic mechanisms of interval timing and attention. In: Meck, W.H. (Ed.), Functional and Neural Mechanisms of Interval Timing. CRC Press, Boca Raton, FL, pp. 317-338]. For example, dopamine agonist methamphetamine increases the speed of an internal clock and resets timing after a gap, while dopamine antagonist haloperidol decreases the speed of an internal clock and stops timing during a gap [Buhusi, C.V., Meck, W.H., 2002. Differential effects of methamphetamine and haloperidol on the control of an internal clock. Behav. Neurosci. 116, 291-297]. Using a 20-s peak-interval procedure with gaps we examined the acute effects of clozapine (2.0mg/kg i.p.), which exerts differential effects on dopamine and serotonin in the cortex and striatum, two brain areas involved in interval timing and working memory. Relative to saline, clozapine injections shifted the response functions leftward both in trials with and without gaps, suggesting that clozapine increased the speed of an internal clock and facilitated the maintenance of the pre-gap interval in working memory. These results suggest that clozapine exerts effects in different brain areas in a manner that allows for the pharmacological separation of clock speed and working memory as a function of peak trials without and with gaps.

Algorithms↗
PubMed1993

Ameliorative effects of the centrally active cholinesterase inhibitor, NIK-247, on impairment of working memory in rats.

Using a three-panel runway task, the effects of NIK-247 on impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia were investigated in rats; these effects were compared with those of the well-known cholinesterase inhibitors, tetrahydroaminoacridine (THA) and physostigmine. Intraperitoneal injection of scopolamine (0.56 mg/kg) significantly increased the number of errors (pushes made on the two incorrect panels of the three-panel gates located at four choice points). NIK-247 (3.2-18 mg/kg PO), THA (1-10 mg/kg PO), and physostigmine (0.1 and 0.32 mg/kg IP) dose-dependently reduced the increase in errors induced by scopolamine. NIK-247 (32 mg/kg) was also effective in reducing the increase in errors produced by lesions of the dorsal hippocampus. A 5-min period of cerebral ischemia markedly increased the number of errors. NIK-247 (3.2 and 10 mg/kg), given immediately after blood flow recirculation and again 20 min before the runway test carried out 24 h after ischemia, significantly reduced the increase in errors expected to occur after ischemia. Tetrahydroaminoacridine (3.2 mg/kg) and physostigmine (0.1 mg/kg) similarly reversed the increased errors in ischemic rats. These results suggest that NIK-247 alleviates the impairment of working memory produced by scopolamine, hippocampal lesions, and cerebral ischemia, possibly through activation of the central cholinergic system.

Acetylcholinesterase↗
PubMed2003

[WMN: a negative ERPs component related to working memory during non-target visual stimuli processing].

OBJECTIVE: To study non-target stimuli processing in the brain. METHOD: Features of the event-related potentials (ERPs) from non-target stimuli during selective response task (SR) was compared with that during visual selective discrimination (DR) task in 26 normal subjects. The stimuli consisted of two color LED flashes (red and green) appeared randomly in left (LVF) or right (RVF) visual field with same probability. ERPs were derived at 9 electrode sites on the scalp under 2 task conditions: a) SR, making switch response to the target (NT) stimuli from LVF or RVF in one direction and making no response to the non-target (NT) ones; b) DR, making switching response to T stimuli differentially, i.e., to the left for T from LVF and to the right for T from RVF. RESULT: 1) the non-target stimuli in DR conditions, compared with that in SR condition, elicited smaller P2 and P3 components and larger N2 component at the frontal brain areas; 2) a significant negative component, named as WMN (working memory negativity), appeared in the non-target ERPs during DR in the period of 100 to 700 ms post stimulation which was predominant at the frontal brain areas. CONCLUSION: According to the major difference between brain activities for non-target stimuli during SR and DR, the predominant appearance of WMN at the frontal brain areas demonstrated that the non-target stimulus processing was an active process and was related to working memory, i.e., the temporary elimination and the retrieval of the response mode which was stored in working memory.

Adolescent↗
PubMed2006

Effects of prenatal marijuana on visuospatial working memory: an fMRI study in young adults.

The long lasting neurophysiological effects of prenatal marijuana exposure on visuospatial working memory were investigated in 18-22 year olds using functional magnetic resonance imaging (fMRI). The participants are members of the Ottawa Prenatal Prospective Study (OPPS), a longitudinal study that provides a unique body of information collected from each participant over 20 years, including prenatal drug history, detailed cognitive/behavioral performance from infancy to young adulthood, and current and past drug usage. This information allowed for the control of potentially confounding drug exposure variables in the statistical analyses. Thirty-one offspring from the OPPS (16 prenatally exposed and 15 nonexposed) performed a visuospatial 2-back task while neural activity was imaged with fMRI. Cognitive performance data were also collected. No significant performance differences were observed when comparing controls versus exposed participants. Multiple regression analyses (including controls with no exposure) revealed that as the amount of prenatal marijuana exposure increased, there was significantly more neural activity in the left inferior and middle frontal gyri, left parahippocampal gyrus, left middle occipital gyrus and left cerebellum. There was also significantly less activity in right inferior and middle frontal gyri. These results suggest that prenatal marijuana exposure alters neural functioning during visuospatial working memory processing in young adulthood.

Adolescent↗
PubMed1988

A new method for studying working memory by using the three-panel runway apparatus in rats.

We designed a new method for studying working memory, by using a repeated acquisition procedure in the three-panel runway apparatus. This apparatus is composed of a start box, a goal box and four consecutive choice points; each choice point consists of three panel gates. Male Wistar rats were trained with 6 consecutive trials (one session) per day. Each trial was performed every two minutes. In this apparatus, rats could pass through only one gate (correct gate) among three panel gates in the direction of the goal box and were given 100 mg food pellets as the positive reinforcement. The sequence of correct gate position in each rat was changed everyday, but not in each session. Error responses (pushing the incorrect gate) were gradually reduced as training was repeated, and the learning was established within 16 training sessions to achieve criterion performance. Intraperitoneal scopolamine and intrahippocampal ethylcholine aziridinium ion (AF64A) produced increases in both the number of errors and the latency in a dose-dependent manner. The increase in errors induced by AF64A did not return to the control level, though the prolonged latency returned to normal. As a conclusion, this experimental procedure using the three-panel runway apparatus would be a useful method for studying working memory, and its memory deficit is involved at least in the dysfunction of the cholinergic system in the hippocampus.

Animals↗
PubMed2005

Dissociation, cognitive failures, and working memory.

The relationships between two personality measures (dissociation and cognitive failures) and different measures of interference from secondary tasks for working memory are investigated. Although the personality and cognitive measures were correlated with one another, canonical and bivariate correlations revealed no systematic relationships between the personality measures and the working memory measures. The upper bounds of the confidence intervals showed that, at most, only 10% of the variance was shared. We discuss the implications for theories of dissociation and cognitive functioning.

Attention↗
PubMed2003

Working memory retention systems: a state of activated long-term memory.

High temporal resolution event-related brain potential and electroencephalographic coherence studies of the neural substrate of short-term storage in working memory indicate that the sustained coactivation of both prefrontal cortex and the posterior cortical systems that participate in the initial perception and comprehension of the retained information are involved in its storage. These studies further show that short-term storage mechanisms involve an increase in neural synchrony between prefrontal cortex and posterior cortex and the enhanced activation of long-term memory representations of material held in short-term memory. This activation begins during the encoding/comprehension phase and evidently is prolonged into the retention phase by attentional drive from prefrontal cortex control systems. A parsimonious interpretation of these findings is that the long-term memory systems associated with the posterior cortical processors provide the necessary representational basis for working memory, with the property of short-term memory decay being primarily due to the posterior system. In this view, there is no reason to posit specialized neural systems whose functions are limited to those of short-term storage buffers. Prefrontal cortex provides the attentional pointer system for maintaining activation in the appropriate posterior processing systems. Short-term memory capacity and phenomena such as displacement of information in short-term memory are determined by limitations on the number of pointers that can be sustained by the prefrontal control systems.

Animals↗
PubMed2003

Chronometry of parietal and prefrontal activations in verbal working memory revealed by transcranial magnetic stimulation.

We explored the temporal dynamics of parietal and prefrontal cortex involvement in verbal working memory employing single-pulse transcranial magnetic stimulation (TMS). In six healthy volunteers the left or right inferior parietal and prefrontal cortex was stimulated with the aid of a frameless stereotactic system. TMS was applied at 10 different time points 140-500 ms into the delay period of a two-back verbal working memory task. A choice reaction task was used as a control task. Interference with task accuracy was induced by TMS earlier in the parietal cortex than in the prefrontal cortex and earlier over the right than the left hemisphere. This suggests a propagation of information flow from posterior to anterior cortical sites converging in the left prefrontal cortex. Significant interference with reaction time was observed after 180 ms with left prefrontal cortex stimulation. These effects were not observed in the control task, underlining the task specificity of our results. We propose that the interference with right-sided prefrontal cortex stimulation leads to impaired performance due to disturbed input into the left prefrontal cortex, whereas left-sided TMS interferes directly with the final information processing. Left- and right-sided brain areas might be involved in parallel processing of semantic and object features of the stimuli, respectively.

Adult↗
PubMed2004

Working memory, inhibition, and fluid intelligence as predictors of performance on Tower of Hanoi and London tasks.

The contributions of working memory, inhibition, and fluid intelligence to performance on the Tower of Hanoi (TOH) and Tower of London (TOL) were examined in 85 undergraduate participants. All three factors accounted for significant variance on the TOH, but only fluid intelligence accounted for significant variance on the TOL. When the contribution of fluid intelligence was accounted for, working memory and inhibition continued to account for significant variance on the TOH. These findings support argument that fluid intelligence contributes to executive functioning, but also show that the executive processes elicited by tasks vary according to task structure.

Adolescent↗
PubMed2005

Measures of working memory, sequence learning, and speech recognition in the elderly.

This study describes the measurement of 2 cognitive functions, working-memory capacity and sequence learning, in 2 groups of listeners: young adults with normal hearing and elderly adults with impaired hearing. The measurement of these 2 cognitive abilities with a unique, nonverbal technique capable of auditory, visual, and auditory-visual stimulation, patterned after the Simon memory game, is described. The use of simple, easily understood items in the test sequences enabled the measurement of these cognitive abilities in older listeners with no apparent impact of age-related hearing loss on the cognitive measures. Age-related cognitive deficits were observed for all 3 modes of stimulation and in both working-memory capacity and sequence-learning ability. The age-related deficits appeared to be greatest, however, for the sequence-learning task. Although it was hypothesized that there might be an association between an individual's performance on these cognitive tasks and his or her performance on various measures of speech recognition, such an association generally was not observed.

Adult↗