Do rat auditory event related potentials exhibit human mismatch negativity attributes related to predictive coding?

ABSTRACT

Rodent models play a significant role in understanding disease mechanisms and the screening of new treatments. With regard to psychiatric disorders such as schizophrenia, however, it is difficult to replicate the human symptoms in rodents because these symptoms are often either 'uniquely human' or are only conveyed via self-report. There is a growing interest in rodent mismatch responses (MMRs) as a translatable 'biomarker' for disorders such as schizophrenia. In this review, we will summarize the attributes of human MMN, and discuss the scope of exploring the attributes of human MMN in rodents. Here, we examine how reliably MMRs that are measured in rats mimic human attributes, and present original data examining whether manipulations of stimulus conditions known to modulate human MMN, do the same for rat MMRs. Using surgically-implanted epidural electroencephalographic electrodes and wireless telemetry in freely-moving rats, we observed human-like modulations of MMRs, namely that larger MMRs were elicited to unexpected (deviant) stimuli that a) had a larger change in pitch compared to the expected (standard) stimulus, b) were less frequently presented (lower probability), and c) had no jitter (stable stimulus onset asynchrony) compared to high jitter. Overall, these findings contribute to the mounting evidence for rat MMRs as a good analogue of human MMN, bolstering the development of a novel approach in future to validate the preclinical models based on a translatable biomarker, MMN.