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PubMed1997

Stability of spatial working memory across the estrous cycle of Long-Evans rats.

In the adult rat, hippocampal dendritic synaptic connectivity in region CA1 fluctuates across the estrous cycle. This study examined the potential functional impact of such fluctuations on spatial working memory in regularly cycling Long-Evans rats. Rats were trained in a delayed non-match-to-sample radial-arm maze task and performance was monitored across the estrous cycle. There were no significant alterations in the acquisition or performance of the working memory task across the estrous cycle, with 1- or 4-h delays imposed between training and testing sessions. However, rats performed the task significantly more slowly on proestrus than on any other estrous cycle day under both delay conditions. These results indicate that while working memory remains stable, sensorimotor or motivational aspects of the performance of this radial-arm maze task may vary across the estrous cycle.

Animals↗
PubMed2004

Impaired working memory for location but not for colour or shape in visual neglect: a comparison of parietal and non-parietal lesions.

Patients with spatial neglect due to right hemisphere pathology may show 'revisiting' behaviour during visual search and cancellation tasks, such that previously encountered targets are treated as if they are new discoveries. Revisiting behaviour is particularly evident when no visible trace is left to inform patients that a particular target has already been detected (Husain et al., 2001; Wojciulik et al., 2001), implying that spatial working memory may be impaired in neglect. To test whether working memory for location is selectively impaired relative to memory for colour and shape, we compared performances of right hemisphere neglect patients with parietal (n = 4) and non-parietal (n = 4) lesions on a change detection task. Patients were presented with a matrix containing four objects in different positions, and required to detect a change in the location, colour or shape of one of the objects following presentation of a brief visual mask. Parietal patients were selectively impaired in detecting location changes, regardless of the horizontal position of the object in the matrix, relative to colour and shape changes. This deficit of spatial working memory was not apparent for neglect patients with lesions that spared the parietal cortex. We conclude that the human parietal cortex is crucially involved in the updating and maintenance of spatial representations across saccades, and that neglect arising from parietal damage causes impairment in these re-mapping mechanisms.

Adult↗
PubMed2001

Steady state visually evoked potential (SSVEP) topography in a graded working memory task.

The steady state visually evoked potential (SSVEP) elicited by a diffuse 13-Hz visual flicker was recorded from 64 scalp sites in 30 subjects performing a low and high demand version of an object working memory task. During the perceptual component of the task, the SSVEP amplitude was reduced at left and right parieto-occipital sites. During the hold or memory component of the task, the SSVEP amplitude exhibited a load-dependent increase at frontal and occipito-parietal sites, while the SSVEP latency exhibited a load-dependent reduction at central and left frontal sites. We suggest that SSVEP amplitude changes index cortical information processing modes in that perceptual processes are associated with an SSVEP amplitude reduction, while holding information in active short-term or working memory is associated with an SSVEP amplitude increase. We also discuss changes in SSVEP amplitude and latency in terms of changes in the behavior of cortico-cortico and thalamo-cortico loops that utilize cortical layer I. Such cortico-cortico and thalamo-cortical loops are also proposed to constitute a neurophysiological mechanism for holding information in working memory.

Adult↗
PubMed2001

Neural correlates of attention and working memory deficits in HIV patients.

OBJECTIVES: To evaluate the neural correlates of attention and working memory deficits in patients with HIV-1. METHOD: fMRI was used to evaluate brain activity in 11 patients with HIV and 11 age-, sex-, education-, and handedness-matched seronegative subjects, while performing a battery of tasks that required different levels of attention for working memory. RESULTS: Patients with HIV showed greater brain activation (blood oxygenation level dependent signal changes) in some regions compared with control subjects while performing the same tasks. For the simpler tasks, patients with HIV showed greater activation in the parietal regions. However, with more difficult tasks, patients with HIV showed greater activation additionally in the frontal lobes. Reaction times during these tasks were slower but accuracy was similar in the patients with HIV compared with control subjects. CONCLUSION: Injury to the neural substrate caused by HIV infection may necessitate greater attentional modulation of the neural circuits, hence a greater use of the brain reserve; additional activation of the frontal lobes is required to perform the more complex tasks. The task-dependent increased frontal activation in patients with HIV suggests that the neural correlate of attentional deficits may be excessive attentional modulation as a result of frontostriatal brain injury.

AIDS Dementia Complex↗
PubMed2004

The neural bases of the effects of item-nonspecific proactive interference in working memory.

We reanalyzed the behavioral and fMRI data from seven previously published studies of working memory in order to assess the behavioral and neural effects of item-nonspecific proactive interference (PI; attributable to the accrual of antecedent information independent of the repetition of particular items). We hypothesized that item-nonspecific PI, implicated in age-related declines in working memory performance, is mediated by the same mechanism(s) that mediate item-specific PI (occurring when an invalid memory probe matches a memorandum from the previous trial). Reaction time increased across trials as a function of position within the block, a trend that reversed across the duration of each multiblock experiment. The fMRI analyses revealed sensitivity to item-nonspecific PI during the probe epoch in the left anterior inferior frontal gyrus and the left dorsolateral prefrontal cortex(PFC). They also revealed a negative trend, across trials, in the transient probe-evoked component of the global signal. A common PFC-based mechanism may mediate many forms of PI.

Adult↗
PubMed1989

Effects of adult age and working memory on reasoning and spatial abilities.

Three predictions were derived from the hypothesis that adult age differences in certain measures of cognitive functioning are attributable to age-related reductions in a processing resource such as working-memory capacity. Each prediction received at least some degree of empirical support in a study involving 120 males ranging between 20 and 79 years of age. First, older adults exhibited greater impairments of performance than did young adults when task complexity increased and more demands were placed on the limited processing resources; second, the magnitudes of these complexity effects were highly correlated across verbal (reasoning) and spatial (paper folding) tasks. Finally, statistical control of an index of a working-memory processing resource attenuated the effects of age on the measures of cognitive performance. It was concluded that further progress in understanding the mechanisms of the relation between age and cognitive functioning will require improved conceptualizations of the nature of working memory or other hypothesized mediating constructs.

Adult↗
PubMed2006

Evaluation of muscarinic and nicotinic receptor antagonists on attention and working memory.

Cholinergic receptor antagonists are commonly used to model attentional and mnemonic impairments associated with neuropsychiatric disorders such as Alzheimer's disease. However, few studies have systematically assessed the effects of these drugs following manipulations that affect attention or working memory within the same task. In the present experiment, rats were trained to discriminate visual signals from "blank" trials when no signal was presented. This task was modified to include retention intervals on some trials to tax working memory. During standard task performance, rats received systemic injections of the muscarinic receptor antagonist, scopolamine, or of the nicotinic receptor antagonist, mecamylamine. A second experiment tested the effects on this task of co-administering doses of scopolamine and mecamylamine that, when administered alone, did not significantly affect task performance. Scopolamine (0.3 and 1.0 mg/kg) decreased detection of 500 ms signals but did not affect accurate identification of non-signals. Scopolamine did not differentially affect performance across the retention interval. Elevated omission rates were associated with high doses of scopolamine or mecamylamine. Combination drug treatment was associated with decreased signal detection and elevated omission rates. Collectively, the data suggest that muscarinic and nicotinic receptor antagonists do not exclusively impair working memory.

Animals↗
PubMed2006

Executive function, working memory, and medication adherence among older adults.

The purpose of this study was to investigate the association between cognitive processes and medication adherence among community-dwelling older adults. Ninety-five participants (M = 78 years) completed a battery of cognitive assessments including measures of executive function, working memory, cued recall, and recognition memory. Medication adherence was examined over 8 weeks for one prescribed medicine by use of an electronic medication-monitoring cap. In a simultaneous regression, the composite of executive function and working memory tasks was the only significant predictor (beta =.44, p <.01). Findings suggest that assessments of executive function and working memory can be used to identify community-dwelling older adults who may be at risk for failure to take medicines as prescribed.

Aged↗
PubMed2006

Prefrontal modulation of working memory performance in brain injury and disease.

The inter-related cognitive constructs of working memory (WM) and processing speed are fundamental components to general intellectual functioning in humans. Importantly, both WM and processing speed are highly susceptible to disruption in cases of brain injury, neurologic illness, and even in normal aging. A goal of this article is to summarize and critique the functional imaging studies of speeded working memory in neurologically impaired populations. This review focuses specifically on the role of the lateral prefrontal cortex in mediating WM performance and integrates the relevant WM literature in healthy adults with the current findings in the clinical literature. One important finding emerging from a summary of this literature is the dissociable contributions made by ventrolateral and dorsolateral prefrontal cortex (VLPFC and DLPFC) in guiding performance on tasks of WM. Throughout this review, it is shown that when cerebral resources are challenged, it is DLPFC, and often right DLPFC specifically, that plays a critical role in modulating WM functioning. In addition, this article will examine the relationship between task performance and brain activation across studies to clarify the role of increased DLPFC activity in clinical samples. Finally, explanations are offered for the observed increased DLPFC activation and the potentially unique role of right DLPFC in mediating WM performance during periods of cerebral challenge.

Animals↗
PubMed2006

Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain.

Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met158 allele and the DAT 3' variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity (as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT 10-repeat allele have the most focused response, whereas the COMT Val and the DAT 9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.

Adult↗
PubMedDate not supplied

Inhibitory control of attention declines more than working memory during normal aging.

Changes in frontostriatal systems are believed to reduce the efficiency of executive cognitive functions during normal aging, especially the inhibitory control of attentional and behavioral responses. To characterize changes during normal aging in sensorimotor, working memory and inhibitory attentional systems, we tested 20 healthy elderly subjects (age 65-80) and 28 young adults (age 18-34) using oculomotor paradigms. Visually guided saccades of elderly subjects showed decreased peak velocity and increased reaction time, but not reduced accuracy, indicating selective age-related declines in sensorimotor systems. In an oculomotor working memory task, memory for spatial location information in elderly subjects was as accurate as in young adults. In contrast, elderly subjects demonstrated a significantly reduced ability to voluntarily inhibit eye movements toward flashed targets on an antisaccade task. These findings indicate changes in frontostriatal systems during normal aging that adversely affect volitional inhibitory processes but spare encoding and retrieval components of spatial working memory.

Adolescent↗
PubMed1998

The effects of MK-801 on spatial working memory and within-session spatial learning.

The present study investigated the effects of the NMDA channel blocker MK-801 (0.05, 0.10, and 0.15 mg/kg) on a task that allows for the assessment of both spatial working memory and within-session spatial learning. During the first trial of each day, subjects were shown the spatial location of a food reward on a six-arm radial-arm maze. During nine subsequent free-choice trials, subjects were reinforced for returning to that same spatial location. The location of the food reward varied across days. Thus, choosing correctly on any given trial required subjects to remember where food had been received during the previous trials of that day. The effects of MK-801 on working memory were assessed by analyzing the overall number of errors committed during the nine free-choice trials of each day. The effects of MK-801 on within-session learning were assessed by comparing the number of errors committed during the first three trials of each day to the number of errors committed during the last three trials of each day. Only the highest dose of MK-801 tested (0.15 mg/kg) impaired spatial working memory. No dose of MK-801 impaired the ability of subjects to acquire spatial information within a given session. The failure of MK-801 to impair within-session spatial learning stands in contrast to the well-known effects of MK-801 on spatial learning measured across days. Thus, when coupled with previous research, the findings of the present study further suggest that the NMDA receptor plays a role in the long-term, but not short-term, storage of spatial information.

Adaptation, Psychological↗
PubMed1990

Effects of increased processing demands on age differences in working memory.

Three studies investigated (a) the plausibility of the claim that increasing the processing demands in a memory task contributes to greater involvement of a central processor and (b) the effects of altering reliance on the central processor on the magnitude of age-related differences in working-memory tasks. In the first study, young adults performed versions of 2 tasks presumed to vary in the degree of reliance on the central processor. In the second and third studies, young and older adults performed versions of a computation-span task that were assumed to vary along a rough continuum of the amount of required processing. The results indicated that although a central processor appears to be involved when working-memory tasks require simultaneous storage and processing of information, age-related differences in working memory seem to be determined at least as much by differences in the capacity of storage as by differences in the efficiency of processing.

Adult↗
PubMed2004

Decline in working memory updating through ageing: intrusion error analyses.

The present research examines the decline in working memory updating through age. Two experiments compared groups of participants in different age ranges (young-old, 55-65 years, old, 66-75 years and old-old, more than 75 years and, in Experiment 2 only, young, 20-30 years). Memory updating tasks were administered, which required participants to remember the smallest items in each list. To perform the task correctly, participants had to update information efficiently, reducing interference from items no longer relevant. Intrusion errors were computed and in the first experiment these were described as "intrusions of irrelevant items" (immediate exclusion) and "intrusions of once relevant items" (delayed exclusion). The oldest adults performed worse in memory updating and made a greater number of intrusion errors of once relevant information. In the second experiment results showed that increases in memory load (number of items that had to be remembered) and updating demand (number of potentially relevant items) impaired performance. The oldest adults had greater difficulty when the task demand was increased. Furthermore, they produced a higher number of intrusion errors, particularly when the updating demand was increased. It therefore appears that elderly people have specific difficulty in updating information in working memory by excluding irrelevant information.

Adult↗
PubMed1998

Effects of cigarette smoking and 12-h abstention on working memory during a serial-probe recognition task.

Nicotine has been shown to affect attentional and mnemonic processes. However, whether these effects are due to changes in perceptual and/or motor aspects of the tasks is not at all clear. This study tested the hypothesis that nicotine from cigarette smoking has differential effects on perceptual and motor processes, as reflected by event-related potentials (ERPs) and reaction times (RTs), respectively, and that perceptual effects may be specific to changes in working memory. ERPs. RTs and performance accuracy were recorded from smokers and nonsmokers during a serial-probe recognition memory task in which lists of words or "memory sets" were followed by a probe word that was either in-set or out-of-set. Smokers were tested in a "smoking" and a 12-h "deprived" condition. Smoking-smokers and deprived-smokers exhibited fast RTs to in-set and out-of-set probes relative to a group of nonsmokers. They exhibited even faster RTs when the inset probe word matched the first or last item in the memory set. Thus, smokers as a group showed enhanced primacy and recency effects suggesting that smoking specifically facilitates processes related to the motor output aspects of working memory. Different effects characterized the electrophysiology. Larger P300s were recorded to in-set compared to out-of-set probes by both subject groups. Smoking smokers exhibited enhanced P300s to both types of probes. When smokers abstained for 12 h (deprived smokers), the differences in P300 amplitude were reduced but not eliminated. Smoking smokers exhibited faster P300 latencies to in-set probes, while deprived smokers showed delayed latencies relative to nonsmokers. Primacy and recency P300 effects characterized nonsmokers and deprived smokers. However, this relationship was reversed in the Smoking condition. These results support the hypotheses that nicotine has distinct effects on memory-related perceptual and motor aspects of working memory. The increase in efficiency of the memory search with nicotine is consistent with the functional role of the cholinergic system in maintaining a state "appropriate for efficient information processing."

Adolescent↗
PubMed1996

Working-memory load and dimensional complexity of the EEG.

This investigation shows that a working-memory load induced by a memory scanning task has an effect on nonlinear descriptors of the EEG dynamics. The effect was locally specific above the fronto-temporal (right) cortex and it may be described as a reduction in the dimensional complexity of cortical brain activity. The meaning of the effects seems to differ from that of EEG spectral power, which varied with time during the experiment and not with changes in the working-memory load conditions. Behaviorally controlled over- and underload led to increased variance of the dimensional complexity, thus indicating that dimensional complexity correlates more closely with actual performance than with more general descriptions of brain states. Habitual response speed had an effect at the parietal lead, thus indicating that fast responders reduced their dimensional complexity as the task demand increased. In contrast, the slower responders showed no such definite trend.

Adult↗
PubMed2005

Are the anterior negativities to grammatical violations indexing working memory?

Anterior negativities obtained when a grammatical rule is violated may reflect highly automatic first-pass parsing processes, the detection of a morphosyntactic mismatch, and/or the inability to assign the incoming word to the current phrase structure. However, for some theorists these negativities rather reflect some aspect of working memory processes. Event-related brain potentials (ERPs) obtained for word category and morphosyntactic violations were directly compared with effects obtained when working memory is particularly demanded (embedding subject- or object-relative clauses), yielding a significant dissociation in terms of topography. Even though, the anterior negativities for grammatical violations vanished when relative clauses were embedded, suggesting that the processes reflected by anterior negativities related to grammatical violations and those related to working memory manipulations, even if different, are placing demands on a common pool of limited resources.

Adolescent↗
PubMed1998

A model of visuospatial working memory in prefrontal cortex: recurrent network and cellular bistability.

We report a computer simulation of the visuospatial delayed-response experiments of Funahashi et al. (1989), using a firing-rate model that combines intrinsic cellular bistability with the recurrent local network architecture of the neocortex. In our model, the visuospatial working memory is stored in the form of a continuum of network activity profiles that coexist with a spontaneous activity state. These neuronal firing patterns provide a population code for the cue position in a graded manner. We show that neuronal persistent activity and tuning curves of delay-period activity (memory fields) can be generated by an excitatory feedback circuit and recurrent synaptic inhibition. However, if the memory fields are constructed solely by network mechanisms, noise may induce a random drift over time in the encoded cue position, so that the working memory storage becomes unreliable. Furthermore, a "distraction" stimulus presented during the delay period produces a systematic shift in the encoded cue position. We found that the working memory performance can be rendered robust against noise and distraction stimuli if single neurons are endowed with cellular bistability (presumably due to intrinsic ion channel mechanisms) that is conditional and realized only with sustained synaptic inputs from the recurrent network. We discuss how cellular bistability at the single cell level may be detected by analysis of spike trains recorded during delay-period activity and how local modulation of intrinsic cell properties and/or synaptic transmission can alter the memory fields of individual neurons in the prefrontal cortex.

Artifacts↗