Qualitatively Different Delay-Dependent Working Memory Distortions in People With Schizophrenia and Healthy Control Participants.

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.

Qualitatively different delay-dependent working memory distortions in people with schizophrenia and healthy control subjects.

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 subjects(HCS). 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 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 from 0 to 8s. Participants were asked to remember the orientation of a teardrop-shaped object and reproduce the orientation after a varying delay period. 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 easily be 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.

Splitting the anterior mitral leaflet impairs left ventricular function in an ovine model.

OBJECTIVES: During mitral valve replacement, the anterior mitral leaflet is usually resected or modified. Anterior leaflet splitting seems the least disruptive modification. Reattachment of the modified leaflet to the annulus reduces the annulopapillary distance. The goal of this study was to quantify the acute effects on left ventricular function of splitting the anterior mitral leaflet and shortening the annulopapillary distance. METHODS: In 6 adult sheep, a wire was placed around the anterior leaflet and exteriorized through the left ventricular wall to enable splitting the leaflet in the beating heart. Releasable snares to reduce annulopapillary distance were likewise positioned and exteriorized. A mechanical mitral prosthesis was inserted to prevent mitral incompetence during external manipulations of the native valve. Instantaneous changes in left ventricular function were recorded before and after shortening the annulopapillary distance, then before and after splitting the anterior leaflet. RESULTS: After splitting the anterior leaflet, preload recruitable stroke work, stroke work, stroke volume, cardiac output, left ventricular end systolic pressure and mean pressure were significantly decreased by 26%, 23%, 12%, 9%, 15% and 11%, respectively. Shortening the annulopapillary distance was associated with significant decreases in the end systolic pressure volume relationship, preload recruitable stroke work, stroke work and left ventricular end systolic pressure by 67%, 33%, 15% and 13%, respectively. Shortening the annulopapillary distance after splitting the leaflet had no significant effect. CONCLUSIONS: Splitting the anterior mitral leaflet acutely impaired left ventricular contractility and haemodynamics in an ovine model. Shortening the annulopapillary distance after leaflet splitting did not further impair left ventricular function.

Analogue Mean Systemic Filling Pressure: a New Volume Management Approach During Percutaneous Left Ventricular Assist Device Therapy.

The absence of an accepted gold standard to estimate volume status is an obstacle for optimal management of left ventricular assist devices (LVADs). The applicability of the analogue mean systemic filling pressure (Pmsa) as a surrogate of the mean circulatory pressure to estimate volume status for patients with LVADs has not been investigated. Variability of flows generated by the Impella CP, a temporary LVAD, should have no physiological impact on fluid status. This translational interventional ovine study demonstrated that Pmsa did not change with variable circulatory flows induced by a continuous flow LVAD (the average dynamic increase in Pmsa of 0.20 ± 0.95 mmHg from zero to maximal Impella flow was not significant (p = 0.68)), confirming applicability of the human Pmsa equation for an ovine LVAD model. The study opens new directions for future translational and human investigations of fluid management using Pmsa for patients with temporary LVADs.

Association Between Failures in Perceptual Updating and the Severity of Psychosis in Schizophrenia.

Importance: Recent accounts suggest that delusions and hallucinations may result from alterations in how prior knowledge is integrated with new information, but experimental evidence supporting this idea has been complex and inconsistent. Evidence from a simpler perceptual task would make clear whether psychotic symptoms are associated with overreliance on prior information and impaired updating. Objective: To investigate whether individuals with schizophrenia or schizoaffective disorder (PSZ) and healthy control individuals (HCs) differ in the ability to update their beliefs based on evidence in a relatively simple perceptual paradigm. Design, Setting, and Participants: This case-control study included individuals who met DSM-IV criteria for PSZ and matched HC participants in 2 independent samples. The PSZ group was recruited from the Maryland Psychiatric Research Center, Yale University, and community clinics, and the HC group was recruited from the community. To test perceptual updating, a random dot kinematogram paradigm was implemented in which dots moving coherently in a single direction were mixed with randomly moving dots. On 50% of trials, the direction of coherent motion changed by 90° midway through the trial. Participants were asked to report the direction perceived at the end of the trial. The Peters Delusions Inventory and Brief Psychiatric Rating Scale (BPRS) were used to quantify the severity of positive symptoms. Data were collected from September 2018 to March 2020 and were analyzed from approximately March 2020 to March 2021. Main Outcomes and Measures: Critical measures included the proportion of responses centered around the initial direction vs the subsequent changed direction and the overall precision of motion perception and reaction times. Results: A total of 48 participants were included in the PSZ group (31 [65%] male; mean [SD] age, 36.56 [9.76] years) and 36 in the HC group (22 [61%] male; mean [SD] age, 35.67 [10.74] years) in the original sample. An independent replication sample included 42 participants in the PSZ group (29 [69%] male; mean [SD] age, 33.98 [11.03] years) and 34 in the HC group (20 [59%] male; mean [SD] age, 34.29 [10.44] years). In line with previous research, patients with PSZ were less precise and had slower reaction times overall. The key finding was that patients with PSZ were significantly more likely (original sample: mean, 27.88 [95% CI, 24.19-31.57]; replication sample: mean, 26.70 [95% CI, 23.53-29.87]) than HC participants (original sample: mean, 18.86 [95% CI, 16.56-21.16]; replication sample: mean, 15.67 [95% CI, 12.61-18.73]) to report the initial motion direction rather than the final one. Moreover, the tendency to report the direction of initial motion correlated with the degree of conviction on the Peters Delusions Inventory (original sample: r = 0.32 [P = .05]; replication sample: r = 0.30 [P = .05]) and the Brief Psychiatric Rating Scale Reality Distortion score (original sample: r = 0.55 [P = .001]; replication sample: r = 0.35 [P = .03]) and severity of hallucinations (original sample: r = 0.39 [P = .02]; replication sample: r = 0.30 [P = .05]). Conclusions and Relevance: The findings of this case-control study suggest that the severity of psychotic symptoms is associated with a tendency to overweight initial information over incoming sensory evidence. These results are consistent with predictive coding accounts of the origins of positive symptoms and suggest that deficits in very elementary perceptual updating may be a critical mechanism in psychosis.

Impaired Filtering and Hyperfocusing: Neural Evidence for Distinct Selective Attention Abnormalities in People with Schizophrenia.

Although schizophrenia is classically thought to involve impaired attentional filtering, people with schizophrenia (PSZ) exhibit a more intense and more exclusive attentional focus than healthy control subjects (HCS) in many tasks. To resolve this contradiction, this functional magnetic resonance imaging study tested the impact of attentional control demands on the modulation of stimulus-induced activation in the fusiform face area and parahippocampal place area when participants (43 PSZ and 43 HCS) were looking for a target face versus house. Stimuli were presented individually, or as face-house overlays that challenged attentional control. Responses were slower for house than face stimuli and when prioritizing houses over faces in overlays, suggesting a difference in salience. Blood-oxygen-level-dependent activity reflected poorer attentional selectivity in PSZ than HCS when attentional control was challenged most, that is, when stimuli were overlaid and the task required detecting the lower-salience house target. By contrast, attentional selectivity was exaggerated in PSZ when control was challenged least, that is, when stimuli were presented sequentially and the task required detecting the higher-salience face target. These findings are consistent with 2 distinct attentional abnormalities in schizophrenia leading to impaired and exaggerated selection under different conditions: attentional control deficits, and hyperfocusing once attention has been directed toward a stimulus.

Oculomotor inhibition and location priming in schizophrenia.

Schizophrenia is widely thought to involve elevated distractibility, which may reflect a general impairment in top-down inhibitory processes. Schizophrenia also appears to involve increased priming of previously performed actions. Here, we used a highly refined eye-tracking paradigm that makes it possible to concurrently assess distractibility, inhibition, and priming. In both healthy control subjects (HCS, N = 41) and people with schizophrenia (PSZ, N = 46), we found that initial saccades were actually less likely to be directed toward a salient "singleton" distractor than toward less salient distractors, reflecting top-down suppression of the singleton. Remarkably, this oculomotor suppression effect was as strong or stronger in PSZ than in HCS, indicating intact inhibitory control. In addition, saccades were frequently directed to the location of the previous-trial target in both groups, but this priming effect was much stronger in PSZ than in HCS. Indeed, PSZ directed gaze toward the location of the previous-trial target as often as they directed gaze to the location of the current-trial target. These results demonstrate that-at least in the context of visual search-PSZ are no more distractable than HCS and are fully capable of inhibiting salient-but-irrelevant stimuli. However, PSZ do exhibit exaggerated priming, focusing on recently attended locations even when this is not beneficial for goal attainment. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Incorporating the anterior mitral leaflet to the annulus impairs left ventricular function in an ovine model.

Objectives: Transcatheter mitral valve prostheses are designed to capture the anterior leaflet and surgical techniques designed to fully preserve the subvalvular apparatus at prosthetic valve insertion both serve to shorten the anterior mitral leaflet height, thus effectively incorporating it into the anterior annulus. This study quantifies the acute effects of incorporating the anterior mitral leaflet into the annulus on left ventricular function. Methods: Fourteen adult sheep (weight, 48.7 ± 6.2 kg) underwent a mechanical mitral valve insertion on normothermic beating-heart cardiopulmonary bypass, with full retention of the native mitral valve but with placement of exteriorized releasable snares around the anterior mitral leaflet. Continuous measurements of left ventricular mechano-energetics were recorded throughout, alternating incorporating and releasing of the anterior mitral leaflet to the mitral annulus. Echocardiography confirmed the incorporation into the annulus and release. Results: The independent indices of left ventricular contractility (ie, end systolic pressure volume relationship and preload recruitable stroke work) were both significantly impaired when the anterior mitral leaflet was incorporated to the annulus and restored after release, as were the hemodynamic parameters: cardiac output, stroke volume, stroke work, and left ventricular pressure decreased by 15%, 17%, 23%, and 11%, respectively. Echocardiography demonstrated increased sphericity of the left ventricle during anterior mitral leaflet incorporation. Conclusions: Incorporating the anterior mitral leaflet to the anterior annulus adversely affected left ventricular contractility, caused distortion of the left ventricle in the form of increased sphericity, and impaired hemodynamic parameters in normal ovine hearts.

Bioprosthetic interstrut distance subtending the preserved anterior mitral leaflet mitigates left ventricular outflow tract obstruction.

Background: The anterior mitral leaflet (AML) contributes to left ventricular (LV) function but is normally excised at the time of a bioprosthetic valve insertion. This study aimed to investigate methods of safely retaining the AML at the time of mitral valve replacement. Methods: Five adult sheep (57 ± 3.8 kg) each underwent 3 insertions of a bioprosthetic mitral valve (asymmetric interstrut sectors) alternating the wide and narrow interstrut distance under the AML. Each insertion was performed on normothermic beating-heart cardiopulmonary bypass, with full retention of the native valve. After each valve insertion, continuous measurements of LV and aortic pressures were recorded with echocardiographic assessment of mitral valve function. If LV outflow tract obstruction (LVOTO) was not seen on the resumption of normal cardiac output, a bolus of adrenaline was given to precipitate it. Results: Thirteen of 15 valve insertions resulted in LVOTO caused by systolic anterior motion (SAM), independent of valve orientation. The wide interstrut distance subtending the AML was associated with a greater requirement for inotropic stress to precipitate an obstruction and was associated with late systolic rather than holosystolic obstruction. Conclusions: The predisposition to and nature of LVOTO due to SAM were associated with the bioprosthetic valve interstrut distance subtending the fully retained AML and may explain the survival differences in such patients. This model represents an effective method for research into prevention of LVOTO following mitral valve replacement with preservation of the native valve.

Antisaccade Deficits in Schizophrenia Can Be Driven by Attentional Relevance of the Stimuli.

The antisaccade task is considered a test of cognitive control because it creates a conflict between the strong bottom-up signal produced by the cue and the top-down goal of shifting gaze to the opposite side of the display. Antisaccade deficits in schizophrenia are thought to reflect impaired top-down inhibition of the prepotent bottom-up response to the cue. However, the cue is also a highly task-relevant stimulus that must be covertly attended to determine where to shift gaze. We tested the hypothesis that difficulty in overcoming the attentional relevance of the cue, rather than its bottom-up salience, is key in producing impaired performance in people with schizophrenia (PSZ). We implemented 3 versions of the antisaccade task in which we varied the bottom-up salience of the cue while holding its attentional relevance constant. We found that difficulty in performing a given antisaccade task-relative to a prosaccade version using the same stimuli-was largely independent of the cue's bottom-up salience. The magnitude of impairment in PSZ relative to control subjects was also independent of bottom-up salience. The greatest impairment was observed in a version where the cue lacked bottom-up salience advantage over other locations. These results indicate that the antisaccade deficit in PSZ does not reflect an impairment in overcoming bottom-up salience of the cue, but PSZ are instead impaired at overcoming its attentional relevance. This deficit may still indicate an underlying inhibitory control impairment but could also reflect a hyperfocusing of attentional resources on the cue.

Increased repulsion of working memory representations in schizophrenia.

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).

Comparison of dynamic changes in stressed intravascular volume, mean systemic filling pressure and cardiovascular compliance: Pilot investigation and study protocol.

The mean systemic filling pressure (MSFP) represents an interaction between intravascular volume and global cardiovascular compliance (GCC). Intravascular volume expansion using fluid resuscitation is the most frequent intervention in intensive care and emergency medicine for patients in shock and with haemodynamic compromise. The relationship between dynamic changes in MSFP, GCC and left ventricular compliance is unknown. We conducted prospective interventional pilot study following euthanasia in post cardiotomy adult sheep, investigating the relationships between changes in MSFP induced by rapid intravascular filling with fluids, global cardiovascular compliance and left ventricular compliance. This pilot investigation suggested a robust correlation between a gradual increase in the intravascular stressed volume from 0 to 40 ml/kg and the MSFP r = 0.708 95% CI 0.435 to 0.862, making feasible future prospective interventional studies. Based on the statistical modelling from the pilot results, we expect to identify a strong correlation of 0.71 ± 0.1 (95% CI) between the MSFP and the stressed intravascular volume in a future study.

Refining the Empirical Constraints on Computational Models of Spatial Working Memory in Schizophrenia.

BACKGROUND: Impairments 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. METHODS: Model 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. RESULTS: PSZ 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. CONCLUSIONS: Consistent 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.

Novel Oral Anticoagulants Compared to Warfarin for Postoperative Atrial Fibrillation After Isolated Coronary Artery Bypass Grafting.

BACKGROUND: Postoperative atrial fibrillation (POAF) is common after cardiac surgery and contributes to short- and long-term morbidity, particularly thromboembolism. Anticoagulation for sustained or recurrent POAF is suggested to reduce thromboembolism. Novel oral anticoagulants may present a safe alternative to warfarin with further benefits including shorter hospital length of stay and better patient convenience. METHODS: A retrospective analysis was performed on all isolated cases of coronary artery surgery (CABG) at our institution between January 2015 and December 2018, totalling 960 patients. Rates of POAF were examined with particular focus on preoperative factors, postoperative outcomes, and anticoagulation practices. RESULTS: The incidence of POAF was 31.8% (305 patients) and was higher in older patients (67.6±9.4 yrs vs 63.0±10.7 yrs, p<0.001), those with a history of cerebrovascular disease (14.6% vs 8.7%, p=0.02), those with higher CHADS-VASc scores (2.5±1.3 vs 2.8±1.3, p<0.001) those who had a postoperative return to theatre (2.6% vs 0.8%, p=0.002), and those with new renal failure (4.9% vs 1.8%, p=0.02). Off-pump surgery was associated with lower incidence of POAF (29.8% vs 37.1%, p=0.03). Patients who developed POAF had significantly longer admissions than those without (12.6±10.6 days vs 9.3±16.3 days, p<0.001). In total, 106 patients (11.0%) went home anticoagulated; 77 (72.6%) on warfarin and 29 (27.4% on a NOAC). Readmission for bleeding was higher in patients on anticoagulation (1.0% vs 0.0%, p=0.02), but did not drive readmission for pericardial effusion (0.3% vs 0.6%, p=0.55). No bleeding complications occurred in patients who were discharged on a NOAC. Overall mortality at median of 2 years was 1.8% (17 patients) and no mortality occurred in any patient discharged on anticoagulation. CONCLUSION: Postoperative atrial fibrillation is a common adverse event and is linked to higher preoperative and postoperative morbidity. Anticoagulation may be safely started in these patients and use of novel anticoagulation does not appear to increase postoperative complications, although overall numbers are low.

Cortical hyperactivation at low working memory load: A primary processing abnormality in people with schizophrenia?

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.

Increased influence of a previously attended feature in people with schizophrenia.

Everyday functioning requires the appropriate allocation of visual attention, which is achieved through multiple mechanisms of attentional guidance. Traditional theories have focused on top-down and bottom-up factors, but implicit learning from recent experience ("selection history") also has a substantial impact on attentional allocation. The present experiment examined the influence of intertrial priming on attentional guidance in people with schizophrenia and matched control subjects. Participants searched for a color pop-out target, which switched randomly between a red target among blue distractors and a blue target among red distractors. We found that performance on the current trial was more influenced by the previous-trial target color in people with schizophrenia than in control subjects. Moreover, this implicit priming effect was greater in individuals with lower working memory capacity (as measured in a separate task). These results suggest that intertrial priming has an exaggerated impact on attentional guidance in people with schizophrenia and that this is associated with other aspects of impaired cognition. Overall, these results are consistent with the hyperfocusing hypothesis, which proposes that a single underlying attentional abnormality may explain a range of atypical effects across perception, attention, and cognition in schizophrenia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

People with schizophrenia show enhanced cognitive costs of maintaining a single item in working memory.

BACKGROUND: Working 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. METHODS: We 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). RESULTS: PSZ 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). CONCLUSIONS: Whereas 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.

Failures in top-down control in schizophrenia revealed by patterns of saccadic eye movements.

Successful execution of many behavioral goals relies on well-organized patterns of saccadic eye movements, and in complex tasks, these patterns can reveal the component processes underlying task performance. The present study examined the pattern of eye movements in a visual search task to provide evidence of attentional control impairments in people with schizophrenia (PSZ). We tested PSZ(N = 38) and nonpsychiatric control subjects (NCS, N = 35) in a task that was designed to stress top-down control by pitting task goals against bottom-up salience. Participants searched for either a low-contrast (nonsalient) or a high-contrast (salient) target among low- and high-contrast distractors. By examining fixations of the low- and high-contrast items, we evaluated the ability of PSZ and NCS to focus on low-salience targets and filter out high-salience distractors (or vice versa). When participants searched for a salient target, both groups successfully focused on relevant, high-contrast stimuli and filtered out target-mismatched, low-contrast stimuli. However, when searching for a nonsalient target, PSZ were impaired at efficiently suppressing high-contrast (salient) distractors. Specifically, PSZ were more likely than NCS to fixate and revisit salient distractors, and they dwelled on these items longer than did NCS. The results provide direct evidence that PSZ are impaired in their ability to utilize top-down goals to overcome the prepotent tendency to focus attention on irrelevant but highly salient information. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Posterior Parietal Cortex Dysfunction Is Central to Working Memory Storage and Broad Cognitive Deficits 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.