Executive control of working memory in schizophrenia

There is considerable evidence that working memory impairment is a common feature of schizophrenia. The present study assessed working memory and executive function in 54 participants with schizophrenia, and a group of 54 normal controls matched to the patients on age, gender and estimated premorbid IQ, using traditional and newer measures of executive function and two dual tasks-Telephone Search with Counting and the Memory Span and Tracking Task. Results indicated that participants with schizophrenia were significantly impaired on all standardised measures of executive function with the exception of a composite measure of the Trail Making Test. Results for the dual task measures demonstrated that while the participants with schizophrenia were unimpaired on immediate digit span recall over a 2-min period, they recalled fewer digit strings and performed more poorly on a tracking task (box-crossing task) compared with controls. In addition, participants with schizophrenia performed more poorly on the tracking task when they were required to simultaneously recall digits strings than when they performed this task alone. Contrary to expectation, results of the telephone search task under dual conditions were not significantly different between groups. These results may reflect the insufficient complexity of the tone-counting task as an interference task. Overall, the present study showed that participants with schizophrenia appear to have a restricted impairment of their working memory system that is evident in tasks in which the visuospatial sketchpad slave system requires central executive control. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Event-related potential correlates of impaired visuospatial working memory in schizophrenia

Previous studies have reported that patients with schizophrenia demonstrate impaired performance during working memory (WM) tasks. The current study aimed to determine whether WM impairments in schizophrenia are accompanied by reduced slow wave (SW) activity during on-line maintenance of mnemonic information. Event-related potentials were obtained from patients with schizophrenia and well controls as they performed a visuospatial delayed response task. On 50% of trials, a distractor stimulus was introduced during the delay. Compared with controls, patients with schizophrenia produced less SW memory negativity, particularly over the right hemisphere, together with reduced frontal enhancement of SW memory negativity in response to distraction. The results indicate that patients with schizophrenia generate less maintenance phase neuronal activity during WM performance, especially under conditions of distraction.

The concurrent validity and test-retest reliability of a visuospatial working memory task

To determine whether the visuospatial n-back working memory task is a reliable and valid measure of cognitive processes believed to underlie intelligence, this study compared the reaction times and accuracy of perforniance of 70 participants, with performance on the Multidimensional Aptitude Battery (MAB). Testing was conducted over two sessions separated by 1 week. Participants completed the MAB during the second test session. Moderate testretest reliability for percentage accuracy scores was found across the four levels of the n-back task, whilst reaction times were highly reliable. Furthermore, participants' performance on the MAB was negatively correlated with accuracy of performance at the easier levels of the n-back task and positively correlated with accuracy of performance at the harder task levels. These findings confirm previous research examining the cognitive basis of intelligence, and suggest that intelligence is the product of faster speed of information processing, as well as superior working memory capacity. (C) 2004 Elsevier Inc. All rights reserved.

Using psilocybin to investigate the relationship between attention, working memory, and the serotonin 1A and 2A receptors

Increasing evidence suggests a link between attention, working memory, serotonin (5-HT), and prefrontal cortex activity. In an attempt to tease out the relationship between these elements, this study tested the effects of the hallucinogenic mixed 5-HT1A/2A receptor agonist psilocybin alone and after pretreatment with the 5-HT2A antagonist ketanserin. Eight healthy human volunteers were rested on a multiple-object tracking task and spatial working memory task under the four conditions: placebo, psilocybin (215 mu g/kg), ketanserin (50 mg), and psilocybin and ketanserin. Psilocybin significantly reduced attentional tracking ability, but had no significant effect on spatial working memory, suggesting a functional dissociation between the two tasks. Pretreatment with ketanserin did not attenuate the effect of psilocybin on attentional performance, suggestinga primary involvement of the 5-HT1A receptor in the observed defecit. Based on physiological and pharmacological data,we speculate that this impaired attentional performance may reflect a reduced ability to suppress or ignore distracting stimuli rather than reduced attentional capacity. The clinical relevance of these results is also discussed.

The effects of task complexity and practice on dual-task interference in visuospatial working memory

Although the n-back task has been widely applied to neuroimagery investigations of working memory (WM), the role of practice effects on behavioural performance of this task has not yet been investigated. The current study aimed to investigate the effects of task complexity and familiarity on the n-back task. Seventy-seven participants (39 male, 38 female) completed a visuospatial n-back task four times, twice in two testing sessions separated by a week. Participants were required to remember either the first, second or third (n-back) most recent letter positions in a continuous sequence and to indicate whether the current item matched or did not match the remembered position. A control task, with no working memory requirements required participants to match to a predetermined stimulus position. In both testing sessions, reaction time (RT) and error rate increased with increasing WM load. An exponential slope for RTs in the first session indicated dual-task interference at the 3-back level. However, a linear slope in the second session indicated a reduction of dual-task interference. Attenuation of interference in the second session suggested a reduction in executive demands of the task with practice. This suggested that practice effects occur within the n-back ask and need to be controlled for in future neuroimagery research using the task.

Searching for the trace: The influence of age, lexical activation and working memory on sentence processing

To investigate the stability of trace reactivation in healthy older adults, 22 older volunteers with no significant neurological history participated in a cross-modal priming task. Whilst both object relative center embedded (ORC) and object relative right branching (ORR) sentences is-ere employed, working memory load was reduced by limiting the number of wordy separating the antecedent front the gap for both sentence types. Analysis of the results did not reveal any significant trace reactivation for the ORC or ORR sentences. The results did reveal, however, a positive correlation between age and semantic printing at the pre-gap position and a negative correlation between age and semantic printing at the gap position for ORC sentences. In contrast, there was no correlation between age and priming effects for the ORR sentences. These results indicated that trace reactivation may be sensitive to a variety of age related factors, including lexical activation and working memory. The implications of these results for sentence processing in the older population arc discussed.

Linkage analyses of event-related potential slow wave phenotypes recorded in a working memory task

Working memory is an essential component of wide-ranging cognitive functions. It is a complex genetic trait probably influenced by numerous genes that individually have only a small influence. These genes may have an amplified influence on phenotypes closer to the gene action. In this study, event-related potential (ERP) phenotypes recorded during a working-memory task were collected from 656 adolescents from 299 families for whom genotypes were available. Univariate linkage analyses using the MERLIN variance-components method were conducted on slow wave phenotypes recorded at multiple sites while participants were required to remember the location of a target. Suggestive linkage (LOD > 2.2) was found on chromosomes 4, 5, 6, 10, 17, and 20. After correcting for multiple testing, suggestive linkage remained on chromosome 10. Empirical thresholds were computed for the most promising phenotypes. Those on chromosome 10 remained suggestive. A number of genes reported to regulate neural differentiation and function (i.e. NRP1, ANK3, and CHAT) were found under these linkage peaks and may influence the levels of neural activity occurring in individuals participating in a spatial working-memory task.