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BACKGROUND: Impairments in working memory (WM) have been well documented in people with schizophrenia (PSZ). However, these quantitative WM impairments can often be explained by nonspecific factors, such as impaired goal maintenance. Here, we used a spatial orientation delayed response task to explore a qualitative difference in WM dynamics between PSZ and healthy control participants (HCs). More specifically, we took advantage of the discovery that WM representations may drift either toward or away from previous trial targets (serial dependence). We tested the hypothesis that WM representations would drift toward the previous trial target in HCs but away from the previous trial target in PSZ. METHODS: We assessed serial dependence in PSZ (n = 31) and HCs (n = 25) using orientation as the to-be-remembered feature and memory delays lasting from 0 to 8 seconds. Participants were asked to remember the orientation of a teardrop-shaped object and reproduce the orientation after a delay period of varying length. RESULTS: Consistent with prior studies, we found that current trial memory representations were less precise in PSZ than in HCs. We also found that WM for the current trial orientation drifted toward the previous trial orientation in HCs (representational attraction) but drifted away from the previous trial orientation in PSZ (representational repulsion). CONCLUSIONS: These results demonstrate a qualitative difference in WM dynamics between PSZ and HCs that cannot be easily explained by nuisance factors such as reduced effort. Most computational neuroscience models also fail to explain these results because they maintain information solely by means of sustained neural firing, which does not extend across trials. The results suggest a fundamental difference between PSZ and HCs in longer-term memory mechanisms that persist across trials, such as short-term potentiation and neuronal adaptation.

Computational neuroscience models propose that working memory (WM) involves recurrent excitatory feedback loops that maintain firing over time along with lateral inhibition that prevents the spreading of activity to other feature values. In behavioral paradigms, this lateral inhibition appears to cause a repulsion of WM representations away from each other and from other strong sources of input. Recent computational models of schizophrenia have proposed that reduction in the strength of inhibition relative to strength of excitation may underlie impaired cognition, and this leads to the prediction that repulsion effects should be reduced in people with schizophrenia spectrum disorders (PSZ) relative to healthy control subjects (HCS). We tested this hypothesis in 2 experiments measuring WM repulsion effects. In Experiment 1, 45 PSZ and 32 HCS remembered the location of a single object relative to a centrally presented visual landmark and reported this location after a short delay. The reported location was repelled away from the landmark in both groups, but this repulsion effect was increased rather than decreased in PSZ relative to HCS. In Experiment 2, 41 PSZ and 34 HCS remembered 2 sequentially presented orientations and reported each orientation after a short delay. The reported orientations were biased away from each other in both groups, and this repulsion effect was again more pronounced in PSZ than in HCS. Contrary to the widespread hypothesis of reduced inhibition in schizophrenia, we provide robust evidence from 2 experiments showing that the behavioral performance of PSZ exhibited an exaggeration rather than a reduction of competitive inhibition. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

BackgroundImpairments in spatial working memory (sWM) have been well documented in schizophrenia. Here we provide a comprehensive test of a microcircuit model of WM performance in schizophrenia that predicts enhanced effects of increasing delay duration and distractors based on a hypothesized imbalance of excitatory and inhibitory processes.MethodsModel predictions were tested in 41 people with schizophrenia (PSZ) and 32 healthy control subjects (HCS) performing an sWM task. In one condition, a single target location was followed by delays of 0, 2, 4, or 8 seconds. In a second condition, distractors were presented during the 4-second delay interval at 20°, 30°, 40°, 50°, or 90° from the original target location.ResultsPSZ showed less precise sWM representations than HCS, and the rate of memory drift over time was greater in PSZ than in HCS. Relative to HCS, the spatial recall responses of PSZ were more repelled by distractors presented close to the target location and more attracted by distractors presented far from the target location. The degree of attraction to distant distractors was correlated with the rate of memory drift in the absence of distractors.ConclusionsConsistent with the microcircuit model, PSZ exhibited both a greater rate of drift and greater attraction to distant distractors relative to HCS. These two effects were correlated, consistent with the proposal that they arise from a single underlying mechanism. However, the repulsion effects produced by nearby distractors were not predicted by the model and thus require an updated modeling framework.

BackgroundWorking memory (WM) deficits are seen as a core deficit in schizophrenia, implicated in the broad cognitive impairment seen in the illness. Here we examine the impact of WM storage of a single item on the operation of other cognitive systems.MethodsWe studied 37 healthy controls (HCS) and 43 people with schizophrenia (PSZ). Each trial consisted of a sequence of two potential target stimuli, T1 and T2. T1 was a letter presented for 100 ms. After delays of 100-800 ms, T2 was presented. T2 was a 1 or a 2 and required a speeded response. In one condition, subjects were instructed to ignore T1 but respond to T2. In another condition, they were required to report T1 after making their speeded response to T2 (i.e. to make a speeded T2 response while holding T1 in WM).ResultsPSZ were dramatically slowed at responding to T2 when T1 was held in WM. A repeated measures ANOVA yielded main effects of group, delay, and condition with a group by condition interaction (p's < 0.001). Across delays, the slowing of the T2 response when required to hold T1 in memory, relative to ignoring T1, was nearly 3 times higher in PSZ than HCS (633 v. 219 ms).ConclusionsWhereas previous studies have focused on reduced storage capacity, the present study found that PSZ are impaired at performing tasks while they are successfully maintaining a single item in WM. This may play a role in the broad cognitive impairment seen in PSZ.

A frequent finding when studying substrates of working memory (WM) deficits in people with schizophrenia (PSZ) is task-induced hyperactivation relative to healthy control subjects (HCS) when WM load is low. Hyperactivation accompanying similar performance is commonly attributed to cognitive deficits rendering relatively easy operations more resource-consuming. To test if hyperactivation at low load really is secondary to cognitive impairment in PSZ, we re-analyzed functional MRI data showing left posterior parietal cortex (PPC) hyperactivation in PSZ when holding a single color-item in WM. In subgroups matched for the number of items successfully stored in WM (K) by excluding the highest-performing HCS and lowest-performing PSZ, performance was almost identical across all set sizes (1-7). While BOLD activation at the larger set sizes did not differ between groups, PSZ still robustly hyperactivated left PPC when a single item had to be maintained. The same pattern was observed in subgroups matched for model-based estimates of WM capacity or attentional lapse rate. Given that in the K-matched subsamples PSZ performed as well as HCS even in the most challenging load conditions and that no BOLD signal difference was seen at high loads, it is implausible that PSZ over-recruited WM-related neural structures because they were more challenged by maintaining a single item in WM. Instead, the findings are consistent with a primary schizophrenia-related processing abnormality as proposed by the hyperfocusing hypothesis, which suggests that an abnormally narrow but intense focusing of processing resources is central to many aspects of impaired cognition in PSZ.

People with schizophrenia demonstrate impairments in selective attention, working memory, and executive function. Given the overlap in these constructs, it is unclear if these represent distinct impairments or different manifestations of one higher-order impairment. To examine this question, we administered tasks from the basic cognitive neuroscience literature to measure visual selective attention, working memory capacity, and executive function in 126 people with schizophrenia and 122 healthy volunteers. Patients demonstrated deficits on all tasks with the exception of selective attention guided by strong bottom-up inputs. Although the measures of top-down control of selective attention, working memory, and executive function were all intercorrelated, several sources of evidence indicate that working memory and executive function are separate sources of variance. Specifically, both working memory and executive function independently contributed to the discrimination of group status and independently accounted for variance in overall general cognitive ability as assessed by the MATRICS battery. These two cognitive functions appear to be separable features of the cognitive impairments observed in schizophrenia.

PFC dysfunction is widely believed to underlie working memory (WM) deficits in people with schizophrenia (PSZ), but few studies have focused on measures of WM storage devoid of manipulation. Research in neurotypical individuals has shown that storage capacity is more closely related to posterior parietal cortex (PPC) than PFC, suggesting that reductions in WM storage capacity in schizophrenia that are associated with broad cognitive deficits may be related to neural activity in PPC. In the present human neuroimaging study, 37 PSZ and 37 matched healthy control subjects of either sex completed a change detection task with varying set sizes while undergoing fMRI. The task was designed to emphasize WM storage with minimal top-down control demands. Whole-brain analysis identified areas in which BOLD activity covaried with the number of items maintained in WM (K), as derived from task performance at a given set size. Across groups, K values independent of set size predicted BOLD activity in PPC, including superior and inferior parietal lobules and intraparietal sulcus, and middle occipital gyrus. Whole-brain interaction analysis found significantly less K-dependent signal modulation in PSZ than healthy control subjects in left PPC, a phenomenon that could not be explained by a narrower K value range. The slope between K and PPC activation statistically accounted for 43.4% of the between-group differences in broad cognitive function. These results indicate that PPC dysfunction is central to WM storage deficits in PSZ and may play a key role in the broad cognitive deficits associated with schizophrenia.SIGNIFICANCE STATEMENT People with schizophrenia exhibit cognitive deficits across a wide range of tasks. Explaining these impairments in terms of a small number of core deficits with clearly defined neural correlates would advance the understanding of the disorder and promote treatment development. We show that a substantial portion of broad cognitive deficits in schizophrenia can be explained by a failure to flexibly modulate posterior parietal cortex activity as a function of the amount of information currently stored in working memory. Working memory deficits have long been considered central to schizophrenia-related cognitive deficits, but the focus has been on paradigms involving some form of top-down control rather than pure storage of information, which may have unduly narrowed the focus on prefrontal dysfunction.

BackgroundAlthough people with schizophrenia (PSZ) frequently exhibit reduced working memory capacity relative to healthy comparison subjects (HCS), the mechanisms that underlie this impairment are not yet known. The present study aimed to assess one putative mechanism: impaired suppression of alpha and beta frequency bands during the delay period of a visual working memory task.MethodsThe electroencephalogram (EEG) was recorded from 30 PSZ and 31 HCS while they completed a change detection task in which they were required to remember a briefly presented array of colored squares over an 1800-ms delay interval.ResultsOverall, we found that PSZ had significantly reduced alpha and beta-band suppression during the delay interval compared to HCS, and that these significant differences emerged early (100-200 ms after the onset of the memory array). Furthermore, the magnitude of suppression was significantly associated with task performance across both groups. Finally, the magnitude of suppression in alpha and beta frequency bands was significantly associated with a range of cognitive measures among HCS, but not PSZ.ConclusionsThese results implicate impaired alpha/beta suppression during the consolidation period of working memory tasks as a promising neural mechanism that constrains capacity in PSZ.

The cognitive impairments associated with schizophrenia have long been known to involve deficits in working memory (WM) capacity. To date, however, the causes of WM capacity deficits remain unknown. The present study examined selective attention impairments as a putative contributor to observed capacity deficits in this population. To test this hypothesis, we used an experimental paradigm that assesses the role of selective attention in WM encoding and has been shown to involve the prefrontal cortex and the basal ganglia. In experiment 1, participants were required to remember the locations of 3 or 5 target items (red circles). In another condition, 3-target items were accompanied by 2 distractor items (yellow circles), which participants were instructed to ignore. People with schizophrenia (PSZ) exhibited significant impairment in memory for the locations of target items, consistent with reduced WM capacity, but PSZ and healthy control subjects did not differ in their ability to filter the distractors. This pattern was replicated in experiment 2 for distractors that were more salient. Taken together, these results demonstrate that reduced WM capacity in PSZ is not attributable to a failure of filtering irrelevant distractors.

Recent research suggests that processing resources are focused more narrowly but more intensely in people with schizophrenia (PSZ) than in healthy control subjects (HCS), possibly reflecting local cortical circuit abnormalities. This hyperfocusing hypothesis leads to the counterintuitive prediction that, although PSZ cannot store as much information in working memory as HCS, the working memory representations that are present in PSZ may be more intense than those in HCS. To test this hypothesis, we used a task in which participants make a saccadic eye movement to a peripheral target and avoid a parafoveal nontarget while they are holding a color in working memory. Previous research with this task has shown that the parafoveal nontarget is more distracting when it matches the color being held in working memory. This effect should be enhanced in PSZ if their working memory representations are more intense. Consistent with this prediction, we found that the effect of a match between the distractor color and the memory color was larger in PSZ than in HCS. We also observed evidence that PSZ hyperfocused spatially on the region surrounding the fixation point. These results provide further evidence that some aspects of cognitive dysfunction in schizophrenia may be a result of a narrower and more intense focusing of processing resources.

Recent studies suggest that people with schizophrenia (PSZ) have difficulty distributing their attention broadly. Other research suggests that PSZ have reduced working memory (WM) capacity. This study tested whether these findings reflect a common underlying deficit. We measured the ability to distribute attention by means of the Useful Field of View (UFOV) task, in which participants must distribute attention so that they can discriminate a foveal target and simultaneously localize a peripheral target. Participants included 50 PSZ and 52 healthy control subjects. We found that PSZ exhibited severe impairments in UFOV performance, that UFOV performance was highly correlated with WM capacity in PSZ (r = -.61), and that UFOV impairments could not be explained by either impaired low-level processing or a generalized deficit. These results suggest that a common mechanism explains deficits in the ability to distribute attention broadly, reduced WM capacity, and other aspects of impaired cognition in schizophrenia. We hypothesize that this mechanism may involve abnormal local circuit dynamics that cause a hyperfocusing of resources onto a small number of internal representations.

Although working memory impairment has been well-documented among people with schizophrenia (PSZ), the underlying mechanism of this impairment remains unknown. The present study was conducted in a large sample of PSZ and healthy control subjects (HCS) to test the hypothesis that one putative mechanism-vulnerability to distraction from task-irrelevant stimuli-(1) can account for working memory impairment among PSZ, and (2) is associated with other neurocognitive and clinical variables that are highly predictive of functional outcome in schizophrenia. Participants (127 PSZ and 124 HCS) completed a visual change detection task in which a distractor stimulus (mask) was presented on half of the trials during the delay period between sample and test array. PSZ lost proportionately more information from working memory than did HCS, but this effect was small (Cohen's d = 0.36-0.38), and large differences between groups in working memory capacity remained when differences in distractibility were factored out. Furthermore, vulnerability to distraction was not strongly associated with any clinical or cognitive variables of interest. These results suggest that, although PSZ may be somewhat more susceptible to distraction than HCS, this impairment is unlikely to be a significant factor accounting for the robust capacity deficits observed in this population.

Recent research has suggested that people with schizophrenia (PSZ) have sensory deficits, especially in the magnocellular pathway, and this has led to the proposal that dysfunctional sensory processing may underlie higher-order cognitive deficits. Here we test the hypothesis that the antisaccade deficit in PSZ reflects dysfunctional magnocellular processing rather than impaired cognitive processing, as indexed by working memory capacity. This is a plausible hypothesis because oculomotor regions have direct magnocellular inputs, and the stimuli used in most antisaccade tasks strongly activate the magnocellular visual pathway. In the current study, we examined both prosaccade and antisaccade performance in PSZ (N = 22) and matched healthy control subjects (HCS; N = 22) with Gabor stimuli designed to preferentially activate the magnocellular pathway, the parvocellular pathway, or both pathways. We also measured working memory capacity. PSZ exhibited impaired antisaccade performance relative to HCS across stimulus types, with impairment even for stimuli that minimized magnocellular activation. Although both sensory thresholds and working memory capacity were impaired in PSZ, only working memory capacity was correlated with antisaccade accuracy, consistent with a cognitive rather than sensory origin for the antisaccade deficit.

Recent research has suggested that people with schizophrenia (PSZ) have sensory deficits, especially in the magnocellular pathway, and this has led to the proposal that dysfunctional sensory processing may underlie higher-order cognitive deficits. Here we test the hypothesis that the antisaccade deficit in PSZ reflects dysfunctional magnocellular processing rather than impaired cognitive processing, as indexed by working memory capacity. This is a plausible hypothesis because oculomotor regions have direct magnocellular inputs, and the stimuli used in most antisaccade tasks strongly activate the magnocellular visual pathway. In the current study, we examined both prosaccade and antisaccade performance in PSZ (N = 22) and matched healthy control subjects (HCS; N = 22) with Gabor stimuli designed to preferentially activate the magno-cellular pathway, the parvocellular pathway, or both pathways. We also measured working memory capacity. PSZ exhibited impaired antisaccade performance relative to HCS across stimulus types, with impairment even for stimuli that minimized magnocellular activation. Although both sensory thresholds and working memory capacity were impaired in PSZ, only working memory capacity was correlated with antisaccade accuracy, consistent with a cognitive rather than sensory origin for the antisaccade deficit. [ABSTRACT FROM AUTHOR]

Working memory impairment is considered a core deficit in schizophrenia, but the precise nature of this deficit has not been determined. Multiple lines of evidence implicate deficits at the encoding stage. During encoding, information is held in a precategorical sensory store termed iconic memory, a literal image of the stimulus with high capacity but rapid decay. Pathologically increased iconic decay could reduce the number of items that can be transferred into working memory before the information is lost and could thus contribute to the working memory deficit seen in the illness. The current study used a partial report procedure to test the hypothesis that patients with schizophrenia (n = 37) display faster iconic memory decay than matched healthy control participants (n = 28). Six letters, arranged in a circle, were presented for 50 ms. Following a variable delay of 0–1000 ms, a central arrow cue indicated the item to be reported. In both patients and control subjects, recall accuracy decreased with increasing cue delay, reflecting decay of the iconic representation of the stimulus array. Patients displayed impaired memory performance across all cue delays, consistent with an impairment in working memory, but the rate of iconic memory decay did not differ between patients and controls. This provides clear evidence against faster loss of iconic memory representations in schizophrenia, ruling out iconic decay as an underlying source of the working memory impairment in this population. Thus, iconic decay rate can be added to a growing list of unimpaired cognitive building blocks in schizophrenia. [ABSTRACT FROM PUBLISHER]

Background: Prior demonstrations of impaired attentional control in schizophrenia focused on conditions in which top-down control is needed to overcome prepotent response tendencies. Attentional control over stimulus processing has received little investigation. Here, we test whether attentional control is impaired during working memory encoding when salient distractors compete with less salient task-relevant stimuli. Methods: Patients with schizophrenia (n = 28) and healthy control subjects (n = 25) performed a visuospatial working memory paradigm in which half of the to-be-encoded stimuli flickered to increase their salience. After a 2-second delay, stimuli reappeared and participants had to decide whether or not a probed item had shifted location. Results: In the unbiased condition where flickering and nonflickering stimuli were equally likely to be probed, both groups displayed a trend toward better memory for the flickering items. In the flicker-bias condition in which the flickering stimuli were likely to be probed, both groups displayed a robust selection advantage for the flickering items. However, in the nonflicker-bias condition in which the nonflickering stimuli were likely to be probed, only healthy control subjects showed selection of the nonflickering items. Patients displayed a trend toward preferential memory for the flickering items, as in the unbiased condition. Conclusions: Both groups were able to select salient over nonsalient stimuli, but patients with schizophrenia were unable to select nonsalient over salient stimuli, consistent with impairment in the effortful control of attention. These findings demonstrate the generality of top-down control failure in schizophrenia in the face of bottom-up competition from salient stimuli as with prepotent response tendencies. [ABSTRACT FROM AUTHOR]

Abstract: People with schizophrenia (PSZ) exhibit signs of reduced working memory (WM) capacity. However, this may reflect an impairment in managing its content, e.g. preventing irrelevant information from taking up available storage space, rather than a true capacity reduction. We tested the ability to eliminate and update WM content in 38 PSZ and 30 healthy control subjects (HCS). Images of real-world objects were presented consecutively, and a tone cued the item most likely to be tested for memory. On half the trials, randomly intermixed, a second tone occurred. Participants were informed that the item cued by the second tone was now the most likely to be tested, and the item cued by the first tone now the least likely, providing incentive to eliminate the first cued item from WM. Both HCS and PSZ displayed a robust performance advantage for cued items. Unexpectedly, PSZ more efficiently removed the no-longer-essential item from WM than HCS. The magnitude of the WM clearance of this first cued item correlated with memory performance for the newly prioritized second cued item in PSZ, indicating that it was adaptive. However, WM clearance was not associated with WM capacity, ruling out the need to budget limited resources as an explanation for greater clearance in PSZ. A robust correlation between WM clearance and poverty of speech in PSZ instead suggests that the propensity to rapidly clear non-essential information and minimize the number of items in WM may be the reflection of a negative symptom trait. This finding may reflect a more general tendency of PSZ to focus processing more narrowly than HCS. [Copyright &y& Elsevier]

This study reports evidence that individuals with schizophrenia (SC) demonstrate intact attentional selection for visual working memory (WM) storage. A group of 62 participants with SC and 55 control participants without SC were studied in a series of 5 experiments that examined the ability to use top-down and bottom-up cues to guide WM encoding, as well as the ability to spontaneously select a subset of representations for storage. Participants with SC exhibited a consistent and robust ability to use selective attention in the control of WM in all 5 experiments, demonstrating a remarkable island of preserved functioning given the broad spectrum of impairments of attention and WM that have been widely reported in those with SC. These findings indicate that attention is not globally impaired in SC and make it possible to delineate more precisely the nature of the specific impairment of attention in this disorder. [ABSTRACT FROM AUTHOR]

Recent research suggests that processing resources are focused more narrowly but more intensely in people with schizophrenia (PSZ) than in healthy control subjects (HCS), possibly reflecting local cortical circuit abnormalities. This hyperfocusing hypothesis leads to the counterintuitive prediction that, although PSZ cannot store as much information in working memory as HCS, the working memory representations that are present in PSZ may be more intense than those in HCS. To test this hypothesis, we used a task in which participants make a saccadic eye movement to a peripheral target and avoid a parafoveal nontarget while they are holding a color in working memory. Previous research with this task has shown that the parafoveal nontarget is more distracting when it matches the color being held in working memory. This effect should be enhanced in PSZ if their working memory representations are more intense. Consistent with this prediction, we found that the effect of a match between the distractor color and the memory color was larger in PSZ than in HCS. We also observed evidence that PSZ hyperfocused spatially on the region surrounding the fixation point. These results provide further evidence that some aspects of cognitive dysfunction in schizophrenia may be a result of a narrower and more intense focusing of processing resources. [ABSTRACT FROM AUTHOR]