Neurophysiological Signatures of Major Depressive Disorder and Frontocentral Gamma Auditory Response Deficits

Background: Aberrant gamma oscillations in major depressive disorder (MDD) have attracted extensive attention, but evidence delineating such neural signatures is lacking. The auditory steady‐state response (ASSR) elicited by periodic auditory stimuli is a robust probe of gamma oscillations. Here, we sought to characterize early transient auditory evoked responses (AEPs) and sustained gamma ASSRs in MDD, thereby identifying reliable neurophysiological signatures and providing preliminary interpretations of gamma auditory response deficits in MDD. Methods: Electroencephalographic data were obtained from 40 first‐episode drug‐naïve patients with MDD and 41 demographically matched healthy controls (HCs) during a 40‐Hz ASSR paradigm, encompassing two periodic stimuli—chirp and click stimuli. Source analysis of transient AEPs was performed to identify generators involved in early information processing dysfunction. In addition, spectrotemporal and spatial characteristics of 40‐Hz ASSRs were analyzed using event‐related spectral perturbation, inter‐trial phase coherence, and functional connectivity index. Results: Compared to HCs, patients showed a reduced P200 amplitude that was source‐localized to the middle temporal gyrus, possibly reflecting an underlying impairment in the processes of early allocation or auditory information perception within the auditory pathways. Meanwhile, attenuated 40‐Hz power and phase coherence, in conjunction with suppressed right frontotemporal and frontocentral connectivity, were observed in MDD, highlighting the multidimensional entrained gamma inhibition. Correlation analyses revealed that the decreased right frontocentral connectivity was strongly related to increased anxiety severity. Importantly, these abnormalities correlated with the patient’s symptoms were only found with the chirp stimulus, suggesting that the chirp stimulus has tremendous potential to reveal specific neurophysiological signatures of MDD. Conclusions: Our data reveal impaired gamma auditory responses in first‐episode drug‐naïve patients with MDD and suggest that right frontocentral connectivity elicited by the chirp stimulus may represent a promising signature for predicting clinical symptoms.