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Neural primacy of the salience processing system in schizophrenia

Palaniyappan, Lena; Simmonite, M.; White, T.P.; Liddle, E.B.; Liddle, P.F.

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Lena Palaniyappan

M. Simmonite

T.P. White

E.B. Liddle

P.F. Liddle


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.


Palaniyappan, L., Simmonite, M., White, T., Liddle, E., & Liddle, P. (2013). Neural primacy of the salience processing system in schizophrenia. Neuron, 79(4),

Journal Article Type Article
Publication Date Aug 21, 2013
Deposit Date Apr 2, 2014
Publicly Available Date Apr 2, 2014
Journal Neuron
Print ISSN 0896-6273
Electronic ISSN 0896-6273
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 79
Issue 4
Public URL
Publisher URL


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