Abstract
Mismatch negativity (MMN) is a scalp-recorded electrical potential that occurs in humans in response to an auditory stimulus that defies previously established patterns of regularity. MMN amplitude is reduced in people with schizophrenia. In this study, we aimed to develop a robust and replicable rat model of MMN, as a platform for a more thorough understanding of the neurobiology underlying MMN. One of the major concerns for animal models of MMN is whether the rodent brain is capable of producing a human-like MMN, which is not a consequence of neural adaptation to repetitive stimuli. We therefore tested several methods that have been used to control for adaptation and differential exogenous responses to stimuli within the oddball paradigm. Epidural electroencephalographic electrodes were surgically implanted over different cortical locations in adult rats. Encephalographic data were recorded using wireless telemetry while the freely-moving rats were presented with auditory oddball stimuli to assess mismatch responses. Three control sequences were utilized: the flip-flop control was used to control for differential responses to the physical characteristics of standards and deviants; the many standards control was used to control for differential adaptation, as was the cascade control. Both adaptation and adaptation-independent deviance detection were observed for high frequency (pitch), but not low frequency deviants. In addition, the many standards control method was found to be the optimal method for observing both adaptation effects and adaptation-independent mismatch responses in rats. Inconclusive results arose from the cascade control design as it is not yet clear whether rats can encode the complex pattern present in the control sequence. These data contribute to a growing body of evidence supporting the hypothesis that rat brain is indeed capable of exhibiting human-like MMN, and that the rat model is a viable platform for the further investigation of the MMN and its associated neurobiology.
Highlights
One of the most commonly reported and replicable electrophysiological abnormalities observed in people with schizophrenia is the reduction in the amplitude of the mismatch negativity (MMN) in response to deviations in the acoustic environment [1,2,3]
In Study 1, the early components, N22 and peak at 37 ms (P37) were larger in response to deviant stimuli (Stimulus Type: N22 F1,8 = 11.22, P = 0.010; P37, F1,8 = 13.11, P = 0.007; Figure 2)
The only effect of gestational day (GD) was seen for the peak at 30 ms (P30) component to high frequencies
Summary
One of the most commonly reported and replicable electrophysiological abnormalities observed in people with schizophrenia is the reduction in the amplitude of the mismatch negativity (MMN) in response to deviations in the acoustic environment [1,2,3]. MMN is primarily generated in the auditory cortex, with some contribution from the frontal cortex and other areas [6,7]. It has been observed in neural activity measured using electroencephalography (EEG) [8], magnetoencephalography [9] and optical imaging [10]. MMN is commonly elicited by presenting deviants that differ from the standards in some simple characteristic feature, such as frequency or duration [8]
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