Neuronal imbalance of excitation and inhibition in schizophrenia: a scoping review of gamma-band ASSR findings

Recent empirical findings suggest that altered neural synchronization, which is hypothesized to be associated with an imbalance of excitatory (E) and inhibitory (I) neuronal activities, may underlie a core pathophysiological mechanism in patients with schizophrenia. The auditory steady-state response (ASSR) examined by electroencephalography (EEG) and magnetoencephalography (MEG) has been proposed as a potential biomarker for evaluating altered neural synchronization in schizophrenia. For this review, we performed a comprehensive literature search for papers published between 1999 and 2021 examining ASSRs in patients with schizophrenia. Almost all EEG-ASSR studies reported gamma-band ASSR reductions, especially to 40-Hz stimuli both in power and/or phase synchronization in chronic and first-episode schizophrenia. In addition, similar to EEG-ASSR findings, MEG-ASSR deficits to 80-Hz stimuli (high gamma) have been reported in patients with schizophrenia. Moreover, the 40-Hz ASSR is likely to be a predictor of the onset of schizophrenia. Notably, increased spontaneous (or ongoing) broadband (30–100 Hz) gamma power has been reported during ASSR tasks, which resembles the increased spontaneous gamma activity reported in animal models of E/I imbalance. Further research on ASSRs and evoked and spontaneous gamma oscillations is expected to elucidate the pathophysiology of schizophrenia with translational implications.