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PubMed2006

Neural correlates of working memory dysfunction in first-episode schizophrenia patients: an fMRI multi-center study.

Working memory dysfunction is a prominent impairment in patients with schizophrenia. Our aim was to determine cerebral dysfunctions by means of functional magnetic resonance imaging (fMRI) in a large sample of first-episode schizophrenia patients during a working memory task. 75 first-episode schizophrenia patients and 81 control subjects, recruited within a multi-center study, performed 2- and 0-back tasks while brain activation was measured with fMRI. In order to guarantee comparability between data quality from different scanners, we developed and adopted a standardized, fully automated quality assurance of scanner hard- and software as well as a measure for in vivo data quality. After these quality-control measures had been implemented, 48 patients and 57 controls were included in the final analysis. During attention-related processes, even when the performance between patients and controls was comparable, there was a recognizable emergence of cerebral dysfunctions with hypoactivations in the ventrolateral prefrontal cortex (VLPFC), in the superior temporal cortex and in the thalamus. During working memory performance, parietal hypoactivations, especially in the precuneus, were prominent and were accompanied by poorer performance in patients. A hyperfrontality emerged in the ventrolateral prefrontal cortex. Hence, results point to a dysfunctional ventrolateral prefrontal-parietal network during working memory in patients, suggesting impairments in basic functions such as retrieval, storage and maintenance. The brain activation pattern of this large and significant sample of first-episode schizophrenia patients indicates an imbalanced system failing to adjust the amount of brain activity required in the cerebral network involved in attention and working memory.

Adolescent↗
PubMed2005

Decreased cortical response to verbal working memory following sleep deprivation.

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.

Adolescent↗
PubMed2003

Spatial working memory ability is a marker of risk-for-psychosis.

BACKGROUND: Working memory has been identified as a core cognitive deficit in schizophrenia that is associated with negative symptoms, but it is unclear whether it is impaired prior to onset of psychosis in symptomatic patients. METHOD: Thirty-eight young people at ultra high-risk (UHR) of developing psychosis (of whom nine later became psychotic) were compared with 49 healthy controls on tests of spatial working memory (SWM) and delayed matching-to-sample (DMTS). RESULTS: Both SWM and DMTS performance was significantly poorer in the UHR groups. Those who later became psychotic generally performed more poorly than those who did not, although this did not reach significance for any measure. A significant association between SWM errors and negative symptoms was seen in the later-psychotic group only (P = 0.02). CONCLUSIONS: Spatial working memory abilities are impaired in those at high-risk for psychosis. The relationship between working memory and negative symptoms may be useful as a predictive tool.

Adolescent↗
PubMed2006

C957T polymorphism of the dopamine D2 receptor gene modulates the effect of nicotine on working memory performance and cortical processing efficiency.

RATIONALE: In both animals and humans, nicotine produces behavioral effects that vary across individuals. Studies examining the role of genetic variability in modulating individual response to nicotine in humans have increased, with recent work showing that genetic variation at the dopamine D2 receptor (DRD2) predicts response to pharmacotherapy for tobacco dependence. OBJECTIVES: To determine whether a polymorphism of the DRD2 gene, C957T, that alters DRD2 binding availability in humans modifies the effects of nicotine on verbal working memory performance and on processing efficiency of brain regions that support verbal working memory. MATERIALS AND METHODS: Working memory and brain function were assessed in 36 adult subjects (15,957T allele carriers and 21,957C homozygotes), each of whom was studied twice, once after placement of a placebo patch and once after placement of a nicotine patch. Brain function was assessed using functional magnetic resonance imaging while the subjects performed a verbal working memory task. RESULTS: During performance of a task with high verbal working memory load, nicotine administration worsened performance accuracy and reduced the processing efficiency of brain regions that support phonological rehearsal during verbal working memory in carriers of the 957T allele. CONCLUSIONS: These findings are consistent with the notion that genetic variation in DRD2 contributes to individual variation in a range of behavioral and brain responses to nicotine in humans.

Adult↗
PubMed2003

Cognitive style, working memory and learning behaviour and attainment in school subjects.

BACKGROUND: Both working memory capacity and cognitive style have independently been found to affect performance on school-type tasks, but their effects in interaction have not been considered. AIMS: The aims of this study were to consider the relationship between working memory, cognitive style and gender on (a) overall learning behaviour, and (b) performance on a range of school subjects. SAMPLE: The sample comprised 206 13-year-old secondary comprehensive school Year 8 pupils, being all pupils in that year who completed the principal assessments. METHOD: The pupils did an assessment of working memory efficiency - the Information Processing Index (Riding, 2000a). They also completed the Cognitive Styles Analysis (Riding, 1991) to determine their positions on the two fundamental cognitive styles, which were indicated by two ratios: the Wholist-Analytic ratio and the Verbal-Imagery ratio. Overall learning behaviour was rated by the pupils' tutors. In addition, attainment in each of 10 subjects was rated by their subject teachers. RESULTS: For overall learning behaviour, there was an interaction between working memory capacity and cognitive style. With the Wholist-Analytic style dimension, memory made a marked difference for Analytics but had little effect for Wholists, and with the Verbal-Imagery dimension Verbalisers were affected but not Imagers. With the school subjects, these differed in terms of their sensitivity to gender, memory and style. CONCLUSION: The results were discussed in terms of differences between the styles in terms of information-processing demands. Practical ways of improving learning performance were also considered.

Adolescent↗
PubMed2002

The development of mental processing: efficiency, working memory, and thinking.

This Monograph aims to contribute to the information processing, the differential, and the developmental modeling of the mind, and to work these into an integrated theory. Toward this aim, a longitudinal study is presented that investigates the relations between processing efficiency, working memory, and problem solving from the age of 8 years to to the age of 16 years. The study involved 113 participants, about equally drawn among 8-, 10-, 12-, and 14-year-olds at the first testing; these participants were tested two more times spaced one year apart. Participants were tested with a large array of tasks addressed to processing efficiency (i.e., speed of processing and inhibition), working memory (in terms of Baddeley's model, phonological storage, visual storage, and the central executive of working memory), and problem solving (quantitative, spatial, and verbal reasoning). Confirmatory factor analysis validated the presence of each of the above dimensions and indicated that they are organized in a three-stratum hierarchy. The first stratum includes all of the individual dimensions mentioned above. These dimensions are organized, at the second stratum, in three constructs: processing efficiency, working memory, and problem solving. Finally, all second-order constructs are strongly related to a third-order general factor. This structure was stable in time. Structural equation modeling indicated that the various dimensions are interrelated in a cascade fashion so that more fundamental dimensions are part of more complex dimensions. That is, speed of processing is the most important aspect of processing efficiency, and it perfectly relates to the condition of inhibition, indicating that the more efficient one is in stimulus encoding and identification, the more efficient one is in inhibition. In turn, processing efficiency is strongly related to the condition of executive processes in working memory, which, in turn, is related to the condition of the two modality-specific stores (phonological and visual). Finally, problem solving is related to processing efficiency and working memory, the central executive in particular. All dimensions appear to change systematically with time. Growth modeling suggested that there are significant individual differences in attainment in each of the three aspects of the mind investigated. Moreover, each of the three aspects of the mind as well as their interrelations change differently during development. Mixture growth modeling suggested that there are four types of developing persons, each defined by a different combination of performance in these aspects of the mind. Some types are more efficient and stable developers than others. These analyses indicated that processing efficiency is a factor closely associated with developmental differences in problem solving, whereas working memory is associated with individual differences. Modeling by logistic equations uncovered the rates and form of change in the various dimensions and their reciprocal interactions during development. These findings are discussed from the point of view of information processing, differential, and developmental models of thinking, and an integrative model is proposed.

Age Factors↗
PubMed1996

Learning-disabled readers' working memory as a function of processing demands.

The purpose of this study was to investigate whether limitations in the enhancement of learning-disabled readers' working memory performance are attributable to process or storage functions. For Experiment 1, performance of reading-disabled, chronological age-matched, and reading level-matched children was compared on verbal and visual-spatial working memory measures under initial (no probes or cues), gain (cues that bring performance to an asymptotic level), and maintenance conditions (asymptotic conditions without cues). The results indicated that (a) learning-disabled readers' working memory performance was comparable on visual-spatial measures, but inferior to CA-matched children on verbal working memory measures; (b) learning-disabled readers' performance was superior to reading-matched counterparts across working memory conditions; and (c) performance differences remained between learning-disabled and CA-matched children or gain and maintenance conditions, even when initial and processing efficiency (probe) scores were partialed out in the analyses. Experiment 2 included the same conditions as Experiment 1, except that verbal short-term memory scores were also partialed out in the analysis. The results indicated that learning-disabled readers are inferior on both verbal and visual-spatial working memory measures when compared to CA-matched children on high demand conditions (maintenance). Two findings that emerged across experiments were (a) intercorrelations among diverse WM measures increased on demanding conditions and (b) verbal WM was not directly related to reading skill. In sum, the results support the notion that learning-disabled readers' poor working memory performance on demanding conditions reflect constraints in a central executive storage system.

Child↗
PubMed1998

The state of functioning of working memory in schizophrenia.

The functioning of working memory in schizophrenic patients according to Baddeley's model was examined in two complementary experiments. Experiment 1 comprised 27 patients and their controls, matched in age and level of education. Of this pool, 20 pairs participated also in Experiment 2. Digit span, reading rate, and immediate serial recall assessed the functioning of the phonological loop. Corsi and pattern span tasks assessed the capacity of visuo-spatial memory. The central executive's ability to monitor two concurrent tasks was evaluated in a dual task paradigm, and its capacity to control action in a random generation task. A preliminary set of analyses showed that the patients' performances were reduced in all tasks explored, except in digit span. This initial pattern changed consistently after controlling for reading rate. While slow and fast reading patients were comparable in demographic and clinical criteria, slow reading patients showed impaired performance in all tasks, whereas fast reading patients exhibited reduced performance in visuo-spatial tasks and in the random generation task only. The state of functioning of working memory in schizophrenia appears, therefore, to vary consistently among the components of the model and is markedly impaired in slow reading patients. The implications of slowness are discussed.

Adult↗
PubMed2000

Visual working memory revealed by repetitive transcranial magnetic stimulation.

We evaluated whether repetitive transcranial magnetic stimulation (rTMS) could be utilized for studying the hemispheric lateralization and anatomical localization of the cortical areas of the visual system that are concerned with object-related visual working memory. In eight normal volunteers, visual working memory was tested during rTMS delivery over nine regions in each hemisphere. Visual working memory was significantly disturbed by rTMS over the right hemisphere compared with the left (P<0.05). The disturbance in visual working memory by rTMS was significant over the right inferior frontal (F8), inferior temporal (T8), and middle parietal (P4) areas compared with the control region (P<0.05). This study suggests that visual working memory is lateralized to the right hemisphere and localized in the right inferior frontal, inferior temporal, and middle-parietal areas. As a non-invasive tool, rTMS may be useful for the functional localization of the working memory system.

Adult↗
PubMed1998

Working memory for nonverbal auditory information in dementia of the Alzheimer type.

Previous studies have revealed working memory impairments in individuals with dementia of the Alzheimer type (DAT) using visually and auditorily presented verbal materials, and visually presented nonverbal materials. Based on findings from behavioral and neuropathological studies, impairments in working memory for auditorily presented nonverbal materials have been hypothesized as well. Results of a study conducted by Kurylo, Corkin, Allard, Zatorre, and Growden (1993), however, failed to support this hypothesis. In the current investigation, perception and working memory for nonverbal auditory information (tones) were assessed using same-different discrimination tasks. Participants included individuals with no dementia, very mild DAT, and mild DAT. Unlike the findings from the study conducted by Kurylo and colleagues, our results suggest intact tone perception but a progressive decline in working memory for auditory nonverbal information with advancing DAT. A similar decline was also noted on a task assessing working memory for auditorily presented verbal information.

Journal Article↗
PubMed2004

Susceptibility of spatial and verbal working memory to demands of the central executive.

We used a dual-task paradigm to examine the degree to which domain-specific spatial and verbal subsystems depend on the domain-general central executive. Forty participants were asked to retain spatial or verbal information while performing a concurrent secondary task related to simple arithmetic. The secondary tasks consisted of three cognitive processes: single-digit addition, a digit-carrying operation, and digit reading. The single-digit addition and carry operation include central executive functioning, while digit reading relies solely on the phonological loop. The single-digit addition caused a performance decrement on the spatial working memory task, while the digit reading impaired performance on the verbal working memory task. The carry operation interfered with recall accuracy on both working memory tasks. The spatial working memory task was significantly correlated with the verbal working memory task only when the secondary task was more demanding on the central executive. Our results suggest that spatial working memory rather than verbal working memory is susceptible to failure of central executive functioning and that the central executive plays an important role in regulating the cognitive demands of different domains.

Journal Article↗
PubMed2000

Cerebral correlates of working memory for temporal information.

Studies of neural correlates of working memory functions in the auditory-verbal, visuo-spatial and visuo-object domain suggest a category-specific organization of working memory processes in prefrontal cortex. Here, we used fMRI to explore brain areas that underlie different working memory operations directed to the temporal domain, which so far has been widely neglected. Significant activations related to memory updating and comparison processes were found right-accentuated in prefrontal and lateral premotor cortices. Furthermore, both subvocal rhythm encoding and maintenance enhanced left-lateralized activity in Broca's and supplementary motor area as well as in the sensorimotor cortex. Hemispheric lateralization effects of brain activity during temporal processing tasks may depend on the presence or absence of subvocal rehearsal strategies.

Adult↗
PubMed2003

Effect of negative emotional content on working memory and long-term memory.

In long-term memory, negative information is better remembered than neutral information. Differences in processes important to working memory may contribute to this emotional memory enhancement. To examine the effect that the emotional content of stimuli has on working memory performance, the authors asked participants to perform working memory tasks with negative and neutral stimuli. Task accuracy was unaffected by the emotional content of the stimuli. Reaction times also did not differ for negative relative to neutral words, but on an n-back task using faces, participants were slower to respond to fearful faces than to neutral faces. These results suggest that although emotional content does not have a robust effect on working memory, in some instances emotional salience can impede working memory performance.

Adult↗
PubMed2004

Spontaneous alpha peak frequency predicts working memory performance across the age span.

Working memory capacity has been consistently shown to decline with increasing age. Mechanisms underlying this decline are poorly understood. One index that has been found to predict performance on memory tests is alpha peak frequency, the peak of spectral alpha power of the EEG. Activity in the alpha band has been also associated with higher cognitive functions including attention and anticipation and has been shown to slow with age. Few studies, however, have examined whether there might be a relationship between WM decline and alpha peak frequency. The present study specifically investigated this relationship. Digit span was used as the index of WM function. The study made use of 550 normal subjects aged between 11 and 70 years in the Brain Resource International Database. The data were acquired from six laboratories located in the USA (2), Europe (2) and Australia (2). Forward and reverse digit span were found to be lower in older relative to younger age groups. Spontaneous alpha peak frequency slowed with age and more so at anterior than posterior sites. Frontal alpha peak frequency was found to be a significant predictor of reverse digit span, with each 1 Hz increase in frequency associated with a 0.21 increase in reverse digit span score and this was independent of age, indicating a positive relationship between alpha peak frequency and working memory performance.

Adolescent↗
PubMedDate not supplied

Information processing in working memory and event-related brain potentials.

Information processing in working memory was investigated in a paradigm with a pseudo-random sequence of visually presented consonants. The subjects' task was to memorize seven sequentially presented letters per trial and to recall the sequence (MEMORY task). Even-related potentials (ERPs) were selectively averaged for each of the seven positions of consonant presentation within a trial. The later a consonant was presented within a trial the smaller the P300 amplitude elicited by the consonant. The number of recall errors increased, however, from first to last presentation position. In a control task identical to the MEMORY condition consonant were presented. To limit the working memory load to one element, subjects had to count the number of letters within trials showing a specific physical criteria. P300 amplitude did not depend on presentation position. P300 was shown to covary with the amount of processing resources available for a task. We assume that increasing working memory load consumes processing resources that are not available for the processing of the incoming stimuli presented later in the trial.

Adult↗
PubMed2005

Cross-modal processing in auditory and visual working memory.

This study aimed to further explore processing of auditory and visual stimuli in working memory. Smith and Jonides (1997) [Smith, E.E., Jonides, J., 1997. Working memory: A view from neuroimaging. Cogn. Psychol. 33, 5-42] described a modified working memory model in which visual input is automatically transformed into a phonological code. To study this process, auditory and the corresponding visual stimuli were presented in a variant of the 2-back task which involved changes from the auditory to the visual modality and vice versa. Brain activation patterns underlying visual and auditory processing as well as transformation mechanisms were analyzed. Results yielded a significant activation in the left primary auditory cortex associated with transformation of visual into auditory information which reflects the matching and recoding of a stored item and its modality. This finding yields empirical evidence for a transformation of visual input into a phonological code, with the auditory cortex as the neural correlate of the recoding process in working memory.

Adult↗
PubMed1997

Working memory failure by combined blockade of muscarinic and beta-adrenergic transmission in the rat hippocampus.

INTRAHIPPOCAMPAL administration of the muscarinic acetylcholine receptor antagonist scopolamine at a dose of 3.2 micrograms/side significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, whereas 0.32 microgram/side scopolamine did not affect working memory errors. The beta-adrenoceptor antagonist propranolol (10 mg/kg, i.p.) had no effect on working memory error, but it produced a significant increase in working memory errors when administered in combination with intrahippocampal scopolamine at the behaviourally ineffective dose (0.32 microgram/side). The increase in working memory errors induced by intrahippocampal administration of 0.32 microgram/side scopolamine to rats treated with 10 mg/kg propranolol was decreased by concurrent injection of the cholinesterase inhibitor physostigmine (3.2 micrograms/side). D-Cycloserine (the partial agonist at the glycine bindings site on the NMDA receptor/channel complex) at a dose of 10 micrograms/side reduced the increase in working memory errors induced by intrahippocampal 0.32 microgram/side scopolamine combined with 10 mg/kg propranolol. These results suggest that neural mechanisms regulated cooperatively by hippocampal muscarinic and beta-adrenergic transmission underlie working memory performance, and that modification of NMDA function contributes to such interactive regulation of working memory processes in the hippocampus.

Adrenergic beta-Antagonists↗
PubMed2005

Individual capacity differences predict working memory performance and prefrontal activity following dopamine receptor stimulation.

Dopamine receptors are abundant in the prefrontal cortex (PFC), a critical region involved in working memory. This pharmacological fMRI study tested the relationships between dopamine, PFC function, and individual differences in working memory capacity. Subjects performed a verbal delayed-recognition task after taking either the dopamine receptor agonist bromocriptine or a placebo. Behavioral effects of bromocriptine treatment depended on subjects' working memory spans, with the greatest behavioral benefit for lower span subjects. After bromocriptine, PFC activity was positively correlated with a measure of cognitive efficiency (RT slope) during the probe period of the task. Less efficient subjects with slower memory retrieval rates had greater PFC activity, whereas more efficient subjects had less activity. After placebo, these measures were uncorrelated. These results support the role of dopamine in verbal working memory and suggest that dopamine may modulate the efficiency of retrieval of items from the contents of working memory. Individual differences in PFC dopamine receptor concentration may thus underlie the behavioral effects of dopamine stimulation on working memory function.

Adult↗