Optimized mismatch negativity paradigm reflects deficits in schizophrenia patients. A combined EEG and MEG study.

Mismatch negativity (MMN) and its neuromagnetic analog (MMNm) are event-related brain responses elicited by changes in a sequence of auditory events and indexes early cognitive processing. It consistently detects neural processing deficits in schizophrenia. So far MMN is assessed with different methods (electroencephalography, EEG; magnetoencephalography, MEG) and with different paradigms: the "traditional" oddball design with rare deviants (20%) or the "optimum" design with 50% deviants varying in one of five parameters each. These MMN measures may not reflect one unitary mechanism which is equally affected in schizophrenia. We compared both designs in 12 patients with schizophrenia and 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 and 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 paradigms improve sensitivity and speed for the detection of schizophrenia endophenotypes. Dysfunctions in this disorder may lie primarily in the fast and automatic encoding of stimulus features at the auditory cortex.