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PubMed1985

Spatial memory in rats: electroconvulsive shock selectively disrupts working memory but spares reference memory.

In two experiments rats were trained until they displayed highly accurate spatial memories when a 4-h delay was imposed between the to-be-remembered event (TBRE) and the retention test in a 12-arm radial maze. If the procedure tested only working memory (WM) electronvulsive shock (ECS) 2 h after the TBRE produced amnesia but ECS immediately after the TBRE was ineffective. If the testing procedure also involved a reference memory (RM) component, ECS degraded WM regardless of whether it was given 0 or 2 h after the TBRE. RM was not affected. With either training procedure administering ECS 2 h before the TBRE was ineffective. Thus, in the radial maze truly old spatial RM was immune to disruption by ECS while more recent WM was vulnerable. Possible explanations of the data are presented.

Animals↗

PubMed1998

Effects of huperzine A on nucleus basalis magnocellularis lesion-induced spatial working memory deficit.

AIM: To study the effects of huperzine A on nucleus basalis magnocellularis (NBM) lesion-induced spatial working memory impairment. METHODS: A delayed-non-match-to-sample radial arm maze task was used to study spatial working memory. The choline acetyltransferase (ChAT) activity was determined by the conversion of [3H]acetyl-CoA to [3H]ACh. RESULTS: Unilateral NBM lesion by kainic acid 0.02 mumol impaired rat's ability to perform this working memory task as evidenced by fewer correct choices after different delay intervals and more total errors to complete the task. This behavioral impairment associated with a decrease in the activity of ChAT by about 40% in the ipsilateral cerebral cortex. Huperzine A (0.2 mg.kg-1 i.p. 30 min before testing) ameliorated this spatial working memory impairment. Physostigmine (0.2-0.3 mg.kg-1 i.p. 20 min before testing) also attenuated the NBM lesion-induced memory deficit. CONCLUSION: The integrity of NBM is critical for spatial working memory processing, and this working memory impairment induced by NBM lesion can be ameliorated by huperzine A and physostigmine.

Alkaloids↗

PubMed2006

The development of strategy use in elementary school children: working memory and individual differences.

The current study tested the development of working memory involvement in children's arithmetic strategy selection and strategy efficiency. To this end, an experiment in which the dual-task method and the choice/no-choice method were combined was administered to 10- to 12-year-olds. Working memory was needed in retrieval, transformation, and counting strategies, but the ratio between available working memory resources and arithmetic task demands changed across development. More frequent retrieval use, more efficient memory retrieval, and more efficient counting processes reduced the working memory requirements. Strategy efficiency and strategy selection were also modified by individual differences such as processing speed, arithmetic skill, gender, and math anxiety. Short-term memory capacity, in contrast, was not related to children's strategy selection or strategy efficiency.

Age Factors↗

PubMedDate not supplied

Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: a positron emission tomography study.

Previous work in nonhuman primates and in patients with frontal lobe damage has suggested that the frontal cortex plays a critical role in the performance of both spatial and nonspatial working memory tasks. The present study used positron emission tomography with magnetic resonance imaging to demonstrate the existence, within the human brain, of two functionally distinct subdivisions of the lateral frontal cortex, which may subserve different aspects of spatial working memory. Five spatial memory tasks were used, which varied in terms of the extent to which they required different executive processes. When the task required the organization and execution of a sequence of spatial moves retained in working memory, significant changes in blood flow were observed in ventrolateral frontal cortex (area 47) bi-laterally. By contrast, when the task required active monitoring and manipulation of spatial information within working memory, additional activation foci were observed in mid-dorsolateral frontal cortex (areas 46 and 9). These findings support a two-stage model of spatial working memory processing within the lateral frontal cortex.

Brain Mapping↗

PubMed2000

LP-BM5 infection impairs spatial working memory in C57BL/6 mice in the Morris water maze.

Previous studies show that the LP-BM5 murine leukemia virus causes an acquired immunodeficiency syndrome in C57BL/6 mice (MAIDS) and impairs learning and memory without gross motor impairment. To assess spatial working memory impairment after LP-BM5 infection and the time course of this impairment, we tested mice in a modified working-memory version of the Morris water maze. Twenty mice were inoculated with LP-BM5; controls received medium (Minimum Essential Medium). In the test procedure, animals had two 1-min training sessions to learn the position of a randomly placed hidden platform. Thirty seconds after the second training session, animals were placed in the maze without the platform, and time and pathlength spent in each quadrant of the maze were measured. For 9 weeks after LP-BM5 infection, both groups showed preference for the target quadrant compared to the opposite quadrant. At 10 and 11 weeks after infection, the LP-BM5 virus infected mice lost this target quadrant preference. We conclude that LP-BM5 infection impaired spatial working memory in a modified working-memory version of the Morris water maze test in C57BL/6 mice at 10 and 11 weeks after virus infection.

Animals↗

PubMed2003

The influence of a working memory load manipulation on language production in schizophrenia.

The present study examined the hypothesis that working memory deficits contribute to both negative thought disorder and some components of formal thought disorder (discourse coherence and fluency deficits) in individuals with schizophrenia. We examined the language produced by 44 patients with either schizophrenia or schizoaffective disorder during baseline and a dual-task condition designed to decrease working memory capacity. Results indicated that decreasing working memory capacity significantly increased negative thought disorder, but not discourse coherence or fluency deficits. However, both negative thought disorder and discourse coherence deficits were significantly correlated with working memory deficits. In addition, increases in negative thought disorder and discourse coherence deficits in the dual-task condition were negatively correlated, consistent with the hypothesis that these two types of language deficits may reflect alternative manifestations of working memory deficits.

Adult↗

PubMed2003

Differences between d-methamphetamine and d-amphetamine in rats: working memory, tolerance, and extinction.

RATIONALE: Previously, we have shown that d-amphetamine (AMPH) was more potent than d-methamphetamine (METH) at increasing extracellular levels of dopamine (DA) in the prefrontal cortex (PFC) at doses that had similar effects in the nucleus accumbens. Since working memory depends on PFC DA, it was postulated that AMPH would also be more potent than METH at affecting working memory. OBJECTIVE: To determine if AMPH is more potent than METH at affecting working memory. METHODS: Working memory was measured in adult female Sprague-Dawley rats using a delayed-alternation T-maze task with multiple delays (1, 10, 60 s) and food rewards. The percentage of food rewards consumed was also recorded. Animals were tested with METH and AMPH before and after a chronic protocol, with measurements of locomotor activity used to test for pharmacological tolerance or sensitization. The effects of METH and AMPH on extinction were also examined by omitting the food rewards from the T-maze. RESULTS. Both METH and AMPH produced dose-related bimodal effects on working memory at the intermediate delay (10 s); however, AMPH was more potent than METH. Both METH and AMPH initially also decreased the percentage of food rewards consumed in the T-maze. After chronic testing, animals displayed tolerance to both the working memory impairments and the reduction in food reward intake produced by AMPH. Animals did not display significant tolerance to the effects of METH on food reward consumption and performed worse in the T-maze after chronic testing. METH, but not AMPH, interfered with extinction. CONCLUSIONS: These results indicate that METH and AMPH differ in altering working memory and the expression of tolerance, perhaps due to differences in behavioral inhibition.

Amphetamines↗

PubMed2001

A slow wave investigation of working memory biases in mood disorders.

Mood-congruent working memory biases were examined in a delayed matching to sample paradigm using the slow wave (SW) event-related brain potential (ERP) component. Mood-congruent working memory biases, indexed by SW amplitudes, were demonstrated among individuals experiencing a major depressive episode (MDE) and nondepressed controls but not individuals with dysthymia. However, analyses of symptom severity demonstrated that those with dysthymia exhibited significantly less negative SW amplitudes with increasing depressive mood severity, whereas individuals with major depression demonstrated more negative SW amplitudes with increasing depressive mood severity. These results are discussed in the context of diagnostic specificity for cognitive biases associated with working memory of mood-disordered individuals.

Adult↗

PubMed1994

Counting on working memory in arithmetic problem solving.

Mental calculation is an important everyday skill involving access to well-learned procedures, problem solving, and working memory. Although there is an active literature on acquiring concepts and procedures for mental arithmetic, relatively little is known about the role of working memory in this task. This paper reports two experiments in which dual-task methodology is used to study the role of components of working memory in mental addition. In Experiment 1, mental addition of auditorily presented two-digit numbers was significantly disrupted by concurrent random letter generation and, to a lesser extent, by concurrent articulatory suppression, but was unimpaired by concurrent hand movement or by presentation of irrelevant pictures. Although the number of errors increased with two of the dual tasks, the incorrect responses tended to be quite close to the correct answer. In Experiment 2, the numbers for addition were presented visually. Here again, random generation produced the largest disruption of mental arithmetic performance, while a smaller amount of disruption was observed for articulatory suppression, hand movement, and unattended auditorily presented two-digit numbers. The overall levels of performance were better and the absolute size of the disruptive effects shown with visual presentation was very small compared with those found for auditory presentation. This pattern of results is consistent with a role for a central executive component of working memory in performing the calculations required for mental addition and in producing approximately correct answers. Visuospatial resources in working memory may also be involved in approximations. The data support the view that the subvocal rehearsal component of working memory provides a means of maintaining accuracy in mental arithmetic, and this matches a similar conclusion derived from previous work on counting. The general implications for the role of working memory in arithmetic problem solving will be discussed.

Adolescent↗

PubMed2006

Neural correlates of enhanced working-memory performance in dissociative disorder: a functional MRI study.

BACKGROUND: Memory functioning has been highlighted as a central issue in pathological dissociation. In non-pathological dissociation, evidence for enhanced working memory has been found, together with greater task-load related activity. So far, no imaging studies have investigated working memory in dissociative patients. METHOD: To assess working memory in dissociative patients functional magnetic resonance imaging was used during performance of a parametric, verbal working-memory task in patients with a dissociative disorder (n=16) and healthy controls (n=16). RESULTS: Imaging data showed that both groups activated brain regions typically involved in working memory, i.e. anterior, dorsolateral and ventrolateral prefrontal cortex (PFC), and parietal cortex. Dissociative patients showed more activation in these areas, particularly in the left anterior PFC, dorsolateral PFC and parietal cortex. In line with these findings, patients made fewer errors with increasing task load compared to controls, despite the fact that they felt more anxious and less concentrated during task performance. CONCLUSIONS: These results extend findings in non-pathological high dissociative individuals, suggesting that trait dissociation is associated with enhanced working-memory capacities. This may distinguish dissociative patients from patients with post-traumatic stress disorder, who are generally characterized by impaired working memory.

Adult↗

PubMed1996

Learning disabled and average readers' working memory and comprehension: does metacognition play a role?

The present study investigates (a) whether learning disabled readers' working memory deficits that underlie poor reading comprehension are related to a general system, and (b) whether metacognition contributes to comprehension beyond what is predicted by working memory and word knowledge. To this end, performance between learning and disabled (N = 60) and average readers (N = 60) was compared on the reading comprehension, reading rate, and vocabulary subtests of the Nelson Skills Reading Test, Sentence Span test composed of high and low imagery words, and a Metacognitive Questionnaire. As expected, differences between groups in working memory, vocabulary, and reading measures emerged, whereas ability groups were statistically comparable on the Metacognitive Questionnaire. A within-group analysis indicated that the correlation patterns between working memory, vocabulary, metacognition, and reading comprehension were not the same between ability groups. For predicting reading comprehension, the metacognitive questionnaire best predicted learning disabled readers' performance, whereas the working memory span measure that included low-imagery words best predicted average achieving readers' comprehension. Overall, the results suggest that the relationship between learning disabled readers' generalised working memory deficits and poor reading comprehension may be mediated by metacognition.

Child↗

PubMed2003

Working memory controls involuntary attention switching: evidence from an auditory distraction paradigm.

One function of working memory is to protect current mental processes against interference. In contrast, to be able to react flexibly on unpredictable environmental changes working memory should not totally be encapsulated from processing task unrelated information; that is, it should remain distractible. By manipulating the task load of the primary task in an auditory distraction paradigm we investigated how these opposing functions are coordinated by working memory. The behavioural results show that distraction effects were still present but reduced markedly with higher task demands. This suggests that working memory exerts some control over involuntary attention. In addition, event-related brain potentials related to the different processing stages reveal that the preattentive change detection system underlying distraction was not modulated by task demand whereas distraction per se was. The present data suggest that working memory is able to coordinate the maintenance of distractibility and the focus on the task at hand.

Acoustic Stimulation↗

PubMed2005

Hippocampal activations during encoding and retrieval in a verbal working memory paradigm.

Though the hippocampus has been associated with encoding and retrieval processes in episodic memory, the precise nature of its involvement in working memory has yet to be determined. This functional magnetic resonance imaging (fMRI) study employed a verbal working memory paradigm that allows for the within-subject comparison of functional activations during encoding, maintenance, and retrieval. In each trial, participants were shown 5 target words and, after an 8 s delay, a series of probe words. Probe words consisted of target matches, phonetically or semantically related foils, or foils unrelated to the target words. Both the left and right hippocampi showed higher mean activation amplitudes during encoding than maintenance. In contrast, the right dorsolateral prefrontal cortex (DLPFC) showed greater activation during maintenance than encoding. Both hippocampal and DLPFC regions were more active during retrieval than maintenance. Furthermore, an analysis of retrieval activation separated by probe type showed a trend toward greater bilateral hippocampal activation for probes related (both semantically and phonetically) to the target than for unrelated probes and still greater activation for target matches. This pattern suggests that there may be roles for the hippocampus and DLPFC in working memory that change as function of information processing stage. Additionally, the trend towards increased involvement of the hippocampus with the increase in relatedness of the probe stimuli to the information maintained is interpreted to be consistent with the role of the hippocampus in recollection-based retrieval in long-term memory and may indicate that this role extends to working memory processes.

Adult↗

PubMed2001

The role of working memory in visual selective attention.

The hypothesis that working memory is crucial for reducing distraction by maintaining the prioritization of relevant information was tested in neuroimaging and psychological experiments with humans. Participants performed a selective attention task that required them to ignore distractor faces while holding in working memory a sequence of digits that were in the same order (low memory load) or a different order (high memory load) on every trial. Higher memory load, associated with increased prefrontal activity, resulted in greater interference effects on behavioral performance from the distractor faces, plus increased face-related activity in the visual cortex. These findings confirm a major role for working memory in the control of visual selective attention.

Adult↗

PubMed2003

Selective alterations in prefrontal cortical GABA neurotransmission in schizophrenia: a novel target for the treatment of working memory dysfunction.

RATIONALE: Disturbances in critical cognitive processes, such as working memory, are now regarded as core features of schizophrenia, but available pharmacological treatments produce little or no improvement in these cognitive deficits. Although other explanations are possible, these cognitive deficits appear to reflect a disturbance in executive control, the processes that facilitate complex information processing and behavior and that include context representation and maintenance, functions dependent on the dorsolateral prefrontal cortex (DLPFC). Studies in non-human primates indicate that normal working memory function depends upon appropriate GABA neurotransmission in the DLPFC, and alterations in markers of GABA neurotransmission are well documented in the DLPFC of subjects with schizophrenia. OBJECTIVES: Thus, the purpose of this paper is to review the nature of the altered GABA neurotransmission in the DLPFC in schizophrenia, and to consider how these findings might inform the search for new treatments for cognitive dysfunction in this illness. RESULTS AND CONCLUSIONS: Postmortem studies suggest that markers of reduced GABA neurotransmission in schizophrenia may be selective for, or at least particularly prominent in, the subclass of GABA neurons, chandelier cells, that provide inhibitory input to the axon initial segment of populations of pyramidal neurons. Given the critical role that chandelier cells play in synchronizing the activity of pyramidal neurons, the pharmacological amelioration of this deficit may be particularly effective in normalizing the neural network activity required for working memory function. Because GABA(A) receptors containing the a(2) subunit are selectively localized to the axon initial segment of pyramidal cells, and appear to be markedly up-regulated in schizophrenia, treatment with novel benzodiazepine-like agents with selective activity at GABA(A) receptors containing the a(2) subunit may be effective adjuvant agents for improving working memory function in schizophrenia.

Animals↗

PubMed1999

Neuropsychological and oculomotor correlates of spatial working memory performance in schizophrenia patients and controls.

Recent reports of spatial working memory deficits in schizophrenia provide evidence for dorsolateral prefrontal cortical (DLPFC) dysfunction. However, the question of how spatial working memory performance relates to other task impairments in schizophrenia considered reflective of frontal dysfunction, such as the Wisconsin Card Sorting Test (WCST) and smooth pursuit eye tracking, has been largely unexplored. Spatial working memory, as measured by a computerized visual-manual delayed response task (DRT), was evaluated in 42 schizophrenia patients and 54 normal controls. Subjects also completed a battery of neuropsychological and oculomotor tasks. Schizophrenia patients performed as accurately as controls on a no-delay, sensory-motor control condition, but showed a significant impairment in spatial accuracy with the addition of an 8-s delay and verbal distraction task. For the patients, working memory impairment was associated with fewer categories on the WCST, impaired eye tracking, fewer words learned on the Rey Auditory Verbal Learning Test, but not with measures of general cognitive and clinical functioning. Results suggest the presence of a sub-group of schizophrenia patients with common pathophysiology that accounts for the co-variance of several tasks implicating prefrontal dysfunction.

Adult↗

PubMed2003

Dimensions of working memory dysfunction in schizophrenia.

The aim of this study was to investigate the underlying structure of eight working memory tests used to assess prefrontal dysfunction in schizophrenia research [Letter-Number Span (LNS), Digit-Symbol Test (DST), Trail-Making Test B (TMT-B), Delayed Response Task (DRT) for spatial working memory, Subject Ordered Pointing Task (SOPT), Dual Tasking (DUAL), Continuous Performance Test (CPT)-Identical Pairs, Wisconsin Card Sorting Test (WCST)]. Sixty-six patients with schizophrenia showed significant working memory performance deficits in all tests when compared with 45 healthy controls. Performance was not systematically related to psychopathology. When differences in IQ were controlled, working memory deficits remained stable except in the WCST. Principal components analyses yielded three components for healthy controls: a comparator function of the central executive defined by a comparison of working memory content with information from the environment, an allocation of attentional resources function, and a maximum storage capacity function. The comparator and maximum storage functions could be replicated in the schizophrenia sample. However, the allocation function did not emerge as an independent component and was replaced by a component defined by the WCST. These findings suggest that working memory is not a unitary concept but rather should be conceptually differentiated as functions of transient storage/active rehearsal capacity and central executive manipulation supporting a previous suggestion proposed by Perry et al. [Schizophr. Bull. 27 (2001) 157].

Adult↗

PubMed2001

The association between antisaccade task and working memory task performance in schizophrenia and bipolar disorder.

To date, the research literature has yielded conflicting reports regarding the specificity of antisaccade deficits to schizophrenia. We sought to examine antisaccade and working memory task performance in schizophrenia patients and bipolar patients, as well as to examine the relationship between the two tasks in both patient populations. Thirty-four schizophrenia patients, 20 bipolar patients, and 30 nonpatient controls were administered saccadic inhibition (antisaccade), working memory, and sensorimotor tasks. Compared with the controls, the schizophrenia patients displayed both antisaccade deficits and working memory deficits. In contrast, the bipolar patients produced significantly more errors on the antisaccade task than the controls, though the bipolar group performed similarly to the control group on the working memory task. Mediational analyses demonstrated that working memory partially mediates the relationship between patients' diagnostic group status and antisaccade task performance; working memory performance contributed uniquely to the prediction of antisaccade task performance in the two patient groups. Antisaccade deficits do not appear specific to schizophrenia. The results suggest that in schizophrenia, working memory and antisaccade tasks are tapping similar cognitive processes, whereas in bipolar patients the processes underlying antisaccade and working memory performance are disparate.

Adult↗