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Working memory constrains abstraction in schizophrenia.

BACKGROUND: Abstraction has long been considered an area of differential cognitive deficit in schizophrenia, primarily because of patients' poor performance on the Wisconsin Card Sorting Test (WCST). Yet, the complexity and multidimensional nature of the WCST increases the likelihood that several different cognitive processes, perhaps mediated by different neural systems, are being tapped. METHODS: In the current study, the Abstraction and Working Memory (AIM) task was designed to disentangle abstraction and working memory so that the effects of each cognitive domain could be independently analyzed. The AIM task and a battery of neuropsychological tests were administered to 62 patients with schizophrenia and 62 matched healthy volunteers. RESULTS: Whereas patients with schizophrenia demonstrated deficits in simple abstraction, they were disproportionately impaired with the addition of a minimal memory requirement. CONCLUSIONS: Group differences on WCST performance appear to be attributable to patients' inability to maintain information over a short delay, before that information is used for more complex cognitive operations.

Adolescent↗

Effect of low-intensity hippocampal stimulation on spatial versus working memory in rats.

A series of experiments was performed to investigate differing predictions from the spatial mapping hypothesis of hippocampal function proposed by O'Keefe and Nadel (1978) and the working memory hypothesis proposed more recently by Olton and his colleagues (Olton, Becker, & Handelmann, 1979). Each of two groups of rats was trained to use a different strategy to locate a submerged platform in a tank of opaque water. The MAP group used a spatial mapping strategy to reach a platform in a fixed location over trials; whereas the CUE group used a guidance strategy, which involved following a cue that signaled the location of a randomly placed platform on each trial. Following acquisition, one-half of each group was given low-level unilateral electrical stimulation of the dentate gyrus and immediately tested on the water maze task. The results of Experiment 1 showed that both the MAP and CUE groups were impaired by stimulation. However, it was observed that there was an inadvertent spatial element involved in the CUE task. When this element was eliminated in Experiment 3, the same CUE animals were not affected by a second series of stimulation trials, whereas the MAP animals continued to show impairment. These results are interpreted as strongly supporting the cognitive mapping hypothesis, while at the same time providing little support for the working memory hypothesis of hippocampal function.

Animals↗

Thalamic-cortical-striatal circuitry subserves working memory during delayed responding on a radial arm maze.

The medial dorsal nuclei of the thalamus (MDNt), the prefrontal cortex, and the ventral striatum form an interconnected neural circuit that may subserve certain types of working memory. The present series of experiments investigated functional interactions between these brain regions in rats during the performance of delayed and nondelayed spatially cued radial-arm maze tasks. In Experiment 1, transient inactivation of the MDNt by a bilateral injection of lidocaine selectively disrupted performance on a delayed task but not on a nondelayed random foraging version of the radial arm maze task. In Experiment 2, asymmetrical lidocaine injections into the MDNt on one side of the brain and the prefrontal cortex on the other transiently disconnected these two brain regions and significantly impaired foraging during the delayed task. Similarly, disconnections between the prefrontal cortex and the nucleus accumbens also disrupted foraging on this task, whereas disconnections between the MDNt and the nucleus accumbens had no effect. These data suggest that serial transmission of information among the MDNt, the prefrontal cortex, and the nucleus accumbens is required when trial-unique, short-term spatial memory is used to guide prospective search behavior. The results are discussed with respect to a distributed neural network linking limbic, thalamic, cortical, and striatal regions, which mediates executive functions of working memory.

Anesthetics, Local↗

Modulation of a brain-behavior relationship in verbal working memory by rTMS.

We investigated whether the brain-behavior relationship (BBR) between regional cerebral blood flow (rCBF) as measured by positron emission tomography (PET) and individual accuracy in verbal working memory (WM) can be modulated by repetitive transcranial magnetic stimulation (rTMS) of the left or right middle frontal gyrus (MFG). Fourteen right-handed male subjects received a 30-s rTMS train (4 Hz, 110% motor threshold) to the left or right MFG during a 2-back WM task using letters as stimuli. Simultaneously an rCBF PET tracer was injected and whole-brain functional images were acquired. A hypothesis-driven region-of-interest-analysis of the left and right MFG BBR as well as an explorative whole-brain analysis correlating the individual accuracy with rCBF was carried out. Without rTMS we found a negative BBR in the left but no significant BBR in the right MFG. This negative BBR is best explained by an increased effort of volunteers with an inferior task performance. Left-sided rTMS led to a shift of the BBR towards the superior frontal gyrus (SFG) and to a positive BBR in anterior parts of the left SFG. With rTMS of the right MFG the BBR was posterior and inferior in the left inferior frontal gyrus. Beyond the cognitive subtraction approach this correlation analysis provides information on how the prefrontal cortex is involved based on individual performance in working memory. The results are discussed along the idea of a short-term plasticity in an active neuronal network that reacts to an rTMS-induced temporary disruption of two different network modules.

Adult↗

[Changes in the spatial organization of cortical electrical activity during increasing working memory load].

Analysis of EEG coherence performed in 60 healthy adult subjects revealed some changes in the spatial organization of cortical electrical activity produced by complication of the context of cognitive performance (increasing the working memory load). Changes in the degree of coherence of cortical potentials within the local areas were observed already at the stage of the "operative readiness" immediately after the instruction, i.e., representation of the cognitive task sequence in the explicit working memory. The observed changes were different in the anterior (decrease in the degree of coherence) and posterior (increase in coherence) areas of the cortex. Context-related increase in the local coherence was more pronounced in the temporal, parietal, and occipital areas of the left hemisphere than in the right hemisphere.

Adolescent↗

Working memory as assessed by subject-ordered tasks in patients with obsessive-compulsive disorder.

We tested patients with obsessive-compulsive disorder (OCD) and normal subjects (n = 18 per group) on a self-paced, working memory task that, based on studies of patients with focal brain lesions and functional brain imaging studies of normals, is largely mediated by prefrontal cortex. The OCD patients had normal working memory spans and normal recognition memory for all types of material tested (abstract words, common objects, and novel nonsense objects). The patients, however, were slow (p < .005), and the time they took to complete the tasks was significantly correlated with ratings of OCD symptoms (r = .539, p < .05) and depression (r = .643, p < .01), but not anxiety. Slowed performance on this self-paced task was discussed in relation to normal response times by OCD patients under typical laboratory conditions. It was suggested that this discrepancy may be related to a broader dissociation between real-world and laboratory performance as seen in some patients with prefrontal lobe dysfunction.

Adult↗

Removing irrelevant information from working memory: a cognitive aging study with the modified Sternberg task.

Two experiments with a modified Sternberg recognition task explored the ability of young and old adults to remove irrelevant information from working memory. The task involved 2 memory sets, 1 of which was later cued as irrelevant. The recognition probe was presented at a variable time after the cue. Two indicators of inhibition, the setsize effect of the irrelevant set and the reaction time cost of intrusion probes (i.e., negative probes present in the irrelevant list), were dissociated. Irrelevant setsize effects lasted less than 1 s after the cue and did not differ between old and young adults. Intrusion costs lasted up to 5 s and were disproportionally large for old adults. With the additional requirement to remember both lists until after the probe, young adults' intrusion costs in Experiment 2 were equivalent to those of old adults in Experiment 1, but the setsize effects of the irrelevant set was larger. The results are compatible with a dual-process model of recognition in combination with a working-memory model distinguishing the focus of attention from the activated portion of long-term memory.

Adult↗

Medial dorsal thalamic lesions and working memory in the rat.

Pigmented rats of the DA strain with either radiofrequency or ibotenic acid lesions of the thalamic nucleus medialis dorsalis were postoperatively given nonspatial and spatial tests of working memory. In the nonspatial task, delayed nonmatching-to-sample, rats with both types of thalamic lesions showed acquisition impairments. The subgroup of rats with nucleus medialis dorsalis lesions that were able to reach the acquisition criterion did, however, perform normally when the retention interval was extended to 60 s. In the spatial task, delayed forced-alternation, rats were tested with differing retention intervals and with both spaced and massed trials. Damage to nucleus medialis dorsalis had no effect on acquisition or on spaced trials, but a slight deficit was found in the animals with radiofrequency lesions under the massed trial condition. Much clearer deficits were, however, present in those animals in which the lesion extended appreciably into the anterior thalamic nuclei. The findings indicate that while cellular damage to nucleus medialis dorsalis may disrupt learning, some impairments in tests of spatial working memory attributed to this nucleus may reflect damage to the adjacent anterior thalamic nuclei.

Animals↗

Effects of diazepam and beta-CCM on working memory in mice: relationships with emotional reactivity.

This study was aimed at determining the effects of systemic administration of diazepam and methyl beta-carboline-3-carboxylate (beta-CCM) both on spatial working memory and on emotional reactivity in mice. Results showed that diazepam and beta-CCM induced opposite effects in both memory and emotional reactivity tests. Indeed, as a function of dose, diazepam reduced anxiogenic-like reactions but increased vulnerability to interference in the memory task at a 30-s but not at a 5-s delay interval. As a function of dose, beta-CCM reduced vulnerability to interference and increased emotional reactivity, these effects being antagonised by concurrent administration of flumazenil (RO 15-1788). Thus, our study showed the bidirectional effects of these two drugs on a spatial working memory task involving a spontaneous processing of information and suggested a direct link between the emotional effects of the drugs and memory performance.

Animals↗

A study of visual and auditory verbal working memory in schizophrenic patients compared to healthy subjects.

Impaired working memory (WM) performance is considered as a central feature of schizophrenia. Divided into two components, verbal and spatial, WM has been shown to involve frontal and parietal regions. Verbal WM can be tested either visually or aurally. The present study aimed to test schizophrenic patients in both visual and auditory verbal WM in order to assess a possible distinct pattern of alteration of these two modalities. Twenty-four schizophrenic patients and 24 healthy controls were compared with 2-back continuous visual and auditory verbal WM testing. Both groups were also tested on a neuropsychological battery including Wisconsin Card Sorting Test (WCST). Schizophrenic patients were less efficient in both verbal WM tests. When taking age and educational level as covariates and both WM modalities as dependent variables, there was no differential effect of modalities across groups. In further exploratory analyses, partial correlations brought association between verbal WM and psychosocial adaptation, WCST and length of illness. These results suggest a similar pattern of alteration of both modalities of verbal WM in schizophrenic patients. The implications of this finding are discussed.

Adolescent↗

A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia.

BACKGROUND: Previous neuroimaging studies of working memory (WM) in schizophrenia, typically focusing on dorsolateral prefrontal cortex, yield conflicting results, possibly because of varied choice of tasks and analysis techniques. We examined neural function changes at several WM loads to derive a more complete picture of WM dysfunction in schizophrenia. METHODS: We used a version of the Sternberg Item Recognition Paradigm to test WM function at five distinct loads. Eighteen schizophrenia patients and 18 matched healthy controls were scanned with functional magnetic resonance imaging at 3 Tesla. RESULTS: Patterns of both overactivation and underactivation in patients were observed depending on WM load. Patients' activation was generally less responsive to load changes than control subjects', and different patterns of between-group differences were observed for memory encoding and retrieval. In the specific case of successful retrieval, patients recruited additional neural circuits unused by control subjects. Behavioral effects were generally consistent with these imaging results. CONCLUSIONS: Differential findings of overactivation and underactivation may be attributable to patients' decreased ability to focus and allocate neural resources at task-appropriate levels. Additionally, differences between encoding and retrieval suggest that WM dysfunction may be manifested differently during the distinct phases of encoding, maintenance, and retrieval.

Adult↗

Propositional reasoning and working memory: the role of prior training and pragmatic content.

Working memory involvement in propositional reasoning was explored after different kinds of training. The training conditions aimed to reduce the impact of non-analytic heuristics and to enhance analytic inference processes according to mental logic theories, the mental model theory, and the theory of pragmatic reasoning schemata. Following an initial training phase, secondary task interference was investigated using concurrent spatial tapping (Experiment 1), random number generation (Experiment 2), and articulatory suppression (Experiment 3). A training condition practicing the construction and use of mental models via a truth table task increased the disruption of reasoning performance by random number generation and articulatory suppression, whereas the other training conditions did not affect susceptibility to secondary task interference. The results corroborate implications of the mental model theory of reasoning.

Adult↗

Spatial working memory in human extrastriate cortex.

The performance of spatial working memory tasks is known to evoke activity in a set of higher-order association areas, including the prefrontal cortex, posterior parietal cortex and the frontal and supplementary eye fields. Recent physiological studies in monkey have shown that memory-related activity also is found in extrastriate cortex [J. Neurophysiol. 84 (2000) 677]. We conducted functional magnetic resonance imaging studies to determine whether human extrastriate cortex contributes to the on-line maintenance of spatial information in an eye movement task. We found that performance of memory-guided saccades, as compared to visually guided saccades, elicited significant activation in two areas of extrastriate cortex: the posterior superior temporal sulcus (PST) and lateral occipitotemporal cortex (LOT). Both areas also were activated during the basic sensorimotor task of visually guided saccades as compared to fixation. We further determined that area LOT is close to but distinct from motion-sensitive area MT+. These findings demonstrate that areas PST and LOT, along with higher-level association cortex, help to encode and maintain spatial representations.

Adult↗

Recent developments in working memory.

Research on the visual and verbal subsystems of working memory has shown vigorous development, with PET, fMRI and behavioral data all supporting separate systems, with further fractionation being likely. Analysis of executive processes is revealing a range of subprocesses, providing a very fruitful field for the interaction of cognitive psychology, neuropsychology and functional imaging.

Brain Mapping↗

Neural basis of protracted developmental changes in visuo-spatial working memory.

Developmental studies have shown that visuo-spatial working memory (VSWM) performance improves throughout childhood and adolescence into young adulthood. The neural basis of this protracted development is poorly understood. In this study, we used functional MRI (fMRI) to examine VSWM function in children, adolescents, and young adults, ages 7-22. Subjects performed a 2-back VSWM experiment that required dynamic storage and manipulation of spatial information. Accuracy and response latency on the VSWM task improved gradually, extending into young adulthood. Age-related increases in brain activation were observed in focal regions of the left and right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex (including Broca's area), left premotor cortex, and left and right posterior parietal cortex. Multiple regression analysis was used to examine the relative contributions of age, accuracy, and response latency on activation. Our analysis showed that age was the most significant predictor of activation in these brain regions. These findings provide strong evidence for a process of protracted functional maturation of bilateral fronto-parietal neural networks involved in VSWM development. At least two neural systems involved in VSWM mature together: (i) a right hemisphere visuo-spatial attentional system, and (ii) a left hemisphere phonological storage and rehearsal system. These observations suggest that visually and verbally mediated mnemonic processes, and their neural representations, develop concurrently during childhood and adolescence and into young adulthood.

Adolescent↗

ERP/CSD indices of impaired verbal working memory subprocesses in schizophrenia.

To disentangle subprocesses of verbal working memory deficits in schizophrenia, long EEG epochs (>10 s) were recorded from 13 patients and 17 healthy adults during a visual word serial position test. ERP generator patterns were summarized by temporal PCA from reference-free current source density (CSD) waveforms to sharpen 31-channel topographies. Patients showed poorer performance and reduced left inferior parietotemporal P3 source. Build-up of mid-frontal negative slow wave (SW) in controls during item encoding, integration, and active maintenance was absent in patients, whereas a sustained mid-frontal SW sink during the retention interval was comparable across groups. Mid-frontal SW sinks (encoding and retention periods) and posterior SW sinks and sources (encoding only) were related to performance in controls only. Data suggest disturbed processes in a frontal-parietotemporal network in schizophrenia, affecting encoding and early item storage.

Adolescent↗

What makes working memory spans so predictive of high-level cognition?

Working memory (WM) span tasks involving a complex activity performed concurrently with item retention have proven to be good predictors of high-level cognitive performance. The present study demonstrates that replacing these complex self-paced activities with simpler but computer-paced processes, such as reading successive letters, yields more predictive WM span measures. This finding suggests that WM span tasks evaluate a fundamental capacity that underpins complex as well as elementary cognitive processes. Moreover, the higher predictive power of computer-paced WM span tasks suggests that strategic factors do not contribute to the relationship between WM spans and high-level cognition.

Aptitude↗

Functional connectivity during working memory maintenance.

Neurophysiological experiments with monkeys have demonstrated that working memory (WM) is associated with persistent neural activity in multiple brain regions, such as the prefrontal cortex (PFC), the parietal cortex, and posterior unimodal association areas. WM maintenance is believed to require the coordination of these brain regions, which do not function in isolation but, rather, interact to maintain visual percepts that are no longer present in the environment. However, single-unit physiology studies and traditional univariate analyses of functional brain imaging data cannot evaluate interactions between distant brain regions, and so evidence of regional integration during WM maintenance is largely indirect. In this study, we utilized a recently developed multivariate analysis method that allows us to explore functional connectivity between brain regions during the distinct stages of a delayed face recognition task. To characterize the neural network mediating the on-line maintenance of faces, the fusiform face area (FFA) was defined as a seed and was then used to generate whole-brain correlation maps. A random effects analysis of the correlation data revealed a network of brain regions exhibiting significant correlations with the FFA seed during the WM delay period. This maintenance network included the dorsolateral and ventrolateral PFC, the premotor cortex, the intraparietal sulcus, the caudate nucleus, the thalamus, the hippocampus, and occipitotemporal regions. These findings support the notion that the coordinated functional interaction between nodes of a widely distributed network underlies the active maintenance of a perceptual representation.

Brain↗