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PubMed1994

Object permanence and working memory in cats (Felis catus).

Cats (Felis catus) find an object when it is visibly moved behind a succession of screens. However, when the object is moved behind a container and is invisibly transferred from the container to the back of a screen, cats try to find the object at or near the container rather than at the true hiding place. Four experiments were conducted to study search behavior and working memory in visible and invisible displacement tests of object permanence. Experiment 1 compared performance in single and in double visible displacement trials. Experiment 2 analyzed search behavior in invisible displacement tests and in analogs using a transparent container. Experiments 3 and 4 tested predictions made from Experiment 1 and 2 in a new situation of object permanence. Results showed that only the position changes that cats have directly perceived are encoded and activated in working memory, because they are unable to represent or infer invisible movements.

Animals↗
PubMed2003

Spatial, contextual and working memory are not affected by the absence of mossy fiber long-term potentiation and depression.

The mossy fibers of the hippocampus display NMDA-receptor independent long-term plasticity. A number of studies addressed the role of mossy fiber long-term plasticity in memory, but have provided contrasting results. Here, we have exploited a genetic model, the rab3A null-mutant, which is characterized by the absence of both mossy fiber long-term potentiation and long-term depression. This mutant was backcrossed to 129S3/SvImJ and C57Bl/6J to obtain standardized genetic backgrounds. Spatial working memory, assessed in the eight-arm radial maze, was unchanged in rab3A null-mutants. Moreover, one-trial cued and contextual fear conditioning was normal. Long-term spatial memory was tested in the Morris water maze. Two different versions of this task were used, an 'easy' version and a 'difficult' one. On both versions, no differences in search time and quadrant preferences were observed. Thus, despite the elimination of mossy fiber long-term plasticity, these tests revealed no impairments in mnemonic capabilities. We conclude that spatial, contextual and working memory do not depend on mossy fiber plasticity.

Animals↗
PubMed1991

The effects of number of trials per day, retention interval, gender and time of day on acquisition of a two-choice, win-stay water-escape working memory task in the rat.

A 2 x 2 x 2 factorial study was conducted to examine the effects of gender, trials/day (TPD), and retention interval (RI) on acquisition of a two-choice win-stay water-escape task in 4-month-old Sprague-Dawley rats. Variations of this task have previously been shown to be sensitive to changes in working memory that occur with age (Means and Kennard, 1991) or to follow treatment with an anxiolytic (Bass et al., 1989) or with cognitive enhancers (Comer and Moore, in press) in males or to estrogen in ovariectomized females (O'Neal et al., 1990). Both training with 1 TPD and with a 5-min RI, time between an information "run" and a test "run", reduced errors during acquisition as compared to giving 3 TPD and a 1-min RI (P less than 0.05 in all cases). Males made fewer errors than did females (P less than 0.05). The three effects were additive: males trained with 1 TPD and a 5-min RI performed best and females trained with 3 TPD and a 1-min RI performed worst. Also, rats given 1 TPD made fewer acquisition errors when trained 2 h before the lights were turned off than when trained during the middle of the light portion of the light/dark cycle (P less than 0.05). Finally, when given 3 TPD, the rats, especially the females, performed significantly worse on their third trial (P less than 0.05). It was concluded that two-choice win-stay water-escape is a very sensitive assay of working memory with much potential for neurobehavioral research.

Animals↗
PubMed2002

Brain mechanisms of visual encoding and working memory in psychometrically identified schizotypal individuals and after acute administration of haloperidol.

A probabilistic association task that manipulated the necessity to temporarily store information was combined with the recording of event-related potentials. In Experiment 1, scores obtained from a positive schizotypy scale were used to categorize participants as either low or high schizotypal individuals. Low, but not high, schizotypal individuals displayed evidence for selective associative learning in the working memory dependent ("trace") version of the task. The amplitudes of the occipito-temporal N150 were attenuated in high schizotypal individuals. In Experiment 2, the intravenous administration of a single dose of haloperidol (0.04 mg/kg), but not of a placebo, strengthened the selectivity of associative learning in the trace version of the task. The amplitudes of the occipito-temporal N150 were augmented by haloperidol. Psychometrically identified schizotypal individuals and normal individuals under mild stress demonstrated defective prioritization of information in working memory and deficient visual encoding. These neurocognitive effects of schizotypy and stress seem to be mediated by the D2 family of dopamine receptors.

Adult↗
PubMed2004

Prefrontal broadband noise, working memory, and genetic risk for schizophrenia.

OBJECTIVE: It has been suggested that increased variability of prefrontal physiological responses may represent a fundamental mechanism underlying frontal lobe deficits in schizophrenia. Increased response variability ("noise") is thought to result from impaired phase resetting of stimulus-induced dynamic changes of ongoing rhythmic oscillations (field potentials) generated in the apical dendrites of pyramidal neurons. In the present study, the authors explored whether this particular physiological abnormality predicts working memory performance and is related to the genetic risk for schizophrenia. METHOD: Prefrontal response variability of discrete frequency components was investigated across a broad frequency range (0.5-45.0 Hz) during processing of an oddball paradigm in patients with schizophrenia (N=66), their clinically unaffected siblings (N=115), and healthy comparison subjects (N=89). RESULTS: As hypothesized, prefrontal noise was negatively correlated with working memory performance across all subjects. In addition, it was observed that prefrontal noise possesses trait characteristics and is strongly associated with genetic risk for schizophrenia. CONCLUSIONS: Frontal lobe-related cognitive function depends on the ability to synchronize cortical pyramidal neurons, which is in part genetically controlled. Increased prefrontal "noise" is an intermediate phenotype related to genetic susceptibility for schizophrenia.

Adult↗
PubMed2000

[Decomposition studies on the core function of working memory].

By means of decomposition we investigated using an experimental design (n = 160) the impact of combinations of processing and retention requirements on performance. Retention-during-processing spans (i.e., dual task requirements with equal importance of both evaluated components) were compared with the "reading" (final word) span of read sentences. In a correlational design, the relationships of these intentional spans and a unintentional indicator of working memory (the pronoun inference distance) were compared with fluid intellectual performances. The effects of processing on the span may not be restricted to articulatory suppression of rehearsal. While the substitution of retention of an additional processing-independent item improved the span, this did not hold for items resulting from processing. Thus, the span is determined by coordination of retention with processing, but neither by an activity without retention nor by retention per se. Coordination requires resources in addition to those required by the activities to be coordinated. Strategies of coordination differing in their efficiency result in different spans. Both unintentional processes and intentional ones contribute to the dual task performance of the retention-during-processing type. The best predictors for fluid verbal and nonverbal intellectual performance are the unintentional (pronoun) inferences and the complex intentional retention-during-processing span. The results are in favor of a working memory model in terms of a set of functions.

Adult↗
PubMedDate not supplied

Exposure to 3,4-methylenedioxymethamphetamine (MDMA) on postnatal days 11-20 induces reference but not working memory deficits in the Morris water maze in rats: implications of prior learning.

3,4-methylenedioxymethamphetamine (MDMA) in previous experiments has been shown to induce long-term spatial and sequential learning and memory deficits in adult offspring after exposure to the drug on postnatal (P) days 11-20, but not after exposure on P1-10. Herein we further tested for the effects of MDMA (0, 5, 10 or 20 mg/kg x 2/day) after exposure on P11-20 on reference and working memory in the Morris water maze (MWM), on reference memory in the Barnes maze, and on cued learning in the visible platform version of the MWM. The MWM and Barnes mazes were counterbalanced such that half the litters received the MWM-first and the other half received the Barnes maze first. Effects on MWM performance as a function of test order were observed. For animals that received the Barnes maze first, spatial MWM learning and memory trends were seen but they were not significantly different between MDMA groups and saline controls. For those receiving the MWM-first, there are consistent impairments on all measures in the MDMA groups compared to controls on MWM performance (latency, path length, and cumulative distance from the goal). On probe trials, MDMA animals receiving the MWM-first showed increased distance from the target site compared to controls. There were no MDMA effects seen on cued trials in the MWM or on straight channel swimming trials regardless of test order, indicating that MDMA had no effects on swimming ability or on the skills needed to learn the MWM. Similarly, there were no effects of MDMA on MWM working memory regardless of test order. No MDMA effects on the Barnes maze were found regardless of test order, however, the interpretation of this finding was compromised by the poor performance of the animals on this task.

Age Factors↗
PubMed2003

Pre-frontal executive committee for perception, working memory, attention, long-term memory, motor control, and thinking: a tutorial review.

As an explicit organizing metaphor, memory aid, and conceptual framework, the prefrontal cortex may be viewed as a five-member 'Executive Committee,' as the prefrontal-control extensions of five sub-and-posterior-cortical systems: (1) the 'Perceiver' (dominant-right-hemisphere ventral-lateral prefrontal cortex--VL/PERC-PFC) is the frontal extension of the ventral perceptual stream (the VL/PERC system) which represents the world and self in object coordinates; (2) the 'Verbalizer' (dominant-left-hemisphere ventral-lateral prefrontal cortex system--VL/VERB-PFC) is the frontal extension of the language stream (the VL/VERB system) which represents the world and self in language coordinates; (3) the 'Motivator' (ventral/medial-orbital pre-frontal cortex--VMO-PFC) is the frontal cortical extension of a subcortical extended-amygdala stream (the VMO system) which represents the world and self in motivational/emotional coordinates; (4) the 'Attender' (dorsal-medial/anterior cingulate--DM/AC-PFC) is the frontal cortical extension of a subcortical extended-hippocampal stream (the DM/AC system) which represents the world and self in spatiotemporal coordinates and directs attention to internal and external events; and (5) the 'Coordinator' (the dorsolateral prefrontal cortex--DL-PFC) is the frontal extension of the dorsal perceptual stream (the DL system) which represents the world and self in body- and eye-coordinates and controls willed action and working memory. This tutorial review examines the interacting roles of these five systems in perception, working memory, attention, long-term memory, motor control, and thinking.

Attention↗
PubMed1992

Effects of strychnine-insensitive glycine receptor antagonists and sigma agents on working memory performance: comparison with dizocilpine and scopolamine.

The strychnine insensitive glycine receptor antagonists (+/-) HA 966 (2.5, 3.5, 4.25 and 5.0mg/kg) and 7 chlorokynurenic acid (5.0, 10.0, and 15.0mg/kg), the putative sigma agents NPC 16377 (5.0 and 8.0mg/kg), BMY 14802 (5.0, 7.5 and 10.0mg/kg), and ifenprodil (5.0 and 7.0mg/kg) and the reference agents scopolamine and dizocilpine [(+) MK 801] were evaluated in a nonspatial delayed matching to sample working memory task in rats. (+/-) HA 966 impaired accuracy at the longest retention interval and decreased response probability measures. 7-Chlorokynurenic acid was essentially without effect. The noncompetitive NMDA antagonist dizocilpine reduced accuracy at all retention intervals, decreased the probability of a choice response and increased the probability of an intertrial interval response. The anticholinergic agent scopolamine selectively reduced accuracy at the longest retention interval but did not affect other performance measures. Sigma agents decreased response probability measures but did not affect accuracy at any retention interval. The results support the notion that sigma agents, glycine antagonists and NMDA antagonists produce different effects in cognitive tasks including working memory performance.

Journal Article↗
PubMed1985

Central cholinergic involvement in working memory: effects of scopolamine on continuous nonmatching and discrimination performance in the rat.

Rats were trained to stable baselines of lever pressing on a variable intertrial interval continuous nonmatching to sample schedule (CNM) or on an analogous discrimination schedule. Scopolamine reduced accuracy of CNM performance to a similar extent over the three intertrial (retention) intervals: 2.5, 5, and 10 s, results indicating that the drug did not affect the time-dependent process of retention in working memory. When baseline levels of performance accuracy were similar in the CNM and discrimination tasks (but stimulus discriminability was greater in the CNM task), scopolamine reduced accuracy equally in the two procedures. Effects of scopolamine on accuracy of noncorrection trial CNM performance were simulated by reducing stimulus discriminability; however, scopolamine disrupted CNM correction trial performance much more than did reductions in stimulus discriminability. It is concluded that scopolamine's effects on working memory are not limited to possible effects on stimulus discrimination: Scopolamine may also affect retrieval of response rules from reference memory.

Animals↗
PubMed2007

Deficits in working memory and motor performance in the APP/PS1ki mouse model for Alzheimer's disease.

The APP/PS1ki mouse model for Alzheimer's disease (AD) exhibits robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss starting at 6 months of age. It expresses human mutant APP751 with the Swedish and London mutations together with two FAD-linked knocked-in mutations (PS1 M233T and PS1 L235P) in the murine PS1 gene. The present report covers a phenotypical analysis of this model using either behavioral tests for working memory and motor performance, as well as an analysis of weight development and body shape. At the age of 6 months, a dramatic, age-dependent change in all of these properties and characteristics was observed, accompanied by a significantly reduced ability to perform working memory and motor tasks. The APP/PS1ki mice were smaller and showed development of a thoracolumbar kyphosis, together with an incremental loss of body weight. While 2-month-old APP/PS1ki mice were inconspicuous in all of these tasks and properties, there is a massive age-related impairment in all tested behavioral paradigms. We have previously reported robust axonal degeneration in brain and spinal cord, as well as abundant hippocampal CA1 neuron loss starting at 6 months of age in the APP/PS1ki mouse model, which coincides with the onset of motor and memory deficits described in the present report.

Alzheimer Disease↗
PubMed2002

Behavioral evidence for working memory of sensory dimension in macaque monkeys.

For animals, which lack language codes, there might be limitations in the use of abstract concepts in guiding their behavior. We trained two macaque monkeys in a computerized version of Wisconsin Card Sorting Task (WCST) with two dimensions (shape and color) to test their capability for memorizing, updating and using representation of sensory dimension. A sample had to be matched with one of three test items by either matching in color or shape. The monkeys had to find the relevant sensory dimension and its sudden changes by trial and error only based on reward and error signals. Both monkeys succeeded in more than ten shifts in the rules within a daily session. Several probe tests showed that the monkeys in fact used the dimension-based matching rules, because the rule shift was generalized from the experience of some samples to all of the others in the sample set, and because the rules were immediately applied to newly introduced samples. The frequent shifts can be overcome only with representation of the sensory dimension in working memory. These results, thus, suggest that nonhuman primates can store sensory dimension such as color and shape in working memory, dynamically update it based on the behavioral outcomes, and use it to guide behavior, despite their lack of apparent language.

Animals↗
PubMed2006

Spatial working memory in obsessive-compulsive disorder improves with clinical response: A functional MRI study.

To date, only a few studies have examined whether executive dysfunctions in obsessive-compulsive disorder (OCD) are state or trait dependent and almost none of these studies have used functional neuroimaging techniques. We conducted a functional MRI study before and after 12 weeks of pharmacological treatment in 14 psychotropic-free patients with OCD without comorbidity. Subjects performed a spatial variant of a working memory task with four increasing levels of difficulty (n-back task). Responders and non-responders did not differ in clinical and demographical characteristics or brain activation patterns before treatment. Performance improved only in responders and was associated with a change in the overall pattern of brain activity during the task. We found no correlations between (changes in) scores on symptom scales, brain activity and performance. Our preliminary findings suggests that spatial working memory deficits in OCD and their functional anatomical correlates, as assessed with a spatial n-back task, are, at least to some extent, state dependent.

Adult↗
PubMed2006

Reaction time, inhibition, working memory and 'delay aversion' performance: genetic influences and their interpretation.

BACKGROUND: For candidate endophenotypes to be useful for psychiatric genetic research, they first of all need to show significant genetic influences. To address the relative lack of previous data, we set to investigate the extent of genetic and environmental influences on performance in a set of theoretically driven cognitive-experimental tasks in a large twin sample. We further aimed to illustrate how test-retest reliability of the measures affects the estimates. METHOD: Four-hundred 7- to 9-year-old twin pairs were assessed individually on tasks measuring reaction time, inhibition, working memory and 'delay aversion' performance. Test-retest reliability data on some of the key measures were available from a previous study. RESULTS: Several key measures of reaction time, inhibition and working-memory performance indicated a moderate degree of genetic influence. Combining data across theoretically related tasks increased the heritability estimates, as illustrated by the heritability estimates of 60% for mean reaction time and 50% for reaction-time variability. Psychometric properties (reliability or ceiling effects) had a substantial influence on the estimates for some measures. CONCLUSIONS: The data support the usefulness of several of the variables for endophenotype studies that aim to link genes to cognitive and motivational processes. Importantly, the data also illustrate specific conditions under which the true extent of genetic influences may be underestimated and hence the usefulness for genetic mapping studies compromised, and suggest ways to address this.

Child↗
PubMed2006

Macrovascular contribution in activation patterns of working memory.

Brain activation maps of blood oxygenation level dependent (BOLD) signals during functional magnetic resonance imaging (fMRI) are sensitive to unwanted contributions from large vessels. Most BOLD-fMRI studies are based on a stimulus-correlated modulation of the MRI signal amplitude that is sensitive to desired microvascular effects and unwanted macrovascular effects. Aiming to suppress macrovascular effects in activation patterns, this BOLD-fMRI study evaluates brain activation during a verbal working memory task (2-back) in healthy volunteers (n=18) using the amplitude and phase components of the MRI signal. The use of the first time point as a phase reference allowed us to eliminate phase wrapping artifacts and increase the statistical power of 'phase' activation, and this information was used to filter out voxels with significant macrovascular (i.e., draining and pial veins) contribution in 'amplitude' activation patterns. Across subjects, the task produced large modulations of the relative phase in the occipital, dorsolateral prefrontal, and parietal cortices, suggesting a common distribution of draining veins in these regions across subjects, and in the rostral frontal cortex, probably associated to stimulus-correlated motion of the head. The phase filtering method partially suppressed BOLD responses in the superior and lateral prefrontal, parietal, and occipital cortices; therefore the commonly reported brain activation in these cortices during working memory tasks may include significant macrovascular contributions. This study suggests that the phase information embedded in the MRI signal can be used to suppress unwanted macrovascular contributions in fMRI studies.

Adult↗
PubMed1999

Simultaneous evaluation of spatial working memory and motivation by the allocentric place discrimination task in the water maze in rats.

In order to evaluate learning and memory deficits separately from and simultaneously with motivational, motor and sensory impairments in identical animals, we developed the allocentric place discrimination task test using a water maze in rats. For this assessment task, two similar, visible platforms, one was fixed and the other was floating, were simultaneously present in a pool, and the working memory of the allocentric place discrimination task was evaluated. After training, the task accuracy was high about 85% correct and animals were used repeatedly. The accuracy decreased significantly when the pool was surrounded with a black curtain. Muscarinic receptor antagonist scopolamine 0.5 mg/kg selectively impaired the accuracy. Muscle relaxant dantrolene 10 mg/kg selectively decreased swimming speed. Under low motivational condition (warm water), still time increased and swimming speed decreased, but the accuracy was not affected. Similar to warm water, opioid receptor agonist morphine 15 mg/kg increased still time and decreased swimming speed. These results suggest that the allocentric place discrimination task is useful in evaluating spatial working memory ability independently of and concurrently with also visual, motor ability and motivation in identical animals.

Analgesics, Opioid↗
PubMed2004

Post-trauma administration of caffeine plus ethanol reduces contusion volume and improves working memory in rats.

It has been demonstrated that ethanol exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI). Recently, it has been reported that co-administration of caffeine (10 mg/kg) and a low amount of alcohol (0.65 g/kg; caffeinol) reduces cortical infarct volume up to 80%, and improves motor coordination, following a rodent model of reversible common carotid/middle cerebral artery occlusion. However, the protective effects of caffeinol following other CNS insults, nor its influence on cognitive function, have been examined. Using a controlled cortical impact model of brain injury, the effect of caffeinol administration on TBI-associated motor and cognitive deficits was assessed. When given 15 min following injury, caffeinol reduced cortical tissue loss and improved working memory. However, no influence on motor skills, Morris water maze performance or associative learning and memory was observed. Delayed administration (6 h post-injury) of caffeinol containing a dose of ethanol (1 g/kg) previously demonstrated to improve motor performance eliminated the working memory benefit and cortical protection. These results indicate that early administration of caffeinol may be beneficial in lessening some of the deficits and cortical tissue loss associated with brain trauma.

Animals↗
PubMed1997

Eye-movements and visual imagery: a working memory approach to the treatment of post-traumatic stress disorder.

It has been claimed that the symptoms of post-traumatic stress disorder (PTSD) can be ameliorated by eye-movement desensitization-reprocessing therapy (EMD-R), a procedure that involves the individual making saccadic eye-movements while imagining the traumatic event. We hypothesized that these eye-movements reduce the vividness of distressing images by disrupting the function of the visuospatial sketchpad (VSSP) of working memory, and that by doing so they reduce the intensity of the emotion associated with the image. This hypothesis was tested by asking non-PTSD participants to form images of neutral and negative pictures under dual task conditions. Their images were less vivid with concurrent eye-movements and with a concurrent spatial tapping task that did not involve eye-movements. In the first three experiments, these secondary tasks did not consistently affect participants' emotional responses to the images. However, Expt 4 used personal recollections as stimuli for the imagery task, and demonstrated a significant reduction in emotional response under the same dual task conditions. These results suggest that, if EMD-R works, it does so by reducing the vividness and emotiveness of traumatic images via the VSSP of working memory. Other visuospatial tasks may also be of therapeutic value.

Adult↗