Abstract
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts broad effects on consciousness and perception. Since NMDA receptor antagonists induce cognitive impairments, ketamine has been used for translational research on several psychiatric diseases, such as schizophrenia. Whereas the effects of ketamine on cognitive functions have been extensively studied, studies on the effects of ketamine on simple sensory information processing remain limited. In this study, we investigated the cortex-wide effects of ketamine administration on auditory information processing in nonhuman primates using whole-cortical electrocorticography (ECoG). We first recorded ECoG from awake monkeys on presenting auditory stimuli of different frequencies or different durations. We observed auditory evoked responses (AERs) across the cortex, including in frontal, parietal, and temporal areas, while feature-specific responses were obtained around the temporal sulcus. Next, we examined the effects of ketamine on cortical auditory information processing. We conducted ECoG recordings from monkeys that had been administered anesthetic doses of ketamine from 10 to 180 min following administration. We observed significant changes in stimulus feature-specific responses. Electrodes showing a frequency preference or offset responses were altered following ketamine administration, while those of the AERs were not strongly influenced. However, the frequency preference of a selected electrode was not significantly altered by ketamine administration over time following administration, while the imbalances in the onset and offset persisted over the course of 150 min following ketamine administration in all three monkeys. These results suggest that ketamine affects the ability to distinguish between sound frequency and duration in different ways. In conclusion, future research on the NMDA sensitivity of cortical wide sensory information processing may provide a new perspective into the development of nonhuman primate models of psychiatric disorders.
Highlights
Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, exerts broad effects on consciousness and perception
Based on reports where NMDA receptor antagonists induce cognitive impairments in nonhuman primates (NHP) [5,6,7,8,9,10], a subanesthetic dose of ketamine has been used for translational research on schizophrenia [6, 9, 11], Alzheimer’s disease [12], and autism spectrum disorder [8]
Gil-da-Costa, Stoner [25] reported reduced mismatch negativity (MMN) in monkeys following the subanesthetic administration of ketamine, as found in humans with schizophrenia [26, 27], and in healthy adult/young subjects having been administered ketamine [4, 28]. These results based on electroencephalograms (EEGs) suggest that ketamine induces changes in neural activity related to early auditory information processing in humans and NHPs, like in schizophrenia patients
Summary
An N-methyl-D-aspartate (NMDA) receptor antagonist, exerts broad effects on consciousness and perception. Based on reports where NMDA receptor antagonists induce cognitive impairments in nonhuman primates (NHP) [5,6,7,8,9,10], a subanesthetic dose of ketamine has been used for translational research on schizophrenia [6, 9, 11], Alzheimer’s disease [12], and autism spectrum disorder [8] These studies suggested that ketamine induces prefrontal cortical dysfunction, while recent studies reported aberrant neuronal oscillations in the prefrontal cortex of NHP [13, 14]. Gil-da-Costa, Stoner [25] reported reduced MMN in monkeys following the subanesthetic administration of ketamine, as found in humans with schizophrenia [26, 27], and in healthy adult/young subjects having been administered ketamine [4, 28] These results based on electroencephalograms (EEGs) suggest that ketamine induces changes in neural activity related to early auditory information processing in humans and NHPs, like in schizophrenia patients. ASSR and MMN, have been extensively studied, the effects of ketamine on auditory information processing itself have only been studied to a limited degree [28, 31]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call