Mismatch negativity predicts psychotic experiences induced by nmda receptor antagonist in healthy volunteers

Background: Previous studies indicate that mismatch negativity (MMN)—a preattentive auditory event-related potential (ERP)–depends on NMDA receptor (NMDAR) functioning. To explore if the strength of MMN generation reflects the functional condition of the NMDAR system in healthy volunteers, we analyzed correlations between MMN recorded before drug administration and subsequent responses to the NMDAR antagonist ketamine or the 5-HT2a agonist psilocybin. Methods: In two separate studies, MMN was recorded to both frequency and duration deviants prior to administration of ketamine or psilocybin. Behavioral and subjective effects of ketamine and psilocybin were assessed with the Brief Psychiatric Rating Scale and the OAV Scale—a rating scale developed to measure altered states of consciousness. Correlations between ERP amplitudes (MMN, N1, and P2) and drug-induced effects were calculated in each study group and compared between them. Results: Smaller MMN to both pitch and duration deviants was significantly correlated to stronger effects during ketamine, but not psilocybin administration. No significant correlations were observed for N1 and P2. Conclusions: Smaller MMN indicates a NMDAR system that is more vulnerable to disruption by the NMDAR antagonist ketamine. MMN generation appears to index the functional state of NMDAR-mediated neurotransmission even in subjects who do not demonstrate any psychopathology.