No Evidence of Phase-Amplitude Coupling in Auditory Steady-State Responses

Phase-amplitude coupling (PAC), reflecting the modulation of high-frequency amplitude by the phase of lower-frequency oscillations, is increasingly recognized as a key mechanism underlying neural information processing. While PAC is typically associated with higher-order perceptual and cognitive processes, some studies explored PAC in relation to auditory steady-state responses (ASSR), a paradigm commonly used to assess gamma-band synchronization. However, findings from these studies remain inconclusive due to methodological variability and challenges in PAC analysis. In this study, we systematically investigated PAC in the EEG signal recorded during 40 Hz auditory steady-state stimulation using a rigorous analysis pipeline with three established PAC estimation methods: Mean Vector Length, Kullback-Leibler Modulation Index, and Phase-Locking Value. Our approach was validated on simulated EEG-like signals and applied to scalp EEG data from 12 participants (26.7±3.6 years, 5 females) in 40 Hz ASSR and resting-state (rsEEG) conditions. We found no significant differences in PAC between ASSR and rsEEG conditions in the ASSR-associated frontocentral region, regardless of PAC estimation methods. Furthermore, individual-specific peak PAC values and their associated frequencies showed no consistent patterns across conditions. These results suggest that PAC is not reliably elicited by auditory steady-state stimulation in EEG, challenging the utility of the ASSR paradigm for assessing PAC.