Abstract
BACKGROUND: Phase-amplitude coupling (PAC) measures the interaction between neural oscillations in different frequency bands and reflects brain functional network coordination in psychiatric patients. The event-related dynamic changes in PAC characteristics and their association with the neural physiological mechanisms under emotional stimulation in major depressive disorder (MDD) remain poorly understood. METHODS: We proposed a cross-sectional study that investigated three PAC methods using simulated data and selected the Gaussian-Copula Event-Related PAC (GC-ERPAC) method for dynamic analysis of 128-channel electroencephalogram data from 53 participants, including 24 patients with MDD and 29 healthy controls (HCs). Participants were exposed to three emotional stimuli (fearful, happy, and sad). The correlation between PAC strengths and clinical scales was then analyzed in each condition. RESULTS: The MDD group exhibited abnormal PAC patterns. With happy stimuli, the strengths of delta-gamma coupling (DGC), theta-gamma coupling (TGC), and alpha-gamma coupling (AGC) in the frontal-parietal regions of the MDD group were lower compared to HCs. With fearful stimuli, the strength of AGC in the occipital region was higher in the MDD group. The correlation between TGC and AGC was weaker for couplings among different frequencies in the MDD group. Additionally, AGC was negatively correlated with the clinical scale in MDD but positively correlated with HCs. CLINICAL TRIAL NUMBER: Not applicable. CONCLUSIONS: This study confirmed that GC-ERPAC was an effective method for revealing emotion recognition features in MDD. We provided novel evidence of abnormal spatiotemporal PAC patterns linked to emotional processing deficits. Reduced DGC and TGC, along with increased AGC, suggest potential biomarkers in MDD.