Effects of Ketamine Administration on Auditory Information Processing in the Neocortex of Nonhuman Primates

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.

Roving oddball paradigm elicits sensory gating, frequency sensitivity, and long-latency response in common marmosets

“…Auditory responses observed from other channels provide some evidence to support the latter explanation, although electrode spacing is too large to provide a more comprehensive analysis of tonotopy. A study with very similar methods demonstrated sensitivity to different frequency tones in different subjects ( Komatsu and Ichinohe, 2020 ), which may be accounted for by the precise location of recording electrodes in relation to tonotopically sensitive regions of the auditory cortex. Analysis of auditory responses to ascending versus descending frequency transitions in the roving oddball sequence indicates that this plays a central role in shaping MMN-like response morphology.…”

“…Their published findings identify an MMN-like response between 50 and 120 ms post-stimulus, providing a basis for the development of the common marmoset as a model of MMN. Mechanisms underlying this response were not discussed at length, although experiments to investigate its potential relationship with NMDA receptor function were proposed; research which has since made progress ( Komatsu and Ichinohe, 2020 ). The authors did not express consideration for alternative explanations for the observed MMN-like response, briefly stating that it conveys information regarding violation of a regularity with the auditory input stream ( Komatsu et al, 2015 ), which is generally in-keeping with the prevailing theoretical interpretation of MMN ( Fitzgerald and Todd, 2020 , Ross and Hamm, 2020 ).…”