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Neural substrates associated with the concurrent performance of dual working memory tasks.

The neural substrates of the dual working memory (WM) process were investigated using concurrent performance of auditory and visual n-back WM tasks. Based on the pre-fMRI behavioral testing, a lettered 1-back WM paradigm was implemented for an fMRI examination of healthy volunteers who performed (1) auditory, (2) visual, and (3) simultaneous visual and auditory WM tasks. The behavioral performance, as measured by the reaction time, was deteriorated in the dual task condition compared to the single task condition. Group analysis of the fMRI data revealed that the majority of activation identified during each component task was concurrently activated in the dual task condition. However, several neural substrates such as left middle frontal gyrus, left superior parietal lobule, posterior aspect of right inferior temporal gyrus, and bilateral parahippocampal gyri were selectively activated during the dual WM task. These data suggest that new neural networks come into play to assist in the greater load placed on the WM with the incongruent stimulation modality, which may also have implications in crossmodal integrative processes.

Acoustic Stimulation↗

Attention-Deficit/Hyperactivity Disorder and working memory: a task switching paradigm.

This study investigated working memory (WM) in children with Attention-Deficit/Hyperactivity Disorder (ADHD) using a task switching paradigm with Stroop color-word stimuli which required participants to switch from color-naming to word-reading. High and low WM load conditions were compared by manipulation of task reminders as a tempo cue. The sample comprised 83 children with ADHD and 29 normal children comparable in age (aged 7 to 13). Within the ADHD group, participants were divided according to the presence or absence of Learning Disability (LD). Results indicated that children with ADHD had slower response times and less accurate responses in general, however, the ADHD groups were not consistently slower in the high WM load condition. Instead, an impairment in adjusting response speed to cope with higher task demands (i.e., high WM load condition) was found. These results do not support the previously documented association between ADHD and a primary deficit in WM for task switching. However, children with ADHD do demonstrate a specific difficulty in slowing down for a demanding task. Present findings suggest that earlier proposals of under-arousal and poor state regulation in ADHD deserve renewed attention.

Analysis of Variance↗

Dopaminergic modulation of visual-spatial working memory in Parkinson's disease.

Visual-spatial working memory (WM) impairment is frequently associated with the early stage of Parkinson's disease (PD). The aim of this study was to evaluate the performance of a group of PD patients in visual-spatial and visual-object WM tasks and to investigate the effect of administering the dopaminergic agonist apomorphine (experiment 1) or the dopamine precursor L-dopa (experiment 2) on the performance of tests assessing these functions. To study WM processes, the PD patients and age-matched normal controls were given an n-back task paradigm. In both experiments, the PD patients were submitted to two evaluations: one after a 12-hour therapy washout and the other 15 min after a subcutaneous infusion of apomorphine (average 0.04 mg/kg) or 20/30 min after L-dopa intake (200 mg p.o.). The apomorphine infusion had a worsening effect on reaction times in both visual-spatial and visual-object WM tasks, but it did not influence performance accuracy. Instead, L-dopa administration had a ameliorative effect on accuracy and reaction times in both visual-spatial and visual-object tasks. These results highlight the role of dopamine in the modulation of the WM function in PD patients.

Apomorphine↗

Order information in working memory: fMRI evidence for parietal and prefrontal mechanisms.

Working memory is thought to include a mechanism that allows for the coding of order information. One question of interest is how order information is coded, and how that code is neurally implemented. Here we report both behavioral and fMRI findings from an experiment involved comparing two tasks, an item-memory task and an order-memory task. In each case, five letters were presented for storage, followed after a brief interval by a set of probe letters. In the case of the item-memory task, the two letters were identical, and the subject responded to the question, "Was this letter one of the items you saw?". In the case of the order-memory task, the letters were different, and subjects responded to the question, "Are these two letters in the order in which you saw them?". Behaviorally, items that were further apart in the sequence that elicited faster reaction times and higher accuracy in the Order task. Areas that were significantly more activated in the Order condition included the parietal and prefrontal cortex. Parietal activations overlapped those involved in number processing, leading to the suggestion that the underlying representation of order and numbers may share a common process, coding for magnitude.

Brain Mapping↗

Some shortcomings of long-term working memory.

Within the framework of their long term working memory theory, Ericsson and Kintsch (1995) propose that experts rapidly store information in long-term memory through two mechanisms: elaboration of long-term memory patterns and schemas and use of retrieval structures. They use chess players' memory as one of their most compelling sources of empirical evidence. In this paper, I show that evidence from chess memory, far from supporting their theory, limits its generality. Evidence from other domains reviewed by Ericsson and Kintsch, such as medical expertise, is not as strong as claimed, and sometimes contradicts the theory outright. I argue that Ericsson and Kintsch's concept of retrieval structure conflates three different types of memory structures that possess quite different properties. One of these types of structures--generic, general purpose retrieval structures--has a narrower use than proposed by Ericsson and Kintsch: it applies only in domains where there is a conscious, deliberate intent by individuals to improve their memory. Other mechanisms, including specific retrieval structures, exist that permit a rapid encoding into long-term memory under other circumstances.

Cognition↗

Effect of huperzine A on working memory in reserpine- or yohimbine-treated monkeys.

The effect of huperzine A, a reversible and selective acetylcholinesterase inhibitor, on reserpine- or yohimbine-induced spatial working memory deficits in monkeys has been examined using the delayed response task that depends on the integrity of prefrontal cortex. Reserpine (0.1 mg/kg, i.m.) or yohimbine (0.01 mg/kg, i.m.) led to significant impairments in the monkeys' ability to perform the delayed response task. Huperzine A (0.01 mg/kg, i.m. in reserpine-treated monkeys; 0.01-0.1 mg/kg, i.m. in yohimbine-treated monkeys) significantly improved the reserpine- or yohimbine-induced memory impairments. The effect of huperzine A on memory impairments exhibited an inverted U-shaped dose-response pattern. Our data suggest that huperzine A may improve working memory via an adrenergic mechanism.

Alkaloids↗

Prose recall and amnesia: implications for the structure of working memory.

Two densely amnesic patients are shown to have good immediate but poor delayed prose recall, a result that presents problems for the current multi-component model of working memory. Examination of a wide sample of memory impaired patients suggests that this pattern occurs in densely amnesic patients who have well-preserved intelligence and good executive capacities. Patients suffering from Alzheimer's disease typically show poor immediate and delayed prose recall, reflecting their combined intellectual and memory deficits. The results are interpreted in terms of a proposed new component of working memory, the episodic buffer.

Adolescent↗

Disruption of a putative working memory task and selective expression of brain c-fos following microwave-induced hyperthermia.

To discern the effects of hyperthermia on working memory, we recorded the ability of rats to discriminate between objects following microwave radiation exposure. Memory changes were evaluated by measuring relative exploration time of a familiar vs. a new stimulus object. A subject that extensively reexplores a stimulus with which it has previous experience is presumed to exhibit memory loss associated with that object. Between training and testing, rats were exposed to various doses of microwave radiation, were sham irradiated, or remained in their home cage. Brain (dural) and rectal temperatures were recorded. To discern brain regions activated or possibly damaged by microwave exposure, we also used immunocytochemistry techniques to identify sites of c-fos protein expression in the brains of several irradiated/sham-irradiated subjects. Rats exposed to > 5 W/kg exhibited hyperthermia when compared to nonirradiated controls. Normothermic control subjects (sham-irradiated rats and rats exposed to 0.1 W/kg) showed a distinct preference for the new object although other microwave-exposed rats (1, 5, 8.5, 9.3, 10 W/kg) did not. Microwave hyperthermia evoked prominent c-fos expression in periventricular strata, hypothalamic nuclei, amygdala, and several areas of the cortex. These data suggest that performance on a putative working memory task may be disrupted by a sufficiently intense microwave-induced hyperthermia. The pattern of expression of the early proto-oncogene c-fos may suggest candidate brain nuclei that mediate the behavioral changes we observed.

Animals↗

Cerebral activation in abstinent ecstasy (MDMA) users during a working memory task: a functional magnetic resonance imaging (fMRI) study.

The popular recreational drug ecstasy (3,4-methylenedioxymethamphetamine=MDMA and related congeners) is neurotoxic upon central serotonergic systems in animal studies. So far, the most convincing evidence for neurotoxicity-related functional deficits in humans derives from neurocognitive studies demonstrating dose-related long-term learning and memory problems in ecstasy users. In our study we used functional magnetic resonance imaging (fMRI) and a working memory task to investigate cerebral activation in eleven heavy, but currently abstinent MDMA users and two equally sized groups of moderate users and non-users. There were no significant group differences in working memory performance and no differences in cortical activation patterns for a conservative level of significance. However, for a more liberal statistical criterion, both user groups showed stronger activations than controls in right parietal cortex. Furthermore, heavy users had a weaker blood oxygenation level-dependent (BOLD) response than moderate users and controls in frontal and temporal areas. Our results may indicate subtle altered brain functioning associated with prior MDMA use, although alternative interpretations of these group differences must be considered.

Adult↗

Studies of working memory using 18FDG-positron emission tomography in normal controls and subjects with epilepsy.

We have studied three groups of subjects with a working memory paradigm, using 18FDG-PET. Controls show the greatest increase on uptake in dorsolateral prefrontal cortex, basal forebrain and angular gyrus. A group of subjects with focal frontal epilepsy did not show increases compared to a control task of attention. Primary generalized epilepsy subjects show the greatest changes in angular gyrus, dorsal temporal, medial frontal and parietal regions. Factor and regression analyses extend these observations and show reliance of both patient groups on the medial and inferior temporal lobe. We propose that the normal network of working memory is disrupted by these two forms of epilepsy and different networks are accessed. Declarative memory may be used as a compensatory system, which results in decreased performance.

Adult↗

Is the focus of attention in working memory expanded through practice?

This article reinvestigates the claim by P. Verhaeghen, J. Cerella, and C. Basak (2004) that the focus of attention in working memory can be expanded from 1 to 4 items through practice. Using a modified version of Verhaeghen et al.'s n-back paradigm, Experiments 1 and 3 show that a signature of a one-item focus, the time cost for switching between items in working memory, persists over practice. Verhaeghen et al. reported a shift over practice from a step function to a linear slope of reaction times over set size and argued that it reflects the expansion of the focus. With an improved counterbalancing scheme, a continuously increasing slope was found even without practice in Experiment 2. The results question the hypothesis that the focus is expanded through practice. They are in line with predictions from a model that distinguishes a one-item focus from a direct-access region holding about 4 items.

Analysis of Variance↗

Executive processes in visual and spatial working memory tasks.

Three experiments are reported, which have investigated the nature of the cognitive mechanisms that underlie performance on specific visuo-spatial working memory tasks, with the emphasis on exploring the extent of central executive involvement. Experiments 1 and 2 employed oral random digit generation as an executive task within a dual-task paradigm. The results of both experiments indicated that visuo-spatial tasks that involve sequential processing of information show more interference with random digit generation than do visuo-spatial tasks that involve simultaneous processing. The third experiment substituted oral random digit generation for executive tasks that did not involve memory for serial order (vigilance tasks adapted from Vandierendonck, De Vooght, & Van der Goten, 1998b). The results indicated significant interference between the vigilance tasks and the sequential visuo-spatial task, but not with the simultaneous visuo-spatial task. Overall the results of the three experiments are interpreted as indicating that serial sequential visuo-spatial tasks involve executive resources to a significantly greater extent than do simultaneous visuo-spatial tasks, and that this can have implications for studies that attempt to make use of such tasks to fractionate separable visual and spatial components within working memory.

Adolescent↗

The reliability and stability of the Turner and Engle working memory task.

The present study explored the psychometric properties of Turner and Engle's (1989) operation span task, a widely used measure of working memory capacity. We administered the task three times to 33 college students, using equivalent test materials. The interval between the first and second administrations was 3 weeks, with 6-7 weeks between the second and third administrations. Alpha coefficients were all .75 or more. Recall accuracy decreased as operation set size increased. Raw test-retest correlations ranged from .67 to .81, the corrected reliability was .88, and stability scores ranged from .76 to .92. Performance improved from the first to the second test. Relative to reported reliabilities of other tasks used to assess individual differences in working memory capacity, the operation span task appears to have several statistical advantages.

Analysis of Variance↗

Blockade of 5-HT2 receptors protects against impairment of working memory following transient forebrain ischemia in the rat.

The effects of the 5-HT2 receptor antagonists pirenperone, cinanserin and ritanserin on impairment of working memory in an animal model of cerebral ischemia were investigated, using a three-panel runway task. A 5-min period of ischemia caused a significant increase in the number of errors (attempts to pass through two incorrect panels of the 3 panel gates at 4 choice points). Pirenperone at 0.32 and 1.0 mg/kg, cinanserin 10 mg/kg and ritanserin 3.2 mg/kg administered i.p. immediately after blood flow reperfusion significantly reduced the increase in errors expected to occur 24 h after the 5 min of ischemia. These results suggest that the blockade of 5-HT2 receptors prevents the impairment of working memory following transient forebrain ischemia.

Animals↗

Reference and working memory of rats following hippocampal damage induced by transient forebrain ischemia.

Acquisition of reference and working memory was evaluated in an animal model of cerebral ischemia. Rats were subjected to 30 minutes of transient forebrain ischemia, allowed to recover, and then tested for 95 trials on an 8-arm maze with 5 arms baited. During the 95 trials post ischemic (PI) rats made significantly more working and reference errors than controls (p less than 0.05). However, an analysis of the last 20 trials (75-95) showed that while PI rats and control rats had comparable reference memory (p greater than 0.8). PI rats tended to have a persistent working memory deficit compared to controls (p less than 0.06). Subsequent morphologic analysis showed that PI rats had almost complete loss of pyramidal neurons in the anterior CA1 region of the hippocampus, moderate to severe loss in mid-dorsal posterior hippocampus, and less damage to the dorsolateral striatum. These results suggest that the PI animal is a reasonable model for the permanent behavioral impairment and pathologic damage found in some human survivors of cardiac arrest.

Animals↗

Involvement of cholinergic mechanisms in impairment of working memory in rats following basolateral amygdaloid lesions.

In order to clarify the role of the amygdala in the working and reference memory of rats in the three-panel runway task, the effects of lesions of subnuclei of the amygdaloid complex on this behavior were studied. Rats that had been trained preoperatively, until they achieved the criterion of learning, were subjected to lesions of the amygdala. In the working memory task, lesions of the basolateral subdivision of the amygdala caused a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points), while lesions of the corticomedial amygdala had no effect on working memory errors. The increase in working errors, observed in basolateral amygdaloid-lesioned rats, declined gradually as retraining sessions were given once each day, reverting to control levels on and after the sixth session. In the reference memory task, the number of errors was not affected by lesions of the basolateral or corticomedial amygdala. The increase in working memory errors, induced by lesions of the basolateral amygdala was significantly reduced by intraperitoneal administration of the inhibitors of cholinesterase, tetrahydroaminoacridine (0.32-1.0 mg/kg) and physostigmine (0.032-0.1 mg/kg), and the muscarinic receptor agonist, oxotremorine (0.1 mg/kg), before the runway test. These findings suggest that the basolateral amygdala is selectively involved in working memory but not in reference memory and that the lowering of central cholinergic function may account for the impairment of working memory, induced by lesions of the basolateral amygdala.

Amygdala↗

Buspirone impairs performance of a three-choice working memory water escape task in rats.

Two studies were conducted to assess the effects of buspirone and alprazolam on a three-choice working memory water escape task. Both studies involved giving rats three daily trials, each trial consisting of an information run during which guillotine doors forced the rats to swim into the correct escape alley and a test run during which the rats could enter any of the three alleys but escape only on entering the same alley to which they had been forced on the information run. In the first experiment, rats were trained to a 70% correct choice criterion with 5-min interrun intervals and then tested for performance with 5, 20, 20 with distraction, and 60-min interrun intervals. In the second experiment, rats in each of the drug groups were tested after receiving one of three different doses of their respective drug. Results suggest that 1.0, 3.0, and 10.0 mg/kg buspirone but not 0.5, 1.0, and 2.0 mg/kg alprazolam impaired performance of rats on a three-choice working memory water escape task.

Alprazolam↗

Further considerations regarding inhibitory processes, working memory, and cognitive aging.

The present study explored the relationship between inhibitory processing (as indexed by identity negative priming in a letter-naming task), working memory, discourse processing, and cognitive aging effects. Consistent with several other recent reports, this study found evidence of intact inhibitory processing, as measured by negative priming, in older adults as well as younger adults. This intact negative priming occurred in conjunction with diminished working memory span and impaired memory in the discourse processing task in the same sample of older adults, further arguing against the likelihood that declines in these areas are caused by impairments in the inhibitory processes measured by negative priming. The implications of these results for theories of cognitive aging and possible reasons for inconsistent findings regarding negative priming effects among the elderly are discussed.

Adolescent↗