Dysregulated brain dynamics in a triple-network saliency model of schizophrenia and its relation to psychosis

Supekar, K., Cai, W., Krishnadas, R. , Palaniyappan, L. and Menon, V. (2019) Dysregulated brain dynamics in a triple-network saliency model of schizophrenia and its relation to psychosis. Biological Psychiatry, 85(1), pp. 60-69. (doi: 10.1016/j.biopsych.2018.07.020) (PMID:30177256)

Abstract

Background: Schizophrenia is a highly disabling psychiatric disorder characterized by a range of positive “psychosis” symptoms. However, the neurobiology of psychosis and associated systems-level disruptions in the brain remain poorly understood. Here, we test an aberrant saliency model of psychosis, which posits that dysregulated dynamic cross-network interactions among the salience network (SN), central executive network, and default mode network contribute to positive symptoms in patients with schizophrenia. Methods: Using task-free functional magnetic resonance imaging data from two independent cohorts, we examined 1) dynamic time-varying cross-network interactions among the SN, central executive network, and default mode network in 130 patients with schizophrenia versus well-matched control subjects; 2) accuracy of a saliency model–based classifier for distinguishing dynamic brain network interactions in patients versus control subjects; and 3) the relation between SN-centered network dynamics and clinical symptoms. Results: In both cohorts, we found that dynamic SN-centered cross-network interactions were significantly reduced, less persistent, and more variable in patients with schizophrenia compared with control subjects. Multivariate classification analysis identified dynamic SN-centered cross-network interaction patterns as factors that distinguish patients from control subjects, with accuracies of 78% and 80% in the two cohorts, respectively. Crucially, in both cohorts, dynamic time-varying measures of SN-centered cross-network interactions were correlated with positive, but not negative, symptoms. Conclusions: Aberrations in time-varying engagement of the SN with the central executive network and default mode network is a clinically relevant neurobiological signature of psychosis in schizophrenia. Our findings provide strong evidence for dysregulated brain dynamics in a triple-network saliency model of schizophrenia and inform theoretically motivated systems neuroscience approaches for characterizing aberrant brain dynamics associated with psychosis.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Krishnadas, Dr Rajeev
• Authors: Supekar, K., Cai, W., Krishnadas, R., Palaniyappan, L., and Menon, V.
• College/School: College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Biological Psychiatry
• Publisher: Elsevier
• ISSN: 0006-3223
• ISSN (Online): 1873-2402
• Published Online: 01 August 2018