Translatability of Scalp EEG Recordings of Duration-Deviant Mismatch Negativity Between Macaques and Humans: A Pilot
Mariko Tada1,2, Yuki Suda3,4, Kenji Kirihara1
1Department of Neuropsychiatry, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
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.
Insights
Duration-deviant MMN (dMMN), a potential schizophrenia biomarker, was observed in macaque EEG recordings. This study demonstrates a comparable dMMN in macaques, advancing non-human primate models for schizophrenia research.
Area of Science:
- Neuroscience
- Psychiatry
- Biomarkers
Background:
- Mismatch negativity (MMN) is an auditory event-related potential (ERP) sensitive to sound changes.
- Reduced MMN in schizophrenia suggests its potential as a biomarker.
- Non-human primate (NHP) models offer translational value for studying MMN due to cortical homology.
Purpose of the Study:
- To investigate the presence of duration-deviant MMN (dMMN) in macaque scalp electroencephalogram (EEG) recordings.
- To establish a comparable NHP model for dMMN, addressing limitations in previous MMN studies.
- To explore the potential of dMMN as a translational biomarker for schizophrenia.
Main Methods:
- Auditory oddball paradigm using standard (100 ms) and deviant (50 ms) duration tones.
- Scalp EEG recordings from frontal electrodes (Fz) in two Japanese macaques.
- Analysis of event-related potentials to identify dMMN characteristics.
Main Results:
- A robust dMMN was observed in both macaques with a latency around 200 ms, similar to human findings.
- dMMN latency was longer compared to frequency-deviant MMN (fMMN).
- The study successfully demonstrated dMMN in an NHP model.
Conclusions:
- The macaque dMMN model replicates human findings, providing a valuable tool for schizophrenia research.
- This advancement bridges basic and clinical research, facilitating the development of novel therapeutic strategies.
- The findings support the utility of dMMN as a translational biomarker for schizophrenia.
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