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Working memory of auditory localization.

To investigate brain mechanisms of sound location memory, we studied the distribution of brain activation with functional magnetic resonance imaging (fMRI) in subjects performing an audiospatial n-back task with three memory load levels. Working memory processing of audiospatial information activated areas in the superior, middle and inferior frontal gyri, and in the posterior parietal and middle temporal cortices. In a control experiment, fMRI during audio- and visuospatial 2-back task performances revealed only few differentially activated subregions between the two tasks. These results demonstrate that working memory processing of auditory locations involves a distributed network of brain areas and suggest that mnemonic processing of audio- and visuospatial information is directed along a common neural pathway in the posterior parietal and prefrontal cortices.

Acoustic Stimulation↗

Abnormal executive function in attention deficit hyperactivity disorder: the effect of stimulant medication and age on spatial working memory.

OBJECTIVE: This study sought to examine the factors associated with spatial working memory and the use of strategies to impairments in spatial working memory in children with attention deficit hyperactivity disorder (ADHD). The developmental trajectories for spatial working memory in medicated and medication naïve children with ADHD were investigated. In addition, the effect of psychostimulant medication on deficits in spatial working memory was examined. METHOD: A cross-sectional study compared performance between 21 psychostimulant medicated children with ADHD, 27 medication naïve children with ADHD and 26 matched control subjects on computerized tests of spatial memory and spatial working memory. RESULTS: Compared with the controls, performance in medication naïve children with ADHD was significantly worse on the spatial working memory task. There was no difference in performance between the medicated children with ADHD and the control subjects on this same task, despite the ongoing symptoms of ADHD in the former group. The pattern of normal and abnormal performance in the ADHD groups was age-independent. CONCLUSIONS: Deficits in executive functions related to spatial working memory do occur in children with ADHD, although the magnitude of these deficits is not related to the child's age or the level of ADHD symptoms. These deficits were not present in the current sample of children who were receiving psychostimulant medication.

Age Factors↗

Age differences in the frontal lateralization of verbal and spatial working memory revealed by PET.

Age-related decline in working memory figures prominently in theories of cognitive aging. However, the effects of aging on the neural substrate of working memory are largely unknown. Positron emission tomography (PET) was used to investigate verbal and spatial short-term storage (3 sec) in older and younger adults. Previous investigations with younger subjects performing these same tasks have revealed asymmetries in the lateral organization of verbal and spatial working memory. Using volume of interest (VOI) analyses that specifically compared activation at sites identified with working memory to their homologous twin in the opposite hemisphere, we show pronounced age differences in this organization, particularly in the frontal lobes: In younger adults, activation is predominantly left lateralized for verbal working memory, and right lateralized for spatial working memory, whereas older adults show a global pattern of anterior bilateral activation for both types of memory. Analyses of frontal subregions indicate that several underlying patterns contribute to global bilaterality in older adults: most notably, bilateral activation in areas associated with rehearsal, and paradoxical laterality in dorsolateral prefrontal sites (DLPFC; greater left activation for spatial and greater right activation for verbal). We consider several mechanisms that could account for these age differences including the possibility that bilateral activation reflects recruitment to compensate for neural decline.

Adult↗

Mnemonic intrusions into working memory in psychometrically identified schizotypal individuals.

Reduced working memory capacity seems to characterize the memory system of individuals from the schizophrenia spectrum. A probabilistic category learning task was designed in order to empirically test the hypothesis that deficient inhibitory control over the contents of working memory may be a fundamental cognitive abnormality of psychometrically identified schizotypal individuals. Two groups of participants were recruited on the basis of their responses on scales measuring psychotic-like experiences in a self-report schizotypy questionnaire. Simple stimuli were presented visually, and participants were instructed to glean the strength of the connection between pairs of stimuli. The experimental task comprised several learning conditions which were designed to assess predictions derived from the inhibition-deficit hypothesis. Working memory-dependent and working memory-independent task conditions allowed to examine the specificity of the putative inhibition deficit. The subjective strength of connections between pairs of stimuli was doubly dissociated as a function of schizotypy (low scorers, high scorers) and learning condition (discriminative, non-discriminative), but only when there was a delay between the to-be-associated stimuli, i.e. when the task was working memory-dependent. The pattern of results is consistent with the inhibition-deficit hypothesis which conjectures that the flow of information through short-term memory features one serious flaw in individuals from the schizophrenia spectrum, namely the occurrence of mnemonic intrusions from long-term memory into working memory.

Cues↗

Spatial working memory in humans as revealed by PET.

The concept of working memory is central to theories of human cognition because working memory is essential to such human skills as language comprehension and deductive reasoning. Working memory is thought to be composed of two parts, a set of buffers that temporarily store information in either a phonological or visuospatial form, and a central executive responsible for various computations such as mental arithmetic. Although most data on working memory come from behavioural studies of normal and brain-injured humans, there is evidence about its physiological basis from invasive studies of monkeys. Here we report positron emission tomography (PET) studies of regional cerebral blood flow in normal humans that reveal activation in right-hemisphere prefrontal, occipital, parietal and premotor cortices accompanying spatial working memory processes. These results begin to uncover the circuitry of a working memory system in humans.

Brain↗

Visual search remains efficient when visual working memory is full.

Many theories of attention have proposed that visual working memory plays an important role in visual search tasks. The present study examined the involvement of visual working memory in search using a dual-task paradigm in which participants performed a visual search task while maintaining no, two, or four objects in visual working memory. The presence of a working memory load added a constant delay to the visual search reaction times, irrespective of the number of items in the visual search array. That is, there was no change in the slope of the function relating reaction time to the number of items in the search array, indicating that the search process itself was not slowed by the memory load. Moreover, the search task did not substantially impair the maintenance of information in visual working memory. These results suggest that visual search requires minimal visual working memory resources, a conclusion that is inconsistent with theories that propose a close link between attention and working memory.

Adult↗

When do visual and verbal memories conflict? The importance of working-memory load and retrieval.

Examinations of interference between verbal and visual materials in working memory have produced mixed results. If there is a central form of storage (e.g., the focus of attention; N. Cowan, 2001), then cross-domain interference should be obtained. The authors examined this question with a visual-array comparison task (S. J. Luck & E. K. Vogel, 1997) combined with various verbal memory load conditions. Interference between tasks occurred if there was explicit retrieval of the verbal load during maintenance of a visual array. The effect was localized in the maintenance period of the visual task and was not the result of articulation per se. Interference also occurred when especially large silent verbal and visual loads were held concurrently. These results suggest central storage along with code-specific passive storage.

Adolescent↗

[Working memory: a neuropsychologic and cerebral imagery approach].

The working memory model proposed by Baddeley and Hitch has frequently been used in cognitive psychology and neuropsychological studies. This model consists of several interacting components, responsible for the storage and processing of the information stored in working memory. Many neuropsychological and functional imagery data are consistent with that formulation of working memory. Moreover, many cognitive tasks have been specifically designed to explore particular aspects of working memory functioning. Taken as a whole, these data confirm that the working memory model remains a useful theoretical framework to explore memory functioning both in normal subjects and in pathological conditions.

Animals↗

Combined D1/D2 receptor stimulation under conditions of dopamine depletion impairs spatial working memory performance in humans.

RATIONALE: The mesocortical dopamine system is regarded as an important modulator of working memory. While it has been established that stimulation of the D1/D2 receptor in primates can improve spatial working memory performance, findings in humans are less consistent. Recent studies in humans suggest that global depletion of dopamine via tyrosine/phenylalanine depletion may impair spatial working memory performance, although these results are also inconsistent, and it has been suggested that task differences may partly underlie the inconsistent findings. OBJECTIVES: This study had two aims: (1) to investigate the effects of acute tyrosine depletion (TPD) on a number of working memory tasks and (2) to examine whether stimulation of D1/D2 receptors under conditions of TPD can attenuate or "reverse" TPD-induced working memory impairments. METHODS: Eighteen healthy male participants performed a spatial working memory delayed-recognition task, non-spatial working memory task and spatial n-back task on three separate occasions, after TPD, TPD and pergolide (D1/D2 agonist), and placebo. RESULTS: TPD did not impair working memory performance on any of the tasks administered. However, stimulation of D1/D2 receptors under TPD conditions caused a subtle impairment in spatial working memory performance. CONCLUSIONS: The finding that D1/D2 stimulation under TPD conditions impairs working memory highlights the complexity of functional effects of augmenting dopaminergic transmission within a dopamine-depleted state. The lack of TPD-related effects on a range of working memory tasks questions the reliability of TPD as a modulator of dopamine function and working memory performance in humans.

Adolescent↗

Short-term memory in Down syndrome: applying the working memory model.

This paper is divided into three sections. The first reviews the evidence for a verbal short-term memory deficit in Down syndrome. Existing research suggests that short-term memory for verbal information tends to be impaired in Down syndrome, in contrast to short-term memory for visual and spatial material. In addition, problems of hearing or speech do not appear to be a major cause of difficulties on tests of verbal short-term memory. This suggests that Down syndrome is associated with a specific memory problem, which we link to a potential deficit in the functioning of the 'phonological loop' of Baddeley's (1986) model of working memory. The second section considers the implications of a phonological loop problem. Because a reasonable amount is known about the normal functioning of the phonological loop, and of its role in language acquisition in typical development, we can make firm predictions as to the likely nature of the short-term memory problem in Down syndrome, and its consequences for language learning. However, we note that the existing evidence from studies with individuals with Down syndrome does not fit well with these predictions. This leads to the third section of the paper, in which we consider key questions to be addressed in future research. We suggest that there are two questions to be answered, which follow directly from the contradictory results outlined in the previous section. These are 'What is the precise nature of the verbal short-term memory deficit in Down syndrome', and 'What are the consequences of this deficit for learning'. We discuss ways in which these questions might be addressed in future work.

Down Syndrome↗

Visual object working memory function and clinical symptoms in schizophrenia.

OBJECTIVE: The presence of working memory deficits suggests abnormalities of prefrontal cortex (PFC) in schizophrenia. Although much is known about spatial working memory deficits in schizophrenia, including its potential as a phenotypic marker, it is unclear whether object working memory is similarly affected. Our goal was to examine nonspatial, object working memory function in relation to clinical symptoms. METHODS: We assessed object working memory and clinical symptoms in 28 schizophrenia patients during acute psychotic episode and 4 months later during partial remission. Delayed-matching-to-sample tasks for familiar object (DMTS-F) and novel shapes (DMTS-N) were used. Symptoms were assessed by the Positive and Negative Syndrome Scale (PANSS). 33 age-matched normal subjects were also tested over the same time period. RESULTS: Acutely psychotic patients showed deficits in both DMTS-F and DMTS-N. Four months later, their DMTS-F performance improved significantly but deficits in DMTS-N were still present. During acute psychosis, symptoms correlated with DMTS-F but not with the DMTS-N. Four months later, negative symptoms correlated with both tasks. CONCLUSIONS: Object working memory as measured by DMTS-N was impaired in schizophrenia patients during both acute and chronic states. When schizophrenia patients were in partial remission, object working memory was associated with negative symptoms.

Acute Disease↗

Spatial working memory deficits in autism.

Previous studies have reported working memory deficits in autism, but this finding has been inconsistent. One possibility is that deficits in this domain may be present only when working memory load exceeds some limited capacity. High-functioning individuals with autism performed the CANTAB computerized test of spatial working memory. Individuals with autism made more errors than a matched group of typically developing controls on this task, and were less likely to consistently use a specific organized search strategy to complete the task. Overall, these results demonstrate reduced spatial working memory abilities in autism, and extend previous findings by demonstrating that these deficits are significant when tasks impose heavier demands on working memory.

Adolescent↗

Working memory and dopamine: clinical and experimental clues.

Working memory has been successively considered as a mnesic or executive process. The cognitive processes involved in working memory and the executive functions are closely linked. Most authors currently agree that executive functions include planning, attentional maintenance, mental flexibility and attentional inhibition. Considering that the role of the central administrator, the main module of the working memory model, is to manage new situations, inhibit old non-pertinent schemes, or carry out attentional control, it is clear that it involves the different executive processes mentioned above. Therefore, even though the working memory model has its origins in the classic concept of short-term memory, it is now situated at the interface between memory and executive functions. The identification of the neuroanatomical support of these processes has been widely explored for many years. The involvement of monoaminergic neurotransmitter systems, and in particular of the dopaminergic system, in these complex cognitive functions has been suggested by numerous studies, both in humans and in non-human primates.

Brain Chemistry↗

Short- and long-term components of working memory in the rat.

Previous experiments suggested that working memory of rats trained on a radial maze can be discussed in terms of its short- and long-term temporal components. For example, in Mizumori, Channon, Rosenzweig, and Bennett's (1985) study, long-term working memory was found to be susceptible to disruption by the protein synthesis inhibitor anisomycin (ANI). In Experiment 1 of this report, we examined the neuropharmacological nature of short-term working memory of rats trained to retrieve food from all arms of a 12-arm radial maze. Delay intervals of varying length were placed between Choices 6 and 7. Lanthanum (LaCl3) and glutamate (GLU) injected bilaterally into the hippocampus effectively impaired retention over short delay intervals, which suggests a possible role for calcium and/or potassium and for glutamate in working memory. However, another equally likely explanation for the amnesic effects of LaCl3 and GLU is that these drugs impaired reference memory. To test more directly the hypothesis that LaCl3, GLU, or ANI might differentially affect working and reference memory, we tested the effects of these drugs on performance of rats trained to retrieve food from only 8 arms of the 12-arm maze in Experiment 2. The remaining 4 arms were never baited, in order to test reference memory function. We predicted that rats would make errors only in baited arms (i.e., errors of working memory). Instead, results of Experiment 2 showed that LaCl3, GLU, or ANI injection produced errors in unbaited arms even before a 120-min delay. If rats were injected with LaCl3 or GLU, baited-arm errors were observed only after the delay period.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The fan effect in fMRI: left hemisphere specialization in verbal working memory.

We studied the fan effect of verbal working memory using functional magnetic resonance imaging (fMRI). Participants were presented with a sentence-pair matching task that described semantic relationships (e.g. classroom-school). Working memory load and semantic processing were manipulated by increasing the number of sentences to be remembered and varying whether they matched expectation. Increased working memory load elicited activation in left dorsal frontal and left inferior parietal regions, and also delayed the hemodynamic responses. Convergent results from semantic matches occurred in the left parietal lobe, whereas, left ventral frontal activation from mismatches diverged from working memory results. The findings were consistent with behavioural and electrophysiological evidence, with the fan effect in fMRI providing novel insight into the spatiotemporal nature of verbal working memory in the left hemisphere.

Adult↗

The alpha-2A-adrenoceptor agonist, guanfacine, increases regional cerebral blood flow in dorsolateral prefrontal cortex of monkeys performing a spatial working memory task.

Research indicates that norepinephrine enhances the working memory functions of the prefrontal cortex (PFC) through actions at post-synaptic, alpha-2A adrenoceptors. The current study examined the effects of the alpha-2A adrenoreceptor agonist, guanfacine (0.7 mg/kg, i.m.), compared to saline on SPECT measures of regional cerebral blood flow (rCBF) in monkeys performing a spatial working memory task. Animals were infused with the SPECT blood flow tracer, Tcm-99m ECD, through an indwelling intravenous catheter while performing the working memory task. Guanfacine treatment significantly improved cognitive performance of the working memory task, and significantly increased rCBF values in the dorsolateral PFC, the brain region most tightly associated with performance of spatial working memory tasks. In contrast, guanfacine had no significant effect on rCBF in the superior temporal cortex, an auditory association area unrelated to task performance. These data are consistent with the hypothesis that alpha-2A adrenoceptor stimulation preferentially enhances functioning of the PFC.

Adrenergic alpha-2 Receptor Agonists↗

Working memory, inhibitory control, and reading disability.

The relationships among working memory, inhibitory control, and reading skills were studied in 966 individuals, 6-49 years old. In addition to a standardized measure of word recognition, they received a working memory (listening span) task in the standard, blocked format (three sets containing two-, three-, or four-item trials) or in a mixed format (three sets each containing two-, three-, and four-item trials) to determine whether scores derived from the standard format are influenced by proactive interference. Intrusion errors were investigated in order to determine whether deficits in working memory were associated with the access, deletion, or restraint functions of inhibitory control. The results indicated that deficits in working memory were characteristic of individuals with reading disabilities at all ages. These deficits may be associated with the access and restraint functions of inhibition. Working memory skills increased until the age of 19. The blocked format showed a gradual decline in adulthood whereas the mixed format did not. The different patterns suggest that the decline in working memory skills associated with aging may result from growing inefficiencies in inhibitory control, and not diminished capacity.

Adolescent↗

A capacity theory of comprehension: individual differences in working memory.

A theory of the way working memory capacity constrains comprehension is proposed. The theory proposes that both processing and storage are mediated by activation and that the total amount of activation available in working memory varies among individuals. Individual differences in working memory capacity for language can account for qualitative and quantitative differences among college-age adults in several aspects of language comprehension. One aspect is syntactic modularity: The larger capacity of some individuals permits interaction among syntactic and pragmatic information, so that their syntactic processes are not informationally encapsulated. Another aspect is syntactic ambiguity: The larger capacity of some individuals permits them to maintain multiple interpretations. The theory is instantiated as a production system model in which the amount of activation available to the model affects how it adapts to the transient computational and storage demands that occur in comprehension.

Concept Formation↗