Classical and controlled auditory mismatch responses to multiple physical deviances in anaesthetised and conscious mice

Abstract

Human mismatch negativity (MMN) is modelled in rodents and other non-human species to examine its underlying neurological mechanisms, primarily described in terms of deviance-detection and adaptation. Using the mouse model, we aim to elucidate subtle dependencies between the mismatch response (MMR) and different physical properties of sound. Epidural field potentials were recorded from urethane-anaesthetised and conscious mice during oddball and many-standards control paradigms; with stimuli varying in duration, frequency, intensity, and interstimulus interval. Resulting auditory evoked potentials, classical MMR (oddball − standard), and controlled MMR (oddball − control) waveforms were analysed. Stimulus duration correlated with stimulus-off response peak latency (p < 0.0001). Frequency (p < 0.0001), intensity (p < 0.0001), and inter-stimulus interval (p < 0.0001) correlated with stimulus-on N 1 and P 1 (conscious only) peak amplitudes. These relationships were instrumental in shaping classical MMR morphology in both anaesthetised and conscious animals, suggesting these waveforms reflect modification of normal auditory processing by different physical properties of stimuli. Controlled MMR waveforms appeared to exhibit habituation to auditory stimulation over time, which was equally observed in response to oddball and standard stimuli. These observations are inconsistent with the mechanisms thought to underlie human MMN, which currently do not address differences due to specific physical features of auditory deviance. Thus, no evidence was found to objectively support the deviance-detection or adaptation hypotheses of MMN in relation to anaesthetised or conscious mice.Mismatch negativity (MMN) is widely believed to reflect pre-attentive sensory-2 memory. It is observed in response to an oddball paradigm, in which many identical 3 standard stimuli are infrequently replaced with deviant oddball stimuli. This study 4 concerns the auditory modality, as does the majority of literature on MMN. Odd-5 ball stimuli may deviate from the standard in any discriminable feature of sound 6 (Pakarinen et al., 2007). The auditory-evoked potential (AEP) from the standard is 7 conventionally subtracted from that of the oddball, generating a difference wave-8 form that constitutes the MMN. This may be referred to as the classical approach. 9 Interestingly, MMN is observed from patients in anaesthetised and comatose states 10 (Fischer et al., 1999(Fischer et al., , 2000Kane et al., 1996), suggesting that the mechanisms re-11 sponsible for its generation are not reliant on consciousness. The prevailing theory 12 is that a mismatch between novel auditory input and a memory-representation, or 13 predictive model, of recently experienced auditory inputs, triggers updating of this 14 model, thereby subconsciously capturing the attention. This manifests in scalp-15 recorded EEG as a MMN component (Winkler et al., 1996). This interpretation has 16 remained largely unchanged since its rationale was first proposed (Näätänen et al., 17...

More evidence for a long-latency mismatch response in urethane-anaesthetised mice

“…Early differences in many-standards control waveforms occurring before 100 ms may be related to differences in stimulus frequency, given the opposing polarities exhibited by ascending and descending frequency changes. Influences of different physical properties of stimuli on AEP and mismatch response waveforms measured from anaesthetised and conscious mice have been quite clearly demonstrated (O'Reilly and Conway, 2019). In contrast, mismatch responses from the oddball paradigm initially display opposite polarity trajectories, presumably due to their opposing frequency deviances, before becoming more coherent and displaying similar waveform morphologies, which may be attributed to their oddball context.…”

Roving oddball paradigm elicits sensory gating, frequency sensitivity, and long-latency response in common marmosets

“…This pattern does not coincide with the marmoset audiogram ( Osmanski and Wang, 2011 ), which exhibits lower hearing thresholds for tone frequencies towards the higher end of those used in this experiment (≈7 kHz). This may refute the suggestion that spectral hearing sensitivity is responsible for overall auditory response amplitudes ( O’Reilly and Conway, 2021 ), or alternatively, perhaps the recording electrode was located nearby a low-frequency representation of the marmoset auditory cortex (see Fig. S2 from Komatsu et al 2015 ), which is known to consist of multiple tonotopic subdivisions ( Tani et al, 2018 ).…”

“…3 b). Interpretation of deviant response enlargement can be debated, with some perhaps arguing that it represents a prediction error signal ( An et al, 2021 ), others that it reflects absence of stimulus-specific adaptation ( May and Tiitinen, 2010 ), and yet others that it reflects a combination of physical sensitivities and general adaptation of the auditory system ( O’Reilly and Conway, 2021 , O’Reilly and O’Reilly, 2021 ). The Dev/S1 minus S2 difference waveform ( Fig.…”

“…For example, it is generally accepted that differential adaptation can explain some of the difference between standard and deviant ERPs. Moreover, modulation of intrinsic, obligatory components of the auditory response caused by physical properties of stimuli can also explain some of these MMN-like waveforms ( O’Reilly, 2021 , O’Reilly and Conway, 2021 ). With that said, the generative mechanisms of MMN and MMN-like responses are worthy of further examination.…”