Theta-phase gamma-amplitude coupling as a neurophysiological marker in neuroleptic-naïve schizophrenia

Theta-phase gamma-amplitude coupling (TGC) was used as an evidence-based tool to reflect the dysfunctional cortico-thalamic interaction in patients with schizophrenia. The aim of the present study was to evaluate the diagnostic utility of TGC. The subjects included 90 patients with schizophrenia and 90 healthy controls. We compared the TGC results between the groups using an analysis of covariance (ANCOVA) to adjust for age and sex and receiver operator characteristic (ROC) curve analyses to examine the discrimination ability of delta to gamma frequency bands and TGC. Patients with schizophrenia showed a significant increase in the resting-state TGC at all 19 electrodes. The analysis of the ROC curves for each frequency band exhibited relatively low classification accuracies for the delta, theta, slow alpha, fast alpha, and beta power. The TGC generated the most accurate results among the electroencephalography (EEG) measures, with an overall classification accuracy of 92.5%. The resting-state TGC value was increased in patients with schizophrenia compared to that in healthy controls and had a higher discriminating ability than the other parameters. These findings may be related to the compensatory hyper-arousal patterns of the dysfunctional default-mode network (DMN) in schizophrenia. Therefore, resting-state TGC is a promising neurophysiological marker of schizophrenia.