Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

Abstract

The insular cortex is one of the brain regions that show consistent abnormalities in both structural and functional neuroimaging studies of schizophrenia. In healthy individuals, the insula has been implicated in a myriad of physiologic functions. The anterior cingulate cortex (ACC) and insula together constitute the salience network, an intrinsic large-scale network showing strong functional connectivity. Considering the insula as a functional unit along with the ACC provides an integrated understanding of the role of the insula in information processing. In this review, we bring together evidence from imaging studies to understand the role of the salience network in schizophrenia and propose a model of insular dysfunction in psychosis.

Fig. 1

Proximal salience refers to a momentary state of neural activity within the salience network generated by the evaluation of external or internal stimuli. The salience network interacts with the interoceptive pathway and prefrontal system to generate the proximal salience that enables a switching between resting mode to task-processing (executive) mode or vice versa. ACC = anterior cingulate cortex; CEN = central executive network; DMN = default mode network.

Fig 2

Insular dysfunction model of psychosis. A dysfunction of the salience network can lead to a cascade of events that result in clinical symptoms of psychosis. Inappropriate proximal salience during self-generated actions result in hallucinations and passivity experiences. Proximal salience inappropriately attached to external stimulus in the context of heightened uncertainty in unusual beliefs and delusions. A failure to engage the task-relevant network when required is associated with disorganization. Failure to generate goal-driven activity is related to psychomotor poverty. CEN = central executive network; DMN = default mode network.