Contextualised Processing of Stimuli Modulates Auditory Mismatch Responses in the Rat.

Abstract

Mismatch negativity (MMN), an auditory prediction error signal, is an enhanced response to unexpected (deviant) stimuli compared to expected (standard) stimuli. There is strong interest in MMN due to reliable findings of reduced MMN in schizophrenia. To interpret reduced MMN in schizophrenia, an enhanced understanding of the factors that influence MMN amplitude could lead to a better understanding of neural mechanisms underpinning the reduction. While several laboratories have observed mismatch responses (MMRs) in rodents, this study assesses how MMR is altered in more complex auditory sequences in rats. Prediction-errors are elicited in relation to "predictive" internal models of regularities. These internal models are updated dynamically when a regularity changes, but human MMN exhibits order effects when two regularities alternate; while deviants in both regularities elicit MMN (ie, the model updates) there is a slower build-up in MMN amplitude over time in the second encountered regularity type. We investigate whether order effects occur in rat MMRs. MMRs were studied to rare ascending and descending frequency deviations in awake, freely moving Wistar rats using wireless telemetry in both separate sequences (one regularity at a time) and in alternating sequences where regularities changed back and forth. The rat MMR did not show order effects, however, substantial MMRs occurred in response to both ascending and descending deviants in the alternating context but to the ascending deviant only when the same regularities were presented separately. The longer-term sequence structure altered prediction-error signalling in rat auditory system revealing a long term context sensitivity in internal models.