Visuo-spatial processing in a dynamic and a static working memory paradigm in schizophrenia.

Recent findings suggest that the visuo-spatial sketchpad (VSSP) may be divided into two sub-components processing dynamic or static visual information. This model may be useful to elucidate the confusion of data concerning the functioning of the VSSP in schizophrenia. The present study examined patients with schizophrenia and matched controls in a new working memory paradigm involving dynamic (the Ball Flight Task - BFT) or static (the Static Pattern Task - SPT) visual stimuli. In the BFT, the responses of the patients were apparently based on the retention of the last set of segments of the perceived trajectory, whereas control subjects relied on a more global strategy. We assume that the patients' performances are the result of a reduced capacity in chunking visual information since they relied mainly on the retention of the last set of segments. This assumption is confirmed by the poor performance of the patients in the static task (SPT), which requires a combination of stimulus components into object representations. We assume that the static/dynamic distinction may help us to understand the VSSP deficits in schizophrenia. This distinction also raises questions about the hypothesis that visuo-spatial working memory can simply be dissociated into visual and spatial sub-components.

Age-related differences on event-related potentials and brain rhythm oscillations during working memory activation.

Previous functional imaging studies have pointed to the compensatory recruitment of cortical circuits in old age in order to counterbalance the loss of neural efficiency and preserve cognitive performance. Recent electroencephalographic (EEG) analyses reported age-related deficits in the amplitude of an early positive-negative working memory (PN(wm)) component as well as changes in working memory (WM)-load related brain oscillations during the successful performance of the n-back task. To explore the age-related differences of EEG activation in the face of increasing WM demands, we assessed the PN(wm) component area, parietal alpha event-related synchronization (ERS) as well as frontal theta ERS in 32 young and 32 elderly healthy individuals who successfully performed a highly WM demanding 3-back task. PN(wm) area increased with higher memory loads (3- and 2-back > 0-back tasks) in younger subjects. Older subjects reached the maximal values for this EEG parameter during the less WM demanding 0-back task. They showed a rapid development of an alpha ERS that reached its maximal amplitude at around 800 ms after stimulus onset. In younger subjects, the late alpha ERS occurred between 1,200 and 2,000 ms and its amplitude was significantly higher compared with elders. Frontal theta ERS culmination peak decreased in a task-independent manner in older compared with younger cases. Only in younger individuals, there was a significant decrease in the phasic frontal theta ERS amplitude in the 2- and 3-back tasks compared with the detection and 0-back tasks. These observations suggest that older adults display a rapid mobilization of their neural generators within the parietal cortex to manage very low demanding WM tasks. Moreover, they are less able to activate frontal theta generators during attentional tasks compared with younger persons.

Working Memory in the Junior/Intermediate Classroom

This research project explored the connection between working memory and children’s learning. The project created a resource titled Working Memory Strategies for the Junior/ Intermediate Educator: A Handbook based on a literature review, the deconstruction of theoretical and empirical studies, teacher resources, and findings from a needs assessment completed by teachers that together show there is insufficient support for teachers working with students who have deficits in working memory along with other common classroom learning disabilities. As learning disabilities become more common in the classroom that increasingly affect working memory in a majority of cases, teachers must be prepared not only to address specific symptoms of the conditions, but also to help students learn how to navigate and become aware of their working memory ability. The handbook thus was developed as a useful resource for teachers looking to expand their knowledge about how learning occurs. A needs assessment completed by junior and intermediate division teachers in Ontario helped determine what educators found most important for inclusion in the handbook, and the same teachers were offered the opportunity to review the completed handbook. Teacher participants provided constructive feedback and indicated that the handbook would be a valuable resource for them and their colleagues when working with students who have working memory issues. It was suggested that the handbook would be useful when creating students’ Individual Education Plans and that the assessment checklist included in the handbook would be an excellent resource for teachers collecting data regarding students’ working memory and ability to learn.

Working memory in Alzheimer’s disease and mild cognitive impairment (MCI) : assessment and intervention

L’objectif principal de cette thèse est d’examiner et d’intervenir auprès des déficits de la mémoire de travail (MdeT) à l’intérieur de deux populations cliniques : la maladie d’Alzheimer (MA) et le trouble cognitif léger (TCL). La thèse se compose de trois articles empiriques. Le but de la première expérimentation était d’examiner les déficits de MdeT dans le vieillissement normal, le TCL et la MA à l’aide de deux versions de l’empan complexe : l’empan de phrases et l’empan arithmétique. De plus, l’effet de «l’oubli» (forgetting) a été mesuré en manipulant la longueur de l’intervalle de rétention. Les résultats aux tâches d’empan complexe indiquent que la MdeT est déficitaire chez les individus atteints de TCL et encore plus chez les gens ayant la MA. Les données recueillies supportent également le rôle de l’oubli à l’intérieur de la MdeT. L’augmentation de l’intervalle de rétention exacerbait le déficit dans la MA et permettait de prédire un pronostic négatif dans le TCL. L’objectif de la deuxième étude était d’examiner la faisabilité d’un programme d’entraînement cognitif à l’ordinateur pour la composante de contrôle attentionnel à l’intérieur de la MdeT. Cette étude a été réalisée auprès de personnes âgées saines et de personnes âgées avec TCL. Les données de cette expérimentation ont révélé des effets positifs de l’entraînement pour les deux groupes de personnes. Toutefois, l’absence d’un groupe contrôle a limité l’interprétation des résultats. Sur la base de ces données, la troisième expérimentation visait à implémenter une étude randomisée à double-insu avec groupe contrôle d’un entraînement du contrôle attentionnel chez des personnes TCL avec atteinte exécutive. Ce protocole impliquait un paradigme de double-tâche composé d’une tâche de détection visuelle et d’une tâche de jugement alpha-arithmétique. Alors que le groupe contrôle pratiquait simplement la double-tâche sur six périodes d’une heure chacune, le groupe expérimental recevait un entraînement de type priorité variable dans lequel les participants devaient gérer leur contrôle attentionnel en variant la proportion de ressources attentionnelles allouée à chaque tâche. Les résultats montrent un effet significatif de l’intervention sur une des deux tâches impliquées (précision à la tâche de détection visuelle) ainsi qu’une tendance au transfert à une autre tâche d’attention divisée, mais peu d’effets de généralisation à d’autres tâches d’attention. En résumé, les données originales rapportées dans la présente thèse démontrent un déficit de la MdeT dans les maladies neurodégénératives liées à l’âge, avec un gradient entre le TCL et la MA. Elles suggèrent également une préservation de la plasticité des capacités attentionnelles chez les personnes à risque de développer une démence.

Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels

Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaMKII and CaMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to changes in the activation state of Akt, mTOR, and the levels of Arc/Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway. (c) 2008 Elsevier Inc. All Fights reserved.

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.

Inefficient Preparatory fMRI-BOLD Network Activations Predict Working Memory Dysfunctions in Patients with Schizophrenia

Patients with schizophrenia show abnormal dynamics and structure of temporally ­coherent networks (TCNs) assessed using fMRI, which undergo adaptive shifts in preparation for a cognitively demanding task. During working memory (WM) tasks, patients with schizophrenia show persistent deficits in TCNs as well as EEG indices of WM. Studying their temporal relationship during WM tasks might provide novel insights into WM performance deficits seen in schizophrenia. Simultaneous EEG-fMRI data were acquired during the performance of a verbal Sternberg WM task with two load levels (load 2 and load 5) in 17 patients with schizophrenia and 17 matched healthy controls. Using covariance mapping, we investigated the relationship of the activity in the TCNs before the memoranda were encoded and EEG spectral power during the retention interval. We assessed four TCNs – default mode network (DMN), dorsal attention network (dAN), left and right working memory networks (WMNs) – and three EEG bands – theta, alpha, and beta. In healthy controls, there was a load-dependent inverse relation between DMN and frontal midline theta power and an anti-correlation between DMN and dAN. Both effects were not significantly detectable in patients. In addition, healthy controls showed a left-lateralized load-dependent recruitment of the WMNs. Activation of the WMNs was bilateral in patients, suggesting more resources were recruited for successful performance on the WM task. Our findings support the notion of schizophrenia patients showing deviations in their neurophysiological responses before the retention of relevant information in a verbal WM task. Thus, treatment strategies as neurofeedback ­targeting prestates could be beneficial as task performance relies on the preparatory state of the brain.

Age-Related Effects in Working Memory Recognition Modulated by Retroactive Interference

One of the main causes for age-related declines in working memory is a higher vulnerability to retroactive interference due to a reduced ability to suppress irrelevant information. However, the underlying neural correlates remain to be established. Magnetoencephalography was used to investigate differential neural patterns in young and older adults performing an interference-based memory task with two experimental conditions, interrupting and distracting, during successful recognition. Behaviorally, both types of retroactive interference significantly impaired accuracy at recognition more in older adults than in young adults with the latter exhibiting greater disruptions by interrupters. Magnetoencephalography revealed the presence of differential age-related neural patterns. Specifically, time-modulated activations in temporo-occipital and superior parietal regions were higher in young adults compared with older adults for the interrupting condition. These results suggest that age-related deficits in inhibitory mechanisms that increase vulnerability to retroactive interference may be associated with neural under-recruitments in a high-interference task.

Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.

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.

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 in schizophrenia and mania: Acute and subacute phases

Baekground: Patients with schizophrenia tend to have impaired performance on tests of working memory (WM). Neurocognitive models have linked WM to certain symptoms of schizophrenia. This study aimed to assess WM in schizophrenia and mania in the acute and subacute phases of the illness and explore correlations between WM and symptom clusters. Methods: A visuo-spatial delayed response task was used to assess WM in schizophrenia (n=20), mania (n= 14) and well controls (n=20). Patients were tested during the first week of an acute admission, and subjects were retested after four weeks. WM, symptoms (PANSS, TLC) and executive ability (COWAT, Stroop, Trail Making) were assessed at both time points. Results: When assessed for overall WM errors (both sensory and memory), there was a significant group difference (F- 11.53, df 2, 40; p