Mismatch Negativity and Theta Oscillations Evoked by Auditory Deviance in Early Schizophrenia

Biol Psychiatry Cogn Neurosci Neuroimaging. 2023 Dec;8(12):1186-1196. doi: 10.1016/j.bpsc.2023.03.004. Epub 2023 Mar 15.

Abstract

Background: Amplitude reduction of mismatch negativity (MMN), an event-related potential component indexing NMDA receptor-dependent auditory echoic memory and predictive coding, is widely replicated in schizophrenia. Time-frequency analyses of single-trial electroencephalography epochs suggest that theta oscillation abnormalities underlie MMN deficits in schizophrenia. However, this has received less attention in early schizophrenia (ESZ).

Methods: Patients with ESZ (n = 89), within 5 years of illness onset, and healthy control subjects (n = 105) completed an electroencephalography MMN paradigm (duration-deviant, pitch-deviant, duration + pitch double-deviant). Repeated measures analyses of variance assessed group differences in MMN, theta intertrial phase coherence (ITC), and theta total power from frontocentral electrodes, after normal age adjustment. Group differences were retested after covarying MMN and theta measures.

Results: Relative to healthy control subjects, patients with ESZ showed auditory deviance deficits. Patients with ESZ had MMN deficits for duration-deviants (p = .041), pitch-deviants (ps = .007), and double-deviants (ps < .047). Patients with ESZ had reduced theta ITC for standards (ps < .040) and duration-deviants (ps < .030). Furthermore, patients with ESZ had reduced theta power across deviants at central electrodes (p = .013). MMN group deficits were not fully accounted for by theta ITC and power, and neither were theta ITC group deficits fully accounted for by MMN. Group differences in theta total power were no longer significant after covarying for MMN.

Conclusions: Patients with ESZ showed reduced MMN and theta total power for all deviant types. Theta ITC showed a relatively specific reduction for duration-deviants. Although MMN and theta ITC were correlated in ESZ, covarying for one did not fully account for deficits in the other, raising the possibility of their sensitivity to dissociable pathophysiological processes.

Keywords: Auditory mismatch negativity; Early schizophrenia; Event-related potential; Theta band oscillatory measures; Time-frequency analysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Electroencephalography
  • Evoked Potentials
  • Evoked Potentials, Auditory / physiology
  • Humans
  • Schizophrenia*