Theta Oscillations Assessed From a Passive Auditory Oddball Paradigm in Individuals at Clinical High-Risk for Psychosis and Healthy Control Individuals: Associations with Clinical Outcomes and Mismatch Negativity.

Background: Reduced mismatch negativity (MMN) is a widely replicated schizophrenia biomarker. Time-frequency analyses suggest that deficient phase synchrony and/or power of electroencephalography (EEG) event-related oscillations, especially theta, contribute to MMN deficits in schizophrenia. Whether theta oscillations assessed from a passive auditory oddball paradigm are abnormal in clinical high-risk for psychosis (CHR-P) individuals and whether these oscillations predict CHR-P clinical outcomes remain unclear. These questions were addressed using data from NAPLS2 (North American Prodrome Longitudinal Study 2). Methods: EEG was recorded from 77 CHR-P individuals who converted to psychosis (CHR-Cs), 238 CHR-P nonconverters (CHR-NCs) who completed a 24-month follow-up, and 241 healthy control (HC) individuals. Theta oscillations elicited by standard and deviant tones were calculated. Theta (4-6 Hz) intertrial phase coherence (ITC) and total power were compared between groups and evaluated as predictors of time to psychosis conversion in the full CHR-P sample. Furthermore, analyses of covariance were used to assess whether theta deficits persisted while covarying for MMN. Results: The CHR-C group, relative to the HC and CHR-NC groups, had reduced theta ITC for standards and deviants ( Conclusions: These results implicate abnormalities in microcircuit generators of theta oscillations in CHR-P individuals at highest risk.