Mismatch negativity (MMN) and its neuromagnetic analog (MMNm) are event-related brain responses elicited by changes in a sequence of auditory events and indexes of early cognitive processing. It consistently detects neural pre-attentive information processing deficits in schizophrenia. So far, MMN can be assessed with different methods (electroencephalography, EEG; magnetoencephalography, MEG) and different paradigms using the “traditional” oddball (20% rare deviants) or the so-called “optimum” (50% rare deviants varying in one of five parameters each) designs but the latter has not been applied to schizophrenia as yet.

Both designs were compared in 12 patients with schizophrenia and 12 healthy controls using MEG and EEG. Automated, observer-independent data analysis rendered the procedures suitable for clinical applications.

The optimum design was fastest to detect MMN changes. MEG had the best signal-to-noise ratio. In addition MMN was mostly reduced in schizophrenia if measured with MEG in the optimum paradigm.

Optimized MMN paradigms - especially MMNm - improve sensitivity and speed for the detection of schizophrenia endophenotypes. Dysfunctions in this disorder may lie primary in the fast and automatic encoding of stimulus features in the auditory cortex. Of note, these MMN optimum measures may not reflect one unitary mechanism that is equally affected in schizophrenia.