Nonhuman primate model of schizophrenia using a noninvasive EEG method.

Area of Science:

• Neuroscience
• Psychiatry
• Pharmacology

Background:

• Schizophrenia is linked to impaired sensory processing and cognitive deficits.
• Mismatch negativity (MMN) and P3a event-related potentials (ERPs) are reduced in schizophrenia and may serve as biomarkers.
• NMDA receptor antagonists like ketamine induce schizophrenia-like symptoms and reduce MMN/P3a in humans.

Purpose of the Study:

• To develop a nonhuman primate (NHP) model of schizophrenia using NMDA-receptor blockade.
• To obtain neurophysiological measures comparable to human studies.
• To investigate the effects of ketamine on sensory and cognitive function in NHPs.

Main Methods:

• Developed methods for recording ERPs in humans and rhesus macaques.
• Identified homologous MMN and P3a ERPs in both species using an auditory oddball paradigm.
• Administered subanesthetic ketamine to NHPs to induce NMDA-receptor blockade.

Main Results:

• Observed homologous MMN and P3a ERPs in humans and macaques.
• Ketamine administration significantly decreased the amplitude of both MMN and P3a ERPs in macaques.
• These findings mirror reductions seen in human schizophrenia patients and ketamine-challenged subjects.

Conclusions:

• A pharmacologically induced NHP model of schizophrenia using ketamine shows promise.
• This model allows for EEG-guided investigations into cellular mechanisms and therapies for schizophrenia.
• The model's relevance extends to other neuropsychiatric disorders linked to the glutamatergic system and ERP deficits.