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PubMed2003

Increased glial metabolites predict increased working memory network activation in HIV brain injury.

Deficits in attention and working memory are common in human immuno deficiency virus type 1 (HIV-1)-infected patients, but the pathophysiology of these deficits is poorly understood. Modern neuroimaging techniques, such as proton magnetic resonance spectroscopy ((1)H MRS) and functional MRI (fMRI), can assess some of the processes underlying HIV brain injury. To evaluate the model that attentional deficits in early HIV brain disease are related to brain inflammation, (1)H MRS and fMRI were performed in 14 HIV-positive subjects [acquired immunodeficiency syndrome (AIDS) dementia complex stage 1 or less]. Increasing attentional load on three working memory tasks was assessed with fMRI, and the concentrations of brain metabolites were measured with (1)H MRS in the frontal gray and white matter, and basal ganglia. Metabolite concentrations were correlated with fMRI blood oxygenation level-dependent (BOLD) signals, using a random-effects linear regression model in SPM99. Several positive correlations were observed between the BOLD signal strength in the working memory network (posterior parietal cortex and lateral prefrontal cortex) and the concentrations of frontal white matter and basal ganglia metabolites that are predominant in glial cells (choline-containing compounds, myo-inositol, and total creatine). In contrast, BOLD signals in the working memory network were not correlated with the concentration of N-acetyl compounds, which are markers of neuronal viability, or with metabolite concentrations in the frontal gray matter. These findings are consistent with previous results that mild HIV brain injury is associated with increased glial activation without major involvement of neuronal abnormalities. We propose that the inflammatory glial abnormalities reduce the efficiency of neural processing, and necessitate compensatory increases in attention in patients, and associated BOLD signals, to perform a given task. The same mechanism may also contribute to cognitive dysfunction in other brain diseases that involve inflammation.

AIDS Dementia Complex↗

PubMed1998

The functional emergence of prefrontally-guided working memory systems in four- to eight-year-old children.

The neural processes that underlie the functional emergence of human cognitive functions, particularly those associated with the prefrontal cortex (PFC), are of growing interest to developmental psychologists and neuroscientists. Specifically, working memory functions have been correlated with PFC activity in nonhuman primates and adult humans but have not been extensively studied in children. We examined the developmental emergence of functions involved in working memory through the use of the Cambridge Neuropsychological Test Automated Battery (CANTAB), a computerized battery of nonverbal visually-presented neuropsychological tests designed to dissociate frontal from temporal lobe behavioral functions. Participants were normal children, aged 4-8 (n = 181) and a small group of young adults (n = 24) who completed measures of Spatial Memory Span, Spatial Working Memory, the Tower of London planning task, Visual Pattern and Spatial Recognition tasks, and a Set-Shifting task. Findings indicate a general age-related progression in ability levels on frontal lobe tasks, with 4-year-olds performing worse than 5- to 7-year-olds on all measures. Eight-year-olds are superior to younger children in their ability to solve complex problems but have not yet reached adult levels of performance on the most difficult items of the Tower of London and Spatial Working Memory tasks. We conclude that the development of working memory functions proceeds dimensionally, starting with refinement of basic perceptual and sensorimotor functions and culminating with the physiological maturation of widespread neural networks that integrate complex processing demands inherent to working memory tasks.

Adolescent↗

PubMed2001

Subjective complaints, verbal fluency, and working memory in mild multiple sclerosis.

Patients with mild multiple sclerosis (MS) regularly report subjective complaints characterized by generalized cognitive inefficiency. A feature of these complaints is reduced verbal fluency, for example, losing the thread of conversation. Mild MS patients and controls were compared on subjective complaints, verbal fluency, and working memory, and the possible role of working memory was investigated. As predicted, subjective difficulties and verbalfluency each correlated with working memory. Subjective difficulties and verbal fluency were also related. Within the control group, the subjective difficulties were associated only with depression. On the other hand, in the MS group, subjective difficulties were unrelated to affective state but were correlated with working memory. For the patients, partialing out depression and anxiety did not influence any of the correlations involving subjective difficulties, verbal fluency, or working memory. These findings support the proposal that working memory impairment underlies subjective complaints of mild MS patients and that verbal dysfluency is part and parcel of this phenomenon.

Adult↗

PubMed1999

Working memory and Wisconsin Card Sorting Test performance in schizotypic individuals: a replication and extension.

The present study examined spatial working memory and Wisconsin Card Sorting Test (WCST) performance in psychosis-prone individuals, either those with extremely high scores on the Social Anhedonia Scale (SocAnh; n = 49) or deviant scores on the Perceptual Aberration-Magical Ideation Scales (Per-Mag; n = 66). Sixty-three individuals with normal scores on the Chapman Psychosis-Proneness Scales served as control subjects. In order to evaluate working memory performance, participants were administered three tasks, namely, sensorimotor, degraded stimulus, and delayed-response tasks. Although the SocAnh and Per-Mag groups displayed poorer performance than control subjects on the working memory task, they did not differ significantly from each other. The SocAnh group exhibited slower reaction times on the working memory task compared to the control group. The groups did not differ in their performance on sensorimotor or degraded stimulus control tasks. Both psychosis-prone groups differed significantly from control subjects in terms of their WCST performance. Working memory performance was inversely associated with the number of perseverative errors (r = -0.17) and the number of trials to complete the first category on the WCST (r= -0.15). These findings extend the literature by indicating that some psychosis-prone individuals with social-interpersonal schizotypal deficits also display subtle spatial working memory impairments.

Adolescent↗

PubMed2006

Working memory, reading, and mathematical skills in children with developmental coordination disorder.

The aim of the present study was investigate the relationship between working memory and reading and mathematical skills in 55 children diagnosed with developmental coordination disorder (DCD). The findings indicate a pervasive memory deficit in all memory measures. In particular, deficits observed in visuospatial short-term and working memory tasks were significantly worse than in the verbal short-term memory ones. On the basis of these deficits, the sample was divided into high and low visuospatial memory ability groups. The low visuospatial memory group performed significantly worse on the attainment measures compared to the high visuospatial memory group, even when the contribution of IQ was taken into account. When the sample was divided into high and low verbal working memory ability groups, verbal working memory skills made a unique contribution to attainment only when verbal IQ was taken into account, but not when performance IQ was statistically controlled. It is possible that the processing demands of the working memory tasks together with the active motor component reflected in the visuospatial memory tasks and performance IQ subtest both play a crucial role in learning in children with DCD.

Child↗

PubMed2002

Age-related working memory impairments in children with prefrontal dysfunction associated with phenylketonuria.

The prefrontal cortex of the brain has been shown to play a crucial role in working memory, and age-related changes in prefrontal function may contribute to the improvements in working memory that are observed during childhood. We examined the developmental trajectory of working memory in school-age children with early-treated phenylketonuria (PKU), a metabolic disorder that results in prefrontal dysfunction. Using a recognition procedure, we evaluated working memory for letters, abstract objects, and spatial locations in 20 children with PKU and 20 typically developing control children. Children in both groups ranged from 6 to 17 years of age. Our findings revealed poorer performance across all three types of materials for children with PKU. In addition, there was a significant difference in the developmental trajectory of working memory for children with PKU as compared with controls. Specifically, deficits were not apparent in younger children with PKU. Instead, deficits were observed only in older children, suggesting the presence of a developmental deficit rather than a developmental delay in the working memory of children with PKU.

Adolescent↗

PubMed2005

Effects of verbal and nonverbal interference on spatial and object visual working memory.

We tested the hypothesis that a verbal coding mechanism is necessarily engaged by object, but not spatial, visual working memory tasks. We employed a dual-task procedure that paired n-back working memory tasks with domain-specific distractor trials inserted into each interstimulus interval of the n-back tasks. In two experiments, object n-back performance demonstrated greater sensitivity to verbal distraction, whereas spatial n-back performance demonstrated greater sensitivity to motion distraction. Visual object and spatial working memory may differ fundamentally in that the mnemonic representation of featural characteristics of objects incorporates a verbal (perhaps semantic) code, whereas the mnemonic representation of the location of objects does not. Thus, the processes supporting working memory for these two types of information may differ in more ways than those dictated by the "what/where" organization of the visual system, a fact more easily reconciled with a component process than a memory systems account of working memory function.

Adolescent↗

PubMed1998

Near-saddle-node bifurcation behavior as dynamics in working memory for goal-directed behavior.

In consideration of working memory as a means for goal-directed behavior in nonstationary environments, we argue that the dynamics of working memory should satisfy two opposing demands: long-term maintenance and quick transition. These two characteristics are contradictory within the linear domain. We propose the near-saddle-node bifurcation behavior of a sigmoidal unit with a self-connection as a candidate of the dynamical mechanism that satisfies both of these demands. It is shown in evolutionary programming experiments that the near-saddle-node bifurcation behavior can be found in recurrent networks optimized for a task that requires efficient use of working memory. The results suggests that the near-saddle-node bifurcation behavior may be a functional necessity for survival in nonstationary environments.

Animals↗

PubMed1997

Scheduling processes in working memory: instructions control the order of memory search and mental arithmetic.

Humans must often use working memory to execute processes one at a time because of its limited capacity. Two experiments tested where limits in access to working memory occur. Subjects searched a short-term memory set for one stimulus digit and performed mental arithmetic with another stimulus digit. In one experiment, they were told to carry out the mental arithmetic before the memory search and to make the arithmetic response first. In the other, they were instructed to perform the tasks in the opposite order. The overt responses were executed in the prescribed order. Moreover, the covert working memory processes were executed in the prescribed order, as revealed by a critical path network analysis of reaction times. Results are explained in terms of a double-bottleneck model in which central processes and responses are constrained to be carried out for one task at a time.

Adult↗

PubMed1997

Increase of extracellular dopamine in primate prefrontal cortex during a working memory task.

Increase of extracellular dopamine in primate prefrontal cortex during a working memory task. J. Neurophysiol. 78: 2795-2798, 1997. The dopamine innervation of the prefrontal cortex is involved importantly in cognitive processes, such as tested in working memory tasks. However, there have been no studies directly investigating prefrontal dopamine levels in relation to cognitive processes. We measured frontal extracellular dopamine concentration using in vivo microdialysis in monkeys performing in a delayed alternation task as a typical working memory paradigm and in a sensory-guided control task. We observed a significant increase in dopamine level in the delayed alternation task as compared both with the sensory-guided control task and the basal resting level. The increase was seen in the dorsolateral prefrontal but not in the arcuate or orbitofrontal areas. The increase appeared to reflect the working memory component of the task and was observed mainly in the lip areas of principal sulcus. Although there was no significant difference in dopamine level between delayed alternation and sensory-guided control tasks in the premotor area, significant increases in dopamine concentration were observed during both tasks as compared with the basal resting level, indicating the importance of premotor dopamine for the motor response itself.

Animals↗

PubMed2003

Deciphering components of impaired working memory in multiple sclerosis.

OBJECTIVE: To identify working memory (WM) impairment by examining components of auditory working memory with the same sample of individuals with multiple sclerosis (MS). BACKGROUND: Although individuals with MS have consistently demonstrated WM impairments, the specific components involved (i.e., central executive versus storage/maintenance) remain unclear. METHOD: Individuals with MS with and without cognitive impairment and healthy controls were administered a task primarily assessing storage and rehearsal/maintenance (auditory n-back) and a task with a significant central executive component (Paced Auditory Serial Addition Task). RESULTS: Results indicate when the phonological loop is minimally challenged, maintenance of information is generally efficient. However, the addition of a central executive component to processing appears to be the key factor in differentiating individuals with MS with cognitive impairment from those without cognitive impairment and healthy controls. CONCLUSIONS: Results indicated that the primary WM impairment in MS is within the central executive rather than the phonological loop.

Acoustic Stimulation↗

PubMed2005

The construct validity of the stanford-binet 5 measures of working memory.

This study examines the validity of the measures of verbal and nonverbal working memory on the Stanford-Binet Fifth Edition (SB5). The validity evidence included Rasch-based, criterion-referenced item mapping, correlations with other clinical measures of memory, and prediction of reading and mathematics scores. The item mapping clearly demonstrates a parallel between increasing item difficulty and a progression of item characteristics that placed increasing demands on verbal and nonverbal working memory. The higher correlations of the SB5 verbal and nonverbal working memory subtests with other measures of verbal and nonverbal memory, respectively, and lower correlations with nonverbal and verbal memory measures, respectively, clearly show convergent and divergent validity. The higher correlations between SB5 verbal working memory and reading skills and between SB5 nonverbal memory and mathematics skills are consistent with past research.

Adolescent↗

PubMed2005

Dopaminergic control of working memory and its relevance to schizophrenia: a circuit dynamics perspective.

This article argues how dopamine controls working memory and how the dysregulation of the dopaminergic system is related to schizophrenia. In the dorsolateral prefrontal cortex, which is the principal part of the working memory system, recurrent excitation is subtly balanced with intracortical inhibition. A potent controller of the dorsolateral prefrontal cortical circuit is the mesocortical dopaminergic system. To understand the characteristics of the dopaminergic control of working memory, the stability of the circuit dynamics under the influence of dopamine has been studied. Recent computational studies suggest that the hyperdopaminergic state is usually stable but the hypodopaminergic state tends to be unstable. The stability also depends on the efficacy of the glutamatergic transmission in the corticomesencephalic projections to dopamine neurons. When this cortical feedback is hypoglutamatergic, the circuit of the dorsolateral prefrontal cortex tends to be unstable, such that a slight increase in dopamine releasability causes a catastrophic jump of the dorsolateral prefrontal cortex activity from a low to a high level. This may account for the seemingly paradoxical overactivation of the dorsolateral prefrontal cortex observed in schizophrenic patients. Given that dopamine transmission is abnormal in the brains of patients with schizophrenia and working memory deficit is a core dysfunction in schizophrenia, the concept of circuit stability would be useful not only for understanding the mechanisms of working memory processing but for developing therapeutic strategies to enhance cognitive functions in schizophrenia.

Dopamine↗

PubMed1998

Neuroimaging analyses of human working memory.

We review a program of research that uses neuroimaging techniques to determine the functional and neural architecture of human working memory. A first set of studies indicates that verbal working memory includes a storage component, which is implemented neurally by areas in the left-hemisphere posterior parietal cortex, and a subvocal rehearsal component, which is implemented by left-hemisphere speech areas, including Broca's area as well as the premotor and supplementary motor areas. We provide a number of neuroimaging dissociations between the storage and rehearsal areas. A second set of studies focuses on spatial working memory and indicates that it is mediated by a network of predominantly right-hemisphere regions that include areas in posterior parietal, occipital, and frontal cortex. We provide some suggestive evidence that these areas, too, divide into storage and rehearsal regions, with right-hemisphere posterior parietal and premotor regions subserving spatial rehearsal. In a final set of studies, we turn to "executive processes," metaprocesses that regulate the processing of working-memory contents. We focus on the executive process of inhibition as it is used in verbal working memory. We provide evidence that such inhibition is mediated by the left-hemisphere prefrontal region and that it can be dissociated from verbal storage and rehearsal processes.

Brain↗

PubMed1997

Working memory deficits in HIV-seropositive drug users.

We studied the integrity of working memory operations in 38 HIV-seropositive and 20 seronegative drug users, using a modified version of the Tower of London task. This new task, the Tower of London-Working Memory version (TOL-WM), includes a delayed-response component in addition to the planning required for successful performance of the standard TOL. Symptomatic HIV-seropositive participants solved significantly fewer TOL-WM problems compared to matched seronegative controls. However, seropositive and seronegative subjects showed similar overall levels of planning efficiency, suggesting that the TOL-WM deficit may be associated primarily with failure to encode or maintain an adequate online memory representation. The results of this study confirm our previous report of a possible working memory deficit in HIV-1 infection and suggest that measures of working memory have particular utility in the evaluation of HIV-related cognitive deficits.

Adult↗

PubMedDate not supplied

Working memory and older adults: implications for occupational therapy.

Atkinson and Shiffrin's (1968) modal model of memory is still commonly used by rehabilitation professionals to evaluate memory impairment in older adults. However, research to date has been unable to indicate that short-term memory declines with age. These findings have led some rehabilitation professionals to mistakenly conclude that short-term memory is not affected by the aging process. This article reviews both the traditional concept of short-term memory, as outlined by Atkinson and Shiffrin, and the more recent conceptualization of short-term memory in terms of Baddeley and Hitch's (1974) model of working memory. The implications of the concept of working memory has implications for occupational therapy interventions for older adults. For example, clients with dementia may experience difficulties in performing tasks that require drawing inferences. Similarly, language that contains vague references may present problems for these clients. In addition, changes in working memory in older adults suggest that they may experience difficulties with medication management and what Rule, Milke, and Dobbs (1992) called wayfinding. Therefore, evaluations of working memory would provide a better indication of older adults' memory performance than the modal model.

Aged↗

PubMed2007

Neural correlates of consolidation in working memory.

Many of our daily activities rely on a brain system called working memory, which implements our ability to encode information for short-term maintenance, possible manipulation, and retrieval. A recent intracranial study of patients performing a paradigmatic working memory task revealed that the maintenance of information involves a distributed network of oscillations in the gamma band (>40 Hz). Using a similar task, we focused on the encoding stage and targeted a process referred to as short-term consolidation, which corresponds to the encoding of novel items in working memory. The paradigm was designed to manipulate the subjects' intention to encode: series of 10 letters were presented, among which only five had to be remembered, as indicated by visual cues preceding or following each letter. During this task we recorded the intracerebral EEG of nine epileptic patients implanted in mesiotemporal structures, perisylvian regions, and prefrontal areas and used time-frequency analysis to search for neural activities simultaneous with the encoding of the letters into working memory. We found such activities in the form of increases of gamma band activity in a set of regions associated with the phonological loop, including the Broca area and the auditory cortex, and in the prefrontal cortex, the pre- and postcentral gyri, the hippocampus, and the fusiform gyrus.

Adult↗

PubMed1996

Consequences of selective blockade of septal noradrenergic afferents on anxiety and spatial working memory performance in mice.

This experiment was designed to investigate the role of septal noradrenergic (NA) afferents in the control of anxiety and spatial working memory. To this end, C57Bl/6 mice were infused bilaterally into the lateral septal nuclei with 500 ng/0.2 microliter of BE 2254, a selective alpha 1 postsynaptic adrenoceptor antagonist. The consequences of this reversible treatment were evaluated 20 min later on the anxiety level measured in an elevated plus-maze and on spatial working memory, evaluated under four different conditions via the learning of a delayed nonmatching to place (DNMTP) rule achieved in an eight-arm radial maze. In these conditions, the BE 2254, as well as the saline-injected control group, showed an elevation of the anxiety level that may be the indirect expression of a nonspecific septal dysfunction induced by the vehicle injection rather than the normal behavioral response produced by the decrease of septal NA activity. This septal dysfunction also impaired spatial working memory but only when mnesic difficulty of the task is increased, suggesting that this impairment expresses a general memory deficit rather than a working memory deficit per se. A lack of spatial working memory deficits in BE 2254 or saline-injected animals was also observed in two other conditions of the behavioral protocol. However, when treatments were applied before the first exposure of animals to the radial maze (exploration session), only the group which received BE 2254 was impaired during the acquisition session for the rule performed 24 h later. This delayed perturbation seems to be linked, at this stage of the learning procedure, to the lack of NA-dependent processes taking place during the exploration session. Taken together, these data suggest that septal NA mechanisms are more essential at initial stage of this learning, when animals process new features of the situation, than during the expression of spatial working memory per se.

Adrenergic Fibers↗