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PubMed1997

Effects of bromocriptine on human subjects depend on working memory capacity.

Pharmacological manipulation of brain dopamine concentration affects visuospatial working memory in humans and in animals, the latter effects localized to the prefrontal cortex. However, the effects of dopamine agonists on humans are poorly understood. We hypothesized that bromocriptine would have an effect on cognitive functions associated with the prefrontal cortex via its effects on cortical dopamine receptors and on subcortical receptors in areas that project to the neocortex. We found that the effect of bromocriptine on young normal subjects depended on the subjects' working memory capacity. High-capacity subjects performed more poorly on the drug, while low-capacity subjects improved. These results demonstrate an empirical link between a dopamine-mediated working memory system and higher cognitive function in humans.

Association Learning↗
PubMed2004

Changes in neuronal activation in patients with bipolar disorder during performance of a working memory task.

OBJECTIVES: Several lines of evidence suggest that deficits in cognition persist in bipolar patients during periods of euthymia. Working memory impairment has been observed in euthymic bipolar patients and noted to be a significant source of functional deficits in psychiatric disorders. Functional changes associated with these cognitive deficits however, remain poorly understood. We hypothesized that patients with bipolar disorder would demonstrate changes in neuronal activation in specific regions forming part of the working memory network. METHODS: Fifteen euthymic bipolar patients and fifteen age- and gender-matched healthy controls were recruited. Subjects participated in fMRI scans during which a two-back working memory task alternated with a zero-back control/attention task using a block-design paradigm. Groups were analyzed separately, and intergroup comparisons were made using an exploratory, voxel-by-voxel analysis. RESULTS: Bipolar patients performed more poorly on the cognitive tasks than did healthy controls (F = 3.77, p = 0.04). After covarying for task performance and reaction time, bipolar patients demonstrated significantly greater activation than healthy subjects in several regions including the fronto-polar prefrontal cortex, temporal cortex, basal ganglia, thalamus, and posterior parietal cortex. No areas showed a significant decrease in activation, compared with healthy controls. CONCLUSIONS: Our findings suggest that decreased working memory performance in bipolar patients reflects specific neurofunctional deficits. These deficits may represent primary areas of neuropathology or be secondary to neuropathology elsewhere in the working memory network. Continued research utilizing other imaging modalities may further clarify the underlying neuropathology involved in these cognitive deficits.

Adult↗
PubMed1997

The capacity of visual working memory for features and conjunctions.

Short-term memory storage can be divided into separate subsystems for verbal information and visual information, and recent studies have begun to delineate the neural substrates of these working-memory systems. Although the verbal storage system has been well characterized, the storage capacity of visual working memory has not yet been established for simple, suprathreshold features or for conjunctions of features. Here we demonstrate that it is possible to retain information about only four colours or orientations in visual working memory at one time. However, it is also possible to retain both the colour and the orientation of four objects, indicating that visual working memory stores integrated objects rather than individual features. Indeed, objects defined by a conjunction of four features can be retained in working memory just as well as single-feature objects, allowing sixteen individual features to be retained when distributed across four objects. Thus, the capacity of visual working memory must be understood in terms of integrated objects rather than individual features, which places significant constraints on cognitive and neurobiological models of the temporary storage of visual information.

Color Perception↗
PubMed1997

Working memory and the syndromes of schizotypal personality.

The aim of this study was to investigate dorsolateral prefrontal function, as assessed by a spatial working memory task, in relation to the syndromal features of schizotypal personality. We found a weak association between a self-report measure of schizotypy and the working memory performance. Those with a high score on the schizotypal personality questionnaire tended to make more errors on the spatial working memory task. One sub-scale of the schizotypal personality questionnaire that taps into social functioning was significantly correlated with working memory deficit. This result suggests the presence of subtle prefrontal deficit in a sub-group of psychometrically ascertained schizotypic individuals and renders support for the past reports of working memory deficit in schizophrenia and schizotypy.

Adult↗
PubMed1997

Working memory and children's mental addition.

Two experiments investigated the extent to which children's mental arithmetic is constrained by working memory rather than their arithmetical competence. A span procedure was used to measure the limit on English- and German-speaking children's ability to add together pairs of multidigit numbers. The children's ages ranged from 7 years 7 months to 11 years 5 months. Spans for mental addition were higher when the numbers to be added were visible throughout calculation than when they were not, consistent with a working memory constraint. Variation in addition span with children's age and with difficulty of the arithmetical operations approximated to a linear function of the speed of adding integers. A similar speed/span relationship has previously been observed for counting span, an artificial task designed to load working memory by combining separate processing and storage subtasks. We conclude that the natural task of mental addition, which combines processing and storage as intrinsic components, reflects working memory in a similar way. Results were remarkably similar both between cultures and across age groups, consistent with the notion of working memory as a general-purpose resource with dynamics that are indifferent to the detailed nature of operations.

Achievement↗
PubMed1993

Working-memory capacity as long-term memory activation: an individual-differences approach.

One explanation of the correlation often observed between working-memory span scores and reading comprehension is that individuals differ in level of activation available for long-term memory units. Two experiments used the fan manipulation to test this idea. In Experiment 1, high- and low-working-memory Ss learned a set of unrelated sentences varying in the number of shared concepts (fan) and then performed speeded recognition for those sentences. Low-working-memory Ss showed a larger increase in recognition time as fan increased. When the slope of the fan effect was partialed out of the relationship between working-memory span and verbal abilities, the relationship was reduced to nonsignificance. In Experiment 2, Ss learned thematically related sentences that varied in fan. Low-span Ss showed the positive fan effect typically found with thematically unrelated sentences, whereas high-span Ss showed a negative fan effect. The results are discussed in terms of a general capacity theory.

Adult↗
PubMed1982

Scopolamine does not disrupt spatial working memory in rats.

The importance of cholinergic systems for spatial working memory was examined by injecting scopolamine at varying times during a 5 hr-long retention interval imposed between the rat's fourth and fifth choices in an 8 arm maze. Regardless of whether or not the testing procedure required the rats to adopt a spatial solution for the task, scopolamine (1.0-5.0 mg/kg) did not impair retention in a manner that was suggestive of an effect on working memory. Modest deficits observed in some conditions appeared to result from drug effects on performance. Previous findings of impaired acquisition of accurate spatial behavior by scopolamine-treated rats evidently reflect an influence of the drug on physiological systems other than those necessary to maintain working memory for spatial information.

Animals↗
PubMed2005

Early, involuntary top-down guidance of attention from working memory.

Four experiments explored the interrelations between working memory, attention, and eye movements. Observers had to identify a tilted line amongst vertical distractors. Each line was surrounded by a colored shape that could be precued by a matching item held in memory. Relative to a neutral baseline, in which no shapes matched the memory item, search was more efficient when the memory cue matched the shape containing the target, and it was less efficient when the cued stimulus contained a distractor. Cuing affected the shortest reaction times and the first saccade in search. The effect occurred even when the memory cue was always invalid but not when the cue did not have to be held in memory. There was also no evidence for priming effects between consecutive trials. The results suggest that there can be early, involuntary top-down directing of attention to a stimulus matching the contents of working memory.

Adolescent↗
PubMed2005

Working memory and flexibility in awareness and attention.

We argue that attention and awareness form the basis of one type of working-memory storage. In contrast to models of working memory in which storage and retrieval occur effortlessly, we document that an attention-demanding goal conflict within a retrieval cue impairs recall from working memory. In a conceptual span task, semantic and color-name cues prompted recall of four consecutive words from a twelve-word list. The first-four, middle-four, and final-four words belonged to different semantic categories (e.g., body parts, animals, and tools) and were shown in different colors (e.g., red, blue, and green). In Experiment 1, the color of the cue matched that of cued items 75% of the time, and the rare mismatch impaired recall. In Experiment 2, though, the color of the cue matched that of the cued items only 25% of the time, and the now-more-frequent mismatches no longer mattered. These results are difficult to explain with passive storage alone and indicate that a processing difficulty impedes recall from working memory, presumably by distracting attention away from its storage function.

Attention↗
PubMed1996

Working memory capacity predicts language comprehension in schizophrenic patients.

The association between language comprehension and working memory capacity was evaluated in 25 male DSM-III-R schizophrenic patients (14 inpatients; 11 outpatients), and in 11 male normal controls (no lifetime DSM-III-R disorder). Patients and controls did not differ significantly on age and education. Language comprehension was examined as a function of two types of processing demand: grammatical complexity (complex versus simple sentences) and presentation rate (accelerated versus conversational). Schizophrenic patients showed significantly reduced language comprehension and decreased working memory capacity for language, compared with controls. Patients showed general difficulty in comprehending accurately, rather than exhibiting problems with specific grammatical structures. Subject groups were highly accurate and did not differ in their ability to perceive the individual words in sentences presented at the accelerated rate (intelligibility). Presentation rate and grammatical complexity affected comprehension accuracy in all groups, however, with increases in rate and complexity producing decreases in understanding. Of most importance, theoretically, is the finding that working memory capacity predicted language comprehension accuracy in both schizophrenic patients and normal controls. Results suggest that language comprehension deficits in schizophrenic patients may involve a general dysfunction that is associated with working memory capacity for language.

Adult↗
PubMed2006

A large-scale neurocomputational model of task-oriented behavior selection and working memory in prefrontal cortex.

The prefrontal cortex (PFC) is crucially involved in the executive component of working memory, representation of task state, and behavior selection. This article presents a large-scale computational model of the PFC and associated brain regions designed to investigate the mechanisms by which working memory and task state interact to select adaptive behaviors from a behavioral repertoire. The model consists of multiple brain regions containing neuronal populations with realistic physiological and anatomical properties, including extrastriate visual cortical regions, the inferotemporal cortex, the PFC, the striatum, and midbrain dopamine (DA) neurons. The onset of a delayed match-to-sample or delayed nonmatch-to-sample task triggers tonic DA release in the PFC causing a switch into a persistent, stimulus-insensitive dynamic state that promotes the maintenance of stimulus representations within prefrontal networks. Other modeled prefrontal and striatal units select cognitive acceptance or rejection behaviors according to which task is active and whether prefrontal working memory representations match the current stimulus. Working memory task performance and memory fields of prefrontal delay units are degraded by extreme elevation or depletion of tonic DA levels. Analyses of cellular and synaptic activity suggest that hyponormal DA levels result in increased prefrontal activation, whereas hypernormal DA levels lead to decreased activation. Our simulation results suggest a range of predictions for behavioral, single-cell, and neuroimaging response data under the proposed task set and under manipulations of DA concentration.

Action Potentials↗
PubMed2003

Individual variation in the spatial reference and working memory assessed under allothetic and idiothetic orientation cues in rat.

The present study was designed to examine which kind of memory: reference or working, better correlates with individual variation in rats' spatial learning abilities. To answer this question two groups of rats were trained to an arbitrary criterion in a partially baited 12-arm radial maze under two different experimental conditions: with or without allothetic cues. After 10 days break, rats were examined under the same conditions for memory retention. Within- and between-group variation in the length of training to criterion, and in the frequency of reference and working memory errors were analysed. The present experiment confirmed the facilitating effect of the presence of distal visual cues on place learning in rats. Task-dependent (between-group) differences in the rate of learning were attributed to differences in the frequency of reference memory errors. Conversely, within-group variation in the rate of task acquisition reflected individual variation in the frequency of working memory errors. These results were looked upon from an evolutionary perspective. Low correlation between reference and working memory errors confirms that these two types of memory have different mechanisms. The fact that differences in the rate of learning were not paralleled by the differences in the memory retention supports the notion that memory acquisition and memory retention are two independent processes.

Animals↗
PubMed2000

A 5-arm maze enables parallel measures of sustained visuo-spatial attention and spatial working memory in mice.

A 5-arm maze has been developed to provide parallel tests of sustained visuo-spatial attention and spatial working memory in mice. C57Bl/6 mice were trained to select, either by immediate response (attention) or by delayed-matching response (working memory), one target arm among the five open arms. For attention testing, mice were first trained to acquire the basic task in which one randomly selected baited arm remained lit until a choice was made. Criterion of >80% correct with a response latency <5 s was attained in 52-56 trials. Following this, attention was tested by using trials wherein light signal durations of 2, 1 or 0.5 s were intermixed to vary attentional load. In the working memory test, mice were submitted to a forced visit to a randomly selected baited arm during a presentation phase. Following a variable retention interval (R.I.), mice were replaced into the maze and rewarded for choosing this arm. Criterion of >80% correct was attained in 35-40 trials and mice exhibited high levels of retention for R.I.s up to 4 h. Results validate the 5-arm maze for evaluation of both sustained visuo-spatial attention and spatial working memory in mice. Both the tasks are rapidly acquired and the 20% chance level provides high resolution for evaluating performance. This comparative strategy allows to dissociate attention and memory and to reveal deficits in these processes during ageing or in knockout strains. The high level of retention performance over R.I.s of 4 h enables studies using pharmacological treatments differentially affecting the acquisition, encoding, retention or retrieval phases of working memory. Furthermore, functional brain imaging studies may be used to identify neuronal networks which are differentially activated during these distinct phases.

Animals↗
PubMed1993

Varieties of working memory as seen in biology and in connectionist/control architectures.

Biological and computational concepts that underlie the nature of working memory are briefly reviewed. The conceptualization of working memory has changed dramatically in the last 30 years. Current biological work has monitored several aspects of memory, including activation decay, sustained activation, long-term connection change, and differential structures for episodic (hippocampal formation) and procedural learning. Current connectionist modeling has identified factors including multiple-region-based processing, control processing as well as data storage, tradeoffs between fast- and slow-connection-change learning effects, and the speeding of acquisition via multiple levels of learning. The need to relate the biological, behavioral, and computational constraints into models of working memory is discussed. Finally, conceptualizations of working memory must acknowledge the need for human learning systems to be robust enough to operate in a dynamic world.

Attention↗
PubMed2004

The irrelevant speech effect and working memory load.

Irrelevant speech impairs the immediate serial recall of visually presented material. Previously, we have shown that the irrelevant speech effect (ISE) was associated with a relative decrease of regional blood flow in cortical regions subserving the verbal working memory, in particular the superior temporal cortex. In this extension of the previous study, the working memory load was increased and an increased activity as a response to irrelevant speech was noted in the dorsolateral prefrontal cortex. We suggest that the two studies together provide some basic insights as to the nature of the irrelevant speech effect. Firstly, no area in the brain can be ascribed as the single locus of the irrelevant speech effect. Instead, the functional neuroanatomical substrate to the effect can be characterized in terms of changes in networks of functionally interrelated areas. Secondly, the areas that are sensitive to the irrelevant speech effect are also generically activated by the verbal working memory task itself. Finally, the impact of irrelevant speech and related brain activity depends on working memory load as indicated by the differences between the present and the previous study. From a brain perspective, the irrelevant speech effect may represent a complex phenomenon that is a composite of several underlying mechanisms, which depending on the working memory load, include top-down inhibition as well as recruitment of compensatory support and control processes. We suggest that, in the low-load condition, a selection process by an inhibitory top-down modulation is sufficient, whereas in the high-load condition, at or above working memory span, auxiliary adaptive cognitive resources are recruited as compensation.

Adult↗
PubMed1998

Double dissociation of processing temporal and spatial information in working memory.

Based on the converging evidence supporting the view of domain specific object and spatial working memory processes, the question was addressed whether the property of domain specificity holds equally for temporal information. Using a selective interference paradigm the objective was to test a dissociation of the processing of temporal duration and spatial location information in working memory of intact human subjects. Subjects performed a temporal and a spatial memory task in which they were required to indicate whether the study and the test stimuli were the same or different in duration (temporal memory) or in location (spatial memory) as primary tasks. Both primary tasks were combined with three types of interference tasks, a spatial classification memory task, a temporal classification memory task and a non-interference baseline task--to be performed in-between the presentation of study and test stimuli. Memory for temporal duration was shown to be impaired by the temporal classification task but not by the spatial classification task; memory for spatial position showed the opposite pattern of impairment. These data thus provide evidence for the view that temporal and spatial working memory contents are subject to selective interference, reflecting a functional dissociation in the processing of temporal duration and spatial location information. The results are interpreted as evidence for the domain specificity in the processing of temporal information in working memory.

Adult↗
PubMed1995

Intrahippocampal administration of (+)-SKF 10,047, a sigma ligand, reverses MK-801-induced impairment of working memory in rats.

In order to clarify the roles of the hippocampal sigma site and phencyclidine (PCP) binding site on the NMDA receptor/channel complex in the regulation of working memory in rats, the effects of intrahippocampal administration of ligands for both binding sites on this behavior were examined with a three-panel runway task. MK-801, a potent noncompetitive NMDA antagonist with high affinity for the PCP site, significantly increased the number of working memory errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points), when injected bilaterally at 0.1 and 0.18 microgram/side into the dorsal hippocampus. However, intrahippocampal injection of (+)-SKF 10,047, a sigma ligand, at doses up to 1.0 microgram/side had no significant effect on the number of working memory errors. The working memory impairment induced by intrahippocampal MK-801 (0.18 microgram/side) was attenuated by concurrent injection of 1.0 microgram/side (+)-SKF 10,047, but not by that of 1.0 microgram/side (-)-SKF 10,047. These results suggest that activation of hippocampal sigma and PCP binding sites exerts antagonistic effects on working memory function, possibly through modulation of NMDA receptor-mediated glutamatergic neurotransmission.

Animals↗
PubMed2000

Test-retest reliability of the dot test of visuospatial working memory in patients with schizophrenia and controls.

To determine the test-retest reliability of the Dot Test of Visuospatial Working Memory, this task was administered to 29 patients with schizophrenia and 19 normal controls on two consecutive days. The test involved "copying" trials followed by "delay" recall trials. For "copying" trials, subjects saw a dot and then drew it on a blank sheet of paper. For "delay" trials, subjects drew the dot following a 10-, 20-, or 30-s delay. The distance between the stimulus and the drawn dot was measured for each trial. The composite score, termed "working memory deficit," is calculated by subtracting the average of the copying trials from the average of the delay trials. Pearson correlations revealed that overall performance in each group was comparable for days 1 and 2. Intra-class correlations of "working memory deficit" on days 1 and 2 were moderate in patients and controls, suggesting that task performance for each subject was similar on the testing days. Test-retest reliability tended to be higher for 10-s delay performance in patients and controls than for longer delay periods. Further analyses suggested that there was no significant learning effect on the task from day 1 to day 2 for either group on any measure. The Dot Test of Visuospatial Working Memory, especially the composite score, has moderate test-retest reliability and is a valuable tool that can be used to assess working memory functions in studies using a repeated-measures design.

Adult↗