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PubMedDate not supplied

A low dose of ethanol impairs working memory in mice in a win-shift foraging paradigm.

Using a test of working memory which is not influenced by learning, the win-shift foraging paradigm, ethanol was found to produce amnesia in mice. This effect was produced by very low doses of ethanol, 0.5 and 1.5 g/kg, which did not alter motivation as measured by latency to leave the start box. These doses of ethanol also did not alter performance in the maze as measured by the time to traverse the maze. These data indicate that low doses of ethanol directly impair working memory--that is, the effects are not due to an alteration in learning. The win-shift foraging paradigm, which is free of some of the problems inherent in passive avoidance paradigms, may be useful in exploring the mechanism of this effect of ethanol.

Amnesia↗
PubMed1996

Effects of Alzene and tacrine on water maze reference and working memory function in medial septal-lesioned rats.

The present study investigated the effects of repeated daily administration of a mixture containing free fatty acids (alpha-linolenic/linoleic acid in a 1:4 ratio at 25 mg/kg i.p., Alzene) on medial septal (MS) lesion-induced impairment of water maze (WM) spatial reference and working memory or passive avoidance (PA) behavior in adult rats (250-275 g at the beginning of the study). Alzene treatment was started 7 days before initiation of behavioral testing (WM reference memory testing on treatment days: 7-9 and 28-30 + passive avoidance on treatment days 31-32; WM working memory testing on treatment days: 7-10 and 38-31 + passive avoidance testing on treatment days 32-33) and continued until the end of the study. Alzene improved WM reference memory (treatment days 7-9 and 28-30) and PA behavior (treatment days 31-32) as effectively as an anti-cholinesterase drug, tacrine 3 mg/kg (i.p.). However, in a separate group of MS-lesioned rats we observed that working memory (treatment days 7-10 and 28-31) was not improved by either Alzene or tacrine treatment. The present results suggest that Alzene treatment improves spatial reference memory and inhibitory avoidance in MS-lesioned rats.

Animals↗
PubMed1991

Working memory deficit in aged rats in delayed nonmatching to position task and effect of physostigmine on performance of young and aged rats.

Young (5 month) and aged (23 month) male rats were tested in delayed nonmatching to position task using a T-maze, and their ability of working memory retention was assessed over interrun intervals ranging between 5 and 300 sec. There were no significant age differences in pretest performance at 0 sec interval, but significant memory loss was observed in aged rats when tested with the interrun intervals. Physostigmine (0.1 and 0.2 mg/kg) improved this age-related decline in working memory in a dose-dependent manner, whereas the treatment slightly but not significantly improved the performance of young rats. These results suggest that the central cholinergic system in aged rats was functionally deteriorated and that stimulation of the system could enhance working memory retention in aged rats.

Aging↗
PubMed2007

Available but unattended conceptual information in working memory: temporarily active semantic content or persistent memory for prior operations?

In 2 experiments, the authors investigated available but unattended information following working memory task demands. The experimental task presented a memory set containing exemplars from 2 conceptual categories. Following instructions to focus attention on only 1 category, priming of both categories was assessed with category comparisons of exemplar pairs. Priming was greatest for the focused category and for exemplars from the memory set (direct priming). Priming also extended to new exemplars of both categories (indirect priming) and showed little decline over more than 1 min of intervening processes. Finally, changing between category exemplars and features across memory set and comparison phases eliminated the indirect priming. These results support a persistent, operation-specific, procedural account of available but unattended conceptual information in working memory.

Adolescent↗
PubMed1998

Enhanced N-methyl-D-aspartate function reverses working memory failure induced by blockade of group I metabotropic glutamate receptors in the rat hippocampus.

Intrahippocampal administration of (R,S)-1-aminoindan-1, 5-dicarboxylic acid (AIDA), a potent and selective antagonist of the group I metabotropic glutamate receptor (mGluR), at doses of 0.32-3.2 microg/side dose-dependently increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup. The increase in working memory errors induced by intrahippocampal 3.2 microg/side AIDA was significantly reduced by concurrent infusion of 10 microg/side D-cycloserine, a partial agonist at the glycine binding site on the N-methyl-D-aspartate (NMDA) receptor/channel complex. These results suggest that positive modulation of the NMDA receptor/ channel through activation of the glycine site can compensate for deficiency of hippocampal group I mGluR-mediated neurotransmission involved in working memory function.

Animals↗
PubMed1999

Towers of Hanoi and London: contribution of working memory and inhibition to performance.

The Tower of Hanoi and Tower of London have become well-established executive function tasks that presumably tap cognitive skills mediated by the frontal cortex. It has been assumed that the two tower tasks are more or less interchangeable and that both measure working memory and inhibition processes. These assumptions were tested in a study involving 37 normal college volunteers (M age = 20 years). Participants were administered the Tower of Hanoi (TOH), Tower of London-Revised (TOL-R), two working memory tests, and two tests of inhibition. The two tower tasks correlated significantly (r = .39), but only moderately. The working memory and inhibition variables explained over one-half of the variance in TOL-R performance; however, there was a relatively weaker contribution of inhibition to TOH performance.

Adult↗
PubMedDate not supplied

Serial position effects in auditory event-related potentials during working memory retrieval.

It is established that recall of an item from a list of sequentially presented items is sensitive to the item's position in the memorized list. However, little is known about the brain mechanisms that mediate these serial position effects. Studies of working memory retrieval using event-related potentials report amplitude reductions during retrieval (auditory cortical N100, neocortical late positive wave [LPW]) as memory load increases. We tested the hypothesis that N100 and LPW amplitudes to probes are also affected by serial position. Event-related potentials were recorded from subjects performing an auditory working memory task. A set of one or five digits was memorized, then subjects classified a probe digit as either present or absent from the memory set. A control task was also given. Amplitudes of the N100 and LPW were reduced in the 5-item versus the 1-item set. In the 5-item set N100 amplitude was significantly larger for the initial (1st) serial position, relative to Positions 2-5, while linear increases in LPW amplitude were seen across serial positions (5th > 1st position). A control task without memorization showed no N100 or LPW amplitude changes with set size or serial position. The findings reveal that the N100 and LPW are influenced differently by serial position during working memory retrieval: N100 shows a primacy effect and LPW demonstrates a recency effect. The results suggest that primacy and recency effects may be mediated by different brain regions at different times during memory retrieval.

Adult↗
PubMed2006

Life-span development of visual working memory: when is feature binding difficult?

We asked whether the ability to keep in working memory the binding between a visual object and its spatial location changes with development across the life span more than memory for item information. Paired arrays of colored squares were identical or differed in the color of one square, and in the latter case, the changed color was unique on that trial (item change) or was duplicated elsewhere in the array (color-location binding change). Children (8-10 and 11-12 years old) and older adults (65-85 years old) showed deficits relative to young adults. These were only partly simulated by dividing attention in young adults. The older adults had an additional deficiency, specifically in binding information, which was evident only when item- and binding-change trials were mixed together. In that situation, the older adults often overlooked the more subtle, binding-type changes. Some working memory processes related to binding undergo life-span development in an inverted-U shape, whereas other, bias- and salience-related processes that influence the use of binding information seem to develop monotonically.

Adolescent↗
PubMed2000

Cholinergic enhancement and increased selectivity of perceptual processing during working memory.

Using functional magnetic resonance imaging, we investigated the mechanism by which cholinergic enhancement improves working memory. We studied the effect of the cholinesterase inhibitor physostigmine on subcomponents of this complex function. Cholinergic enhancement increased the selectivity of neural responses in extrastriate cortices during visual working memory, particularly during encoding. It also increased the participation of ventral extrastriate cortex during memory maintenance and decreased the participation of anterior prefrontal cortex. These results indicate that cholinergic enhancement improves memory performance by augmenting the selectivity of perceptual processing during encoding, thereby simplifying processing demands during memory maintenance and reducing the need for prefrontal participation.

Acetylcholine↗
PubMed2004

Age-related changes in antisaccade task performance: inhibitory control or working-memory engagement?

In antisaccade tasks, subjects are required to generate a saccade in the direction opposite to the location of a sudden-onset target stimulus. Compared to young adults, older adults tend to make more reflex-like eye movements towards the target, and/or show longer saccadic onset latencies on correct direct antisaccades. To better understand the nature of these effects of aging on antisaccade performance, we examined the role of age-related deficiencies in inhibitory control vis-a-vis age changes in the engagement of working memory. Inhibitory demands were manipulated using fixation-offset conditions, while working-memory demands were manipulated by varying memory-updating requirements. The results indicate that inhibitory oculomotor functions remain largely intact with advancing age; older adults' performance breaks down only when their limited working-memory capacity is taxed by increasing updating demands.

Adolescent↗
PubMed2005

Computational models of working memory: putting long-term memory into context.

Detailed computational modeling of human memory has typically been aimed at either short-term (working) memory or long-term memory in isolation. However, recent research highlights the importance of interactions between these systems for both item and order information. At the same time, computational models of both systems are beginning to converge onto a common framework in which items are associated with an evolving "context" signal and subsequently compete with one another at recall. We review some of these models, and discuss a common mechanism capable of modelling working memory and its interaction with long-term memory, focussing on memory for verbal sequences.

Attention↗
PubMed2006

Concomitant deficits in working memory and fear extinction are functionally dissociated from reduced anxiety in metabotropic glutamate receptor 7-deficient mice.

Metabotropic glutamate receptor 7 (mGluR7), a receptor with a distinct brain distribution and a putative role in anxiety, emotional responding, and spatial working memory, could be an interesting therapeutic target for fear and anxiety disorders. mGluR7-deficient (mGluR7-/-) mice showed essentially normal performance in tests for neuromotor and exploratory activity and passive avoidance learning but prominent anxiolytic behavior in two anxiety tests. They showed a delayed learning curve during the acquisition of the hidden-platform water maze, and three interspersed probe trials indicated that mGluR7-/- mice were slower to acquire spatial information. Working memory in the water maze task and the radial arm maze was impaired in mGluR7-/- mice compared with mGluR7+/+. mGluR7-/- mice also displayed a higher resistance to extinction of fear-elicited response suppression in a conditioned emotional response protocol. In a non-fear-based water maze protocol, mGluR7-/- mice displayed similar delayed extinction. These observed behavioral changes are probably not attributable to changes in AMPA or NMDA receptor function because expression levels of AMPA and NMDA receptors were unaltered. Extinction of conditioned fear is an active and context-dependent form of inhibitory learning and an experimental model for therapeutic fear reduction. It appears to depend on glutamatergic and higher-level brain functions similar to those involved in spatial working memory but functionally dissociated from those that mediate constitutional responses in anxiety tests.

Analysis of Variance↗
PubMed2005

Working memory capacity, indirect semantic priming, and stroop interference: pattern of interindividual prefrontal performance differences in healthy volunteers.

Using neuropsychological models of prefrontal function, the authors investigated the pattern of interindividual prefrontal performance differences in healthy volunteers. Using a correlation and an extreme group approach, they compared verbal and visuospatial working memory capacity with performance on the Stroop interference task as a measure of executive control and on the direct and indirect semantic priming tasks as a measure of semantic access. Subjects with low visuospatial working memory capacity exhibited increased Stroop interference Subjects with low verbal memory capacity showed increased priming and Stroop interference only. The study shows that prefrontal functioning varies interindividually, forming patterns of performance differences. These findings suggest that working memory, executive control, and semantic retrieval are functionally related to some extent.

Adult↗
PubMed2002

Effects of smoking abstinence on visuospatial working memory function in schizophrenia.

Schizophrenic patients have impairments in cognitive function, including deficits in visuospatial working memory (VSWM). VSWM is mediated, in part, by prefrontal cortical dopamine (DA) function, and dysregulation of prefrontal cortical DA systems may contribute to the pathophysiology of schizophrenia. Nicotine has complex effects on spatial working memory (SWM) in animal studies, with most studies demonstrating enhancement of SWM. Cigarette smoking is highly prevalent in schizophrenia, and these patients may smoke cigarettes to remediate cognitive deficits. The present study examined the effects of acute (<1 week) and prolonged (8-10 weeks) smoking abstinence on VSWM in schizophrenic (n = 23) and control (n = 29) nicotine-dependent cigarette smokers during placebo-controlled smoking cessation trials. Schizophrenic and control smoking patients had significant impairments in VSWM compared to non-smoking controls, after adjusting for differences in age, education and depressive symptoms. Schizophrenic smokers who quit smoking had further impairments in VSWM, and control quitters had improvements in VSWM. Abstinence-induced changes in VSWM varied as a function of gender in controls, but not in schizophrenics. These changes in VSWM appeared to be independent of study medications, and smoking abstinence did not significantly alter performance on the Stroop Color Word Test in either group. These results suggest that smoking abstinence differentially alters VSWM in schizophrenic vs. control smokers, and that cigarette smoking has beneficial effects on VSWM in schizophrenic, but not control, smokers.

Adult↗
PubMed2006

Differential working memory impairment in bipolar disorder and schizophrenia: effects of lifetime history of psychosis.

BACKGROUND: Although bipolar disorder and schizophrenia have long been viewed as distinct illnesses, there is growing evidence that these two complex diseases share some common genes, which may manifest as overlapping neuropsychological impairments. Although working memory dysfunction has been proposed to be central to the pathophysiology of schizophrenia, it has received less attention in studies of bipolar disorder. METHOD: We applied measures of working memory to patients with schizophrenia (n = 15), patients with schizoaffective disorder (n = 15), patients with psychotic (n = 11) and non-psychotic (n = 15) bipolar disorder, and demographically matched healthy subjects (n = 32), in order to determine the extent to which these groups show common or unique impairments. RESULTS: While patients with bipolar disorder (with and without psychotic features) and those with schizophrenia/schizoaffective disorder were impaired on backward digit span, only patients with a lifetime history of psychotic features, regardless of diagnosis, were impaired on spatial delayed response task. CONCLUSIONS: Backward digit span performance is comparable in bipolar disorder and schizophrenia, and may be an appropriate endophenotypic marker that cuts across diagnostic categories. In contrast, spatial working memory performance clearly distinguishes non-psychotic bipolar disorder patients from patients with functional psychosis.

Adult↗
PubMed1997

Supranormal stimulation of D1 dopamine receptors in the rodent prefrontal cortex impairs spatial working memory performance.

Although previous research has emphasized the beneficial effects of dopamine (DA) on functions of the prefrontal cortex (PFC), recent studies of animals exposed to mild stress indicate that excessive DA receptor stimulation may be detrimental to the spatial working memory functions of the PFC (Arnsten and Goldman-Rakic, 1990; Murphy et al., 1994, 1996a,b, 1997). In particular, these studies have suggested that supranormal stimulation of D1 receptors may contribute to the detrimental actions of DA in the PFC (Murphy et al., 1994, 1996a). The current study directly tested this hypothesis by examining the effects of infusing a full D1 receptor agonist, SKF 81297, into the PFC of rats performing a spatial working memory task, delayed alternation. SKF 81297 produced a dose-related impairment in delayed-alternation performance. The impairment was reversed by pretreatment with a D1 receptor antagonist, SCH 23390, consistent with drug actions at D1 receptors. SCH 23390 by itself had no effect on performance, although slightly higher doses impaired performance (Murphy et al., 1994, 1996a). There was a significant relationship between infusion location and drug efficacy; animals with cannulae anterior to the PFC were not impaired by SKF 81297 infusions. Taken together, these results demonstrate that supranormal D1 receptor stimulation in the PFC is sufficient to impair PFC working memory function. These cognitive data are consistent with recent electrophysiological studies of D1 receptor mechanisms affecting the PFC (Williams and Goldman-Rakic, 1995; Yang and Seamans, 1996). Increased D1 receptor stimulation during stress may serve to take the PFC "off-line" to allow posterior cortical and subcortical structures to regulate behavior, but may contribute to the vulnerability of the PFC in many neuropsychiatric disorders.

Animals↗
PubMed1999

The cerebellum and cognition: cerebellar lesions do not impair spatial working memory or visual associative learning in monkeys.

Anatomical studies in non-human primates have shown that the cerebellum has prominent connections with the dorsal, but not the ventral, visual pathways of the cerebral cortex. Recently, it has been shown that the dorsolateral prefrontal cortex (DPFC) and cerebellum are interconnected in monkeys. This has been cited in support of the view that the cerebellum may be involved in cognitive functions, e.g. working memory. Six monkeys (Macaca fascicularis) were therefore trained on a classic test of working memory, the spatial delayed alternation (SDA) task, and also on a visual concurrent discrimination (VCD) task. Excitotoxic lesions were made in the lateral cerebellar nuclei, bilaterally, in three of the animals. When retested after surgery the lesioned animals were as quick to relearn both tasks as the remaining unoperated animals. However, when the response times (RT) for each task were directly compared, on the SDA task the monkeys with cerebellar lesions were relatively slow to decide where to respond. We argue that on the SDA task animals can prepare their responses between trials whereas this is not possible on the VCD task, and that the cerebellar lesions may disrupt this response preparation. We subsequently made bilateral lesions in the DPFC of the control animals and retested them on the SDA task. These monkeys failed to relearn the task. The results show that, unlike the dorsal prefrontal cortex, the cerebellum is not essential for working memory or the executive processes that are necessary for correct performance, though it may contribute to the preparation of responses.

Animals↗
PubMed2002

Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats.

The interactions between the median raphe nucleus (MRN) serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 microg/side) produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus.

Animals↗