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PubMed2005

Essential hypotension is accompanied by deficits in attention and working memory.

In the present study, the authors investigated the relationship between low blood pressure (BP) and attentional performance through the application of a multidimensional diagnostic approach. The authors compared 40 subjects with essential hypotension (mean systolic BP = 97.6 mmHg) with 40 normotensive controls (mean systolic BP = 124.1 mmHg) using 6 computer-based tasks measuring tonic and phasic alertness; selective, divided, and sustained attention; and working memory. To control for possible confounders, the authors used a test battery examining motor performance and a mood questionnaire. BP was monitored continuously during the entire experiment. Hypotensives showed prolonged execution times in each of the attentional tasks (p < .001). Moderately decreased accuracy was found in the tests assessing sustained attention (p = .059) and working memory (p = .012). Moreover hypotensives showed smaller elevations in BP during the execution of the cognitive tasks. This study is the first to demonstrate the relationship between BP and cognitive performance while controlling for motor function and mood.

Adult↗
PubMed2004

The neural mechanisms of object working memory: what is where in the infant brain?

The question of how representational capacities develop in humans has been engaging cognitive psychologists for decades. Looking time studies have explored when infants start to show signs of perceiving and remembering the properties of specific objects at specific locations. Here we integrate these findings into the neuroscientific framework of human visual working memory. We suggest that the development of a system involving the temporal cortex, thalamic and hippocampal structures and possibly the dorsolateral prefrontal cortex (later in development) can account for these behavioral results. Our explanation differs from most of the current approaches in developmental science as we put less emphasis on the contribution of lateral prefrontal areas. We discuss shortcomings of the theories that propose a functional subdivision of these areas and their difficulty in accounting for results from monkey lesion and infant studies. We believe that this shift in focus is desirable both in light of what recent results on medial temporal lobe processing reveal about object working memory, and given how well these results fit the behavioral developmental data.

Animals↗
PubMed2003

Dissociable neural mechanisms underlying response-based and familiarity-based conflict in working memory.

Cognitive control requires the resolution of interference among competing and potentially conflicting representations. Such conflict can emerge at different points between stimulus input and response generation, with the net effect being that of compromising performance. The goal of this article was to dissociate the neural mechanisms underlying different sources of conflict to elucidate the architecture of the neural systems that implement cognitive control. By using functional magnetic resonance imaging and a verbal working memory task (item recognition), we examined brain activity related to two kinds of conflict with comparable behavioral consequences. In a trial of our item-recognition task, participants saw four letters, followed by a retention interval, and a probe letter that did or did not match one of the letters held in working memory (positive probe and negative probe, respectively). On some trials, conflict arose solely because of the current negative probe having a high familiarity, due to its membership in the immediately preceding trial's target set. On other trials, additional conflict arose because of the current negative probe having also been a positive probe on the immediately preceding trial, producing response-level conflict. Consistent with previous work, conflict due to high familiarity was associated with left prefrontal activation, but not with anterior cingulate activation. The response-conflict condition, when compared with high-familiarity conflict trials, was associated with anterior cingulate cortex activation, but with no additional left prefrontal activation. This double dissociation points to differing contributions of specific cortical areas to cognitive control, which are based on the source of conflict.

Conflict, Psychological↗
PubMed2003

Working memory and relational reasoning in Klinefelter syndrome.

Klinefelter syndrome (KS) is a sex chromosome abnormality associated with male infertility and mild cognitive deficits. Individuals with KS have been reported to have impaired verbal ability, as well as deficits in executive function. To further understand the nature of their deficits, we assessed specific elements of frontal lobe function such as working memory and relational reasoning. Men with KS exhibited a deficit in a transitive inference task in which participants ordered a set of names based on a list of propositions about the relative heights of the people named. This deficit was present even for items in which the propositions were given in order, so a chaining strategy could be used. Men with KS are also impaired on the n-back task, which uses letters as stimuli. In contrast, these men performed as well as controls in nonverbal reasoning (Raven's Progressive Matrices). These results suggest that men with KS have intact nonverbal reasoning abilities, but that a difficulty in encoding verbal information into working memory may underlie their executive and linguistic impairments.

Adult↗
PubMed2004

Effect of relaxation on working memory and the Bispectral Index of the EEG.

Beneficial effects of relaxation on cardiovascular and immune functions and on memory has been implied but an empirical relationship between task performance and anxiety reduction has not been reported. In this study, we investigated whether guided imagery of relatively short duration would decrease S-Anxiety and electroencephalogram Bispectral Index and improve working memory. 42 participants (age: M=39, SD=11, 14 men, 28 women, university students and VA Medical Center employees, recruited by their professor or by fellow employees) underwent relaxation by 16-min. guided imagery or no treatment (control). Spielberger's State-Trait Anxiety Inventory and the WAIS-III Letter-Number Sequencing Test were administered before and after relaxation. S-Anxiety and BIS Index decreased and the Letter-Number test score increased by 30% after relaxation but not in the control group. This score was higher for participants with low anxiety and BIS Index. There was no significant difference between the groups before treatment. The results suggest that guided imagery of short duration produces relaxation as measured by psychological and neurophysiological indices and improves working memory performance.

Adolescent↗
PubMed2004

Is the unilateral lesion of the left substantia nigra pars compacta sufficient to induce working memory impairment in rats?

Adult male Wistar rats with a substantia nigra pars compacta (SNc) lesion induced by intranigral administration of 1 micromol 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were used as a model of early phase Parkinson's disease (PD). This lesion caused a partial depletion of striatal dopamine (DA). The animals were submitted to a spatial working memory version of the water maze task in which they had to find a hidden (submersed) platform using online-maintained information that the platform remains in the same place during four consecutive trials, but that it is moved to another place every training day. Left, but not right SNc-lesioned rats were impaired in finding the platform in the second trial. This result suggests that the left SNc plays a key role in spatial working memory. Control experiments ruled out the possibility that motor impairment, sensory neglect, and/or impairment in the mental representation of the contralateral spatial environment had affected performance of the SNc-lesioned rats.

Analysis of Variance↗
PubMed1998

Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia.

Functional magnetic resonance imaging (fMRI) is a potential paradigm shift in psychiatric neuroimaging. The technique provides individual, rather than group-averaged, functional neuroimaging data, but subtle methodological confounds represent unique challenges for psychiatric research. As an exemplar of the unique potential and problems of fMRI, we present a study of 10 inpatients with schizophrenia and 10 controls performing a novel "n back" working memory (WM) task. We emphasize two key design steps: (1) the use of an internal activation standard (i.e., a physiological control region) to address activation validity, and (2) the assessment of signal stability to control for "activation" artifacts arising from unequal signal variance across groups. In the initial analysis, all but one of the patients failed to activate dorsolateral prefrontal cortex (DLPFC) during the working memory task. However, some patients (and one control) also tended to show sparse control region activation in spite of normal motor performance, a result that raises doubts about the validity of the initial analysis and concerns about unequal subject motion. Subjects were then matched for signal variance (voxel stability), producing a subset of six patients and six controls. In this comparison, the internal activation standard (i.e., motor activation) was similar in both groups, and five of six patients, including two whom were neuroleptic-naive, failed to activate DLPFC. In addition, a tendency for overactivation of parietal cortex was seen. These results illustrate some of the promise and pitfalls of fMRI. Although fMRI generates individual brain maps, a specialized survey of the data is necessary to avoid spurious or unreliable findings, related to artifacts such as motion, which are likely to be frequent in psychiatric patients.

Adult↗
PubMed2006

Working memory deficits in transgenic rats overexpressing human adenosine A2A receptors in the brain.

Adenosine receptors in the central nervous system have been implicated in the modulation of different behavioural patterns and cognitive functions although the specific role of A(2A) receptor (A(2A)R) subtype in learning and memory is still unclear. In the present work we establish a novel transgenic rat strain, TGR(NSEhA2A), overexpressing adenosine A(2A)Rs mainly in the cerebral cortex, the hippocampal formation, and the cerebellum. Thereafter, we explore the relevance of this A(2A)Rs overexpression for learning and memory function. Animals were behaviourally assessed in several learning and memory tasks (6-arms radial tunnel maze, T-maze, object recognition, and several Morris water maze paradigms) and other tests for spontaneous motor activity (open field, hexagonal tunnel maze) and anxiety (plus maze) as modification of these behaviours may interfere with the assessment of cognitive function. Neither motor performance and emotional/anxious-like behaviours were altered by overexpression of A(2A)Rs. TGR(NSEhA2A) showed normal hippocampal-dependent learning of spatial reference memory. However, they presented working memory deficits as detected by performance of constant errors in the blind arms of the 6 arm radial tunnel maze, reduced recognition of a novel object and a lack of learning improvement over four trials on the same day which was not observed over consecutive days in a repeated acquisition paradigm in the Morris water maze. Given the interdependence between adenosinic and dopaminergic function, the present results render the novel TGR(NSEhA2A) as a putative animal model for the working memory deficits and cognitive disruptions related to overstimulation of cortical A(2A)Rs or to dopaminergic prefrontal dysfunction as seen in schizophrenic or Parkinson's disease patients.

Analysis of Variance↗
PubMed2004

Task analysis complements neuroimaging: an example from working memory research.

When functional neuroimaging researchers draw conclusions about the sensory, cognitive, or motor processes that are associated with changes in brain activity, they are making assumptions about the component processes involved in performing a complex behavioral task. We demonstrate the danger in making such assumptions using, as an example, the n-back task, which has been widely used in neuroimaging studies of working memory. Neuroimaging researchers have assumed that the letter n-back task only engages processes involved in the short-term maintenance and manipulation of verbal information. We report three behavioral experiments demonstrating that the letter n-back task additionally recruits spatial processes. A fourth experiment suggested that the location n-back task may recruit verbal processes in addition to spatial processes. These results call into question conclusions that have been drawn about the neural basis of working memory. More broadly, our results demonstrate that task analysis is a vital partner of neuroimaging in the cognitive neuroscience enterprise.

Acoustic Stimulation↗
PubMed2003

Symbolic control of visual attention: The role of working memory and attentional control settings.

This study examined how 1 symbol is selected to control the allocation of attention when several symbols appear in the visual field. In Experiments 1-3, the critical target feature was color, and it was found that uninformative central arrows that matched the color of the target were selected and produced unintentional shifts of attention (i.e., involuntary, initiated slowly, producing long-lasting facilitatory effects). Experiment 4 tested whether such selection is the result of an attentional filter or of a competition bias due to a match of incoming information against integrated object representations stored in working memory. Here, the critical feature was shape and color was irrelevant, but matching color arrows were still selected. Thus, features of objects in working memory will bias the selection of symbols in the visual field, and such selected symbols are capable of producing unintentional shifts of attention. ((c) 2003 APA, all rights reserved)

Adult↗
PubMed2002

Reading, syntactic, orthographic, and working memory skills of bilingual Arabic-English speaking Canadian children.

This study assessed the reading, language, and memory skills of 56 bilingual Arab-Canadian children age's 9-14. English was their main instructional language, and Arabic was the language spoken at home. All children attended a Heritage Language Program in Toronto where they were taught to read and write Arabic. The children were administered word and pseudo-word reading, language, and working memory tests in English and Arabic. The majority of the children showed at least adequate proficiency in both languages. There was a significant relationship between the acquisition of word and pseudo-word reading working memory, and syntactic awareness skills in the two languages. The poor readers in Arabic had lower scores on all linguistic tasks, except the visual task. There were no significant differences between bilingual English Arabic children and monolingual English-speaking children on the reading, language, and memory tasks. However, bilingual English Arabic children who had reading problems in English had higher scores on English pseudo-word reading and spelling tasks than monolingual English-speaking children with reading disabilities, probably because of positive transfer from the regular nature of Arabic orthography. In this case, bilingualism does not appear to have negative consequences for the development of language reading skills in both languages--Arabic and English--despite the different nature of the two orthographies.

Adolescent↗
PubMed2001

Saccadic hypometria in drug-naive and drug-treated schizophrenic patients: a working memory deficit?

In certain conditions patients with schizophrenia make markedly smaller (hypometric) saccades than controls. This hypometria has been thought to reflect dopaminergic blockade as a result of antipsychotic medication. We tested this hypothesis by comparing the performance of an antipsychotic-naïve group and an antipsychotic-treated group of first-episode schizophrenic patients on a predictive saccade paradigm. We explored the possibility that hypometria reflects a spatial working memory deficit by correlating performance on neuropsychological tests of mnemonic function with saccadic accuracy. Both the drug-naïve and treated schizophrenic patients made hypometric saccades when compared with a group of matched controls. Primary saccade amplitude also correlated significantly with performance on some of the neuropsychological tests. These results are discussed in terms of the roles of cortical dopamine and working memory deficits in schizophrenic patients.

Adult↗
PubMed1997

Independent coding of target distance and direction in visuo-spatial working memory.

The organization of manual reaching movements suggests considerable independence in the initial programming with respect to the direction and the distance of the intended movement. It was hypothesized that short-term memory for a visually-presented location within reaching space, in the absence of other allocentric reference points, might also be represented in a motoric code, showing similar independence in the encoding of direction and distance. This hypothesis was tested in two experiments, using adult human subjects who were required to remember the location of a briefly presented luminous spot. Stimuli were presented in the dark, thus providing purely egocentric spatial information. After the specified delay, subjects were instructed to point to the remembered location. In Exp. 1, temporal decay of location memory was studied, over a range of 4-30 s. The results showed that (a) memory for both the direction and the distance of the visual target location declined over time, at about the same rate for both parameters; however, (b) errors of distance were much greater in the left than in the right hemispace, whereas direction errors showed no such effect; (c) the distance and direction errors were essentially uncorrelated, at all delays. These findings suggest independent representation of these two parameters in working memory. In Exp. 2 the subjects were required to remember the locations of two visual stimuli presented sequentially, one after the other. Only after both stimuli had been presented did the subject receive a signal from the experimenter as to which one was to be pointed to. The results showed that the encoding of a second location selectively interfered with memory for the direction but not for the distance of the to-be-remembered target location. As in Exp. 1, direction and distance errors were again uncorrelated. The results of both experiments indicate that memory for egocentrically-specified visual locations can encode the direction and distance of the target independently. Use of motor-related representation in spatial working memory is thus strongly suggested. The findings are discussed in the context of multiple representations of space in visuo-spatial short-term memory.

Adult↗
PubMed1986

Control of eye movements by working memory load.

During steady keying at a text processor touch typists scan copy and display in a repetitive way. Within a single cycle a certain text string is read from the copy by the subject and subsequently the remaining time is used to check the typed keys on the display. This behavioral pattern allows to analyse the input-output relationship between read characters and typed keys with respect to the storage characteristics of the working memory. In order to achieve a continuous transcription process the reading time is negatively correlated with the checking time. This allows to investigate the amount of information stored during the reading time and the chunking strategies. On the basis of model simulations evidence is provided that working memory load is not determined by a fixed capacity limit but by an increasing probability that the reading process is interrupted at the next word delimiter.

Eye Movements↗
PubMed2003

Multiple-object working memory--a model for behavioral performance.

In a psychophysics experiment, monkeys were shown a sequence of two to eight images, randomly chosen out of a set of 16, each image followed by a delay interval, the last image in the sequence being a repetition of any (one) of the images shown in the sequence. The monkeys learned to recognize the repetition of an image. The performance level was studied as a function of the number of images separating cue (image that will be repeated) from match for different sequence lengths, as well as at fixed cue-match separation versus length of sequence. These experimental results are interpreted as features of multi-item working memory in the framework of a recurrent neural network. It is shown that a model network can sustain multi-item working memory. Fluctuations due to the finite size of the network, together with a single extra ingredient, related to expectation of reward, account for the dependence of the performance on the cue-position, as well as for the dependence of performance on sequence length for fixed cue-match separation.

Animals↗
PubMed1992

Galanin in the medial septal area impairs working memory.

Galanin, a peptide of 29 amino acids, is co-localized with acetylcholine in a subpopulation of neurons of the medial septal area (MSA) that project to the hippocampus. Galanin reverses the actions of acetylcholine in several biochemical and behavioral procedures, and may be involved in memory processes. To test the possibility that galanin acts on the cell bodies of MSA neurons, two measures of septohippocampal function were assessed following intra-septal microinfusion of galanin or two synthetic fragments of galanin (1-16 and 21-29). The behavioral measure was choice accuracy in a working memory task in a T-maze. The electrophysiological measure was hippocampal theta activity recorded from the dentate hilus. The galanin fragment, 1-16, and the complete peptide, 1-29, decreased choice accuracy and decreased hippocampal theta activity in a dose-dependent fashion. Saline and the 21-29 fragment had no effect on choice accuracy and hippocampal theta. Sensorimotor performance was unaffected. These findings demonstrate that galanin impairs working memory when administered directly into the MSA and suggest that galanin inhibits MSA neural activity.

Animals↗
PubMed2002

Effects of repeated treatment with amphetamine or phencyclidine on working memory in the rat.

Repeated exposure to psychomotor stimulants produces long-lasting molecular, cellular and locomotor behavioral changes. Such changes are likely to contribute to the development of drug addiction and psychosis. It is not clear whether these durable changes are accompanied by lasting changes in cognition. We examined the long-term effects of repeated treatment with phencyclidine (PCP) or amphetamine on working memory, using a discrete, paired-trials, delayed-alternation task sensitive to the acute effects of PCP and amphetamine, and to the integrity of the prefrontal cortex. Twice daily treatment with PCP (5.0 mg/kg) or amphetamine (2.5 mg/kg) for 5 days did not produce lasting, significant impairments in alternation performance in comparison to either pre-treatment baseline performance or to the vehicle-treated group. Subsequent challenge doses of PCP (1, 3 and 5 mg/kg) produced alternation deficits in vehicle, PCP, and amphetamine pre-treated groups that were dependent on dose, but not on pre-treatment regimen. However, rats pre-treated with PCP showed a trend towards sensitization in response to PCP challenge. The present data suggest that psychostimulant treatment regimens that are reported to produce long-lasting changes in neural morphology and locomotor behavior may not produce equally durable changes in working memory.

Amphetamine↗
PubMed2003

Spike-driven synaptic dynamics generating working memory states.

The collective behavior of a network, modeling a cortical module of spiking neurons connected by plastic synapses is studied. A detailed spike-driven synaptic dynamics is simulated in a large network of spiking neurons, implementing the full double dynamics of neurons and synapses. The repeated presentation of a set of external stimuli is shown to structure the network to the point of sustaining working memory (selective delay activity). When the synaptic dynamics is analyzed as a function of pre- and postsynaptic spike rates in functionally defined populations, it reveals a novel variation of the Hebbian plasticity paradigm: in any functional set of synapses between pairs of neurons (e.g., stimulated-stimulated, stimulated-delay, stimulated-spontaneous), there is a finite probability of potentiation as well as of depression. This leads to a saturation of potentiation or depression at the level of the ratio of the two probabilities. When one of the two probabilities is very high relative to the other, the familiar Hebbian mechanism is recovered. But where correlated working memory is formed, it prevents overlearning. Constraints relevant to the stability of the acquired synaptic structure and the regimes of global activity allowing for structuring are expressed in terms of the parameters describing the single-synapse dynamics. The synaptic dynamics is discussed in the light of experiments observing precise spike timing effects and related issues of biological plausibility.

Action Potentials↗