Discriminative analysis of non-linear brain connectivity in schizophrenia: an fMRI Study

Background: Dysfunctional integration of distributed brain networks is believed to be the cause of schizophrenia, and resting-state functional connectivity analyses of schizophrenia have attracted considerable attention in recent years. Unfortunately, existing functional connectivity analyses of schizophrenia have been mostly limited to linear associations. Objective: The objective of the present study is to evaluate the discriminative power of non-linear functional connectivity and identify its changes in schizophrenia. Method: A novel measure utilizing the extended maximal information coefficient was introduced to construct non-linear functional connectivity. In conjunction with multivariate pattern analysis, the new functional connectivity successfully discriminated schizophrenic patients from healthy controls with relative higher accuracy rate than the linear measure. Result: We found that the strength of the identified non-linear functional connections involved in the classification increased in patients with schizophrenia, which was opposed to its linear counterpart. Further functional network analysis revealed that the changes of the non-linear and linear connectivity have similar but not completely the same spatial distribution in human brain. Conclusion: The classification results suggest that the non-linear functional connectivity provided useful discriminative power in diagnosis of schizophrenia, and the inverse but similar spatial distributed changes between the non-linear and linear measure may indicate the underlying compensatory mechanism and the complex neuronal synchronization underlying the symptom of schizophrenia.