Integrated mismatch negativity (MMN i ): a noise-free representation of evoked responses allowing single-point distribution-free statistical tests Curtis W. Ponton a, *, Manuel Don a , Jos J. Eggermont b , Betty Kwong a a Department of Electrophysiology, House Ear Institute, 2100 West 3rd Street, 5th Floor, Los Angeles, CA 90057, USA b Behavioral Neuroscience Group, Department of Psychology, University of Calgary, Calgary, Canada Accepted for publication: 6 December 1996 Abstract If the repeated presentation of a single (standard) auditory stimulus is randomly interspersed with a second acoustically different (deviant) stimulus, the cortical activity evoked by the deviant stimulus can contain a negative component known as the mismatch negativity (MMN). The MMN is derived by subtracting the averaged response evoked by the standard stimulus from that evoked by the deviant stimulus. When the magnitude of the response is small or the signal-to-noise ratio is poor, it is difficult to judge the presence or absence of the MMN simply by visual inspection, and statistical detection techniques become necessary. A method of analysis is proposed to quantify the magnitude and statistically evaluate the presence of the MMN based on time-integrated evoked responses. This paper demonstrates the use of this integrated mismatch negativity (MMN i ) analysis to detect the MMN evoked by stimulus contrasts near the perceptual threshold of two subjects. The MMN i , by virtue of being equivalent to a low-pass filtered response, presents an almost noise-free estimate of MMN magnitude. A single measure of the integrated evoked response at a fixed time point is used in a distribution-free statistic that compares the magnitude of the averaged response evoked by the deviant stimulus with a magnitude distribution derived from 200 subaveraged responses to the standard stimulus (with the number of sweeps per average equal to that of the deviant stimulus). This allows a calculation of the exact probability for the null hypothesis that the negative magnitude of the response evoked by the deviant stimulus is drawn from the magnitude distribution of responses evoked by the standard stimulus. Rejection of this hypothesis provides objective evidence of the presence of the MMN.  1997 Elsevier Science Ireland Ltd. Keywords: Single (standard) auditory stimulus; Acoustically different (deviant) stimulus; Negative component; Mismatch negativity (MMN); Statistical evaluation 1. Introduction The mismatch negativity (MMN), originally described by Na ¨a ¨ta ¨nen et al. (1978), can be generated by presenting a series of identical (standard) auditory stimuli interspersed occasionally with a randomly placed, low probability, acoustically different (deviant) stimulus. The MMN is derived by subtracting the averaged response evoked by the standard stimulus from that evoked by the deviant stimulus. According to Na ¨a ¨ta ¨nen (1995), the mismatch negativity (MMN) indicates discrimination of change in the acoustic features of a stimulus. Changes in MMN amplitude and latency correlate well with the magnitude of the perceptual difference between the standard and the deviant stimulus. As the perceptual difference decreases, MMN amplitude decreases and peak latency increases (Sams et al., 1985; Na ¨a ¨ta ¨nen et al., 1989; Na ¨a ¨ta ¨nen, 1990; Kraus et al., 1995). For small perceptual differences between the standard and deviant stimulus, as may occur between two speech tokens in a consonant-vowel continuum (Kraus et al., 1995), it becomes increasingly difficult to judge the pre- sence or absence of the MMN simply by visual inspection of the evoked response waveform. In such cases, statistical detection techniques become necessary. Most of the tech- niques used thus far convert the grand average standard and deviant responses into subaverages. Point-by-point pair-wise comparisons are then performed between these two groups of subaverages using t tests. Adjustments for multiple t tests and for correlations between adjacent data Electroencephalography and clinical Neurophysiology 104 (1997) 143–150 0168-5597/97/$17.00  1997 Elsevier Science Ireland Ltd. All rights reserved PII S0921-884X(97)96104-X EEP 96104 * Corresponding author. Tel.: +1 213 483 4431; fax: +1 213 413 6739; e-mail: ponton@hei.org.