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PubMed1999

Storage and processing in visuo-spatial working memory.

Visuo-spatial working memory has been used to account for performance in a wide range of visuo-spatial tasks, including perceptuo-motor tracking and immediate recall of visually presented patterns. However a developing body of evidence points to a fractionation of the concept into visuo-spatial processing that calls on general purpose executive resources, and a visual 'cache' memory for temporary storage in on-line cognition. Two related experiments are described which address whether processing and temporary memory draw on overlapping or on distinct resources in working memory. Experiment 1 demonstrates that participants can accurately respond to a series of targets appearing in random locations whether or not they have the additional load of retaining and subsequently recalling the appearance of each target. Memory for target appearance likewise is largely unaffected by the additional load of requiring a response to each target. Experiment 2 demonstrates similar findings when verbal labeling of the patterns is inhibited through the use of articulatory suppression. Results are interpreted as consistent with a multiple component working memory system.

Adult↗
PubMed2000

A beneficial effect of estrogen on working memory in postmenopausal women taking hormone replacement therapy.

Recent neurophysiological data suggest that the prefrontal cortex (PFC) may be susceptible to modulation by estrogen. In humans, the PFC mediates a number of cognitive processes that contribute to memory function, particularly working memory. The present study examined whether memory tasks that recruit PFC-dependent information processing might exhibit estrogen sensitivity in women. Performance on several memory tasks, including measures of working memory, was evaluated in three groups of postmenopausal women: (1) women who were tested when taking estrogen only (n = 38, M(age) = 55.1 years), (2) women who were tested when taking estrogen and a progestin concurrently (n = 23, M(age) = 55.9 years), and (3) women who were not taking hormone replacement therapy (n = 35, M(age) = 56.0 years). Estrogen users exhibited significantly better performance on a verbal task and on a spatial task, each with a prominent working memory component, but did not differ from nonusers on control tasks involving simple passive recall. These findings are consistent with the hypothesis that estrogen is active within PFC and is capable of influencing functions dependent on this region. The results of this study raise the possibility that estrogen may play a role in maintaining certain frontal lobe functions in women.

Affect↗
PubMed1988

Multiple memory deficits in patients with multiple sclerosis. Exploring the working memory system.

Some patients with multiple sclerosis (MS) demonstrate impaired memory. A group of 16 patients with MS who were mildly to moderately affected (Kurtzke Expanded Disability Status Scale Score = 3.8) were studied, and they were compared with a matched control group on tests of "working memory." The working memory system was explored by evaluating the amount of information that can temporarily be held in a buffer system during encoding. Results indicated that patients with MS have difficulty in processing information at the level of a hypothesized articulatory loop in working memory. This deficit was correlated with their retrieval of verbal information from long-term memory, as well as how accurately they processed verbal information presented at a rapid rate. There was no significant relationship between ratings of MS severity or number of plaques visualized on magnetic resonance imaging scans and the degree of working memory deficit.

Adult↗
PubMed2001

Infralimbic muscarinic M1 receptors modulate anxiety-like behaviour and spontaneous working memory in mice.

RATIONALE: Spontaneous working memory and anxiety-like behaviour can be concurrently influenced following kappa 1 opioid agonist or antagonist infusions in the infralimbic (IL) area of the ventromedial prefrontal cortex (vmPFC) in CD-1 mice. OBJECTIVE: The present study sought to evaluate whether acetylcholine (ACh) muscarinic (M) receptor drugs can similarly influence these cognitive-behavioural processes in the IL cortex. METHOD: Anxiety was evaluated in the elevated plusmaze and spontaneous working memory was evaluated in the Y-maze following scopolamine, pirenzepine or McN-A-343 infusion in the IL cortex. RESULTS: In experiment 1, the non-specific muscarinic receptor antagonist, scopolamine, was anxiogenic in trial 1 (5, 10 and 20 nmol), but did not influence behaviour in trial 2 (no-injection) in the elevated plus-maze 24 h later. In week 2, scopolamine disrupted spontaneous working memory in the Y-maze at the highest dose (20 nmol). In experiment 2, pretreatment with the M1 antagonist, pirenzepine, was anxiolytic in trial 1 (5 and 10 nmol), as well as in trial 2 (no-injection) in the elevated plus-maze 24 h later (0.25, 1.25, 2.5, 5 and 10 nmol). In week 2, pirenzepine disrupted spontaneous working memory in the Y-maze (2.5, 5 and 10 nmol). In experiment 3, pretreatment with the M1 agonist, McN-A-343, was anxiogenic in trial 1 (2.5, 5, 10 and 20 nmol), as well as in trial 2 (no-injection) in the elevated plus-maze 24 h later (2.5, 5, 10 and 20 nmol). In week 2, McN-A-343 enhanced spontaneous working memory in the Y-maze (2.5, 5, 10 and 20 nmol). CONCLUSIONS: (1) Enhanced ACh transmission in the vmPFC induces anxiety in challenging environments and enhances spontaneous working memory performance. (2) Blocking or activating postsynaptic M1 receptors in the vmPFC may truncate or exaggerate, respectively, afferent anxiety-relevant information. (3) IL pirenzepine and McN-A-343 exert long-term opposite effects on aversive learning during trial 1 in the elevated plus-maze.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed2004

When visual and verbal memories compete: evidence of cross-domain limits in working memory.

Recently, investigators have suggested that visual working memory operates in a manner unaffected by the retention of verbal material. We question that conclusion on the basis of a simple dual-task experiment designed to rule out phonological memory and to identify a more central faculty as the source of a shared limitation. With a visual working memory task in which two arrays of color squares were to be compared, performance was unaffected by concurrent recitation of a two-digit list or a known seven-digit sequence. However, visual working memory performance decreased markedly when paired with a load of seven random digits. This was not a simple tradeoff, inasmuch as errors on the visual array and high digit load tasks tended to co-occur. Working memory for digits and visual information thus are both subject to at least one type of shared limit, not just domain-specific limitations. The nature of the shared limit is discussed.

Adolescent↗
PubMedDate not supplied

Working memory deficits in BXSB mice with neocortical ectopias.

Approximately 40-60% of BXSB/MpJ-Yaa mice exhibit neocortical ectopias, which are misplaced clusters of neurons in layer I of cortex. These ectopias are usually located in the prefrontal and/or motor region of cortex in BXSB mice, and are similar in appearance to those found in postmortem analyses of the brains of dyslexic humans. Several within-strain learning differences between mice with ectopias and those without have been reported. In particular, ectopic BXSB mice exhibited superior reference memory learning, but inferior working memory learning in several studies from our laboratory. This study used the Morris water maze delayed matching-to sample task and the water radial-arm maze to asses working memory in female BXSB mice with and without ectopias. In the delayed matching-to sample task, a hidden escape platform remained in a constant position for each four-trial session, but changed position between sessions. Trial 2 was the measure of working memory, i.e., how well did the mouse remember where the platform was located for that session. In the water version of the eight-arm radial maze, hidden escape platforms were located in four of the eight arms, and each platform was removed from the maze once found. This enabled us to assess working and reference memory simultaneously. Ectopic mice demonstrated working memory deficits during the first part of the delayed matching-to sample task compared to nonectopics. Similarly, ectopics made more working memory errors during the latter half of radial-arm maze testing, while not differing from nonectopics in reference memory performance. Additionally, there were significant correlations between measures of working memory in the radial-arm maze and working memory in a delayed matching-to-sample task. These findings are in agreement with other studies demonstrating working memory deficits in ectopic BXSB mice.

Animals↗
PubMed2005

Verbal and spatial working memory in autism.

Verbal and spatial working memory were examined in high-functioning children, adolescents, and adults with autism compared to age and cognitive-matched controls. No deficit was found in verbal working memory in the individuals with autism using an N-back letter task and standardized measures. The distinction between the N-back task and others used previously to infer a working memory deficit in autism is that this task does not involve a complex cognitive demand. Deficits were found in spatial working memory. Understanding the basis for the dissociation between intact verbal working memory and impaired spatial working memory and the breakdown that occurs in verbal working memory as information processing demands are increased will likely provide valuable insights into the neural basis of autism.

Adolescent↗
PubMed2005

Self-ordered pointing in children with autism: failure to use verbal mediation in the service of working memory?

This study tested the hypothesis that children with autism are impaired in using verbal encoding and rehearsal strategies in the service of working memory. Participants were 24 high-ability, school-age children with autism and a comparison group matched on verbal and non-verbal IQ, receptive and expressive vocabulary, and visual memory. Working memory was assessed using verbal and non-verbal variants of a non-spatial, self-ordered pointing test [Petrides, M., & Milner, B. (1982). Deficits on subject-ordered tasks after frontal- and temporal-lobe lesions in man. Neuropsychologia, 20, 249-262] in which children had to point to a new stimulus in a set upon each presentation without repeating a previous choice. In the verbal condition, the stimuli were pictures of concrete, nameable objects, whereas in the non-verbal condition, the stimuli were not easily named or verbally encoded. Participants were also administered a verbal span task to assess non-executive verbal rehearsal skills. Although the two groups were equivalent in verbal rehearsal skills, the autism group performed significantly less well in the verbal, but not the non-verbal, self-ordered pointing test. These findings suggested that children with autism are deficient in the use of verbal mediation strategies to maintain and monitor goal-related information in working memory. The findings are discussed in terms of possible autistic impairments in episodic memory as well as working memory.

Adolescent↗
PubMed2004

Regulation of working memory by dopamine D4 receptor in rats.

Working memory is regulated by neurotransmitters in prefrontal cortex (PFC), including dopamine and norepinephrine. Previous studies of dopamine function in working memory have focused on the D1 and D2 receptors, with most evidence suggesting a dominant role for the D1 receptor. Since the dopamine D4 receptor is highly expressed in PFC, we hypothesize that it may also contribute to working memory. To test this hypothesis, we examined behavioral effects of L-745,870, a highly selective, centrally active, D4 antagonist, using a delayed alternation task in rats. Task performance was dose-dependently affected by the D4 antagonist, depending on individual baseline functional status of working memory. In rats with good baseline performance, the D4 antagonist had no effects at low doses, whereas high doses disrupted working memory. In rats with poor baseline working memory, the D4 antagonist significantly improved working memory at low doses, and higher doses were not distinguishable from vehicle controls. Effects of the D4 antagonist among poor performers were most robust when task demand for working memory was high, with lesser effects at lower demand level, suggesting that such effects were selective for working memory. The present findings indicate a significant role of the D4 receptor in working memory, and suggest innovative, D4-based, treatment of cognitive deficits associated with neuropsychiatric disorders.

Animals↗
PubMed2001

Remitted schizophrenia-spectrum patients with spared working memory show information processing abnormalities.

Working memory and information processing abnormalities are often reported in schizophrenia. The aim of this study was to examine visual backward masking (BM) functions in remitted schizophrenia-spectrum patients with spared working memory functions. Seventy-two patients with DSM-IV schizophrenia-spectrum disorders were screened using the Wisconsin Card Sorting Test (WCST) and the digit span forward/backward tasks. Patients with spared WCST and digit span performances were selected and administered a spatial working memory test and two BM procedures (target identification and location). The schizophrenia-spectrum group with spared WCST and digit span performances included individuals with schizophreniform disorder (N=11), schizophrenia (N=2), and schizoaffective disorder (N=2). These patients were clinically remitted and demonstrated spared IQ, normal spatial working memory, and relatively high psychosocial functioning. However, there was a significant impairment in the BM procedure, most prominently in the target location task and at short interstimulus intervals. These results suggest that the BM dysfunction is a trait marker of schizophrenia-spectrum disorders and may be present in the absence of working memory abnormalities.

Adult↗
PubMed2004

The effect of memory load on cortical activity in the spatial working memory circuit.

Accumulating evidence from electrophysiology and neuroimaging studies suggests that spatial working memory is subserved by a network of frontal and parietal regions. In the present study, we parametrically varied the memory set size (one to four spatial locations) of a delayed-response task and applied time-resolved fMRI to study the influence of memory load upon the spatial working memory circuit. Our behavioral results showed that performance deteriorates (lower accuracy and longer reaction time) as memory load increases. Memory load influenced cortical activity during the cue, delay, and response phases of the delayed-response task. Although delay-related activity in many regions increased with increasing memory load, it also was significantly reduced in the middle frontal gyrus and frontal eye fields and leveled off in the parietal areas when memory load increased further. Delay-related activity in the left posterior parietal cortex was also lower during the error trials, in comparison with the correct trials. Our findings indicate that the delay period activity in the spatial working memory circuit is load sensitive and that the attenuation of this signal is the neural manifestation of performance limitation in the face of excessive memory load.

Adolescent↗
PubMed2004

Functional dissociations within the inferior parietal cortex in verbal working memory.

Neuroimaging studies of working memory have revealed two sites in the left supramarginal gyrus that may support the short-term storage of phonological information. Activation in the left dorsal aspect of the inferior parietal cortex (DIPC) has been observed in contrasts of working memory load, whereas activation in the ventral aspect of the inferior parietal cortex (VIPC) has been found primarily in contrast of information type (verbal vs. nonverbal). Our goal was to determine whether these two areas are functionally distinct or if instead they are part of a homogeneous region with large variations in the focus of peak activity. Toward this end, we used fMRI to assess the neural response in two working memory tasks (N-back and item recognition) in which we also manipulated memory load and the type of information to be recalled (verbal vs. nonverbal). We found both DIPC and VIPC activation in the same group of subjects and further demonstrated that they have differential sensitivity to our experimental factors. Only the DIPC showed robust load effects, whereas only the VIPC showed reliable effects of information type. These results help to account for the differences observed in between-subject comparisons, and they indicate that the two regions are functionally dissociable. In contrast to the DIPC, activity of the VIPC was also recruited in the fixation and low-load conditions, a surprising result that has not been fully explored in prior studies. Despite their distinctive patterns of performance, neither of these regions displayed a pattern of activity that entirely corresponds to common assumptions of a dedicated phonological short-term store (STS). Instead, we hypothesize that the DIPC may support domain-general executive processes, while the VIPC may support phonological encoding-recoding processes central to a variety of language tasks.

Adult↗
PubMed2002

Visual perceptual and working memory impairments in schizophrenia.

BACKGROUND: Impairments in working memory have been proposed to underlie a broad range of cognitive deficits seen in schizophrenia. Visual working memory impairments are frequently reported in schizophrenia. Investigations of visual working memory generally assume intact visual information processing, despite evidence of visual perceptual impairments in schizophrenia. In this study, we evaluated the integrity of the perceptual system for object and spatial visual information and the relevant working memory system, after adjusting for individual perceptual performance differences. METHODS: Thirty patients with schizophrenia and 20 healthy control subjects underwent testing using a task of perceptual discrimination of spatial and object visual stimuli. For testing visual working memory, a delay was introduced to the perceptual discrimination task. A thresholding procedure was used so that each subject adequately perceived the information during the working memory test. RESULTS: Subjects with schizophrenia exhibited impaired performance relative to controls for object and spatial visual perceptual discrimination. The extent of impairment was greater for the object than for the spatial test. After controlling for perceptual impairments, the subjects with schizophrenia exhibited impaired performance relative to controls for the spatial working memory test but not the object working memory test. CONCLUSIONS: Findings implicate dysfunction of posterior brain areas that mediate visual perceptual processing and the prefrontal areas involved in the active maintenance of information during delay intervals. However, the systems that govern object and spatial visual perception and working memory appear to be affected differentially by schizophrenia.

Adult↗
PubMed2002

Variability of EEG synchronization during a working memory task in healthy subjects.

Working memory is associated with an increase in EEG theta synchronization and a decrease in lower alpha band synchronization. We investigated whether such changes in mean synchronization level are accompanied by changes in small scale fluctuations of synchronization. EEGs (19 channels; average reference; sample frequency 250 Hz) were recorded in 21 healthy subjects (12 males; mean age 62.5 years; S.D. 2.1) at rest and during a visual working memory condition. EEG synchronization was computed in six frequency bands (2-6; 6-10; 10-14; 14-18; 18-22; 22-50 Hz) using the synchronization likelihood. Variability of the synchronization was quantified with synchronization entropy. During the working memory condition synchronization increased in the 2-6 Hz band, and decreased in the 6-10, 14-18 and 18-22 Hz bands. Working memory was associated with increased variability in the 2-6 Hz band, and decreased variability in the 6-10 Hz band and, to a lesser extent, in the 14-18 and 18-22 Hz bands. Working memory is accompanied not only by characteristic changes in the mean level of interactions between neural networks, but also by changes in small scale fluctuations in such interactions. Strong, but rapidly fluctuating coupling between neural systems might provide a mechanism to optimize the balance between local differentiation and global integration of brain activity.

Adult↗
PubMed1998

The role of prefrontal cortex in working memory: examining the contents of consciousness.

Working memory enables us to hold in our 'mind's eye' the contents of our conscious awareness, even in the absence of sensory input, by maintaining an active representation of information for a brief period of time. In this review we consider the functional organization of the prefrontal cortex and its role in this cognitive process. First, we present evidence from brain-imaging studies that prefrontal cortex shows sustained activity during the delay period of visual working memory tasks, indicating that this cortex maintains on-line representations of stimuli after they are removed from view. We then present evidence for domain specificity within frontal cortex based on the type of information, with object working memory mediated by more ventral frontal regions and spatial working memory mediated by more dorsal frontal regions. We also propose that a second dimension for domain specificity within prefrontal cortex might exist for object working memory on the basis of the type of representation, with analytic representations maintained preferentially in the left hemisphere and image-based representations maintained preferentially in the right hemisphere. Furthermore, we discuss the possibility that there are prefrontal areas brought into play during the monitoring and manipulation of information in working memory in addition to those engaged during the maintenance of this information. Finally, we consider the relationship of prefrontal areas important for working memory, both to posterior visual processing areas and to prefrontal areas associated with long-term memory.

Animals↗
PubMedDate not supplied

When the central executive lets us down: schemas, attention, and load in a generative working memory task.

Participants were asked to generate a single sequence of numbers in between two bounds. By varying the requested sequence length and way in which the question is posed, this paradigm enables assessment of the contributions to central executive functioning of schema, focus of attention, and load. With sequences of three or four numbers, a quarter of the sample failed fully to comply with the instructions. They generated an incorrect number of numbers or went outside the specified bounds. With sequences of six numbers, more than half of the sample infringed one or more of the constraints. Participants consistently generated sequences with particular generic properties. The overall frequency and patterns of infringements suggest that a substantial proportion of participants focused their conceptual attention on sequence content and often neglected the problem of how thelength and boundary constraints were going to be evaluated either before or during response delivery.

Attention↗
PubMedDate not supplied

Behavioral studies of the effects of moderate oligemic hypoxia caused by bilateral clamping of carotid arteries in mice. Impairment of spatial working memory.

The experiments carried out on Albino Swiss mice indicated that bilateral clamping of carotid arteries (BCCA) for 30 min caused no neuronal damage but produced an increase in GABA content in the hippocampus, striatum and frontal cortex. The behavioral studies have shown that BCCA did not influence the motor coordination, the spontaneous locomotor activity, the reactivity to pain and the cataleptic response to haloperidol of the mice. However, a significant increase in amphetamine-induced hyperactivity was observed after BCCA. In mice, BCCA did not impair long-term memory and spatial working memory, reflected by alternation behavior in the Y-maze. The same dose of scopolamine impaired the working memory in mice which underwent BCCA much more than sham-operated controls. Naftidrofuryl improved the working memory in mice subjected to BCCA as measured 48 h after the surgery. Pretreatment with naftidrofuryl protected the animals against the impairment of alternation behavior caused by scopolamine administration.

Anesthesia↗
PubMed2005

Maintenance of multiple working memory items by temporal segmentation.

Experimental work based on single cell recordings supports the hypothesis that working memory representations are retained by sustained neuronal firing. While this hypothesis can account for the maintenance of a single memory item, it remains unclear how multiple working memory items are represented. This account will discuss the possible physiological mechanism responsible for the maintenance of multiple working memory items including mechanisms based on sustained firing and synaptic encoding. The focus will be on temporal segmentation by phase encoding, namely the idea that several working memory items are activated sequentially at different points in time. It has been proposed that a mechanism of nested gamma (30-80 Hz) and theta (4-8 Hz) oscillations is responsible for controlling the reactivation of the memory list. This mechanism has been shown to be compatible with multiple behavioral findings on working memory such as the data from the Sternberg experiment. The theta/gamma mechanism has also received support from a large set of electrophysiological findings, however, more experimental work is required to further substantiate or falsify the model.

Action Potentials↗