Double-epoch subtraction reveals long-latency mismatch response in urethane-anaesthetized mice

Jamie A. O'Reilly

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Background: Anaesthetized rodents are examined for their capacity to model human mismatch negativity (MMN). In the present study, oddball and deviant-alone control paradigms, with stimuli varying in frequency (ascending and descending) and intensity (louder and quieter), were presented to anaesthetized mice to determine whether they elicit a translational mismatch response (MMR). New method: Resulting waveforms displayed long-latency (>200 ms post-stimulus) components, only made fully visible from oddball paradigm data by applying a double-epoch subtraction. In this approach, an extended epoch containing two consecutive standard evoked responses was subtracted from the response to an oddball followed by a standard (i.e. oddball:standard – standard:standard). Results: The trailing standard responses effectively cancelled each other out, revealing biphasic long-latency components. These MMR waveforms correlated strongly with deviant-alone paradigm evoked potentials >200 ms post-stimulus, potentially indicative of shared underlying mechanisms. Interestingly, these components were absent from the quieter oddball MMR. Comparison with existing method(s): Classical mismatch negativity computation is incapable of fully characterizing the long-latency biphasic response observed from this study, due to the inbuilt constraint of a single stimulus epoch. These results also suggest that the deviant-alone paradigm may be considered akin to a positive control for sensory-memory disruption, widely thought to be at the root of MMN generation in humans. Conclusions: Long-latency auditory evoked potential components are observed from anaesthetized mice in response to frequency and increasing intensity oddball stimuli. These display some congruencies with human MMN.
Original languageEnglish
Article number108375
Number of pages10
JournalJournal of Neuroscience Methods
Early online date25 Jul 2019
Publication statusPublished - 1 Oct 2019


  • mismatch response
  • mismatch negativity
  • long-latency potential
  • oddball paradigm
  • deviant-alone control

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