The Concept of Salience Network Dysfunction in Schizophrenia: From Neuroimaging Observations to Therapeutic Opportunities

A large body of neuroimaging literature suggests that distributed regions in the brain form coordinated largescale networks that show reliable patterns of connectivity when observed using either functional or structural magnetic resonance imaging (MRI) methods. Functional activation within these networks provides a robust and reliable representation of dynamic brain states observed during information processing. One such network comprised of anterior frontoinsular cortex (aFI) and anterior cingulate cortex (ACC) is called the Salience Network (SN). SN has been identified as a system that enables the switch between various dynamic brain states. SN dysfunction has been proposed as a mechanistic model for several core symptoms of schizophrenia. In this review, we explore how various risk factors of schizophrenia could operate through the dysfunctional SN to generate symptoms of psychosis. We also consider the putative neurochemical basis for the SN dysfunction in schizophrenia, and suggest that the SN dysfunction is a viable therapeutic target for a combined pharmacological and cognitive training treatment approach. This combination approach, termed as Brain Network Modulation, could exploit neuronal plasticity to reverse a key pathophysiological deficit in schizophrenia.