Electrocorticographic effects of acute ketamine on non-human primate brains

Abstract

Objective: Acute blockade of glutamate N-methyl-D-aspartate (NMDA) receptors by ketamine induces symptoms and electrophysiological changes similar to schizophrenia. Previous studies have shown that ketamine elicits aberrant gamma oscillations in several cortical areas and impairs coupling strength between the low-frequency phase and fast frequency amplitude (PAC), which plays an important role in integrating functional information. Approach: This study utilized a customized wireless electrocorticography (ECoG) recording device to collect subdural signals from the somatosensory and primary auditory cortices in two monkeys. Ketamine was administered at a dose of 3 mg/kg (intramuscular) or 0.56 mg/kg (intravenous) to elicit brain oscillation reactions. We analyzed the raw data using methods such as power spectral density, time-frequency spectra, and PAC. Main results: Acute ketamine triggered broadband gamma and high gamma oscillation power and decreased lower frequencies. The effect was stronger in the primary auditory cortex than in the somatosensory area. The coupling strength between the low phase of theta and the faster amplitude of gamma/high gamma bands was increased by a lower dose (0.56 mg/kg iv) and decreased with a higher dose (3 mg/kg im) ketamine. Significance: Our results showed that lower and higher doses of ketamine elicited differential effects on theta-gamma PAC. These findings support the utility of ECoG models as a translational platform for pharmacodynamic research in future research.

Chronic subdural electrocorticography in nonhuman primates by an implantable wireless device for brain-machine interfaces

“…We have shown the time-frequency spectrogram results of the 40-Hz ASSR, and ketamine-induced power increase in the gamma and high-gamma bands (24). In this chronic experiment, we demonstrated similar results to those obtained in the acute phase.…”

“…In this study, we aimed to validate the long-term biocompatibility of the device and assess the quality of the ECoG signal after 15 months of implantation. Previously, we published evaluation results of the electrode array on beagles and signal quality tests in the acute phase (4,24). As a follow-up analysis of the device, we computed the average RMS and PSD of the signal, plotted the time-frequency spectrogram of the raw data, examined the post-mortem histology results, and compared the results with those of the acute phase.…”

Chronic subdural electrocorticography in nonhuman primates by an implantable wireless device for brain-machine interfaces

“…We have shown the time-frequency spectrogram results of the 40-Hz ASSR, and ketamine-induced power increase in the broad gamma and high-gamma bands ( Yan et al, 2022 ). These two well-established neuroscientific biomarkers were used to evaluate functionality of the device and to show its capacity to detect signals.…”

“…In this study, we aimed to validate the long-term biocompatibility of the implanted electrode array and casing, and assess the quality of the ECoG signal after 15 months of implantation. Previously, we published evaluation results of the electrode array and device in the acute phase ( Yan et al, 2020 , 2022 ). As a follow-up analysis of the device, we computed the average RMS and PSD of the signal, plotted the time-frequency spectrogram of the raw data, examined the post-mortem histology results, and compared the results with those of the acute phase.…”

The effect of ketamine and D-cycloserine on the high frequency resting EEG spectrum in humans

“…More recently gamma oscillations (up to 100 Hz) have been investigated, with methods for dealing with the noise being developed (Nottage et al 2013;Nottage and Horder 2015) and successfully applied to human pharmacological data . Animal electrophysiology studies show that gamma is not the highest frequency band to be of interest in pharmacological investigations, as recent pre-clinical work has shown clear drug-related effects in high-frequency oscillations (HFO) (100-170 Hz) (Hunt et al 2006, Hansen, Agerskov et al 2019, Yan, Suzuki et al 2022. Furthermore, oscillations in this frequency band also occur in humans as they have been observed in intracranial recordings of people with epilepsy.…”