Nonhuman primate model of schizophrenia using a noninvasive EEG method
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There is growing evidence that impaired sensory-processing significantly contributes to the cognitive deficits found in schizophrenia. For example, the mismatch negativity (MMN) and P3a event-related potentials (ERPs), neurophysiological indices of sensory and cognitive function, are reduced in schizophrenia patients and may be used as biomarkers of the disease. In agreement with glutamatergic theories of schizophrenia, NMDA antagonists, such as ketamine, elicit many symptoms of schizophrenia when administered to normal subjects, including reductions in the MMN and the P3a. We sought to develop a nonhuman primate (NHP) model of schizophrenia based on NMDA-receptor blockade using subanesthetic administration of ketamine. This provided neurophysiological measures of sensory and cognitive function that were directly comparable to those recorded from humans. We first developed methods that allowed recording of ERPs from humans and rhesus macaques and found homologous MMN and P3a ERPs during an auditory oddball paradigm. We then investigated the effect of ketamine on these ERPs in macaques. As found in humans with schizophrenia, as well as in normal subjects given ketamine, we observed a significant decrease in amplitude of both ERPs. Our findings suggest the potential of a pharmacologically induced model of schizophrenia in NHPs that can pave the way for EEG-guided investigations into cellular mechanisms and therapies. Furthermore, given the established link between these ERPs, the glutamatergic system, and deficits in other neuropsychiatric disorders, our model can be used to investigate a wide range of pathologies.
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MMN has been tied to impaired neurotransmission at NMDARs based upon both intracranial and surface recordings in non-human primates and ketamine challenge studies in healthy human volunteers.
“MMN has been tied to impaired neurotransmission at NMDARs based upon both intracranial (54) and surface (55) recordings in non-human primates and ketamine challenge studies in healthy human volunteers (rev. in 3).”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [55]
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- Authors
- Gil-da-Costa, R., Stoner, G. R., Fung, R., & Albright, T. D.
- Affiliations
- Salk Institute for Biological Studies (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-08-19
- Volume
- 110
- Issue
- 38
- Pages
- 15425-15430
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3780912
- OpenAlex
- W2055726044
- Cited by
- 182
- References
- 37
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 16 · 2023: 5 · 2022: 17 · 2021: 8 · 2020: 15 · 2019: 25 · 2018: 13 · 2017: 10 · 2016: 12 · 2015: 23 · 2014: 12 · 2013: 4
- FWCI
- 12.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- schizophrenia, nonhuman primate model, ketamine, NMDA receptor antagonism, mismatch negativity, P3a, event-related potentials, auditory oddball paradigm, rhesus monkeys, glutamatergic system, sensory processing deficits, cognitive impairment, biomarkers, subanesthetic ketamine
- MeSH terms
- Acoustic Stimulation, Adult, Animals, Brain Mapping, Disease Models, Animal, Electroencephalography, Evoked Potentials, Humans, Ketamine, Macaca mulatta, Male, Schizophrenia, Receptors, N-Methyl-D-Aspartate
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