Background Impaired working memory is a core cognitive deficit in both bipolar disorder and schizophrenia. Its study might yield crucial insights into the underpinnings of both disorders on the cognitive and neurophysiological level. Visual working memory capacity is a particularly promising construct for such translational studies. However, it has not yet been investigated across the full spectrum of both disorders. The aim of our study was to compare the degree of reductions of visual working memory capacity in patients with bipolar disorder (PBD) and patients with schizophrenia (PSZ) using a paradigm well established in cognitive neuroscience. Methods 62 PBD, 64 PSZ, and 70 healthy controls (HC) completed a canonical visual change detection task. Participants had to encode the color of four circles and indicate after a short delay whether the color of one of the circles had changed or not. We estimated working memory capacity using Pashler’s K. Results Working memory capacity was significantly reduced in both PBD and PSZ compared to HC. We observed a small effect size (r = .202) for the difference between HC and PBD and a medium effect size (r = .370) for the difference between HC and PSZ. Working memory capacity in PSZ was also significantly reduced compared to PBD with a small effect size (r = .201). Thus, PBD showed an intermediate level of impairment. Conclusions These findings provide evidence for a gradient of reduced working memory capacity in bipolar disorder and schizophrenia, with PSZ showing the strongest degree of impairment. This underscores the importance of disturbed information processing for both bipolar disorder and schizophrenia. Our results are compatible with the cognitive manifestation of a neurodevelopmental gradient affecting bipolar disorder to a lesser degree than schizophrenia. They also highlight the relevance of visual working memory capacity for the development of both behavior- and brain-based transdiagnostic biomarkers.

Objective: People with schizophrenia (PSZ) are impaired in the attentional prioritization of non-salient but relevant stimuli over salient but irrelevant distractors during visual working memory (VWM) encoding. Conversely, the guidance of top-down attention by external predictive cues is intact. Yet, it is unknown whether this preserved ability can help PSZ overcome impaired attentional prioritization in the presence of salient distractors. Methods: We employed a visuospatial change-detection task using four Gabor Patches with differing orientations in 69 PSZ and 74 healthy controls (HCS). Two patches flickered to reflect saliency and either a predictive or a non-predictive cue was displayed resulting in four conditions. Results: Across all conditions, PSZ stored significantly less information in VWM than HCS (all p < 0.001). With a non-predictive cue, PSZ stored significantly more salient than non-salient information (t140 = 5.66, p < 0.001, dt = 0.5). With a predictive cue, PSZ stored significantly more non-salient information (t140 = 5.70, p < 0.001, dt = 0.5). Conclusion: Our findings support a bottom-up bias in schizophrenia with performance significantly better for visually salient information in the absence of a predictive cue. These results indicate that bottom-up attentional prioritization is disrupted in schizophrenia, but the top-down utilization of cues is intact. We conclude that additional top-down information significantly improves performance in PSZ when non-salient visual information needs to be encoded in working memory.

Studying the visual system with fMRI often requires using localizer paradigms to define regions of interest (ROIs). However, the considerable interindividual variability of the cerebral cortex represents a crucial confound for group-level analyses. Cortex-based alignment (CBA) techniques reliably reduce interindividual macroanatomical variability. Yet, their utility has not been assessed for visual field localizer paradigms, which map specific parts of the visual field within retinotopically organized visual areas. We evaluated CBA for an attention-enhanced visual field localizer, mapping homologous parts of each visual quadrant in 50 participants. We compared CBA with volume-based alignment and a surface-based analysis, which did not include macroanatomical alignment. CBA led to the strongest increase in the probability of activation overlap (up to 86%). At the group level, CBA led to the most consistent increase in ROI size while preserving vertical ROI symmetry. Overall, our results indicate that in addition to the increased signal-to-noise ratio of a surface-based analysis, macroanatomical alignment considerably improves statistical power. These findings confirm and extend the utility of CBA for the study of the visual system in the context of group analyses. CBA should be particularly relevant when studying neuropsychiatric disorders with abnormally increased interindividual macroanatomical variability.

Pervasive and wide-ranging cognitive deficits are a core feature of schizophrenia and an important determinant of long-term functional outcome. The lack of sufficiently effective treatments for cognitive impairment associated with schizophrenia (CIAS) represents a major unmet need and a central roadblock towards recovery. This is partly due to the current therapeutic focus on clinical symptoms, and the relative neglect of cognitive impairments despite their functionally disabling effects. Furthermore, effective treatment is impeded by our limited knowledge of the complex pathophysiology, which gives rise to perturbed information processing. Here, we review mechanisms and effectiveness of available pharmacological and non-pharmacological treatments for CIAS. Current evidence indicates, that while techniques which broadly enhance neural plasticity show the greatest therapeutic potential, effect sizes are at best moderate. Among other reasons, this is due to a considerable heterogeneity of responses to individual interventions. Furthermore, we discuss how recent conceptual advances in operationalizing cognitive impairments based on cognitive neuroscience have the potential to address these issues and facilitate the development of novel treatment strategies for CIAS. This includes more clearly elucidating pathophysiological mechanisms in both humans and animal models, identifying new treatment targets as well as establishing biomarkers for a better prediction of treatment responses.

The study of the visual system and its role for human cognition in health and disease with fMRI often requires the use of localizer paradigms to define anatomical regions of interest (ROIs). However, the considerable degree of interindividual variability of the cerebral cortex represents an important confound, especially when analyzing visual localizer data on the group level. Cortex-based alignment (CBA) techniques lead to a reliable reduction of interindividual anatomical variability. Yet, the potential benefits of CBA has not been investigated for visual field localizer paradigms used to map specific parts of the visual field within retinotopically organized early visual areas. We evaluated CBA for an attention-enhanced visual field localizer mapping a homologous part of each visual quadrant in a cohort of 50 participants. After CBA, group ROIs showed markedly increased spatial consistency. CBA also led to an increase in the probability of activation overlap of up to forty percent. Furthermore, the size of group ROIs for the lower visual hemifield was larger than for the upper visual hemifield after CBA. This asymmetry, which mirrors previous findings from electrophysiological and fMRI studies, was not detectable before CBA. Our results confirm and extend the utility of CBA for the study of the visual system particularly in the context of group analyses. This method should be particularly important for the study of neuropsychiatric disorders with abnormally increased interindividual anatomical variability.