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PubMed2003

A new electrophysiological index for working memory load in humans.

Working memory, the ability to store and simultaneously manipulate information, is affected in several neuropsychiatric disorders which lead to severe cognitive and functional deficits. An electrophysiological marker for this process could help identify early cerebral function abnormalities. In subjects performing working memory-specific n-back tasks, event-related potential analysis revealed a positive-negative waveform (PNwm) component modulated in amplitude by working memory load. It occurs in the expected time range for this process, 140-280 ms after stimulus onset, superimposed on the classical P200 and N200 components. Independent Component Analysis extracted two functional components with latencies and topographical scalp distributions similar to the PNwm. Our results imply that the PNwm represents a new electrophysiological index for working memory load in humans.

Adult↗
PubMed2005

Neurophysiological correlates of age-related changes in working memory capacity.

Cognitive abilities such as working memory (WM) capacity decrease with age. To determine the neurophysiological correlates of age-related reduction in working memory capacity, we studied 10 young subjects (<35 years of age; mean age=29) and twelve older subjects (>55 years of age; mean age=59) with whole brain blood oxygenation-level dependent (BOLD) fMRI on a 1.5 T GE MR scanner using a SPIRAL FLASH pulse sequence (TE=24 ms, TR=56 ms, FA=60 degrees , voxel dimensions=3.75 mm(3)). Subjects performed a modified version of the "n" back working memory task at different levels of increasing working memory load (1-Back, 2-Back and 3-Back). Older subjects performed as well as the younger subjects at 1-Back (p=0.4), but performed worse than the younger subjects at 2-Back (p<0.01) and 3-Back (p=0.06). Older subjects had significantly longer reaction time (RT) than younger subjects (p<0.04) at all levels of task difficulty. Image analysis using SPM 99 revealed a similar distribution of cortical activity between younger and older subjects at all task levels. However, an analysis of variance revealed a significant group x task interaction in the prefrontal cortex bilaterally; within working memory capacity, as in 1-Back when the older subjects performed as well as the younger subjects, they showed greater prefrontal cortical (BA 9) activity bilaterally. At higher working memory loads, however, when they performed worse then the younger subjects, the older subjects showed relatively reduced activity in these prefrontal regions. These data suggest that, within capacity, compensatory mechanisms such as additional prefrontal cortical activity are called upon to maintain proficiency in task performance. As cognitive demand increases, however, they are pushed past a threshold beyond which physiological compensation cannot be made and, a decline in performance occurs.

Adult↗
PubMed1996

Event-related potentials reveal topographical and temporal distinct neuronal activation patterns for spatial and object working memory.

This study examined whether working memory processes for object and spatial information are associated with different patterns of ERP activity. Subjects performed two versions of a delayed match-to-sample task in which either object forms or two-dimensional spatial configurations (S1) had to be encoded and retained in working memory for 6800 ms for comparison with a subsequent stimulus (S2). Event-related potentials (ERPs) were recorded from 29 electrode sites in the S1-S2 interval. Negative slow wave activity in the ERP varied with both, the type of memory task and the amount of materials held in working memory. When spatial information was maintained in working memory negative slow wave activity rapidly rose at recording sites overlying posterior parietal and occipital cortical areas. At these recording sites, slow wave increased in amplitude with increasing spatial memory load. For object information, load-sensitive negative slow wave activity was obtained approximately 2000 ms later than in the spatial task and it was focused to mid-frontal recording sites. Moreover, in the object memory task more pronounced negative slow wave activity was found at right inferior temporal recording sites indicating a larger involvement of the right temporal lobe in the processing of object as compared to spatial information. The results provide evidence for the notion that encoding and retention processes for object information and for spatial information can be functionally dissociated and involve differential patterns of neuronal activation rapidly shifting in time.

Adult↗
PubMed1999

Effects of mammillary body lesions on spatial reference and working memory tasks.

This work examines the effects of electrolytic mammillary body (MB) lesions on the performance of rats in different spatial memory tasks in the Morris water maze. The first experiment assessed the effect of MB lesion on performance in a spatial reference memory task (place learning with multiple trials). The second experiment examined the effect of a lesion in this nucleus on performance in a spatial working memory task (single-trial place learning). The results show that lesion of the MB impairs the animals performance in spatial working memory tasks but does not impair acquisition in spatial reference memory tasks (place learning, transfer task, reversal task) or in a visual-cued task. However, the deficit in the spatial working memory task does not appear to vary with the delay between acquisition and retention trials (30 s and 5 min). Our results demonstrate a clear role of the mammillary bodies in the processing of spatial information in a working memory task. Lesion of the MB impairs performance in a working memory task but does not affect reference memory processes.

Animals↗
PubMed2005

Past experience influences object representation in working memory.

The nature of object representation in working memory is vital to establishing the capacity of working memory, which in turn shapes the limits of visual cognition and awareness. Although current theories discuss whether representations in working memory are feature-based or object-based, no theory has considered the role of past experience. However, work with humans and non-human primates suggests that once participants learn which features are important for category membership, these diagnostic features become more salient than non-diagnostic features in long-term memory and object recognition. Critically, the brain areas involved in this diagnosticity effect are also recruited during working memory tasks. We report two experiments testing whether a diagnosticity effect exists in working memory; and whether it is present when visual information is encoded into working memory, or if it is the result of maintenance within working memory. Results showed a diagnosticity effect which was present at encoding. Maintenance did not influence the nature of object representation in working memory. These findings show that the meaning we glean from our past experience has a profound influence on the nature of object representation in working memory.

Adult↗
PubMed2005

Attentional interference in judgments of musical timbre: individual differences in working memory.

Researchers have shown that working memory is related to a variety of high-level cognitive processes. However, the results of recent research have suggested that may be because of its role in attentional control. In the present experiment, the authors investigated that hypothesis by using an attentional interference task with musical stimuli. Listeners were asked to monitor one ear for either a clarinet or violin tone and to ignore any information in the other ear. On some of the trials, they heard only one tone and on other trials, either the same instrument in both ears or different instruments. Individual differences were measured in working memory and musical experience. The results showed more attentional interference in the different-instrument condition for participants with lower working memory scores, which suggested that working memory involves the ability to control attention to inhibit irrelevant information.

Adult↗
PubMed1998

An area specialized for spatial working memory in human frontal cortex.

Working memory is the process of maintaining an active representation of information so that it is available for use. In monkeys, a prefrontal cortical region important for spatial working memory lies in and around the principal sulcus, but in humans the location, and even the existence, of a region for spatial working memory is in dispute. By using functional magnetic resonance imaging in humans, an area in the superior frontal sulcus was identified that is specialized for spatial working memory. This area is located more superiorly and posteriorly in the human than in the monkey brain, which may explain why it was not recognized previously.

Animals↗
PubMed2006

Feature-based memory-driven attentional capture: visual working memory content affects visual attention.

In 7 experiments, the authors explored whether visual attention (the ability to select relevant visual information) and visual working memory (the ability to retain relevant visual information) share the same content representations. The presence of singleton distractors interfered more strongly with a visual search task when it was accompanied by an additional memory task. Singleton distractors interfered even more when they were identical or related to the object held in memory, but only when it was difficult to verbalize the memory content. Furthermore, this content-specific interaction occurred for features that were relevant to the memory task but not for irrelevant features of the same object or for once-remembered objects that could be forgotten. Finally, memory-related distractors attracted more eye movements but did not result in longer fixations. The results demonstrate memory-driven attentional capture on the basis of content-specific representations.

Adolescent↗
PubMed2005

Divergent trajectories in the aging mind: changes in working memory for affective versus visual information with age.

Working memory mediates the short-term maintenance of information. Virtually all empirical research on working memory involves investigations of working memory for verbal and visual information. Whereas aging is typically associated with a deficit in working memory for these types of information, recent findings suggestive of relatively well-preserved long-term memory for emotional information in older adults raise questions about working memory for emotional material. This study examined age differences in working memory for emotional versus visual information. Findings demonstrate that, despite an age-related deficit for the latter, working memory for emotion was unimpaired. Further, older adults exhibited superior performance on positive relative to negative emotion trials, whereas their younger counterparts exhibited the opposite pattern.

Adolescent↗
PubMed1999

Delayed recognition memory in Parkinson's disease: a role for working memory?

Immediate and delayed recognition memory for words was examined in a sample of 16 non-demented patients with Parkinson's disease and 16 normal control participants of equivalent age and educational attainment. The patients, relative to control participants, had intact immediate but impaired delayed recognition memory performance. Patients were also impaired on tests of free and cued recall, working memory and a measure of psychomotor processing speed. Processing speed was a significant covariate for delayed recognition, free and cued recall and working memory performance, but not for immediate recognition performance. These results suggest that the same cognitive processes which support performance on tests of recall and working memory also support performance on tests of delayed recognition.

Aged↗
PubMed1999

Event-related potential correlates of individual differences in working memory capacity.

The capacity of working memory has been suggested to differ among people and these differences affect performance in a wide variety of cognitive tasks. This study explored electrophysiological correlates of individual differences in working memory capacity by means of event-related potentials. Thirty-four healthy students performed two- and five-choice reaction time tasks. In the two-choice reaction time (2CRT) task, two digits (3 and 7) were presented visually with probabilities of .20 and .80. In the five-choice reaction time (5CRT) task, five digits (3, 4, 5, 6, and 7) were presented equiprobably in a random order. Participants were required to press a button corresponding to each digit with a different finger. Working memory capacity of each participant was assessed by the reading span test originated by M. Daneman and P.A. Carpenter (1980). Participants with high reading span produced larger P300s than did persons with low reading span in the 5CRT task, but the difference was not significant in the 2CRT task. It had been suggested that individual differences in working memory capacity would affect initial stages of information processing as early as 300 ms after stimulus onset.

Adult↗
PubMed2002

Concurrent performance of two memory tasks: evidence for domain-specific working memory systems.

Previous studies of dual-task coordination in working memory have shown a lack of dual-task interference when a verbal memory task is combined with concurrent perceptuomotor tracking. Two experiments are reported in which participants were required to perform pairwise combinations of (1) a verbal memory task, a visual memory task, and perceptuomotor tracking (Experiment 1), and (2) pairwise combinations of the two memory tasks and articulatory suppression (Experiment 2). Tracking resulted in no disruption of the verbal memory preload over and above the impact of a delay in recall and showed only minimal disruption of the retention of the visual memory load. Performing an ongoing verbal memory task had virtually no impact on retention of a visual memory preload or vice versa, indicating that performing two demanding memory tasks results in little mutual interference. Experiment 2 also showed minimal disruption when the two memory tasks were combined, although verbal memory (but not visual memory) was clearly disrupted by articulatory suppression interpolated between presentation and recall. These data suggest that a multiple-component working memory model provides a better account for performance in concurrent immediate memory tasks than do theories that assume a single processing and storage system or a limited-capacity attentional system coupled with activated memory traces.

Adult↗
PubMed2005

Investigating principles of human brain function underlying working memory: what insights from schizophrenia?

Working memory dysfunction is a core component of schizophrenia, which likely contributes substantially to the pervasive and profound cognitive deficits observed in patients with this illness. Developments in functional imaging have facilitated the investigation of the neural basis of these cognitive deficits. A strong tradition within neuropsychology has been that circumscribed lesions provide observations which constrain theoretical models, and generate testable predictions on the basis of observed relationships between structural abnormalities and behavioral dysfunction. In this article, the extent to which the neuropsychological tradition can be applied to neuropsychiatry to advance understanding of the biological basis of working memory is addressed. Empirical studies in schizophrenia research are reviewed in relation to principles of normal brain function sub-serving working memory: the functional role of the lateral prefrontal cortex, physiological response capacity constraints, inter-regional functional integration, and compensatory adaptations. However, complex heterogeneous psychiatric disorders such as schizophrenia cannot be considered akin to a pure lesion model, and there are considerable methodological challenges in interpreting disruptions of working memory in psychiatric conditions, resulting from clinical, treatment and performance related confounds. The increasing use of psychopharmacological models of disease in healthy human subjects is therefore considered as an attempt to address, or to some extent circumvent these issues.

Animals↗
PubMed2003

Selective attention to elements in working memory.

Three experiments with an arithmetic working memory task examine the object switch effect first reported by Garavan (1998), which was interpreted as evidence for a focus of attention within working memory. Experiments 1a and 1b showed object switch costs with a task that requires selective access to items in working memory, but did not involve counting, and did not require updating of working memory contents, thus ruling out two alternative explanations of Garavan's results. Experiment 2 showed object switch costs with a task that required no selective access to working memory contents, but involved updating, thus providing evidence for a second component to the overall object switch costs. Further analyses revealed that the object switch cost increased with memory set size; that there were (smaller) switch costs when the switch was to an item of the same type; that repeating an arithmetic operation does not have the same effect as repeating the object it is applied to; and that object switching is not mediated by backward inhibition of the previously focused object.

Adult↗
PubMed2006

Adverse effects of risperidone on spatial working memory in first-episode schizophrenia.

CONTEXT: Working memory impairments are a central neurocognitive feature of schizophrenia. The nature of these impairments early in the course of illness and the impact of antipsychotic drug treatment on these deficits are not well understood. The oculomotor delayed response task is a translational spatial working memory paradigm used to characterize the neurophysiologic and neurochemical aspects of working memory in the primate brain. OBJECTIVE: To examine oculomotor delayed response task performance in patients with first-episode schizophrenia before and after antipsychotic drug treatment. DESIGN, SETTING, AND PARTICIPANTS: Twenty-five antipsychotic drug-naive, acutely ill patients with first-episode schizophrenia performed an oculomotor delayed response task at baseline before any drug treatment and again after 6 weeks of risperidone treatment. Twenty-five matched healthy controls were studied in parallel. MAIN OUTCOME MEASURE: Accuracy for remembered spatial locations on an oculomotor delayed response task. RESULTS: Before treatment, patients demonstrated baseline impairment in the ability to maintain spatial location information in working memory at longer delay-period durations (8 seconds), when maintenance demands on working memory were greatest. After 6 weeks of risperidone treatment and significant clinical improvement, this pretreatment impairment worsened such that patients were uniformly impaired across all delay period durations (1-8 seconds). This occurred in the absence of any generalized adverse effect on oculomotor systems or significant extrapyramidal adverse effects. CONCLUSIONS: Deficits in the maintenance of spatial information in working memory are present early in the course of illness. Risperidone treatment exacerbated these deficits, perhaps by impairing the encoding of information into working memory. Studies with nonhuman primates performing oculomotor delayed response tasks suggest that the apparent adverse effect of risperidone might result from treatment-related changes in modulatory functions of prefrontal D1 receptor systems.

Acute Disease↗
PubMed2005

Processing efficiency of a verbal working memory system is modulated by amphetamine: an fMRI investigation.

RATIONALE: Working memory performance may be improved or decreased by amphetamine, depending on baseline working memory capacity and amphetamine dosage. This variable effect suggests an optimal range of monaminergic activity for working memory, either below or above which it is compromised. We directly tested this possibility with human participants by varying amphetamine dosage and measuring the efficiency of cortical processing in brain regions associated with working memory. OBJECTIVES: The modulation of cortical processing in a verbal working memory network by dextroamphetamine (D-amph) was examined using BOLD functional magnetic resonance imaging (fMRI) with healthy participants. The goal of the study was to test the hypothesis of an inverted U-shaped relationship between D-amph dose and processing efficiency of a verbal working memory system. METHODS: D-amph dosage was increased cumulatively every 2 h across four scanning sessions collected in a single day. The primary measure used for analyses in this study was the extent of activation in brain regions empirically defined as a working memory network. RESULTS: An inverted U-shaped relationship was observed between the amount of D-amph administered and working memory processing efficiency. This relationship was specific to brain areas functionally defined as working memory regions and to the encoding/maintenance phase (as opposed to the response phase) of the task. CONCLUSION: The results are consistent with the hypothesis that the neurochemical effects of amphetamine modulate the efficiency of a verbal working memory system. The effect of amphetamine on working memory in healthy individuals may provide insight regarding the working memory deficits seen in schizophrenia, given the overlap between neurochemical systems affected by amphetamine, and those disordered in schizophrenia.

Adult↗
PubMedDate not supplied

Activation of human prefrontal cortex during spatial and nonspatial working memory tasks measured by functional MRI.

Separate working memory domains for spatial location, and for objects, faces, and patterns, have been identified in the prefrontal cortex (PFC) of nonhuman primates. We have used functional magnetic resonance imaging to examine whether spatial and nonspatial visual working memory processes are similarly dissociable in human PFC. Subjects performed tasks which required them to remember either the location or shape of successive visual stimuli. We found that the mnemonic component of the working memory tasks affected the hemispheric pattern of PFC activation. The spatial (LOCATION) working memory task preferentially activated the middle frontal gyrus (MFG) in the right hemisphere, while the nonspatial (SHAPE) working memory task activated the MFG in both hemispheres. Furthermore, the area of activation in the left hemisphere extended into the inferior frontal gyrus for nonspatial SHAPE task. A perceptual target (DOT) detection task also activated the MFG bilaterally, but at a level approximately half that of the working memory tasks. The activation in the MFG occurred within 3-6 s of task onset and declined following task offset. Time-course analysis revealed a different pattern for cingulate gyrus, in which activation occurred upon task completion. Cingulate gyrus activation was greatest following the SHAPE task and was greater in the left hemisphere. The present results support the prominent role of the PFC and, specifically, the MFG in working memory, and indicate that the mnemonic content of the task affects the relative weighting of hemispheric activation.

Adult↗
PubMed2006

Suppressed working memory on the WMS-III as a marker for poor effort.

The purpose of this study was to examine the clinical utility of memory minus Working Memory Index (memory-WMI) discrepancy scores on the WMS-III for detecting poor effort in 145 personal injury litigants (19 poor effort, 126 adequate effort). On average, participants in the poor effort group performed significantly lower on all WMS-III memory indexes and demonstrated larger memory-WMI discrepancy scores compared to participants in the adequate effort group. Discriminant function analyses using memory-WMI discrepancy scores as independent variables revealed poor overall classification rates (60.0% to 63.4%). Based on the prevalence of unusually suppressed attention-concentration ability relative to memory functioning using unidirectional memory-WMI discrepancy scores, high specificity and negative predictive power values were found. However, there was unacceptably low sensitivity and positive predictive power. These results suggest that memory-WMI discrepancy scores on the WMS-III do not provide clinically useful information regarding response set and should be used cautiously as an indicator of poor effort.

Adult↗