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Neuron. 2013 Aug 21;79(4):814-28. doi: 10.1016/j.neuron.2013.06.027.

Neural primacy of the salience processing system in schizophrenia.

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Centre for Translational Neuroimaging in Mental Health, Division of Psychiatry, University of Nottingham, Nottingham NG7 2TU, UK.


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.

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