No abstract

Abbreviations: AEP, auditory evoked potential; DEV CTR , deviant stimulus in the many-standards control paradigm; DEV OD , deviant stimulus in the oddball paradigm; ISI, inter-stimulus interval; MMN, mismatch negativity; MMR, mismatch response; MMR classic , conventional MMR, calculated by DEV OD-STD OD ; MMR control , controlled MMR, calculated by DEV OD-DEV CTR ; N1, first large negative amplitude peak observed in the AEP; P1, first large positive amplitude peak observed in the AEP of conscious mice; P off , positive amplitude peak following stimulus termination; SPL, sound pressure level; SSA, stimulus-specific adaptation; STD control , comparison of STD OD-STD CTR ; STD CTR , standard stimulus in the many-standards control paradigm; STD OD , standard stimulus in the oddball paradigm.

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:standardstandard:standard). Results The trailing standard responses effectively cancelled each other out, revealing biphasic longlatency 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.

The ability to respond appropriately to sensory information received from the external environment is among the most fundamental capabilities of central nervous systems. In the auditory domain, processes underlying this behaviour are studied by measuring auditory‐evoked electrophysiology during sequences of sounds with predetermined regularities. Identifying neural correlates of ensuing auditory novelty responses is supported by research in experimental animals. In the present study, we reanalysed epidural field potential recordings from the auditory cortex of anaesthetised mice during frequency and intensity oddball stimulation. Multivariate pattern analysis (MVPA) and hierarchical recurrent neural network (RNN) modelling were adopted to explore these data with greater resolution than previously considered using conventional methods. Time‐wise and generalised temporal decoding MVPA approaches revealed previously underestimated asymmetry between responses to sound‐level transitions in the intensity oddball paradigm, in contrast with tone frequency changes. After training, the cross‐validated RNN model architecture with four hidden layers produced output waveforms in response to simulated auditory inputs that were strongly correlated with grand‐average auditory‐evoked potential waveforms (r2 > .9). Units in hidden layers were classified based on their temporal response properties and characterised using principal component analysis and sample entropy. These demonstrated spontaneous alpha rhythms, sound onset and offset responses and putative ‘safety’ and ‘danger’ units activated by relatively inconspicuous and salient changes in auditory inputs, respectively. The hypothesised existence of corresponding biological neural sources is naturally derived from this model. If proven, this could have significant implications for prevailing theories of auditory processing.