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PubMed2004

Selective D2 receptor actions on the functional circuitry of working memory.

Prefrontal neurons engaged by working memory tasks express a sequence of phasic and tonic activations linked to a train of sensory, mnemonic, and response-related events. Here, we report that the dopamine D2 receptor selectively modulates the neural activities associated with memory-guided saccades in oculomotor delayed-response tasks yet has little or no effect on the persistent mnemonic-related activity, which is instead modulated by D1 receptors. This associates the D2 receptor with a specific component of working memory circuitry and fractionates the modulatory effects of D1 and D2 receptors on the neural machinery of a cognitive process.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2006

Memory performance profile in occupational chronic solvent encephalopathy suggests working memory dysfunction.

This pilot study characterizes memory functioning of 11 men with occupational chronic solvent encephalopathy (CSE). Pattern (PRM) and spatial recognition (SRM), spatial span (SSP), spatial working memory (SWM), and paired associate learning (PAL) from Cambridge Neuropsychological Test Automated Battery were performed twice. The most sensitive variables to show impairment were PAL trials, SRM total correct, and SWM number of between-search errors. The majority of the CSE patients demonstrated mild deficits. The most persistent dysfunction was in tasks demanding working memory processing, which predicted well the CSE status. Qualitatively, the memory deficits resemble those seen in moderate or severe Parkinson's disease.

Association Learning↗
PubMed1999

Neurobehavioral evidence for working-memory deficits in school-aged children with histories of prematurity.

Cognitive performance in 7- to 9-year-old preterm neonatal intensive-care survivors was compared with that in age-matched control children. Non-verbal memory span, spatial working-memory abilities, planning, set-shifting, and recognition memory for both spatial and patterned stimuli were assessed using the Cambridge Neuropsychological Testing Automated Battery. Relative to children in the control group, neonatal intensive-care unit (NICU) survivors demonstrated 25% more memory errors on the spatial working-memory task. Their use of strategy on this task was similar to a control group of 5-year-olds. Planning times on 'Tower of London' problems were long relative to those of term controls. NICU survivors demonstrated poorer pattern recognition as well as a shorter spatial memory span. The groups did not differ in visual-discrimination learning or in spatial-recognition memory. No specific neonatal risk factor accounted for the observed differences, although scores on the Neurobiological Risk Score (NBRS), a composite measure of neonatal risk, did predict several aspects of later task performance. Whether these data reflect a developmental delay in brain maturation in NICU survivors or the presence of a permanent information-processing deficit due to adverse neonatal events must be assessed through continued follow-up.

Child↗
PubMed2001

Age-related changes in regional activation during working memory in young adults: an fMRI study.

Several lines of evidence suggest that working memory diminishes with advancing age, with concomitant functional changes in associated neuronal activation in frontal cortical regions and hippocampi. No studies to date, however, have investigated age-related changes in neuronal activation in these regions during performance of a working memory task in younger subjects without working memory deficits. In this study, we utilized fMRI to examine changes in brain activation with increasing age in specific regions-of-interest. Eleven healthy subjects performed a "two-back" working memory task and a matched "zero-back" attention task during fMRI. There was no association between age and performance on either task. Left hippocampal activation significantly correlated with age (P = 0.01) and right hippocampal activation showed an association with age (P = 0.09). This study demonstrates that increasing age is associated with increased activation of hippocampus even in young patients without evidence of working memory deficits and suggests that functional changes may precede overt evidence of working memory deficits.

Adult↗
PubMed2005

Successful declarative memory formation is associated with ongoing activity during encoding in a distributed neocortical network related to working memory: a magnetoencephalography study.

The aim of the present study was to investigate the spatio-temporal characteristics of the neural correlates of declarative memory formation as assessed by the subsequent memory effect, i.e. the difference in encoding activity between subsequently remembered and subsequently forgotten items. Different operations could account for these effects. In particular, it has been proposed that successful memory formation depends on the organization of the information at the time of encoding, an operation accomplished by the working memory system. Consequently, functional magnetic resonance imaging studies have already shown that the very same regions that are involved in certain working memory processes are also involved in declarative memory formation. Here, we used magnetoencephalography to investigate whether the subsequent memory effects in these regions are present throughout picture stimulus presentation, postulating ongoing working memory operations as an effective factor. The results showed that subsequent memory effects began to appear after about 300 ms post stimulus onset over bilateral temporal areas and left parietal regions and were sustained throughout the recording epoch (1000 ms). Roughly parallel to these effects, we identified a left frontal subsequent memory effect, which, however, was less sustained than the other effects. In addition, we revealed a late subsequent memory effect over the right occipital region, which has not been described previously in the event-related potential literature. These sustained subsequent memory effects are suggestive of working memory processes that may enable deep semantic and perceptual processing. Additionally, contextually constrained visual perception after top-down modulation may account for a more efficient encoding of the complex scene.

Adult↗
PubMed2005

Beyond heritability: neurotransmitter genes differentially modulate visuospatial attention and working memory.

A cued, visuospatial attention task and a working memory task were administered to 89 healthy adults genotyped for a T-to-C polymorphism in CHRNA4, a nicotinic receptor subunit gene. Increasing gene dose of the C allele of the CHRNA4 gene (i.e., no C alleles, one C allele, two C alleles) was associated with increased reaction time (RT) benefits of valid attentional cuing and reduced RT costs of invalid cues, but was not associated with working memory performance. In a second experiment, 103 healthy persons were genotyped for a G-to-A polymorphism of the dopamine beta-hydroxylase (DBH) gene. Increasing gene dose of the G allele of the DBH gene was associated with increased working memory accuracy at a high memory load. However, there was no consistent association between the DBH gene and visuospatial attention. Thus, a double dissociation was observed, with visuospatial attention associated with CHRNA4 but not the DBH gene and, conversely, working memory associated with the DBH gene but not CHRNA4. The results show that normal allelic variations in single neurotransmitter genes modulate individual differences in processing components of cognitive functions in healthy individuals.

Adult↗
PubMed2001

Working memory for location and time: activity in prefrontal area 46 relates to selection rather than maintenance in memory.

The role of the dorsal prefrontal cortex in working memory remains controversial. Influential proposals include a role in the maintenance of domain-specific information, and the processes of executive functions on remembered information. We used event-related functional magnetic resonance imaging to demonstrate a functional dissociation within prefrontal cortex in terms of the components of complex working memory tasks. The maintenance in working memory of spatial locations and their temporal order was associated with activation of area 8 and intraparietal cortex. In contrast, the selection of one location, according to its order, was associated with a distinct frontoparietal network, including dorsolateral prefrontal area 46, ventrolateral prefrontal cortex and anterior cingulate cortex and medial parietal cortex. The different contributions of these areas to selection are considered in the light of recent electrophysiological and lesion studies. We suggest a general role of the dorsolateral prefrontal area 46 in attentional selection, including selection from within working memory.

Adult↗
PubMed1999

The acetylcholinesterase inhibitor, ENA 713 (Exelon), attenuates the working memory impairment induced by scopolamine in an operant DNMTP task in rats.

RATIONALE: The disruption of working memory in the delayed non-matching to position (DNMTP) task by the muscarinic antagonist, scopolamine, is considered to be a model of the spatial working memory deficit in Alzheimer's disease (AD) patients. OBJECTIVE: To investigate whether ENA 713 (Exelon) (0.1, 0.5 mg/kg, IP), an acetylcholinesterase inhibitor, would reverse the effects of scopolamine in the DNMTP task. METHODS: Male Lister Hooded rats were trained to criterion in an operant DNMTP task (0- to 16-s delay intervals) before receiving vehicle, scopolamine (0.05 mg/kg, SC) alone, ENA 713 (0.1, 0.5 mg/kg, IP) alone, or combinations of scopolamine and ENA 713, in two variations of the task - with and without barriers inserted between the food magazine and the two levers. Barriers were inserted to prevent the use of positional strategies to perform the task, since this behaviour may confound the conclusions of the effect of drugs on working memory. RESULTS: It was found that: (i) scopolamine significantly reduced choice accuracy delay-dependently in both test situations while modifying non-mnemonic measures of task performance delay-independently, indicating an impairment of working memory; (ii) ENA 713 (0.5 mg/kg) significantly attenuated the scopolamine-induced impairment of working memory and significantly reduced the scopolamine-induced changes in some non-mnemonic measures of task performance; (iii) the presence of barriers did not alter the effects of scopolamine and ENA 713 on working memory. CONCLUSION: ENA 713 reversed the working memory deficit induced by scopolamine. These results are consistent with the attenuation of learning and memory disruptions due to cholinergic dysfunction by ENA 713 in other preclinical assays, and predict a drug-induced improvement in working memory in AD patients.

Animals↗
PubMed1998

Human prefrontal cortex is not specific for working memory: a functional MRI study.

Lesion studies in monkeys have provided evidence that lateral prefrontal cortex is necessary for working memory, the cognitive processes involved in the temporary maintenance and manipulation of information. Monkey electrophysiological studies, however, have also observed prefrontal neuronal activity associated with cognitive processes that are nonmnemonic. We tested the hypothesis that the same regions of human prefrontal cortex that demonstrate activity during working memory tasks would also demonstrate activity during tasks without working memory demands. During echoplanar fMRI imaging, subjects performed a three-condition experiment (working memory task, nonworking memory task, rest). In the working memory task, subjects observed serially presented stimuli and determined if each stimulus was the same as that presented two stimuli back. The nonworking memory task in Experiment 1 required subjects to identify a single predetermined stimulus; in Experiment 2, subjects were required to make a button press to every stimulus. In all subjects in both experiments, the working memory task exhibited greater prefrontal cortical activity compared to either nonworking memory task. In these same prefrontal regions, greater activation was also observed during both nonworking memory tasks compared to rest. We conclude that human lateral prefrontal cortex supports processes in addition to working memory. Thus, reverse inference of the form "if prefrontal cortex is active, working memory is engaged" is not supported.

Adult↗
PubMed1997

Dissociation of visual and spatial processing in working memory.

Although models of working memory originally included visuo-spatial memory as an undifferentiated component, recent work indicates that spatial location is separable from other visual characteristics. The evidence which is derived from interference, however, typically requires the division of conscious attention between primary and interference tasks. In the present experiments the differential effects of an unattended flickering surround upon serial recall of a central stimulus presentation were investigated. Colour changes in the surround created more interference than achromatic flicker when the task was to report either the colours or the patterns presented in the target. When the locations of the targets were required, however, the situation was reversed and the achromatic flicker created more interference than did the colour flicker. It is suggested that this double dissociation of identification and location is best understood in terms of differential involvement of the magnocellular and parvocellular pathways.

Adult↗
PubMed1994

Characteristics of visual interference with visuospatial working memory.

Recent discussions of visuospatial working memory have suggested that this subsystem may incorporate a visual buffer which holds visuospatial information relatively passively. Empirical investigations of visual interference with information held within a visuospatial subsystem have yielded somewhat equivocal results. Nonetheless, evidence from Logie (1986) has indicated that visuospatial processing can be disrupted by passive exposure to irrelevant visual material in a manner analogous to the disruption of serial verbal recall by exposure to irrelevant speech. This paper reports two experiments which explore whether such irrelevant visual input is disruptive to storage of imaginal information in a primarily spatial task--the Brooks spatial matrix task. Experiment 1 shows that exposure to irrelevant visual input during encoding selectively disrupts performance on a spatial, but not a verbal, version of the task. The extent of such disruption is shown to be independent of the visual complexity of the material, its similarity to the to-be-remembered information, or a change in state, with a static white square pattern yielding equivalent disruption to that produced by changing matrix patterns. The second experiment indicates that this pattern of effects is robust, and that such disruption is evident at an equivalent level when the visual material is present only during a 20-second retention interval. These results are interpreted as evidence of obligatory access of external visual material to a passive visual buffer. Implications for the nature of a visuospatial subsystem in working memory are discussed.

Adult↗
PubMed2005

Spatial working memory deficit correlates with disorganization symptoms and social functioning in schizophrenia.

Both spatial working memory deficit and disorganization symptoms have been considered significant components of schizophrenic impairment involved with the dorsolateral prefrontal cortex. The purpose of the present study was to investigate the relationships among spatial working memory, psychiatric symptoms including disorganization symptoms, and social functioning in schizophrenia. Fifty clinically stable patients with schizophrenia and 34 healthy controls participated in the study. Patients were rated with the Brief Psychiatric Rating Scale and the Rehabilitation Evaluation Hall and Baker. The Advanced Trail Making Test was used to evaluate spatial working memory. Patients demonstrated significantly reduced spatial working memory compared to that of healthy controls. Spatial working memory in patients correlated significantly with social functioning such as self-care skills, community skills and speech disturbance, and with disorganization symptoms. Disorganization symptoms also correlated with these aspects of social functioning. In conclusion it is suggested that both spatial working memory deficit and disorganization symptoms, which are impairments involved with the dorsolateral prefrontal cortex dysfunction, can serve as effective predictors of social functioning.

Adult↗
PubMed2002

Neocortical system abnormalities in autism: an fMRI study of spatial working memory.

OBJECTIVE: To test the hypothesis that deficits in spatial working memory in autism are due to abnormalities in prefrontal circuitry. METHODS: Functional MRI (fMRI) at 3 T was performed in 11 rigorously diagnosed non-mentally retarded autistic and six healthy volunteers while they performed an oculomotor spatial working memory task and a visually guided saccade task. RESULTS: Autistic subjects demonstrated significantly less task-related activation in dorsolateral prefrontal cortex (Brodmann area [BA] 9/46) and posterior cingulate cortex (BA 23) in comparison with healthy subjects during a spatial working memory task. In contrast, activation of autistic individuals was not reduced in other regions comprising the neural circuitry for spatial working memory including the cortical eye fields, anterior cingulate cortex, insula, basal ganglia, thalamus, and lateral cerebellum. Autistic subjects also did not demonstrate reduced activation in any brain regions while performing visually guided saccades. CONCLUSION: Impairments in executive cognitive processes in autism may be subserved by abnormalities in neocortical circuitry as evidenced by decreased activation in prefrontal and posterior cingulate circuitry during a spatial working memory task.

Adult↗
PubMed2006

Deficits in working memory in young adults with reading disabilities.

UNLABELLED: The purpose of the present study was to assess the extent to which reading disabilities (RD) in young adults are related to deficits in specific aspects of temporary storage of verbal information, namely, memory span and the central executive (CE) component of working memory. Thirty-two native Hebrew-speaking young adults with and without RD were administered a battery of memory tasks. These tasks included Digit Span Forward and Backward tests and a new version of the Token Test (TT) which is aimed at detecting subtle deficits in auditory verbal working memory. Results showed significantly poorer performance of the RD participants than the controls on the memory tests, especially on tasks that tax the CE. These findings, albeit preliminary, support the general working memory deficit hypothesis in individuals with RD, indicating that both memory span and the CE are deficient. LEARNING OUTCOMES: As a result of this activity, the reader will able to describe the different components of the verbal working memory and the debate concerning the origin of working memory deficits in individuals with reading disabilities. The reader will also be able to apply clinical suggestions as to how one might assess components of working memory.

Adult↗
PubMed2001

Processing and storage in working memory span.

Two experiments are reported that address theoretical assumptions as to the nature of working memory involved in working memory span tasks (Daneman & Carpenter, 1980). Experiment 1 used a version of the sentence span task, and Experiment 2 combined arithmetic verification with recall of presented words. In each experiment, working memory processing span was assessed independently of temporary storage span prior to their combination. Combined task performance under high demand for each component resulted in substantial residual performance for both task elements, particularly in Experiment 2. The results do not challenge the utility of the sentence span task as a measure of on-line cognition, but they raise concerns as to how resource might be allocated to processing and storage elements of the task within a single flexible resource pool, or between different resources of a multiple component working memory system. Although both models lack predictive power regarding resource allocation in these tasks, the multiple resource model appears to offer the better account.

Adult↗
PubMed1999

Ventral hippocampal ibotenic acid lesions block chronic nicotine-induced spatial working memory improvement in rats.

Chronic nicotine infusions have been found to significantly improve working memory performance in the radial-arm maze. This effect is blocked by co-infusions of the nicotinic antagonist mecamylamine. Acute nicotine injections also improve working memory performance in the radial-arm maze. This effect is also blocked by mecamylamine co-administration. Recent local infusions studies have demonstrated the importance of the ventral hippocampus for nicotinic involvement in memory. Local infusions of mecamylamine, DHbetaE or MLA impair working memory performance on the radial-arm maze. The current study was conducted to determine the importance of the ventral hippocampus for the chronic effects of nicotine. Rats were trained on the working memory task in an eight-arm radial maze. After acquisition they underwent either infusions of ibotenic acid lesions or vehicle infusions and received subcutaneous implants of osmotic minipumps that delivered either nicotine at a dose of 5 mg kg-1 day-1 or vehicle in a 2x2 design. The rats then were given 2 days of recovery and were tested on the radial-arm maze three times per week for the next 4 weeks. As seen in previous studies, in the sham lesioned group nicotine infusions caused a significant improvement in choice accuracy. In contrast no nicotine-induced improvement was seen in the rats after ibotenic acid lesions of the ventral hippocampus. The effect of nicotine was blocked even though this lesion did not cause a deficit in performance. Previous work showed that chronic nicotine infusion still caused a significant improvement in working memory performance in the radial-arm maze after knife-cut lesions of the fimbria-fornix carrying the septo-hippocampal cholinergic innervation. Thus it appears that it is the postsynaptic nicotinic receptors in the ventral hippocampus which are critically important for the expression of the chronic nicotine induced working memory improvement.

Animals↗
PubMed2003

Subdissociative dose ketamine produces a deficit in manipulation but not maintenance of the contents of working memory.

We investigated the effects of subdissociative dose ketamine on executive processes during a working memory task. A total of 11 healthy volunteers participated in a double-blind, placebo-controlled, randomized, within-subjects study. They attended on three occasions, receiving intravenous infusions of placebo, a lower ketamine dose, and a higher ketamine dose. On each occasion, they underwent a series of tasks engaging working memory function in verbal and visuo-spatial domains. Further tasks explored aspects of long-term memory, planning, attention, and perceptual processing. With respect to working memory/executive function, a highly specific pattern of impairment was observed. Impairments were seen only at the higher dose of ketamine and restricted to a subgroup of the verbal working memory tasks: While visuo-spatial working memory showed no evidence of impairment, and while simple maintenance processes during verbal working memory were also unimpaired, higher dose ketamine produced a significant impairment in the manipulation of information within working memory. This process-specific effect of ketamine was reflected in a drug-by-task interaction. The specificity of this ketamine effect suggests that the earliest effect of NMDA receptor blockade is in higher order control of executive function rather than in more basic maintenance processes.

Adolescent↗
PubMed2004

Nonverbal working memory deficits in schizophrenia patients: evidence of a supramodal executive processing deficit.

BACKGROUND: Although there have been several investigations of spatial working memory performance in schizophrenia patients, there have been considerably fewer studies of object working memory. The purpose of the present investigation was to evaluate the domain specificity of nonverbal working memory impairment in schizophrenia patients. METHODS: Delayed match-to-sample tasks involving spatial, identity and affective information were administered to schizophrenia and schizophrenia-spectrum patients (n=36) and normal controls (n=29). RESULTS: Using visual stimuli that can be considered prototypical of object vision, namely, faces we observed that schizophrenia patients perform poorly on working memory tasks that are based on the identity and/or features of the stimulus (i.e., object-based working memory tasks) as well as on a working memory task based on the spatial location of the stimulus. We observed significant associations between global ratings of negative symptoms and working memory performance. CONCLUSIONS: These data demonstrate that the working memory deficit displayed by schizophrenia and schizophrenia-spectrum patients extends to nonspatial visual domains.

Adult↗