Dataset Information

Functional Dissociation of Confident and Not-Confident Errors in the Spatial Delayed Response Task Demonstrates Impairments in Working Memory Encoding and Maintenance in Schizophrenia.

ABSTRACT: Even though extensively investigated, the nature of working memory (WM) deficits in patients with schizophrenia (PSZ) is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT), we have recently demonstrated that incorrect yet confident responses (which we labeled as false memory errors) rather than incorrect/not-confident responses reflect failures of WM encoding, which was also impaired in PSZ. In the present study, we provide further evidence for a functional dissociation between confident and not-confident errors by manipulating the demands on WM maintenance, i.e., the length over which information has to be maintained in WM. Furthermore, we investigate whether these functionally distinguishable WM processes are impaired in PSZ. Twenty-four PSZ and 24 demographically matched healthy controls (HC) performed a spatial DRT in which the length of the delay period was varied between 1, 2, 4, and 6 s. In each trial, participants also rated their level of response confidence. Across both groups, longer delays led to increased rates of incorrect/not-confident responses, while incorrect/confident responses were not affected by delay length. This functional dissociation provides additional support for our proposal that false memory errors (i.e., confident errors) reflect problems at the level of WM encoding, while not-confident errors reflect failures of WM maintenance. Schizophrenic patients showed increased numbers of both confident and not-confident errors, suggesting that both sub-processes of WM-encoding and maintenance-are impaired in schizophrenia. Combined with the delay length-dependent functional dissociation, we propose that these impairments in schizophrenic patients are functionally distinguishable.

SUBMITTER: Mayer JS

PROVIDER: S-EPMC5987160 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Functional Dissociation of Confident and Not-Confident Errors in the Spatial Delayed Response Task Demonstrates Impairments in Working Memory Encoding and Maintenance in Schizophrenia.

Mayer Jutta S JS Stäblein Michael M Oertel-Knöchel Viola V Fiebach Christian J CJ

Frontiers in psychiatry 20180529

Even though extensively investigated, the nature of working memory (WM) deficits in patients with schizophrenia (PSZ) is not yet fully understood. In particular, the contribution of different WM sub-processes to the severe WM deficit observed in PSZ is a matter of debate. So far, most research has focused on impaired WM maintenance. By analyzing different types of errors in a spatial delayed response task (DRT), we have recently demonstrated that incorrect yet confident responses (which we label ...[more]

PMID: 29896123

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Project description:Access to WM can be restricted on the basis of goal-relevant properties such as spatial location. However, the extent of voluntary control over which features of an attended multi-feature object are encoded and maintained in WM is debated. Some evidence suggests that attending to an object leads to obligatory storage of all of its features, whereas other evidence suggests that access to WM can be restricted to only goal-relevant features. Another possibility is that all features are initially encoded, but irrelevant features are removed from WM over time. To address these various possibilities, we used pattern classification of EEG signals to track the temporal evolution of representations reflecting the encoding and storage of task-relevant and irrelevant features in WM. In different blocks, participants remembered the orientation, color or both orientation and color of a colored, oriented grating. The color and orientation of the grating was randomly drawn from two distinct feature bins on each trial. To examine trial-specific activity reflecting storage of the object's features, a support vector machine (SVM) classifier was trained to classify what bin the stimulus features came from. Importantly, for orientation, the classifier produced reliably above-chance classification across the delay when orientation was task-relevant but not when it was task-irrelevant. Interestingly, orientation could be accurately classified on trials for which both orientation and color were remembered. Moreover, a separate measure corresponding to the probability of a feature belonging to the correct bin was significantly higher when orientation was task-relevant compared to task-irrelevant during encoding. Above-chance classification for color was only present during the initial 500 msec across all conditions. Our results suggest that although information about all of an object's features is present in the initial stimulus-evoked neural response, information about the task-irrelevant features is attenuated during stimulus encoding and is largely absent throughout the delay.

Project description:We present a workflow using an ETD-optimised version of Mascot Percolator and a modified version of SLoMo (turbo-SLoMo) for analysis of phosphoproteomic data. We have benchmarked this against several database searching algorithms and phosphorylation site localisation tools and show that it offers highly sensitive and confident phosphopeptide identification and site assignment with PSM-level statistics, enabling rigorous comparison of data acquisition methods. We analysed the Plasmodium falciparum schizont phosphoproteome using for the first time, a data-dependent neutral loss-triggered-ETD (DDNL) strategy and a conventional decision-tree method. At a posterior error probability threshold of 0.01, similar numbers of PSMs were identified using both methods with a 73% overlap in phosphopeptide identifications. The false discovery rate associated with spectral pairs where DDNL CID/ETD identified the same phosphopeptide was <1%. 72% of phosphorylation site assignments using turbo-SLoMo without any score filtering, were identical and 99.8% of these cases are associated with a false localisation rate of <5%. We show that DDNL acquisition is a useful approach for phosphoproteomics and results in an increased confidence in phosphopeptide identification without compromising sensitivity or duty cycle. Furthermore, the combination of Mascot Percolator and turbo-SLoMo represents a robust workflow for phosphoproteomic data analysis using CID and ETD fragmentation.Biological significanceProtein phosphorylation is a ubiquitous post-translational modification that regulates protein function. Mass spectrometry-based approaches have revolutionised its analysis on a large-scale but phosphorylation sites are often identified by single phosphopeptides and therefore require more rigorous data analysis to unsure that sites are identified with high confidence for follow-up experiments to investigate their biological significance. The coverage and confidence of phosphoproteomic experiments can be enhanced by the use of multiple complementary fragmentation methods. Here we have benchmarked a data analysis pipeline for analysis of phosphoproteomic data generated using CID and ETD fragmentation and used it to demonstrate the utility of a data-dependent neutral loss triggered ETD fragmentation strategy for high confidence phosphopeptide identification and phosphorylation site localisation.

Dataset Information

Functional Dissociation of Confident and Not-Confident Errors in the Spatial Delayed Response Task Demonstrates Impairments in Working Memory Encoding and Maintenance in Schizophrenia.

Publications

Functional Dissociation of Confident and Not-Confident Errors in the Spatial Delayed Response Task Demonstrates Impairments in Working Memory Encoding and Maintenance in Schizophrenia.

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