Network hub centrality and working memory performance in schizophrenia

Cognitive impairment, and working memory deficits in particular, are debilitating, treatment-resistant aspects of schizophrenia. Dysfunction of brain network hubs, putatively related to altered neurodevelopment, is thought to underlie the cognitive symptoms associated with this illness. Here, we used weighted degree, a robust graph theory metric representing the number of weighted connections to a node, to quantify centrality in cortical hubs in 29 patients with schizophrenia and 29 age- and gender-matched healthy controls and identify the critical nodes that underlie working memory performance. In both patients and controls, elevated weighted degree in the default mode network (DMN) was generally associated with poorer performance (accuracy and reaction time). Higher degree in the ventral attention network (VAN) nodes in the right superior temporal cortex was associated with better performance (accuracy) in patients. Degree in several prefrontal and parietal areas was associated with cognitive performance only in patients. In regions that are critical for sustained attention, these correlations were primarily driven by between-network connectivity in patients. Moreover, a cross-validated prediction analysis showed that a linear model using a summary degree score can be used to predict an individual's working memory accuracy (r = 0.35). Our results suggest that schizophrenia is associated with dysfunctional hubs in the cortical systems supporting internal and external cognition and highlight the importance of topological network analysis in the search of biomarkers for cognitive deficits in schizophrenia.