40-Hz Auditory Steady-State Responses Characterize Circuit Dysfunctions and Predict Clinical Outcomes in Clinical High-Risk for Psychosis Participants: A Magnetoencephalography Study

Background: This study aimed to examine whether 40-Hz auditory steady-state responses (ASSRs) are impaired in participants at clinical high-risk for psychosis (CHR-P) and predict clinical outcomes. Methods: Magnetoencephalography data were collected during a 40-Hz ASSR paradigm for a group of 116 CHR-P participants, 33 patients with first-episode psychosis (15 antipsychotic-naive), a psychosis risk–negative group (n = 38), and 49 healthy control subjects. Analysis of group differences of 40-Hz intertrial phase coherence and 40-Hz amplitude focused on right Heschl’s gyrus, superior temporal gyrus, hippocampus, and thalamus after establishing significant activations during 40-Hz ASSR stimulation. Linear regression and linear discriminant analyses were used to predict clinical outcomes in CHR-P participants, including transition to psychosis and persistence of attenuated psychotic symptoms (APSs). Results: CHR-P participants and patients with first-episode psychosis were impaired in 40-Hz amplitude in the right thalamus and hippocampus. In addition, patients with first-episode psychosis were impaired in 40-Hz amplitude in the right Heschl’s gyrus, and CHR-P participants in 40-Hz intertrial phase coherence in the right Heschl’s gyrus. The 40-Hz ASSR deficits were pronounced in CHR-P participants who later transitioned to psychosis (n = 13) or showed persistent APSs (n = 34). Importantly, both APS persistence and transition to psychosis were predicted by 40-Hz ASSR impairments, with ASSR activity in the right hippocampus, superior temporal gyrus, and middle temporal gyrus correctly classifying 69.2% individuals with nonpersistent APSs and 73.5% individuals with persistent APSs (area under the curve = 0.842), and right thalamus 40-Hz activity correctly classifying 76.9% transitioned and 53.6% nontransitioned CHR-P participants (area under the curve = 0.695). Conclusions: Our data indicate that deficits in gamma-band entrainment in the primary auditory cortex and subcortical areas constitute a potential biomarker for predicting clinical outcomes in CHR-P participants.