Neural primacy of the salience processing system in schizophrenia

Neuron. 2013 Aug 21;79(4):814-28. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / therapeutic use
  • Brain / blood supply
  • Brain / drug effects
  • Brain / physiopathology*
  • Brain Mapping*
  • Female
  • Functional Laterality
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Imaging
  • Male
  • 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
  • Rest
  • Schizophrenia / drug therapy
  • Schizophrenia / pathology*
  • Statistics as Topic
  • Time Factors
  • Young Adult


  • Antipsychotic Agents
  • Oxygen