Abstract
Mismatch negativity (MMN) is a negative deflection of the auditory event-related potential (ERP) elicited by an abrupt change in a sound presented repeatedly. In patients with schizophrenia, MMN is consistently reduced, which makes it a promising biomarker. A non-human primate (NHP) model of MMN based on scalp electroencephalogram (EEG) recordings can provide a useful translational tool, given the high structural homology of the prefrontal and auditory cortices between NHPs, such as macaques, and humans. However, in previous MMN studies, the NHP models used did not allow for comparison with humans because of differences in task settings. Moreover, duration-deviant MMN (dMMN), whose reduction is larger than that in the frequency-deviant MMN (fMMN) in patients with schizophrenia, has never been demonstrated in NHP models. In this study, we determined whether dMMN can be observed in macaque scalp EEG recordings. EEGs were recorded from frontal electrodes (Fz) in two Japanese macaques. Consistent with clinical settings, auditory stimuli consisted of two pure tones, a standard and a deviant tone, in an oddball paradigm. The deviant and standard tones differed in duration (50 and 100 ms for the standard and deviant tones, respectively). A robust dMMN with a latency of around 200 ms, comparable to that in humans, was observed in both monkeys. A comparison with fMMN showed that the dMMN latency was the longer of the two. By bridging the gap between basic and clinical research, our results will contribute to the development of innovative therapeutic strategies for schizophrenia.
Highlights
Abnormal auditory information processing is a key feature of schizophrenia [1]
The event-related potential (ERP) to the standard and deviant stimuli were significantly different between the positive deflection and second negative deflection
Previous studies have reported MMN-like responses in non-human primate (NHP), this is the first NHP study to report an MMN-like response during a duration-deviant experiment
Summary
Abnormal auditory information processing is a key feature of schizophrenia [1]. Mismatch negativity (MMN) is an electrophysiological response, generally elicited in an auditory oddball paradigm [2]. Given its reliability across repeated experiments, MMN is a promising biomarker [3, 4]. MMN amplitude reduction is one of the most robust of several neurophysiological and neurocognitive biomarkers in patients with schizophrenia [5]. The relationship of MMN to the functional abilities of patients, assessed using the Global Assessment of Functioning Scale (GAF) [3, 18,19,20,21,22,23], for example, is of clinical value
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