Abnormal phase-amplitude coupling in patients with first-episode schizophrenia during the auditory steady-state response and resting states.

The auditory steady-state response (ASSR) is a robust index for schizophrenia. Abnormal phase-amplitude coupling (PAC) in schizophrenia might be influenced by the confounding factors of illness stages and antipsychotic treatments. To exclude the effects of confounding factors, we examined abnormal PAC in antipsychotic-naïve patients with first-episode schizophrenia (FES) during the ASSR. 67 FES and 84 healthy controls (CON) were recruited and their EEG data were collected during the 20 Hz ASSR, 30 Hz ASSR, 40 Hz ASSR, and resting states. All the possible PAC patterns at Fz were compared between FES and CON, and the electrodes of abnormal PACs were explored. Results showed that FES had significantly higher beta-high gamma PAC at the prefrontal cortex and lower theta-low gamma PAC at the fronto-central cortex than CON during all the three ASSR blocks but not in the Resting block. FES showed lower correlations of PAC values between any two of the ASSR blocks than CON. Beta-high gamma PAC was negatively correlated with the cognitive scores of visual learning and attention, while theta-low gamma PAC was positively correlated with the score of symbol coding. Abnormal PAC of FES in specific brain regions may provide electrophysiological biomarkers for abnormal circuits.