Disrupted pathways from limbic areas to thalamus in schizophrenia highlighted by whole-brain resting-state effective connectivity analysis.

BACKGROUND

Numerous neuroimaging studies have revealed that schizophrenia was characterized by wide-spread dysconnection among brain regions during rest measured by functional connectivity (FC). In contrast with FC, effective connectivity (EC) provides information about directionality of brain connections and is thus valuable in mechanistic investigation of schizophrenic brain. However, a systematic characterization of whole-brain resting-state EC (rsEC) and how it captures different information compared with resting-state FC (rsFC) in schizophrenia are still lacking.

AIMS: To systematically characterize the abnormalities of rsEC, compared with rsFC, in schizophrenia, and to test its discriminative power as a neuroimaging marker for schizophrenia diagnosis.

METHOD: Whole-brain rsEC and rsFC networks were constructed using resting-state fMRI data and compared between 103 patients with schizophrenia and 110 healthy participants. Pattern classifications between patients and controls based on whole-brain rsEC and rsFC were further performed using multivariate pattern analysis.

RESULTS

We identified 17 rsEC significantly disrupted (mostly decreased) in patients, among which all were associated with the thalamus and 15 were from limbic areas (including hippocampus, parahippocampus and cingulate cortex) to the thalamus. In contrast, abnormal rsFC were widely distributed in the whole brain. The classification accuracies for distinguishing patients and controls using whole-brain rsEC and rsFC patterns were 78.6% and 82.7%, respectively, and was further improved to 84.5% when combining rsEC and rsFC.

CONCLUSIONS

Schizophrenia is featured by disrupted 'limbic areas-to-thalamus' rsEC, in contrast with diffusively altered rsFC. Moreover, both rsEC and rsFC contain valuable and complementary information which may be used as diagnostic markers for schizophrenia.