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PubMed2001

Functional magnetic resonance imaging of working memory impairment after traumatic brain injury.

OBJECTIVES: To examine patterns of brain activation while performing a working memory task in persons with moderate to severe traumatic brain injury (TBI) and healthy controls. It is well established that working memory is an area of cognition that is especially vulnerable to disruption after TBI. Although much has been learned about the system of cerebral representation of working memory in healthy people, little is known about how this system is disrupted by TBI. METHODS: Functional magnetic resonance imaging (fMRI) was used to assess brain activation during a working memory task (a modified version of the paced auditory serial addition test) in nine patients with TBI and seven healthy controls. RESULTS: Patients with TBI were able to perform the task, but made significantly more errors than healthy controls. Cerebral activation in both groups was found in similar regions of the frontal, parietal, and temporal lobes, and resembled patterns of activation found in previous neuroimaging studies of working memory in healthy persons. However, compared with the healthy controls, the TBI group displayed a pattern of cerebral activation that was more regionally dispersed and more lateralised to the right hemisphere. Differences in lateralisation were particularly evident in the frontal lobes. CONCLUSIONS: Impairment of working memory in TBI seems to be associated with alterations in functional cerebral activity.

Adult↗
PubMed2007

Verbal working memory in children with mild intellectual disabilities.

BACKGROUND: Previous research into working memory of individuals with intellectual disabilities (ID) has established clear deficits. The current study examined working memory in children with mild ID (IQ 55-85) within the framework of the Baddeley model, fractionating working memory into a central executive and two slave systems, the phonological loop and visuo-spatial sketchpad. METHOD: Working memory was investigated in three groups: 50 children with mild ID (mean age 15 years 3 months), 25 chronological age-matched control children (mean age 15 years 3 months) and 25 mental age-matched control children (mean age 10 years 10 months). The groups were given multiple assessments of the phonological-loop and central-executive components. RESULTS: The results showed that the children with mild ID had an intact automatic rehearsal, but performed poorly on phonological-loop capacity and central-executive tests when compared with children matched for chronological age, while there were only minimal differences relative to the performance of the children matched for mental age. CONCLUSIONS: This overall pattern of results is consistent with a developmental delay account of mild ID. The finding of a phonological-loop capacity deficit has important implications for the remedial training of children with mild ID.

Adolescent↗
PubMed2006

The multi-component model of working memory: explorations in experimental cognitive psychology.

There are a number of ways one can hope to describe and explain cognitive abilities, each of them contributing a unique and valuable perspective. Cognitive psychology tries to develop and test functional accounts of cognitive systems that explain the capacities and properties of cognitive abilities as revealed by empirical data gathered by a range of behavioral experimental paradigms. Much of the research in the cognitive psychology of working memory has been strongly influenced by the multi-component model of working memory [Baddeley AD, Hitch GJ (1974) Working memory. In: Recent advances in learning and motivation, Vol. 8 (Bower GA, ed), pp 47-90. New York: Academic Press; Baddeley AD (1986) Working memory. Oxford, UK: Clarendon Press; Baddeley A. Working memory: Thought and action. Oxford: Oxford University Press, in press]. By expanding the notion of a passive short-term memory to an active system that provides the basis for complex cognitive abilities, the model has opened up numerous questions and new lines of research. In this paper we present the current revision of the multi-component model that encompasses a central executive, two unimodal storage systems: a phonological loop and a visuospatial sketchpad, and a further component, a multimodal store capable of integrating information into unitary episodic representations, termed episodic buffer. We review recent empirical data within experimental cognitive psychology that has shaped the development of the multicomponent model and the understanding of the capacities and properties of working memory. Research based largely on dual-task experimental designs and on neuropsychological evidence has yielded valuable information about the fractionation of working memory into independent stores and processes, the nature of representations in individual stores, the mechanisms of their maintenance and manipulation, the way the components of working memory relate to each other, and the role they play in other cognitive abilities. With many questions still open and new issues emerging, we believe that the multicomponent model will continue to stimulate research while providing a comprehensive functional description of working memory.

Brain↗
PubMed2006

Trauma-related deficits in working memory.

INTRODUCTION: The aim of the study was to evaluate trauma-related impairments of working memory in psychiatric outpatients, and the mediating role of processing speed, anxiety and depression in the cognitive decrements. METHODS: This research applied a comprehensive assessment protocol including an evaluation of psychopathological and neuropsychological functioning in psychiatric outpatients. Patients with trauma history (n = 33) were compared to patients without such a history (n = 30). We collected information regarding age, gender, culture level, profession level, alcohol abuse, anxiety, and depression symptoms. Working memory and speed processing were assessed with standardised neuropsychological instruments. Data analysis was accomplished using parametric statistics, and a hierarchical multiple regression model was used to regress working memory performance scores against the trauma variable, anxiety-depression scores, and speed processing. RESULTS: The groups differed by gender, not by age, education level, socioeconomic status and alcohol abuse. Analysis of cognitive data revealed specific trauma-related deficits in working memory. Moreover, the trauma-exposed subjects scored higher on anxiety/depression scales, and lower on processing speed tests. The regression revealed significant impairment in working memory partially mediated by speed processing, but not by anxiety or depression. CONCLUSIONS: These findings confirmed the trauma-related impairments in working memory and the paramount importance for these impairments of reduced processing speed rather than emotional factors.

Adolescent↗
PubMed2005

Study on EEG power and coherence in patients with mild cognitive impairment during working memory task.

To investigate the features of electroencephalography (EEG) power and coherence at rest and during a working memory task of patients with mild cognitive impairment (MCI). Thirty-five patients (17 males, 18 females; 52-71 years old) and 34 sex- and age-matched controls (17 males, 17 females; 51-63 years old) were recruited in the present study. Mini-Mental State Examination (MMSE) of 35 patients with MCI and 34 normal controls revealed that the scores of MCI patients did not differ significantly from those of normal controls (P>0.05). Then, EEGs at rest and during working memory task with three levels of working memory load were recorded. The EEG power was computed over 10 channels: right and left frontal (F3, F4), central (C3, C4), parietal (P3, P4), temporal (T5, T6) and occipital (O1, O2); inter-hemispheric coherences were computed from five electrode pairs of F3-F4, C3-C4, P3-P4, T5-T6 and O1-O2 for delta (1.0-3.5 Hz), theta (4.0-7.5 Hz), alpha-1 (8.0-10.0 Hz), alpha-2 (10.5 -13.0 Hz), beta-1 (13.5-18.0 Hz) and beta-2 (18.5-30.0 Hz) frequency bands. All values of the EEG power of MCI patients were found to be higher than those of normal controls at rest and during working memory tasks. Furthermore, the values of EEG power in the theta, alpha-1, alpha-2 and beta-1 bands of patients with MCI were significantly high (P<0.05) in comparison with those of normal controls. Correlation analysis indicated a significant negative correlation between the EEG powers and MMSE scores. In addition, during working memory tasks, the EEG coherences in all bands were significantly higher in the MCI group in comparison with those in the control group (P<0.05). However, there was no significant difference in EEG coherences between two groups at rest. These findings comprise evidence that MCI patients have higher EEG power at rest, and higher EEG power and coherence during working conditions. It suggests that MCI may be associated with compensatory processes at rest and during working memory tasks. Moreover, failure of normal cortical connections may be exist in MCI patients.

Aged↗
PubMed1999

The role of the agranular insular cortex in working memory for food reward value and allocentric space in rats.

The present experiment examined the effects of quinolinic acid (125 mM) lesions of the agranular insular area on working memory for food reward value and working memory for spatial locations. In both tasks a go/no-go procedure was used. Working memory for food reward value was assessed using a delayed conditional discrimination in which either a 20% or 45% sugar content cereal was associated with a reinforcement and the other cereal was not. In the spatial locations task, rats were allowed to enter 12 arms in a radial maze for a food reinforcement. Of the 12 arm presentations, three or four arms were presented for a second time in a session which did not contain a reinforcement. The number of trials between the 1st and 2nd presentation of an arm ranged from 0 to 6 (lags). Working memory was assessed by the latency to enter an arm during the 2nd presentation. In the food reward value task, agranular insular lesions produced memory deficits in a delay-dependent manner. In contrast, agranular insular lesions did not impair working memory for spatial locations. These results add to accumulating evidence suggesting that different types of working memory are distributed across separate prefrontal subregions.

Animals↗
PubMed2000

Activity in human frontal cortex associated with spatial working memory and saccadic behavior.

We examined, with event-related fMRI, two hypotheses about the organization of human working memory function in frontal cortex: (1) that a region immediately anterior to the frontal eye fields (FEF) (superior frontal cortex, SFC) is specialized for spatial working memory (Courtney, et al., 1998); and (2) that dorsolateral prefrontal cortex (PFC) plays a privileged role in the manipulation of spatial stimuli held in working memory (Owen, et al., 1996; Petrides 1994). Our delayed-response task featured 2-D arrays of irregularly arranged squares that were highlighted serially in a random sequence. The Forward Memory condition required maintenance of the spatio-temporal sequence, the Manipulate Memory condition required reordering this sequence into a new spatially defined order, the Guided Saccade condition required saccades to highlighted squares in the array, but no memory, and the Free Saccade condition required self-paced, horizontal saccades. The comparison of fMRI signal intensity associated with 2-D saccade generation (Guided Saccades) versus fMRI signal intensity associated with the delay period of the working memorials condition revealed no evidence for greater working memory-related activity than saccade-related activity in SFC in any individual subject, nor at the level of the group, and greater 2-D saccade than delay-period activity in three of five subjects. These results fail to support the hypothesis that spatial working memory-related activity is represented preferentially in a region of SFC anterior to the FEF (Courtney, et al., 1998). The comparison of maintenance versus manipulation of spatio-temporal information in working memory revealed significantly greater activity associated with the latter in dorsolateral PFC, but not in ventrolateral PFC or in SFC. These results suggest that the delay-related function of SFC is limited to the maintenance of spatial information, and that this region does not support the nonmnemonic executive control functions supported by dorsolateral PFC. These results also indicate that the preferential recruitment of dorsolateral PFC for the manipulation of information held in working memory applies to tasks employing spatial stimuli, as well as to tasks employing verbal stimuli (D'Esposito, et al., 1999); Petrides et al., 1993; Postle et al., 1999).

Acoustic Stimulation↗
PubMed2003

Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression.

BACKGROUND: A large number of studies suggest the presence of deficits in dorsolateral prefrontal cortex function during performance of working memory tasks in individuals with schizophrenia. However, working memory deficits may also present in other psychiatric disorders, such as major depression. It is not clear whether people with major depression also demonstrate impaired prefrontal activation during performance of working memory tasks. METHODS: We used functional magnetic resonance imaging to assess the patterns of cortical activation associated with the performance of a 2-back version of the N-Back task (working memory) in 38 individuals with schizophrenia and 14 with major depression. RESULTS: We found significant group differences in the activation of dorsolateral prefrontal cortex associated with working memory performance. Consistent with prior research, participants with schizophrenia failed to show activation of right dorsolateral prefrontal cortex in response to working memory tasks demands, whereas those with major depression showed clear activation of right and left dorsolateral prefrontal cortex as well as bilateral activation of inferior and superior frontal cortex. CONCLUSIONS: During performance of working memory tasks, deficits in prefrontal activation, including dorsolateral regions, are more severe in participants with schizophrenia (most of whom were recently released outpatients) than in unmedicated outpatients with acute nonpsychotic major depression.

Adult↗
PubMed2001

Dissociation of the neural systems for working memory maintenance of verbal and nonspatial visual information.

Working memory for names and faces was investigated to ascertain whether verbal and nonspatial visual information is maintained in working memory by separate neural systems. The subjects performed a delayed match-to-sample task for famous or unfamous faces and names and a sensorimotor control task. Several occipital, temporal, parietal, and prefrontal areas were activated during all memory delays, in comparison with the control delays. Greater delay activity for unfamous faces than for names was obtained in the right fusiform gyrus, right inferior frontal gyrus (IFG), right IFG/precentral gyrus, and right medial superior frontal gyrus, whereas greater delay activity for unfamous names than for faces was observed in the precuneus, left insula/postcentral gyrus, and left IFG/precentral gyrus. There was no significant difference in the prefrontal activity in the comparison between famous faces and names. Greater delay activity for famous names than for faces was obtained in visual association and parietal areas. The results indicate that there is a functional dissociation based on information type within the neural system that is responsible for working memory maintenance of verbal and nonspatial visual information.

Adult↗
PubMed2005

Effects of aging and working memory demands on prospective memory.

The current study used event-related brain potentials (ERPs) to examine the effects of aging, increasing the working memory demands of the ongoing activity, and a prospective memory load on the neural correlates of prospective remembering and target recognition. The behavioral data revealed that the success of prospective memory was sensitive to working memory load in younger, but not older, adults and that a prospective memory load had a greater effect on the performance of older adults than that of younger adults. The ERP data revealed age-related differences in the neural correlates of the detection of prospective cues, post-retrieval processes that support prospective memory, and target recognition. Our results support the hypothesis that there are age-related differences in the ability to recruit preparatory attentional processes that underlie prospective memory, and demonstrate that younger and older adults may recruit somewhat different neural generators to support prospective memory and working memory.

Adolescent↗
PubMed2000

Specific relationship between prefrontal neuronal N-acetylaspartate and activation of the working memory cortical network in schizophrenia.

OBJECTIVE: Abnormal activation of the dorsolateral prefrontal cortex and a related cortical network during working memory tasks has been demonstrated in patients with schizophrenia, but the responsible mechanism has not been identified. The present study was performed to determine whether neuronal pathology of the dorsolateral prefrontal cortex is linked to the activation of the working memory cortical network in patients with schizophrenia. METHOD: The brains of 13 patients with schizophrenia and 13 comparison subjects were studied with proton magnetic resonance spectroscopic ((1)H-MRS) imaging (to measure N-acetylaspartate as a marker of neuronal pathology) and with [(15)O]water positron emission tomography (PET) during performance of the Wisconsin Card Sorting Test (to measure activation of the working memory cortical network). An independent cohort of patients (N=7) was also studied in a post hoc experiment with (1)H-MRS imaging and with the same PET technique during performance of another working memory task (the "N-back" task). RESULTS: Measures of N-acetylaspartate in the dorsolateral prefrontal cortex strongly correlated with activation of the distributed working memory network, including the dorsolateral prefrontal, temporal, and inferior parietal cortices, during both working memory tasks in the two independent groups of patients with schizophrenia. In contrast, N-acetylaspartate in other cortical regions and in comparison subjects did not show these relationships. CONCLUSIONS: These findings directly implicate a population of dorsolateral prefrontal cortex neurons as selectively accounting for the activity of the distributed working memory cortical network in schizophrenia and complement other evidence that dorsolateral prefrontal cortex connectivity is fundamental to the pathophysiology of the disorder.

Adult↗
PubMed2004

Pharmacological manipulation of human working memory.

RATIONALE: The goal of this paper is to briefly overview human studies that have examined pharmacological agents designed to enhance working memory function, with the idea of providing clues as to promising avenues to follow for the development of drugs likely to enhance working memory and other cognitive processes in individuals with schizophrenia. OBJECTIVES: We reviewed the studies that have used pharmacological agents designed to target the dopamine system, the noradrenergic system, the acetycholine system, the serotonin system, and the glycine site on NMDA receptors. RESULTS: There are a large number of studies suggesting that dopamine agents can enhance working memory, though there remain conflicting issues regarding the role that baseline performance plays in modulating the influence of drug and the importance of different dopamine receptors. There is also consistent evidence that cholinesterase inhibitors can enhance working memory function, potentially through improved encoding of the information. There is less consistent evidence that noradrenergic alpha-2 agonists consistently improve working memory in humans, despite the large animal literature suggesting that these agents should have a beneficial effect on memory. As of yet, there is little evidence that agents targeting the glycine site of the NMDA receptor improve working memory, and data to suggest that enhancement of the serotonin system impairs working memory. CONCLUSIONS: Compounds geared towards enhancing the dopamine system and the acetycholine system remain promising avenues for the development of pro-cognitive drugs, though further work is clearly needed on developing agents that may more selectively target specific receptors.

Adrenergic Agents↗
PubMed2004

Attention deficit/hyperactivity disorder and working memory in clinically referred adults.

A current theory of attention deficit/hyperactivity disorder (ADHD) implicates a dysfunction in working memory as a significant factor in ADHD. The Working Memory Indexes of the Wechsler Adult Intelligence Scale--Third Edition (WAIS-III; The Psychological Corporation, 1997a) and the Wechsler Memory Scale--Third Edition (WMS-III; The Psychological Corp -oration, 1997b) were used to evaluate this theory. Seventy adults clinically diagnosed with ADHD (mean age = 25) and who were previously administered the WAIS-III and WMS-III were reviewed to determine the association between working memory and ADHD symptomology. The respondent was asked to estimate the frequency of occurrence of ADHD symptoms by completing the Brown ADD Scales (Brown, 1996). Results indicated no significant relationship between working memory and self-reported symptoms, although the Working Memory Indexes of the WAIS-III and the WMS-III were significantly correlated. Implications for current ADHD theory and suggestions for future research were discussed.

Adolescent↗
PubMedDate not supplied

Prenatal cocaine exposure does not alter working memory in adult rats.

The present study was designed to assess working memory in adult rats exposed to intravenous cocaine in utero, as part of an examination of various cognitive and affective functions. The study included four groups: a saline control and three groups exposed to ascending doses of cocaine from gestational days 8 to 21 (0.5, 1.0, or 3.0 mg/kg). This exposure regimen (route of administration and dose) has been shown to accurately reproduce the pharmacokinetic profile and physiological effects of human recreational cocaine use. This report describes the results of a series of automated alternation tasks, in which the animals were rewarded for alternating their responses between two response ports on successive trials. In the final task, the delay between trials varied randomly between 0, 20, 40, and 80 s, thereby varying the retention interval. Although performance declined dramatically as the retention interval increased, the rate of this decline did not differ across treatment groups. These results suggest that prenatal cocaine exposure, at doses that model recreational use, does not produce lasting changes in explicit memory or working memory. However, subtle, sex-specific effects of prenatal cocaine exposure were seen on measures that indicate impairments in sustained attention and "readiness", as well as altered reactivity to task-related stressors such as waiting for long and unpredictable delays.

Animals↗
PubMed2007

Distinction between perceptual and attentional processing in working memory tasks: a study of phase-locked and induced oscillatory brain dynamics.

Working memory involves the short-term storage and manipulation of information necessary for cognitive performance, including comprehension, learning, reasoning and planning. Although electroencephalogram (EEG) rhythms are modulated during working memory, the temporal relationship of EEG oscillations with the eliciting event has not been well studied. In particular, the dynamics of the neural network supporting memory processes may be best captured in induced oscillations, characterized by a loose temporal link with the stimulus. In order to differentiate induced from evoked functional processes, the present study proposes a time-frequency analysis of the 3 to 30 Hz EEG oscillatory activity in a verbal n-back working memory paradigm. Control tasks were designed to identify oscillatory activity related to stimulus presentation (passive task) and focused attention to the stimulus (detection task). Evoked theta activity (4-8 Hz) phase-locked to the visual stimulus was evidenced in the parieto-occipital region for all tasks. In parallel, induced theta activity was recorded in the frontal region for detection and n-back memory tasks, but not for the passive task, suggesting its dependency on focused attention to the stimulus. Sustained induced oscillatory activity was identified in relation to working memory in the theta and beta (15-25 Hz) frequency bands, larger for the highest memory load. Its late occurrence limited to nonmatched items suggests that it could be related to item retention and active maintenance for further task requirements. Induced theta and beta activities displayed respectively a frontal and parietal topographical distribution, providing further functional information on the fronto-posterior network supporting working memory.

Adult↗
PubMed2003

Using executive heterogeneity to explore the nature of working memory deficits in Parkinson's disease.

Idiopathic Parkinson's disease (IPD) is characterised by a triad of motor symptoms, namely bradykinesia, rigidity and resting tremor, although cognitive impairment is a common feature of the disease and has been accepted as one of the strong predictors of quality of life in such patients. Neuropsychological testing in Parkinson's disease often reveals a pattern of cognitive impairment similar to that observed in patients with frontal lobe lesions, although clear differences between the two groups have also often been reported. This apparent inconsistency in the literature may reflect heterogeneity among different groups of patients with Parkinson's disease, although to date this possibility has not been formally addressed. In this study, two groups of patients with Parkinson's disease were assessed on a novel verbal memory task, which allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm. The two groups were selected according to either good or bad performance on a 'standard', visuospatial test of executive function (The Tower of London Task), but were well matched on all other demographic and cognitive measures tested. The sub-group of Parkinson's disease patients with Tower of London defined executive deficit were specifically impaired at manipulating information within verbal working memory, both compared to controls and to the group of patients with no predefined executive impairments. In contrast, the three groups did not differ in their ability to maintain or retrieve information within verbal working memory. Given the known preferential role of the dorsolateral frontal cortex in higher executive functions, (including both planning and the manipulation of information within working memory), these results suggest that, in a subset of Parkinson's disease patients, it is the frontostriatal circuitry involving this region which is primarily affected, while other components of this circuitry may be relatively spared. The results also suggest that performance on the Tower of London task may prove to be a useful discriminant variable in defining the nature of cognitive heterogeneity in Parkinson's disease.

Aged↗
PubMed2003

The modulatory effects of dopamine D1 and D2 receptor function on object working memory in humans.

The role of dopamine D1 and D2 receptors in modulating object working memory in humans is poorly understood. The current study was designed to investigate the effects of D1 and D2 receptor modulation on object working memory. Twelve healthy subjects underwent testing under three conditions (0.05 mg pergolide (D1/D2 receptor agonist), 2.5 mg bromocriptine (D2 receptor agonist) and placebo] in a double-blind, placebo-controlled repeated measures design. Subjects performed the object working memory N-back task pre-drug and 1.5 h and 3 h post-drug administration. Neither pergolide nor bromocriptine had an effect on object working memory performance. These findings suggest that object working memory may not be modulated by D1 and D2 receptors in humans.

Adolescent↗
PubMed2001

Distinct contributions of glutamate and dopamine receptors to temporal aspects of rodent working memory using a clinically relevant task.

RATIONALE: Understanding the mechanistic basis of working memory, the capacity to hold representation "on line," is important for delineating the processes involved in higher cognitive functions and the pathophysiology of thought disorders. OBJECTIVES: We compared the contribution of glutamate and dopamine receptor subtypes to temporal aspects of working memory using a modified rodent spatial working memory task that incorporates important elements of clinical working memory tasks. METHODS: A discrete paired-trial variable-delay T-maze task was used. Initial characterization studies indicated that performance on this task is stable at seconds-long retention intervals, is sensitive to retention interval and proactive interference, and is dependent on the integrity of the medial prefrontal cortex. RESULTS: Consistent with clinical findings, low dose amphetamine (0.25 mg/kg) produced a delay-dependent improvement in performance, while higher doses impaired performance at all retention intervals. D1 receptor blockade produced the predicted dose- and delay-dependent impairment. D2 receptor blockade had no effect. Activation of metabotropic glutamate 2/3 (mGluR2/3) receptors, which in the prefrontal cortex inhibits the slow asynchronous phase of glutamate release, also produced a delay-dependent impairment. Low doses of an AMPA/kainate antagonist had effects similar to the mGluR2/3 agonist. In contrast, NMDA receptor antagonist-induced impairment was memory load-insensitive, resulting in chance-level performance at all retention intervals. CONCLUSIONS: These findings suggest that activation of NMDA receptors is necessary for the formation of mnemonic encoding while modulatory components involving slow asynchronous release of glutamate and phasic release of dopamine contribute to the active maintenance of information during the delay period.

Amphetamine↗