Neural Primacy of the Salience Processing System in Schizophrenia

• Published in: Neuron (Cambridge, Mass.) Vol. 79; no. 4; pp. 814 - 828
• Main Authors: Palaniyappan, Lena, Simmonite, Molly, White, Thomas P., Liddle, Elizabeth B., Liddle, Peter F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 21-08-2013; Elsevier Limited; Cell Press
• Subjects: Adult; Antipsychotic Agents - therapeutic use; Brain; Brain - blood supply; Brain - drug effects; Brain - physiopathology; Brain Mapping; Female; Functional Laterality; Humans; Image Processing, Computer-Assisted; Influence; Magnetic Resonance Imaging; Male; Medical imaging; Models, Statistical; Nerve Net - blood supply; Nerve Net - drug effects; Nerve Net - physiopathology; Neural Networks (Computer); Neural Pathways - blood supply; Neural Pathways - drug effects; Neural Pathways - physiopathology; Oxygen; Psychiatric Status Rating Scales; Recruitment; Rest; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - pathology; Statistics as Topic; Studies; Time Factors; Young Adult
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.06.027

For effective information processing, two large-scale distributed neural networks appear to be critical: a multimodal executive system anchored on the dorsolateral prefrontal cortex (DLPFC) and a salience system anchored on the anterior insula. Aberrant interaction among distributed networks is a feature of psychiatric disorders such as schizophrenia. We used whole-brain Granger causal modeling using resting fMRI and observed a significant failure of both the feedforward and reciprocal influence between the insula and the DLPFC in schizophrenia. Further, a significant failure of directed influence from bilateral visual cortices to the insula was also seen in patients. These findings provide compelling evidence for a breakdown of the salience-execution loop in the clinical expression of psychosis. In addition, this offers a parsimonious explanation for the often-observed “frontal inefficiency,” the failure to recruit prefrontal system when salient or novel information becomes available in patients with schizophrenia.
•A salience-executive loop emerges on fMRI whole-brain Granger causal analysis•At rest, DLPFC has inhibitory Granger influence on the salience network•In schizophrenia, the salience-executive interaction is diminished•Visual cortex fails to influence the salience network in schizophrenia
Palaniyappan et al. show that in patients with schizophrenia, a reciprocal salience-execution loop involving anterior insula and dorsolateral prefrontal cortex disintegrates along with a failure of hierarchical influence from sensory regions to the salience processing system.