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PubMed1992

Intrahippocampal injections of benzodiazepine and muscimol impair working memory but not reference memory of rats in the three-panel runway task.

In a three-panel runway task, the benzodiazepine chlordiazepoxide at 3.2 and 10 mg/kg i.p. significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in a test of working memory, but it had no effect on errors in a test of reference memory. This effect of 10 mg/kg chlordiazepoxide on working memory was blocked by the benzodiazepine receptor antagonist flumazenil at 10 mg/kg. Intrahippocampal injection of chlordiazepoxide at 10 and 32 micrograms/side significantly increased the number of working memory errors. This effect of intrahippocampal chlordiazepoxide (32 micrograms/side) was attenuated not only by flumazenil at 10 mg/kg but also by the gamma-aminobutyric acid (GABA)A receptor antagonist bicuculline at 3.2 mg/kg. Intrahippocampal injection of the GABAA receptor agonist muscimol at 100 and 320 ng/side also significantly increased working memory errors. Neither chlordiazepoxide nor muscimol affected the number of reference memory errors when injected into the hippocampus at doses up to 32 micrograms/side or 320 ng/side, respectively. These results suggest that activation of the GABAA/benzodiazepine receptor complex in the hippocampus impairs working memory, but does not affect reference memory.

Animals↗
PubMed2006

Long-term effects of frequent cannabis use on working memory and attention: an fMRI study.

RATIONALE: Excessive use of cannabis may have long-term effects on cognitive abilities. Mild impairments have been found in several cognitive domains, particularly in memory and attention. It is not clear, however, whether these effects also occur with moderate, recreational use of cannabis. Furthermore, little is known about underlying brain correlates. OBJECTIVES: The aim of this study is to assess brain function in frequent but relatively moderate cannabis users in the domains of working memory and selective attention. METHODS: Functional magnetic resonance imaging was used to examine verbal working memory and visuo-auditory selective attention in ten frequent cannabis users (after 1 week of abstinence) and ten non-using healthy controls. Groups were similar in age, gender and estimated IQ. RESULTS: Cannabis users and controls performed equally well during the working memory task and the selective attention task. Furthermore, cannabis users did not differ from controls in terms of overall patterns of brain activity in the regions involved in these cognitive functions. However, for working memory, a more specific region-of-interest analysis showed that, in comparison to the controls, cannabis users displayed a significant alteration in brain activity in the left superior parietal cortex. CONCLUSION: No evidence was found for long-term deficits in working memory and selective attention in frequent cannabis users after 1 week of abstinence. Nonetheless, frequent cannabis use may affect brain function, as indicated by altered neurophysiological dynamics in the left superior parietal cortex during working memory processing.

Adult↗
PubMed1997

Stimulation and blockade of alpha1 adrenoceptors affect behavioural activity, but not spatial working memory assessed by delayed non-matching to position task in rats.

The present study investigated the role of alpha1 adrenergic receptors in the modulation of working memory and behavioural activity by assessing the effects of alpha1 adrenergic receptor stimulation or blockade on the performance of rats in a delayed non-matching to position task. St-587 (a putative agonist of alpha1 adrenoceptors) at a dose of 100 microg/kg slightly increased choice accuracy (per cent correct responses) of rats, but the effect was delay-independent which is interpreted as an improvement in choice accuracy and non-mnemonic (non-working memory) in character. Neither St-587 (300 or 1000 microg/kg) nor prazosin (a prototype antagonist of alpha1 adrenoceptors) (100 or 300 microg/kg) significantly affected the choice accuracy of rats in this task. Prazosin 300 microg/kg lengthened the latency for correct responses in the working memory task but did not affect food collection latencies. This combination of effects may reflect decreased motor output. St-587 300 and 1000 microg/kg, but not prazosin, increased food collection latencies in the working memory task. Thus, the present results suggest that alpha1 adrenergic receptors do not play any important role in spatial working memory as assessed using the delayed non-matching to position task, but that modulation of alpha1 adrenoceptors may affect motor activity and motivation in rats.

Adrenergic alpha-Agonists↗
PubMed2004

Prefrontal cortical activation associated with working memory in adults and preschool children: an event-related optical topography study.

It is well known that lateral areas of the prefrontal cortex (LPFC) play a central role in working memory (a critical basis of various cognitive functions), but it remains unknown whether the LPFC of children of preschool age is responsible for working memory. To address this issue, we adopted a recently developed non-invasive imaging technique, optical topography (OT), which can potentially be applied to functional mapping in childhood. We firstly examined changes of activity in the LPFC using OT while adult subjects performed an item-recognition task, which requires working memory, under different memory-load conditions. We observed activation in the bilateral LPFC during performance of this task, the magnitude of which differed depending on memory-load. Then, we applied the same technique on 5- and 6-year-old children and observed the activation associated with working memory in the LPFC. Areas and properties of such activity were similar in adults and preschool children. Thus, for the first time, we demonstrate that the LPFC of preschoolers is active during working memory processes, indicating that in 5- and 6-year-old children, the LPFC has already developed processing of this important cognitive function.

Adult↗
PubMed1992

Working memory constraints on the processing of syntactic ambiguity.

We propose a model that explains how the working-memory capacity of a comprehender can constrain syntactic parsing and thereby affect the processing of syntactic ambiguities. The model's predictions are examined in four experiments that measure the reading times for two constructions that contain a temporary syntactic ambiguity. An example of the syntactic ambiguity is The soldiers warned about the dangers . . . ; the verb warned may either be the main verb, in which case soldiers is the agent; or the verb warned may introduce a relative clause, in which case soldiers is the patient of warned rather than the agent, as in The soldiers warned about the dangers conducted the midnight raid. The model proposes that both alternative interpretations of warned are initially activated. However, the duration for which both interpretations are maintained depends, in part, on the reader's working-memory capacity, which can be assessed by the Reading Span task (Daneman & Carpenter, 1980). The word-by-word reading times indicate that all subjects do additional processing after encountering an ambiguity, suggesting that they generate both representations. Furthermore, readers with larger working-memory capacities maintain both representations for some period of time (several words), whereas readers with smaller working-memory capacities revert to maintaining only the more likely representation.

Adult↗
PubMedDate not supplied

[Working memory abilities and the severity of phonological disorders].

BACKGROUND: Working memory. AIM: To verify the performance of working memory abilities and their relation with the severity of phonological disorders. METHOD: 45 children, with ages between 5.0 and 7.11 years, with evolutional phonological disorders (EFD), 17 female and 18 male, were evaluated. All subjects were assessed using the Child Phonological Evaluation proposed by Yavas et al. (1991). The severity of the disorder was determined by the Percentage of Correct Consonants (PCC) proposed by Shriberg and Kwiatkowski (1982), classifying the phonological disorder as severe, moderate-severe, average-moderate and average. After that, subtest 5 of the Psycholinguistic Abilities Test (ITPA--Bogossian & Santos, 1977) and the non-word repetition test (Kessler, 1997) were applied. RESULTS: After analyzing the data according the statistical tests of Kruskal Wallis and Duncan, it was verified that the performance of moderate-severe and severe individuals in the non-word repetition test was inferior to that of average-moderate and average individuals. However, performance results in the digit repetition test did not present a positive correlation with severity. CONCLUSION: The performance of phonological memory has a relation with the severity of phonological disorders. This allows us to accept the idea that the phonologic memory is related to speech production. Regarding the central executor, the results indicate that the performance in digit repetition, used to assess the central executor, did not present a correlation with the severity of the disorder. This can be justified by the fact that the central executor is more directly related to vocabulary acquisition and is responsible for processing and storing information.

Analysis of Variance↗
PubMed2002

Sustained attention deficit in bipolar disorder is not a working memory impairment in disguise.

Euthymic patients with bipolar disorder have been reported to show persistent deficits in sustained attention. However, the sustained attention task which was used also placed demands on working memory. Bipolar disorder patients in the euthymic state were therefore compared with healthy controls on two measures of sustained attention with and without a working memory component. Signal detection methodology was applied to the results. Euthymic patients with bipolar disorder were particularly impaired at detecting targets in the sustained attention task without a working memory component. This deficit was still apparent in a sub-group of patients who were not currently receiving lithium medication. By contrast, performance in the sustained attention task involving working memory task was not significantly different in the two groups. Sustained attention deficits apparent during the euthymic period of bipolar disorder cannot be explained in terms of working memory impairment and represents a reduced inherent capacity rather than a change in response bias. Deficits in sustaining attention may help explain the difficulties in psychological and occupational functioning in bipolar disorder patients during remission.

Adult↗
PubMed2006

Articulatory rehearsal in verbal working memory: a possible neurocognitive endophenotype that differentiates between schizophrenia and schizoaffective disorder.

Recent fMRI studies have identified brain systems underlying different components of working memory in healthy individuals. The aim of this study was to compare the functional integrity of these neural networks in terms of behavioural performance in patients with schizophrenia, schizoaffective disorder and healthy controls. In order to detect specific working memory deficits based on dysfunctions of underlying brain circuits we used the same verbal and visuospatial Sternberg item-recognition tasks as in previous neuroimaging studies. Clinical and performance data from matched groups consisting of 14 subjects each were statistically analyzed. Schizophrenic patients exhibited pronounced impairments of both verbal and visuospatial working memory, whereas verbal working memory performance was preserved in schizoaffective patients. The findings provide first evidence that dysfunction of a brain system subserving articulatory rehearsal could represent a biological marker which differentiates between schizophrenia and schizoaffective disorder.

Adult↗
PubMedDate not supplied

Dopamine controls fundamental cognitive operations of multi-target spatial working memory.

This study addresses computationally how the prefrontal cortical circuit performs operations of multiple items in spatial working memory. The basic idea is that dopamine controls the circuit dynamics for the operations by changing the ratio of the NMDA-channel transmission to the AMPA-channel transmission. There is evidence that this ratio is a function of dopamine D1 receptor activation. The simulation shows that the model circuit performs several different operations of multi-target spatial working memory depending on this ratio. When the ratio is low, 'replacement' occurs from the previously loaded target to a new one. In intermediate levels of the ratio, a new target is 'added' to the previously loaded target, resulting in the coexistence of more than one target. For higher ratios, the circuit 'rejects' other succeedingly received target stimuli. This study suggests four important issues: First, the cortical circuit can perform operations of multi-target spatial working memory. Second, the circuit can switch the modes of the operations by changing the NMDA-to-AMPA ratio. Third, dopamine would have major roles in the operations of multi-target spatial working memory. Fourth, the intracortical inhibition (especially of the cross-directional) plays an important role in regulating the competition between targets.

Animals↗
PubMed1999

Eye movements and spatial working memory in Parkinson's disease.

Mechanisms of spatial working memory and eye movement control were investigated in eight mild to moderate Parkinson's disease patients (PDs). Subjects were presented with a sequence of four targets which had to be memorized and then recalled by moving their eyes to fixate the four locations in the correct order. Two variations on this procedure were used in which either a different sequence of lights was presented on each trial, or an identical sequence of lights was repeated on each trial. In both conditions subjects made memory-guided eye movements in the dark, without any visual cues to eye movement accuracy or the locations of the previously illuminated lights. Analysis of the amplitude of the primary eye movement and final eye position for each step in the sequence showed that PDs made several discrete saccadic eye movements of reduced amplitude before reaching the final eye position (multi-stepping). When a novel target sequence had to be memorized on each trial, the final eye position reached by PDs for each location was also found to undershoot relative to controls. In contrast, when an identical sequence of targets was repeated on each trial, PDs' final eye position was found to be normal, although primary movement amplitudes were still reduced. PDs showed no multi-stepping and normal final eye position gain under conditions for which the target lights in the sequence were illuminated during movement execution. PDs also made an increased proportion of overt errors in target sequence recall. Parallel neuropsychological testing in PDs and controls revealed that error rates in the sequential memory-guided saccade task were significantly correlated with performance in a task thought to be sensitive to spatial working memory dysfunction. The findings suggest that short-term spatial memory representations are disrupted in the early stages of PD.

Aged↗
PubMed2004

Functional brain mapping of the macaque related to spatial working memory as revealed by PET.

To define the cortical areas that subserve spatial working memory in a nonhuman primate, we measured regional cerebral blood flow (rCBF) with [(15)O]H(2)O and positron emission tomography while monkeys performed a visually guided saccade (VGS) task and an oculomotor delayed-response (ODR) task. Both Statistical Parametric Mapping and regions of interest-based analyses revealed an increase of rCBF in the area surrounding the principal sulcus (PS), the superior convexity, the anterior bank of the arcuate sulcus (AS), the lateral orbitofrontal cortex (lOFC), the frontal pole (FP), the anterior cingulate cortex (ACC), the lateral bank of the intraparietal sulcus (lIPS) and the prestriate cortex. In the prefrontal cortex (PS, superior convexity, AS, lOFC and FP), rCBF values correlated positively with ODR task performance scores. From the hippocampus, rCBF values correlated negatively with ODR task performance. From the AS, superior convexity, lOFC, FP, ACC and lIPS, rCBF values of the PS correlated positively with rCBF values and negatively with hippocampus rCBF values. These results suggest that neural circuitry in the prefrontal cortex directly contributes the spatial working memory processes and that, in spatial working memory processes, the posterior parietal cortex and hippocampus have a different role to the prefrontal cortex.

Animals↗
PubMed2005

Working memory impairment in a transgenic amyloid precursor protein TgCRND8 mouse model of Alzheimer's disease.

The most profound deficits observed in Alzheimer's disease (AD) are in domains of episodic and working memory systems. Transgenic (Tg) mice expressing mutated human amyloid precursor protein (APP) genes offer a model to study the effect of AD pathology on cognition. We reported previously that APP TgCRND8 mice showed deficits in a reference and working memory evaluated in a Morris water-maze test. In this study, we evaluated the working memory of TgCRND8 mice comparing two training paradigms in a six-arm radial water maze. In the first paradigm, the exploration of the maze was constrained, forcing the mice to use a spatial mapping strategy. In the second paradigm, mice were unconstrained in their exploration of the maze. TgCRND8 mice proved to be significantly impaired in spatial working memory in both paradigms as compared with their non-transgenic littermates. The analysis of data revealed that forcing mice to use a spatial strategy during training caused only a moderate improvement in the performance of all mice. However, unconstrained exploration of the maze not only resulted in a fast learning in control mice, but also facilitated the development of a chaining strategy in spatially impaired TgCRND8 mice. In conclusion, TgCRND8 mice showed impairment in spatial working memory but retained a plasticity to choose alternative search strategies.

Alzheimer Disease↗
PubMed2000

Spatial working memory is independent of hippocampal CA1 long-term potentiation in rats.

This study investigated the relationship between spatial working memory and hippocampal long-term potentiation (LTP) using the allocentric place discrimination task (APDT) in rats, in which the selection accuracy is a good index for spatial working memory. Either the selective M1 muscarinic receptor antagonist pirenzepine (50 microg) or the choline uptake inhibitor hemicholinium-3 (5 microg) impaired APDT selection accuracy, but neither affected the induction of LTP in the hippocampal CA1 region in anesthetized rats. In contrast, the selective N-methyl-D-aspartate receptor antagonist D-amino-5-phosphonopentanoate (200 nmol) did not impair APDT selection accuracy but completely blocked hippocampal CA1 LTP. These results suggest that spatial working memory is independent of hippocampal CA1 LTP and that the central cholinergic system is involved in spatial working memory, but not through the modulation of hippocampal CAI LTP.

Animals↗
PubMed2001

Prefrontal cortical representation of visuospatial working memory in monkeys examined by local inactivation with muscimol.

In primates, dorsolateral areas of the prefrontal cortex (PFC) play a major role in visuospatial working memory. To examine the functional organization of the PFC for representing visuospatial working memory, we produced reversible local inactivation, with the local injection of muscimol (5 microg, 1 microl), at various sites (n = 100) in the dorsolateral PFC of monkeys and observed the behavioral consequences in an oculomotor delayed-response task that required memory-guided saccades for locations throughout both visual fields. At 82 sites, the local injection of muscimol induced deficits in memory-guided saccades to a few specific, usually contralateral, target locations that varied with the location of the injection site. Such deficits depended on the delay length, and longer delays were associated with larger deficits in memory-guided saccades. The injection sites and affected spatial locations of the target showed a gross topographical relationship. No deficits appeared for a control task in which the subject was required to make a visually guided saccade to a visible target. These findings suggest that a specific site in the dorsolateral PFC is responsible for the working memory process for a specific visuospatial coordinate to guide goal-directed behavior. Further, memoranda for specific visuospatial coordinates appear to be represented in a topographical memory map within the dorsolateral PFC to represent visuospatial working memory processes.

Animals↗
PubMed1989

Working memory in skilled and less skilled readers.

This study assessed skilled and less skilled readers' working memory performance. Fifty skilled and less skilled readers at two age levels were presented with sentence span and concurrent memory tasks. The span task results indicated that working memory differences exist between reading groups. The concurrent task revealed performance deficits for less skilled readers across verbal and nonverbal conditions, suggesting a central processing deficiency. Age differences were isolated to skilled readers. It was concluded that less skilled readers' working memory deficiencies were pervasive in the sense that they involve deficiencies in memory components related to central executive processing.

Attention↗
PubMed2000

Cholinergic and glutamatergic activation reverses working memory failure by hippocampal histamine H1 receptor blockade in rats.

Intrahippocampal administration of the histamine H1 receptor antagonist pyrilamine (3.2-32 ug/ side) but not the histamine H2 receptor antagonist cimetidine (1.0-10 microg/side) increased the number of errors in the working memory task with a three-panel runway setup. The increase in working memory errors induced by intrahippocampal 32 microg/side pyrilamine was significantly reduced by concurrent infusion of the histamine H1 receptor agonist 2-pyridylethylamine (3.2 and 10 microg/side). The cholinesterase inhibitor physostigmine ( 1.0 and 3.2 microg/side) and D-cycloserine (0.32 and 1.0 microg/side), the partial agonist at the glycine binding site on the NMDA receptor/channel complex, reduced the increase in working memory errors induced by intrahippocampal 32 microg/side pyrilamine. These results suggest that the hippocampal histaminergic activity via histamine H1 receptor is necessary for normal working memory processes and that the septohippocampal cholinergic activation and positive modulation of the NMDA receptor/channel through activation of the glycine site can alleviate dysfunction of hippocampal histamine H1 receptor-mediated neurotransmission involved in working memory function.

Acetylcholine↗
PubMed2004

The contributions of attention and working memory to age differences in concept identification.

The contributions of attention and working memory to adult age differences in concept identification were examined in two experiments using the standard version of the California Card Sorting Test plus two modified versions. Older adults demonstrated global reductions in their ability to identify concepts whether sorting stimuli, identifying concepts used by the examiner, or generating concepts from abstract cues. Although age differences in selective attention and interference control did not contribute to these deficits, reduced working memory accounted for the age-related increase in perseverative errors. Our conclusions focus on whether impairments in working memory might fully account for age differences in concept identification.

Adolescent↗
PubMed1993

Working memory deficits induced by intrahippocampal administration of 8-OH-DPAT, a 5-HT1A receptor agonist, in the rat.

In a test of working memory using a three-panel runway task, the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), at 1.0 mg/kg i.p. significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel gates at four choice points), but it had no effect on errors in a test of reference memory. Intrahippocampal injection of 8-OH-DPAT at 10 micrograms/side also significantly increased the number of working memory errors, without affecting that of reference memory errors. The effect of intrahippocampal 8-OH-DPAT (10 micrograms/side) on working memory was blocked by the 5-HT1A receptor antagonist, (-)-propranolol, at 5 mg/kg i.p. These results suggest that activation of hippocampal 5-HT1A receptors impairs working memory, but does not affect retention of reference memory.

8-Hydroxy-2-(di-n-propylamino)tetralin↗