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Fimbria-fornix lesions impair spatial working memory but not cognitive mapping.

Three experiments were designed to evaluate the relative merits of two theories of hippocampal function, the cognitive mapping theory and the working memory theory. Rats were tested in a series of maze tasks that varied in memory requirements. In the experiments that required cognitive mapping but not working memory (Experiments 1 and 3), rats with fimbria-fornix lesions reached stable levels of performance that were as accurate as those of control rats, and they also performed accurately during transfer tests, results demonstrating that they used a cognitive mapping strategy to solve the discrimination. In the experiment that required working memory (Experiment 2), rats with fimbria-fornix lesions performed at chance levels during all of postoperative testing, and they distributed their choices randomly between the correct and the incorrect goals. These results are seen as generally refuting the predictions made by the cognitive mapping theory and supporting the predictions made by the working memory theory. Additional analyses (Experiment 3) examined the nature of a transitory impairment exhibited by rats with fimbria-fornix lesions in two tasks that did not require working memory. Postoperatively, the performance of the rats with lesions was initially impaired but recovered to normal levels with a time course similar to that seen during preoperative acquisition. These results are seen as requiring an extension of the working memory theory of hippocampal function, and discussion is focused on the possibility of a temporary retrograde amnesia following fimbria-fornix lesions and the distinctions between different types of memory abilities.

Animals↗

Verbal and visuospatial working memory deficits in children with Down syndrome.

The hypothesis that deficits of children with Down syndrome on working memory tasks are more evident the higher the control required and for verbal than visuospatial tasks was tested. Two groups of children, one with Down syndrome, who ranged in age from 7 to 18, and a control group were assessed with batteries of verbal and visuospatial working memory tests requiring different levels of control. On tasks requiring low control, children with Down syndrome showed impairment of verbal but not visuospatial working memory tasks. As the requirement for control increased, they showed greater impairment on both tasks. Children with Down syndrome were comparatively better in visuospatial than verbal tasks. Implications of these results for working memory models and the role of working memory in intelligence were discussed.

Adolescent↗

Effects of working memory load on long-term word priming.

Three experiments assessed the role of verbal and visuo-spatial working memory in supporting long-term repetition priming for written words. In Experiment 1, two priming tasks (word stem completion and category-exemplar production) were included with three levels of load on working memory: (1) without memory load, (2) memory load that involved storing a string of six digits, and (3) memory load that involved storing a graphic shape. Experiments 2 and 3 compared the effects of a verbal (Experiment 2) or a visual (Experiment 3) working memory load at encoding on both an implicit (word stem completion) and an explicit test (cued recall). The results show no effect of memory load in any of the implicit memory tests, suggesting that priming does not rely on working memory resources. By contrast, loading working memory at encoding causes a significant disruptive effect on the explicit memory test for words when the load is verbal but not visual.

Adult↗

A role for prefrontal calcium-sensitive protein phosphatase and kinase activities in working memory.

The prefrontal cortex is involved in the integration and interpretation of information for directing thoughts and planning action. Working memory is defined as the active maintenance of information in mind and is thought to lie at the core of many prefrontal functions. Although dopamine and other neurotransmitters have been implicated, the intracellular events activated by their receptors that influence working memory are poorly understood. We demonstrate that working memory involves transient changes in prefrontal G(q/11)-signaling and in calcium-dependent intracellular protein phosphatase and kinase activity. Interestingly, inhibition of the calcium activated phosphatase calcineurin impaired, while calcium/calmodulin dependent kinase II (CaMKII) and calcium-dependent protein kinase C (PKC) enhanced, working memory. Our findings suggest that the active maintenance of information required for working memory involves transient changes in the balance of these enzymes' activities.

Animals↗

Working memory correlates of three symptom clusters in schizophrenia.

This study was designed to examine whether discrete working memory deficits underlie positive, negative and disorganised symptoms of schizophrenia. Symptom dimension ratings were assigned to 52 outpatients with schizophrenia (ICD-10 criteria), using items drawn from the Positive and Negative Syndrome Scale (PANSS). Linear regression and correlational analyses were conducted to examine whether symptom dimension scores were related to performance on several tests of working memory function. Severity of negative symptoms correlated with reduced production of words during a verbal fluency task, impaired ability to hold letter and number sequences on-line and manipulate them simultaneously, reduced performance during a dual task, and compromised visuospatial working memory under distraction-free conditions. Severity of disorganisation symptoms correlated with impaired visuospatial working memory under conditions of distraction, failure of inhibition during a verbal fluency task, perseverative responding on a test of set-shifting ability, and impaired ability to judge the veracity of simple declarative statements. Severity of positive symptoms was uncorrelated with performance on any of the measures examined. The present study provides evidence that the positive, negative and disorganised symptom dimensions of the PANSS constitute independent clusters, associated with unique patterns of working memory impairment.

Adult↗

Theory of mind and executive function: working-memory capacity and inhibitory control as predictors of false-belief task performance.

This study of the relationship between theory of mind and executive function examined whether on the false-belief task age differences between 3 and 5 ears of age are related to development of working-memory capacity and inhibitory processes. 72 children completed tasks measuring false belief, working memory, and inhibition. Significant age effects were observed for false-belief and working-memory performance, as well as for the false-alarm and perseveration measures of inhibition. A simultaneous multiple linear regression specified the contribution of age, inhibition, and working memory to the prediction of false-belief performance. This model was significant, explaining a total of 36% of the variance. To examine the independent contributions of the working-memory and inhibition variables, after controlling for age, two hierarchical multiple linear regressions were conducted. These multiple regression analyses indicate that working memory and inhibition make small, overlapping contributions to false-belief performance after accounting for age, but that working memory, as measured in this study, is a somewhat better predictor of false-belief understanding than is inhibition.

Adult↗

Memory in pregnancy. I: Subjective experiences and objective assessment of implicit, explicit and working memory in primigravid and primiparous women.

This study investigated the belief held by over 50% of parous women that they are more forgetful during pregnancy and postpartum relative to other times. Comparisons were made between both the reported and objective memory performances of three groups of women (n = 20 per group), (1) primigravid, (2) primiparous (baby younger than 12 months), and (3) never been pregnant, matched on age and education levels. Participants completed a questionnaire on demographic, health, and sleep details, the Inventory of Memory Experiences, and tests of implicit, explicit, and working memory. The groups did not differ on self-rated levels of physical or emotional health, or anxiety level. The primigravid and primiparous groups reported overall poorer memory performance since pregnancy relative to controls. The primigravid group also reported significantly more sleep disruption, with this being a significant predictor of reported memory change. On the objective tests, there were no differences between groups on the implicit and explicit memory tests, but the primigravid and primiparous groups scored significantly lower on a test of working memory. Self-reports of memory change during pregnancy and postpartum may be related to life changes, such as sleep change, and may reflect changed perceptions rather than objective changes.

Adult↗

The role of working memory in motor learning and performance.

Three experiments explore the role of working memory in motor skill acquisition and performance. Traditional theories postulate that skill acquisition proceeds through stages of knowing, which are initially declarative but later procedural. The reported experiments challenge that view and support an independent, parallel processing model, which predicts that procedural and declarative knowledge can be acquired separately and that the former does not depend on the availability of working memory, whereas, the latter does. The behaviour of these two processes was manipulated by providing or withholding visual (and auditory) appraisal of outcome feedback. Withholding feedback was predicted to inhibit the use of working memory to appraise success and, thus, prevent the formation of declarative knowledge without affecting the accumulation of procedural knowledge. While the first experiment failed to support these predictions, the second and third experiments demonstrated that procedural and declarative knowledge can be acquired independently. It is suggested that the availability of working memory is crucial to motor performance only when the learner has come to rely on its use.

Adult↗

Working memory in chess.

Three experiments investigated the role of working memory in various aspects of thinking in chess. Experiment 1 examined the immediate memory for briefly presented chess positions from master games in players from a wide range of abilities, following the imposition of various secondary tasks designed to block separate components of working memory. Suppression of the articulatory loop (by preventing subvocal rehearsal) had no effect on measures of recall, whereas blocking the visuospatial sketchpad (by manipulation of a keypad) and blocking the central executive (by random letter generation) had equivalent disruptive effects, in comparison with a control condition. Experiment 2 investigated the effects of similar secondary tasks on the solution (i.e., move selection) of tactical chess positions, and a similar pattern was found, except that blocking the central executive was much more disruptive than in Experiment 1. Experiment 3 compared performance on two types of primary task, one concerned with solving chess positions as in Experiment 2, and the other a sentence-rearrangement task. The secondary tasks in each case were both designed to block the central executive, but one was verbal (vocal generation of random numbers), while the other was spatial in nature (random generation of keypresses). Performance of the spatial secondary task was affected to a greater extent by the chess primary task than by the verbal primary task, whereas there were no differential effects on these secondary tasks by the verbal primary task. In none of the three experiments were there any differential effects between weak and strong players. These results are interpreted in the context of the working-memory model and previous theories of the nature of cognition in chess.

Adult↗

Working memory and sleep in 6- to 13-year-old schoolchildren.

OBJECTIVE: To study the associations between sleep quality/quantity and performance in auditory/visual working memory tasks of different load levels. METHOD: Sixty schoolchildren aged 6 to 13 years from normal school classes voluntarily participated. Actigraphy measurement was done during a typical school week for 72 consecutive hours. It was timed together with the working memory experiments to obtain information on children's sleep during that period. The n-back task paradigm was used to examine auditory and visual working memory functions. RESULTS: Lower sleep efficiency and longer sleep latency were associated with a higher percentage of incorrect responses in working memory tasks at all memory load levels (partial correlations, controlling for age, all p values < .05, except in visual 0-back and auditive 2-back tasks); shorter sleep duration was associated with performing tasks at the highest load level only (partial correlations, controlling for age,p < .05). Also in general linear models (controlling for age, gender, and socioeconomic status), sleep efficiency (F = 11.706, p = .050) and latency (F = 3.588, p = .034) were significantly associated with the mean incorrect response rate in auditory working memory tasks. CONCLUSIONS: Sleep quality and quantity affect performance of working memory tasks in school-age children. In children with learning difficulties the possibility of underlying sleep problems should be excluded.

Adolescent↗

Conditional reasoning and the Tower of Hanoi: the role of spatial and verbal working memory.

This paper reports a study that investigated the relationships between verbal and spatial measures of working memory capacity and performance on the Tower of Hanoi and a conditional reasoning task. Four working memory measures were included, a simple word span, a simple spatial span, a complex verbal span and a complex spatial span. The participants were 70 undergraduate students. Solution time on the Tower of Hanoi task correlated highly with both measures of spatial memory capacity, but not with the verbal working memory spans. In contrast, logical performance on the conditional reasoning task correlated highly with the complex verbal working memory span, but not with the spatial spans. A confirmatory factor analysis of the data elicited a best-fit model comprising a correlated spatial and verbal factor. The results are interpreted in the context of recent work that suggests a dissociation between spatial and verbal resources at the level of the central executive.

Cognition↗

Hippocampal and amygdaloid involvement in nonspatial and spatial working memory in rats: effects of delay and interference.

Parametric manipulations of the task demand were used to examine the role of the hippocampus and amygdala in nonspatial and spatial working memory in rats. Hippocampal lesions produced an immediate and long-lasting impairment of nonspatial working memory in an operant task. The memory deficits increased as the delay interval and the amount of proactive interference increased. Hippocampal lesions severely impaired spatial working memory in spatial alternation. Extensive postoperative testing reduced the magnitude of impairment of nonspatial but not spatial working memory. Amygdaloid lesions did not impair any aspect of performance in 2 tasks. The results suggest that the hippocampus, but not the amygdala, is involved in working memory and the task demand is a critical determinant for observing impairments of nonspatial working memory following hippocampal lesions.

Amygdala↗

The Adaptive Digit Ordering Test: clinical application, reliability, and validity of a verbal working memory test.

In the face of ample experimental evidence on the importance of working memory capacity for everyday life, there is a growing need for measures suited for clinical assessment of working memory. For this purpose, the Adaptive Digit Ordering Test (DOT-A), a new version of a digit ordering test introduced by Cooper et al. [Brain 114 (1991) 2095], was developed in analogy to the Digit spans. In Study 1, we investigated DOT-A performance in patients with Parkinson's disease (PD) and patients with frontal lobe damage, as these groups often exhibit working memory impairments within the framework of executive dysfunctions. In comparison with matched controls, both patient groups showed reduced performance in DOT-A but not in Digit span performance. This pattern was found to be particularly sensitive for patients with PD. In Study 2, DOT-A performance was assessed in 50 healthy subjects carefully selected according to demographic criteria in order to ensure representativity. Parallel test and split-half correlations indicated sufficient reliability of the DOT-A. Concurrent validity was confirmed by significant correlation with a well-established working memory test (two-back task). We conclude that DOT-A is a promising diagnostic instrument, and its economy and direct comparability to the Wechsler Digit spans and high sensitivity for patient populations make it especially well-suited for assessment in clinical practice.

Journal Article↗

Noradrenergic blockade and numeric working memory in humans.

To investigate the noradrenergic modulation of working memory in humans single doses of two beta-blockers [either 25 mg of propranolol (lipophilic) or 50 mg of atenolol (hydrophilic)] or placebo were administered to young healthy volunteers (16 subjects per drug condition) performing a numerical working memory task that requires either short-term maintenance or maintenance plus manipulation of visually presented four-number sequences. Higher manipulation costs (i.e. process-specific slowing of reaction times in the manipulation conditions compared to the control condition) were observed after propranolol but not after atenolol. The propranolol effect was mainly observed in subjects with low emotional arousal (i.e. low state anxiety rating at baseline). Because both beta-blockers induced a comparable decrease of blood pressure and pulse, the propranolol effect on the 'working component' of working memory is considered to be a central, presumably prefrontal one.

Adrenergic beta-Antagonists↗

Nonspatial and subdivision-specific working memory deficits after selective lesions of the avian prefrontal cortex.

Association areas in the avian forebrain are shown to subserve higher cognitive functions, including working memory. One of these areas, the neostriatum caudolaterale (NCL) of pigeons, has been functionally compared with the mammalian prefrontal cortex (PFC) because of its prominent role in spatial delay and reversal tasks and its innervation by the dopaminergic system that modulates these functions. However, whereas the PFC maintains in working memory information of different domains, the essential role of the NCL in working memory has been demonstrated only for spatial tasks. To investigate whether the avian NCL is also crucial for nonspatial working memory functions, pigeons were tested in an object-related (color) delayed matching-to-sample (DMTS) task. Bilateral lesions were placed in the entire, dorsal, or ventral NCL to test for possible functional subdivisions that were proposed to exist on the basis of neurochemical and behavioral data. Pigeons with total, dorsal, and ventral NCL lesions showed significant deficits in their DMTS performance, whereas controls were not impaired. Thus, the avian NCL is critically involved in nonspatial working memory processes. Recovery from performance deficits was observed in animals with ventral or total NCL lesions, whereas animals with dorsal NCL lesions showed no improvement. Ventral NCL may mediate perseverative behavior, whereas dorsal NCL might be involved in active working memory. Differences in the connections of these subdivisions with striatal areas and other association areas in the frontomedial forebrain underline functional differences. The data indicate a possible segregation of functions in the avian NCL.

Animals↗

Are planning, working memory, and inhibition associated with individual differences in preschool ADHD symptoms?

The association between executive function (EF; planning, working memory, and inhibition) and individual differences in symptoms of attention deficit hyperactivity disorder (ADHD) was explored in a sample of preschool children. One hundred sixty children (between the ages of 3 years, 0 months and 5 years, 6 months), selected so as to oversample high ADHD scorers, performed 3 tasks previously shown to measure planning (Tower of London), working memory (Noisy Book) and inhibition ("Puppet Says..."). EF measures were reliable (kappa > .77) and were correlated with IQ (rs > .38) and age (rs > .59). Once IQ and age were controlled, planning and working memory (r = .41) were correlated. Planning and working memory were not correlated with inhibition (rs < .20). There was no association between ADHD and working memory or planning (rs < .12). There was a significant negative association between ADHD and conduct problems and inhibition (r = -.30 and r = -.25, respectively). Only the link with ADHD persisted after the effects of other factors were controlled for in a multiple regression. Specific deficits in inhibitory control rather than general EF deficits are associated with ADHD in the preschool period. This association is linear in nature, supporting the idea that ADHD is better seen as a continuum rather than a discrete category. This association provides evidence for Barkley's (1997) view that ADHD is underpinned by inhibitory deficits in the preschool period.

Attention Deficit Disorder with Hyperactivity↗

Effects of transient cerebral ischemia in gerbils on working memory performance in the delayed nonmatching to position task using a T-maze.

To examine the working memory performance, gerbils were tested in the delayed nonmatching to position task using a T-maze, and the effects of cerebral ischemia on the performance were examined. There were no significant differences between gerbils and rats in the alternation performance without delay and with the interrun intervals ranging from 10 to 810 sec. These data suggest that this task is useful for assessing working memory in gerbils as well as in rats. Scopolamine (0.1 and 0.2 mg/kg) impaired the working memory performance in both species. Bilateral occlusion of the common carotid arteries for 5 min severely impaired the choice accuracy in the gerbils 1 to 3 days after the operation. This memory impairment was observed even at the shortest interval. One month after the operation, partial behavioral recovery was observed in the ischemic gerbils, in spite of a marked loss of the pyramidal cells in the hippocampus CA1 sector. These data indicate that the working memory performance is highly vulnerable to the cerebral ischemia and that the ischemic operation transiently but severely impairs the acquisition process of the working memory in gerbils.

Animals↗

A functional MRI study of working memory task in euthymic bipolar disorder: evidence for task-specific dysfunction.

OBJECTIVES: Even when euthymic bipolar disorder patients can have persistent deficits in working memory, but the neural basis of this deficit remains unclear. We undertook an functional magnetic resonance imaging investigation of euthymic bipolar disorder patients performing two working memory paradigms; the two-back and Sternberg tasks, selected to examine the central executive and the phonological loop respectively. We hypothesized that neuronal dysfunction would be specific to the network underlying the executive rather than the phonological loop component of working memory. METHODS: Twelve right-handed euthymic bipolar I males receiving lithium carbonate monotherapy were matched with 12 controls. The two-back task comprised a single working memory load contrasted with baseline vigilance condition. The Sternberg paradigm used a parametric design incorporating variable working memory load with fixed delay between presentation of an array of items to be remembered and a target item. Functional activation data were acquired during performance of the tasks and were analysed to produce brain activation maps representing significant group differences in activation (ANOVA). Load-response curves were derived from the Sternberg task data set. RESULTS: There were no significant between-group differences (t-test) in performance of the two-back task, or in 2 x 5 group by memory load ANOVA for the performance data from Sternberg task. In the two-back task, compared with controls bipolar disorder patients showed reductions in bilateral frontal, temporal and parietal activation, and increased activations with the left precentral, right medial frontal and left supramarginal gyri. No between-group differences were observed in the Sternberg task at any working memory load. CONCLUSIONS: Our findings support the notion that, in euthymic bipolar disorder, failure to engage fronto-executive function underpins the core neuropsychological deficits.

Bipolar Disorder↗