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.

Effects of memory load and distraction on performance and event-related slow potentials in a visuospatial working memory task

Brain electrical activity related to working memory was recorded at 15 scalp electrodes during a visuospatial delayed response task. Participants (N = 18) touched the remembered position of a target on a computer screen after either a 1 or 8 sec delay. These memory trials were compared to sensory trials in which the target remained present throughout the delay and response periods. Distracter stimuli identical to the target were briefly presented during the delay on 30% of trials. Responses were less accurate in memory than sensory trials, especially after the long delay. During the delay slow potentials developed that were significantly more negative in memory than sensory trials. The difference between memory and sensory trials was greater at anterior than posterior electrodes. On trials with distracters, the slow potentials generated by memory trials showed further enhancement of negativity whereas there were minimal effects on accuracy of performance. The results provide evidence that engagement of visuospatial working memory generates slow wave negativity with a timing and distribution consistent with frontal activation. Enhanced brain activity associated with working memory is required to maintain performance in the presence of distraction. © 1997 by the Massachusetts Institute of Technology

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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Encoding dysfunctions in a dynamic-static paradigm for visuospatial working memory in first-episode psychosis patients: a 2-year follow-up study.

Aim: To investigate static and dynamic visuospatial working memory (VSWM) processes in first-episode psychosis (FEP) patients and explore the validity of such measures as specific trait markers of schizophrenia. Methods: Twenty FEP patients and 20 age-, sex-, laterality- and education-matched controls carried out a dynamic and static VSWM paradigm. At 2-year follow up 13 patients met Diagnostic and Statistical Manual (of Mental Health Disorders) - Fourth Edition (DSM-IV) criteria for schizophrenia, 1 for bipolar disorder, 1 for brief psychotic episode and 5 for schizotypal personality disorder. Results: Compared with controls, the 20 FEP patients showed severe impairment in the dynamic VSWM condition but much less impairment in the static condition. No specific bias in stimulus selection was detected in the two tasks. Two-year follow-up evaluations suggested poorer baseline scores on the dynamic task clearly differentiated the 13 FEP patients who developed schizophrenia from the seven who did not. Conclusions: Results suggest deficits in VSWM in FEP patients. Specific exploratory analyses further suggest that deficit in monitoring-manipulation VSWM processes, especially involved in our dynamic VSWM task, can be a reliable marker of schizophrenia.

Visuospatial working memory deficits and visual pursuit impairments are not directly related in schizophrenia.

OBJECTIVE: Patients with schizophrenia show deficits in visuospatial working memory and visual pursuit processes. It is currently unclear, however, whether both impairments are related to a common neuropathological origin. The purpose of the present study was therefore to examine the possible relations between the encoding and the discrimination of dynamic visuospatial stimuli in schizophrenia. METHOD: Sixteen outpatients with schizophrenia and 16 control subjects were asked to encode complex disc displacements presented on a screen. After a delay, participants had to identify the previously presented disc trajectory from a choice of six static linear paths, among which were five incorrect paths. The precision of visual pursuit eye movements during the initial presentation of the dynamic stimulus was assessed. The fixations and scanning time in definite regions of the six paths presented during the discrimination phase were investigated. RESULTS: In comparison with controls, patients showed poorer task performance, reduced pursuit accuracy during incorrect trials and less time scanning the correct stimulus or the incorrect paths approximating its global structure. Patients also spent less time scanning the leftmost portion of the correct path even when making a correct choice. The accuracy of visual pursuit and head movements, however, was not correlated with task performance. CONCLUSIONS: The present study provides direct support for the hypothesis that active integration of visuospatial information within working memory is deficient in schizophrenia. In contrast, a general impairment of oculomotor mechanisms involved in smooth pursuit did not appear to be directly related to lower visuospatial working memory performance in schizophrenia.

Age, sex, and performance influence the visuospatial working memory network in childhood

This study describes the influence of age, sex, and working memory (WM) performance on the visuospatial WM network. Thirty-nine healthy children (7-12 years) completed a dot location functional magnetic resonance imaging (fMRI) task. Percent signal change measured the intensity and laterality indices measured the asymmetry of activation in frontal and parietal brain regions. Old children showed greater intensity of activation in parietal regions than young children but no differences in lateralization were observed. Intensity of activation was similar across sex and WM performance groups. Girls and high WM performers showed more right-sided lateralization of parietal regions than boys and low WM performers.

Visuospatial working memory in very preterm and term born children - Impact of age and performance

Working memory is crucial for meeting the challenges of daily life and performing academic tasks, such as reading or arithmetic. Very preterm born children are at risk of low working memory capacity. The aim of this study was to examine the visuospatial working memory network of school-aged preterm children and to determine the effect of age and performance on the neural working memory network. Working memory was assessed in 41 very preterm born children and 36 term born controls (aged 7–12 years) using functional magnetic resonance imaging (fMRI) and neuropsychological assessment. While preterm children and controls showed equal working memory performance, preterm children showed less involvement of the right middle frontal gyrus, but higher fMRI activation in superior frontal regions than controls. The younger and low-performing preterm children presented an atypical working memory network whereas the older high-performing preterm children recruited a working memory network similar to the controls. Results suggest that younger and low-performing preterm children show signs of less neural efficiency in frontal brain areas. With increasing age and performance, compensational mechanisms seem to occur, so that in preterm children, the typical visuospatial working memory network is established by the age of 12 years.

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.

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.

Working memory in schizophrenia and mania: Correlation with symptoms during the acute and subacute phases

Objective: The aims of this study were to examine working memory in the acute-subacute phase of schizophrenia and mania and to examine correlations between working memory and specific symptom domains. Method: Visuospatial working memory and symptom profiles were assessed in three groups (schizophrenia group, n=19; mania, n=12; controls, n=19) on two occasions separated by 4 weeks. Results: Both patient groups had significant deficits on working memory compared to the well controls and the schizophrenia and mania groups were equally impaired. All groups showed equivalent improvement over time. In the patient groups, impaired working memory was significantly correlated with the presence of both negative symptoms and positive thought disorder. Conclusion: Impaired wet-king memory is found in both schizophrenia and mania during the acute-subacute phases. Further research is required in order to clarify the neurocognitive mechanisms linking impaired working memory with both negative symptoms and positive thought disorder.

Prefrontal inhibition of threat processing reduces working memory interference

Bottom-up processes can interrupt ongoing cognitive processing in order to adaptively respond to emotional stimuli of high potential significance, such as those that threaten wellbeing. However it is vital that this interference can be modulated in certain contexts to focus on current tasks. Deficits in the ability to maintain the appropriate balance between cognitive and emotional demands can severely impact on day-to-day activities. This fMRI study examined this interaction between threat processing and cognition; 18 adult participants performed a visuospatial working memory (WM) task with two load conditions, in the presence and absence of anxiety induction by threat of electric shock. Threat of shock interfered with performance in the low cognitive load condition; however interference was eradicated under high load, consistent with engagement of emotion regulation mechanisms. Under low load the amygdala showed significant activation to threat of shock that was modulated by high cognitive load. A directed top-down control contrast identified two regions associated with top-down control; ventrolateral PFC and dorsal ACC. Dynamic causal modeling provided further evidence that under high cognitive load, top-down inhibition is exerted on the amygdala and its outputs to prefrontal regions. Additionally, we hypothesized that individual differences in a separate, non-emotional top-down control task would predict the recruitment of dorsal ACC and ventrolateral PFC during top-down control of threat. Consistent with this, performance on a separate dichotic listening task predicted dorsal ACC and ventrolateral PFC activation during high WM load under threat of shock, though activation in these regions did not directly correlate with WM performance. Together, the findings suggest that under high cognitive load and threat, top-down control is exerted by dACC and vlPFC to inhibit threat processing, thus enabling WM performance without threat-related interference.

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.