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.