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The mismatch response (MMR) is thought to be a neurophysiological measure of novel auditory detection that could serve as a translational biomarker of various neurological diseases. When recorded with electroencephalography (EEG) or magnetoencephalography (MEG), the MMR is traditionally extracted by subtracting the event-related potential/field (ERP/ERF) elicited in response to "deviant" sounds that occur randomly within a train of repetitive "standard" sounds. To overcome the limitations of this subtraction procedure, we propose a novel method which we call weighted-BSS<inf>T/k</inf>, which uses only the deviant response to derive the MMR. We hypothesized that this novel weighted-BSS<inf>T/k</inf> method highlights responses related to the detection of the deviant stimulus and is more sensitive than independent component analysis (ICA). To test this hypothesis and the validity and efficacy of the weighted-BSS<inf>T/k</inf> in comparison with ICA (infomax), we evaluated the methods in 12 healthy adults. Auditory stimuli were presented at a constant rate of 2 Hz. Frequency MMRs at a sensor level were obtained from the bilateral temporal lobes with the subtraction approach at 96&#x2013;276 ms (the MMR time range), defined on the basis of spatio-temporal cluster permutation analysis. In the application of the weighted-BSS<inf>T/k</inf>, the deviant responses were given a constant weight on the MMR time range. The ERF elicited by the weighted deviant responses demonstrated one or a few dominant components representing the MMR with a high signal-to-noise ratio and similar topography to that of the sensor space analysis using the subtraction approach. In contrast, infomax or weighted-infomax revealed many minor or pseudo components as constituents of the MMR. Our new approach may assist in using the MMR in basic and clinical research.Clinical Relevance&#x2014;Our proposed method opens a new and potentially useful way to analyze event-related MEG/EEG data.

A novel time-delayed correlation method decomposes mismatch response without using subtraction