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PubMed2003

Haloperidol increases the disruptive effect of alcohol on spatial working memory in rats: a dopaminergic modulation in the medial prefrontal cortex.

RATIONALE: The prefrontal cortex (PFC) has been considered the anatomic site for working memory. The medial portion of the PFC (mPFC) is also part of a "brain reward circuit" as constituted by the mesocorticolimbic dopaminergic system. OBJECTIVE: This study examined the effects of acute administration of alcohol (ETOH) in the mPFC or systemically on the performance of 5-s or 1-h delayed tasks in an eight-arm radial maze. Effects of haloperidol (HAL), a dopamine antagonist, combined with ETOH, were also examined in a 1-h delayed task. METHODS: Male Wistar rats trained in the radial maze and with bilateral cannulae implanted in the mPFC received intraperitoneal (IP) or intracortical (IC) drug administration. RESULTS: As compared to saline (SAL) IC, ETOH IC in doses of 100 microg and 180 microg (5 min before session) increased significantly the number of errors in the 1-h and 5-s post-delay performance, respectively. HAL in doses with little or no effect alone IC (10 or 32 microg, 10 min before session) or IP (3.2 mg/kg, 35 min before session) increased the disruptive effect of ETOH IC (100 microg) on 1-h delayed task. CONCLUSIONS: These results showed that ETOH administered directly in the mPFC disrupts short- and long-term spatial working memory. The increase of the disruptive effect of ETOH produced by a dopaminergic blockage, particularly in the mPFC, suggests that the dopaminergic neurotransmission in this cortical area might modulate ETOH effects on spatial working memory.

Animals↗
PubMed2005

[Working memory in basic learning processes].

INTRODUCTION AND DEVELOPMENT: Working or operative memory is considered to be a distinctive element of executive functioning. Nowadays, thanks to neuroimaging studies, it is known that the dorsolateral prefrontal cortex plays a crucial role in working memory. It has been observed that during the intervals when information is being retained, intense and persistent activity is going on in the region, as shown by the delayed response times. Working memory is fundamental for the analysis and synthesis of information, the retention of data needed to perform a particular mental process, carrying out priming (impression in memory of something that has been experienced, such as words, objects or events, for example), carrying out pre-functional tutoring activities and post-functional monitoring. CONCLUSIONS: Disorders affecting the fundamental mechanisms of working memory will give rise to a dysfunction that will exert an influence on innumerable formal academic learning processes such as difficulty in focusing attention, difficulty in inhibiting irrelevant stimuli, difficulty in recognising priority patterns, inability to recognise hierarchies and the meaning of stimuli (analysis and synthesis), problems in establishing an intention, and difficulty in recognising and selecting the goals that are best suited to solving a problem. It will also involve the impossibility to establish a plan to achieve goals, inability to analyse the activities required to accomplish an objective and difficulties in carrying out a plan, since it becomes impossible to monitor or modify the task to fit the original plans.

Learning↗
PubMed1994

Working memory and prefrontal cortex.

Several different types of memory have recently been proposed, some of which are believed to operate within specific areas in the brain. In this article, we will discuss the relationship between the prefrontal cortex and working memory, which is a recently proposed type of short-term memory. The tight relationship between the prefrontal cortex and working memory has been supported by recent human and animal studies. This relationship provides good evidence that a particular type of memory is related to a particular brain structure, and can be used as an important model for understanding the neuronal mechanisms of memory. In this article, we will present a modular model based on recent neurophysiological results and discuss for spatial working memory processes in the prefrontal cortex.

Animals↗
PubMed1996

Neural mechanisms of visual working memory in prefrontal cortex of the macaque.

Prefrontal (PF) cells were studied in monkeys performing a delayed matching to sample task, which requires working memory. The stimuli were complex visual patterns and to solve the task, the monkeys had to discriminate among the stimuli, maintain a memory of the sample stimulus during the delay periods, and evaluate whether a test stimulus matched the sample presented earlier in the trial. PF cells have properties consistent with a role in all three of these operations. Approximately 25% of the cells responded selectively to different visual stimuli. Half of the cells showed heightened activity during the delay after the sample and, for many of these cells, the magnitude of delay activity was selective for different samples. Finally, more than half of the cells responded differently to the test stimuli depending on whether they matched the sample. Because inferior temporal (IT) cortex also is important for working memory, we compared PF cells with IT cells studied in the same task. Compared with IT cortex, PF responses were less often stimulus-selective but conveyed more information about whether a given test stimulus was a match to the sample. Furthermore, sample-selective delay activity in PF cortex was maintained throughout the trial even when other test stimuli intervened during the delay, whereas delay activity in IT cortex was disrupted by intervening stimuli. The results suggest that PF cortex plays a primary role in working memory tasks and may be a source of feedback inputs to IT cortex, biasing activity in favor of behaviorally relevant stimuli.

Animals↗
PubMed1998

Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex.

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.

Brain Mapping↗
PubMed2006

Working memory components and imagery instructions in the elaboration of a spatial mental model.

The paper investigates the involvement of verbal and visuo-spatial working memory during the processing of spatial texts via a dual-task paradigm. Subjects were presented with three texts describing locations from a route perspective, and had either to imagine themselves moving along a route in surroundings or to rehearse verbal information. Concurrently they had to perform a spatial tapping task, an articulatory task, or no secondary task. Performance on a verification test used to assess the product of comprehension showed that the concurrent tapping task impaired performance in the imagery instructions group but not in the repetition instructions group, and caused the beneficial effect of imagery instructions to vanish. This result was not observed with the articulatory task, where interference effects were similar in both instructions groups. Performance on the concurrent tasks confirmed the pattern obtained with the verification test. In addition, results seem partly dependent on the capacity of spatial working memory as measured by the Corsi Blocks Test. We argue that these results clarify the processes of the construction of a spatial mental model, and confirm that the visuo-spatial working memory is involved in mental imagery.

Adult↗
PubMed1993

The effects of novel cholinesterase inhibitors and selective muscarinic receptor agonists in tests of reference and working memory.

In recent years muscarinic receptor agonists and cholinesterase inhibitors have been developed for the treatment of Alzheimer's disease. We have evaluated examples from both classes of compounds in rodent tests of reference and working memory, as well as tests that are sensitive to the side-effects of these compounds. Thus, three selective muscarinic receptor partial agonists L-689,660, (M1/M3), AF102B (M1/M3) and L-687,306 (M1) and two cholinesterase inhibitors, E2020 and eptastigmine, were compared in a mouse tail-flick (TF) test, a rat response sensitivity (RS) test, in rat tests of reference memory, passive avoidance (PA) or conditioned suppression of drinking (CSD), and working memory (delayed-matching-to-position, DMTP). In the TF test, all of the compounds tested, with the exception of L-687,306, (1.0-30.0 mg/kg) dose-dependently induced antinociception of which L-689,660 was the most potent (minimum effective dose (MED) = 0.03 mg/kg). In the RS test, all of the compounds, but again with the exception of L-687,306, (1.0-30.0 mg/kg), dose-dependently reduced response rates, of which L-689,660 was again the most potent (MED = 0.1 mg/kg). In the reference memory test, all the compounds reversed the effects of a scopolamine-induced deficit with L-687,306 being the most potent (MED = 0.01 mg/kg). By contrast, in the DMTP test, although both the cholinesterase inhibitors and L-687,306 reversed the effects of scopolamine-induced deficit, L-689,660 and AF102B were without effects. These results suggest that cholinesterase inhibitors and low efficacy M1 selective muscarinic receptor agonists can reverse the effects of a scopolamine-induced deficit in animal tests of reference and working memory at doses that do not induce the side-effects usually associated with cholinomimetics.

Animals↗
PubMed2005

Working memory and intelligence--their correlation and their relation: comment on Ackerman, Beier, and Boyle (2005).

On the basis of a meta-analysis of pairwise correlations between working memory tasks and cognitive ability measures, P. L. Ackerman, M. E. Beier, and M. O. Boyle (2005; see record 2004-22408-002) claimed that working memory capacity (WMC) shares less than 25% of its variance with general intelligence (g) and with reasoning ability. In this comment, the authors argue that this is an underestimation because of several methodological shortcomings and biases. A reanalysis of the data reported in Ackerman et al. using the correct statistical procedures demonstrates that g and WMC are very highly correlated. On a conceptual level, the authors point out that WMC should be regarded as an explanatory construct for intellectual abilities. Theories of working memory do not claim that WMC is isomorphic with intelligence factors but that it is a very strong predictor of reasoning ability and also predicts general fluid intelligence and g.

Humans↗
PubMed2001

Expressive writing can increase working memory capacity.

The effect of emotional disclosure through expressive writing on available working memory (WM) capacity was examined in 2 semester-long experiments. In the first study, 35 freshmen assigned to write about their thoughts and feelings about coming to college demonstrated larger working memory gains 7 weeks later compared with 36 writers assigned to a trivial topic. Increased use of cause and insight words was associated with greater WM improvements. In the second study, students (n = 34) who wrote about a negative personal experience enjoyed greater WM improvements and declines in intrusive thinking compared with students who wrote about a positive experience (n = 33) or a trivial topic (n = 34). The results are discussed in terms of a model grounded in cognitive and social psychological theory in which expressive writing reduces intrusive and avoidant thinking about a stressful experience, thus freeing WM resources.

Adaptation, Psychological↗
PubMed2005

Working memory in cigarette smokers: comparison to non-smokers and effects of abstinence.

The present study was designed to examine the effect of cigarette smoking and withdrawal on working memory. Participants included 15 smokers and 22 matched non-smokers. For both groups the N-Back Task (of working memory) was administered in two test blocks on each of two days. On one day, smokers were tested after >or=13 h abstinence; on the other day, testing began or=13 h but not <or=1 h abstinence was significantly less accurate than that of non-smokers. A within-subject comparison revealed that in the abstinence session, smokers had significantly longer response latencies (in the 2-back condition) and made more overall errors compared to the satiety session. Smoking between test blocks in the abstinence session did not significantly affect performance although it significantly reduced craving. These findings provide further evidence for a deficit in working memory associated with acute abstinence from smoking, which may contribute to the difficulty of smoking cessation.

Adult↗
PubMed2004

Hemispheric specialization of the lateral prefrontal cortex for strategic processing during spatial and shape working memory.

OBJECTIVE: We investigated whether spatial working memory (WM) is associated with functional specialization of the right prefrontal cortex (PFC) relative to WM for shapes. We designed spatial and shape WM tasks that are relatively easy to perform and that minimize both task-switching and manipulation demands. The tasks use identical stimuli and require the same motor response. METHODS: We presented 12 subjects with target shapes that appeared in particular locations. Subjects maintained either the location or the shape of the targets in WM and responded to each probe by indicating whether it was a target. During a non-WM control task, subjects indicated whether the probe appeared on the right or left side of the screen. Subjects were scanned with a 3.0 T Siemens scanner and data were analyzed using SPM99. The WM tasks were compared to identify PFC activation that was different for spatial versus shape WM. Each WM task was also compared to the control task. RESULTS: compared with shape WM, spatial WM performance was faster and more accurate and was associated with increased right ventrolateral and frontopolar PFC activation. In contrast, compared to spatial WM, shape WM was associated with increased left ventrolateral PFC activity. CONCLUSIONS: These findings demonstrate hemispheric specialization for spatial versus shape WM in the ventrolateral PFC. The increased activity in the right PFC for spatial WM cannot be attributed to increased task difficulty, the stimuli used, or the response requirements. Rather, we propose that differences in performance and activation reflect the use of configural processing strategies for spatial WM.

Adult↗
PubMed2006

Neural mechanisms for response selection: comparing selection of responses and items from working memory.

Recent functional imaging studies of working memory (WM) have suggested a relationship between the requirement for response selection and activity in dorsolateral prefrontal (DLPFC) and parietal regions. Although a number of WM operations are likely to occur during response selection, the current study was particularly interested in the contribution of this neural network to WM-based response selection when compared to the selection of an item from a list being maintained in memory, during a verbal learning task. The design manipulated stimulus-response mappings so that selecting an item from memory was not always accompanied with selecting a motor response. Functional activation during selection supported previous findings of fronto-parietal involvement, although in contrast to previous findings left, rather than right, DLPFC activity was significantly more active for selecting a memory-guided motor response, when compared to selecting an item currently maintained in memory or executing a memory-guided response. Our results contribute to the debate over the role of fronto-parietal activity during WM tasks, suggesting that this activity appears particularly related to response selection, potentially supporting the hypothesized role of prefrontal activity in biasing attention toward task-relevant material in more posterior regions.

Cerebral Cortex↗
PubMed2005

Working memory in primate sensory systems.

Sensory working memory consists of the short-term storage of sensory stimuli to guide behaviour. There is increasing evidence that elemental sensory dimensions - such as object motion in the visual system or the frequency of a sound in the auditory system - are stored by segregated feature-selective systems that include not only the prefrontal and parietal cortex, but also areas of sensory cortex that carry out relatively early stages of processing. These circuits seem to have a dual function: precise sensory encoding and short-term storage of this information. New results provide insights into how activity in these circuits represents the remembered sensory stimuli.

Animals↗
PubMed2006

Reversal of brain injury-induced prefrontal glutamic acid decarboxylase expression and working memory deficits by D1 receptor antagonism.

Working memory (WM), the ability to transiently hold information in mind, is essential for high-level cognitive functions that are often impaired in brain-injured patients. The cellular and molecular mechanisms contributing to WM deficits, which can manifest in the absence of overt damage, in these patients are unknown. The function of the dorsolateral prefrontal cortex in humans and monkeys, and the medial prefrontal cortex (mPFC), in rodents is critical for WM. We demonstrate that controlled cortical impact injury of rats causes a long-lasting WM impairment that is associated with increased levels of the GABA-synthesizing enzyme glutamic acid decarboxylase 67 (GAD67) in the mPFC for up to 1 month after injury. A single administration of dopamine D1 antagonists at 14 d after injury is sufficient to decrease GAD67 levels and restore WM for at least 1 week. These findings indicate that inhibition of prefrontal neuronal activity contributes to WM deficits and that strategies to reduce GAD67 expression can offer prolonged WM improvement in brain-injured patients.

Animals↗
PubMedDate not supplied

Parallel working memory for spatial location and food-related object cues in foraging pigeons: binocular and lateralized monocular performance.

During foraging, animals can increase their success by both remembering feeding sites and remembering food-related object cues. Because earlier studies have tested either the site or object memory in isolation, the aim of the present study was to evaluate how efficiently birds can utilize both memories simultaneously. Furthermore, the idea was tested that lateralization might be the principle of brain organization that allows for efficient parallel processing. Pigeons learned to search for food in a complex maze with 16 baited sites. To obtain the maximum reward they had to perform two tasks in parallel, a spatial working memory task and an object-specific working memory task. Birds performed well on this dual task but, compared with spatial working memory alone, they were impaired during the first choices of a trial (Experiment 1). When the left and the right brain hemispheres were tested separately by means of monocular occlusion (Experiment 2), object discrimination was better when birds used their right eye/left hemisphere. This was most pronounced during the first choices of a trial. On the spatial component of the task, performance on binocular trials was better than on monocular trials, but monocularly both hemispheres performed at the same level. Results show that on this dual task, discrimination of food-related object cues predominantly involved the left brain hemisphere whereas both hemispheres contributed equally to spatial performance.

Animal Feed↗
PubMed2006

Effects of verbal working memory deficits on metaphor comprehension in patients with Parkinson's disease.

This research studied one aspect of pragmatic language processing, the ability to understand metaphorical language, to determine whether patients with Parkinson disease (PD) are impaired for these abilities, and whether cognitive resource limitations/fronto-striatal dysfunction contributes to these deficits. Seventeen PD participants and healthy controls (HC) completed a series of neuropsychological tests and performed a metaphor comprehension task following the methods of Gernsbacher and colleagues [Gernsbacher, M. A., Keysar, B., Robertson, R. R. W., & Werner, N. K. (2001). The role of suppression and enhancement in understanding metaphors. Journal of Memory and Language, 45, 433-450.] When participants in the PD group were identified as "impaired" or "unimpaired" relative to the control group on a measure of verbal working memory span, we found that only PD participants with impaired working memory were simultaneously impaired in the processing of metaphorical language. Based on our findings we argue that certain "complex" forms of language processing such as metaphor interpretation are highly dependent on intact fronto-striatal systems for working memory which are frequently, although not always, compromised during the early course of PD.

Aged↗
PubMed2001

Spatial working memory improvement by an alpha2-adrenoceptor agonist dexmedetomidine is not mediated through alpha2C-adrenoceptor.

1. Aged alpha2C-adrenoceptor knockout and wild type mice were used to investigate whether alpha2C-adrenoceptors are involved in mediating the beneficial effects of alpha2-adrenoceptor agonist, dexmedetomidine, on spatial working memory. 2. A win-stay task in the radial arm maze was used to dissociate the effects of dexmedetomidine on working vs. reference memory. In addition, the animals were tested in simple response habit learning in the T-maze. 3. Knockout mice made more working memory errors after the change of the baited arm in radial arm maze, but after training reached again as accurate level of performance as wild type controls. Dexmedetomidine 5 and 10 microg/kg alleviated the increase in spatial working memory errors after the change of the baited arm in knockout mice. Knockout and wild type mice performed equally well in T-maze, and dexmedetomidine had no effect on this simple response learning. 4. The present results indicate that alpha2-adrenoceptor agonists have a selective effect on spatial working memory not only in monkeys but also in mice. Further, this study confirms our earlier finding that the presence of alpha2C-adrenoceptors is not necessary for the spatial working memory enhancing effect of alpha2-adrenoceptor agonists.

Adrenergic alpha-Agonists↗
PubMed2002

Counting on working memory in simple arithmetic when counting is used for problem solving.

A concurrent-task methodology was used to investigate relations between the availability of aspects of working memory resources and both strategy selection and execution while simple addition equations (e.g., 4 + 3 = 8) were being verified. Consistent with prior research in which production trials have been used, undergraduates selected a variety of procedures other than retrieval. Availability of working memory resources did not generally affect strategy selection. Disrupting central executive and phonological aspects of memory affected strategy execution, but only when min counting was used to solve the problems. These and other features of the results suggest that availability of working memory resources does not contribute to individual differences in strategy selection and time to execute retrieval processes.

Humans↗