Mismatch Negativity: Translating the Potential

The mismatch negativity (MMN) component of the auditory event-related potential has become a valuable tool in cognitive neuroscience. Its reduced size in persons with schizophrenia is of unknown origin but theories proposed include links to problems in experience-dependent plasticity reliant on N-methyl-d-aspartate glutamate receptors. In this review we address the utility of this tool in revealing the nature and time course of problems in perceptual inference in this illness together with its potential for use in translational research testing animal models of schizophrenia-related phenotypes. Specifically, we review the reasons for interest in MMN in schizophrenia, issues pertaining to the measurement of MMN, its use as a vulnerability index for the development of schizophrenia, the pharmacological sensitivity of MMN and the progress in developing animal models of MMN. Within this process we highlight the challenges posed by knowledge gaps pertaining to the tool and the pharmacology of the underlying system

Surprising sequential effects on MMN

The mismatch negativity (MMN) is conceptualised as a confidence-weighted error signal elicited when a deviation violates the predicted next-state based on regularity. The mechanisms underpinning its generation remain contentious. Smaller MMN response is a robust finding in schizophrenia and reduced amplitude may implicate impairment in prediction-error signalling. An enriched understanding of factors that influence MMN size in healthy people is a prerequisite for translating the relevance of reduced MMN in schizophrenia. This paper features two studies designed to explore factors that impact MMN in healthy individuals. Study 1 confirms that MMN amplitude does not faithfully reflect transition statistics and is susceptible to order-driven bias. In Study 2, we demonstrate that an order-driven bias remains despite repeated encounters with sound sequences. These data demonstrate that factors that impact on MMN size in non-clinical groups are not fully understood and that some mechanisms driving relevance filtering are likely influenced by ‘top-down’ expectations

Altering the primacy bias – How does a prior task affect mismatch negativity (MMN)?

The role in which two tones are first encountered in an unattended oddball sequence affects how deviance detection, reflected by mismatch negativity (MMN), treats them later when the roles reverse: a “primacy bias”. We tested whether this effect is modulated by previous behavioural relevance assigned to the two tones. To this end, sequences in which the roles of the two tones alternated were preceded by a go-nogo task in which tones were presented with equal probability. Half of the participants were asked to respond to the short sounds, the other half to long sounds. Primacy bias was initially abolished but returned dependent upon the gostimulus the participant was assigned. Results demonstrate a long-term impact of prior learning on deviance detection; and that even when prior importance/equivalence is learned, the bias ultimately returns. Results are discussed in terms of persistent go-stimulus-specific changes in responsiveness to sound

The cognitive resource and foreknowledge dependence of auditory perceptual inference

Auditory perceptual inference engages learning of complex statistical information about the environment. Inferences assist us to simplify perception highlighting what can be predicted on the basis of prior learning (through the formation of internal “prediction” models) and what might be new, potentially necessitating an investment of resources to remodel predictions. In the present study, we tested the hypothesis that sound sequences with multiple levels of predictability may rely on cognitive resources and be cognitively penetrable to a greater extent than was previously shown by studies presenting simpler sound sequences. Auditory-evoked potentials (AEPs) were recorded from 117 participants. All participants heard the exact same sound sequence but under different conditions: 51 while watching a DVD movie and 66 while performing a cognitively demanding task. Participants were asked to ignore the sounds and focus their attention on the movie/task. However, prior to commencing the experiment we manipulated what participants knew about the sound sequence by providing explicit sequence information to 15 and 34 of the participants in the DVD and cognitive-task conditions, respectively, and no information to the others. The results demonstrated that although local pattern violations elicited distinctive AEP responses (namely, mismatch negativity), the way the amplitude of this response was modulated by sequence learning over time was dependent upon both task and explicit sequence knowledge. The implications are discussed with reference to how the division of available attention resources between the primary task and concurrent sound impacts what is learned

Epidural Auditory Event-Related Potentials in the Rat to Frequency and duration Deviants: Evidence of Mismatch Negativity?

The capacity of the human brain to detect deviance in the acoustic environment pre-attentively is reflected in a brain event-related potential (ERP), mismatch negativity (MMN). MMN is observed in response to the presentation of rare oddball sounds that deviate from an otherwise regular pattern of frequent background standard sounds. While the primate and cat auditory cortex (AC) exhibit MMN-like activity, it is unclear whether the rodent AC produces a deviant response that reflects deviance detection in a background of regularities evident in recent auditory stimulus history or differential adaptation of neuronal responses due to rarity of the deviant sound. We examined whether MMN-like activity occurs in epidural AC potentials in awake and anesthetized rats to high and low frequency and long and short duration deviant sounds. ERPs to deviants were compared with ERPs to common standards and also with ERPs to deviants when interspersed with many different standards to control for background regularity effects. High frequency (HF) and long duration deviant ERPs in the awake rat showed evidence of deviance detection, consisting of negative displacements of the deviant ERP relative to ERPs to both common standards and deviants with many standards. The HF deviant MMN-like response was also sensitive to the extent of regularity in recent acoustic stimulation. Anesthesia in contrast resulted in positive displacements of deviant ERPs. Our results suggest that epidural MMN-like potentials to HF sounds in awake rats encode deviance in an analogous manner to the human MMN, laying the foundation for animal models of disorders characterized by disrupted MMN generation, such as schizophrenia

The specificity of pathogenic oxidative stress in schizophrenia

Abstract not available

Familial analysis of MMN in cannabis users: A case study

Abstract presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australi

An investigation of mismatch negativity in current and ex-cannabis users using a feature controlled method

Abstract presented at the 23rd Australasian Society for Psychophysiology Conference, 20-22 Nov 2013, Wollongong, Australi

What controls gain in gain control? Mismatch negativity (MMN), priors and system biases

Repetitious patterns enable the auditory system to form prediction models specifying the most likely characteristics of subsequent sounds. Pattern deviations elicit mismatch negativity (MMN), the amplitude of which is modulated by the size of the deviation and confidence in the model. Todd et al. (2001; 2013) demonstrated that a multi-timescale sequence reveals a bias that profoundly distorts the impact of local sound statistics on the MMN amplitude. Two sounds alternate roles as repetitious “standard” and rare “deviant” rapidly (every 0.8 minutes) or slowly (every 2.4 minutes). The bias manifests as larger MMN to the sound first encountered as deviant in slow compared to fast changing sequences, but no difference for the sound first encountered as a standard. We propose that the bias is due to how Bayesian priors shape filters of sound relevance. By examining the time-course of change in MMN amplitude we show that the bias manifests immediately after roles change but rapidly disappears thereafter. The bias was reflected in the response to deviant sounds only (not in response to standards), consistent with precision estimates extracted from second order patterns modulating gain differentially for the two sounds.. Evoked responses to deviants suggest that pattern extraction and reactivation of priors can operate over tens of minutes or longer. Both MMN and deviant responses establish that: (1) priors are defined by the most proximally encountered probability distribution when one exists but; (2) when no prior exists, one is instantiated by sequence onset characteristics; and (3) priors require context interruption to be updated