RESUMEN
NMDA receptor inhibition has been identified as a key functional property of numerous psychoactive drugs, anesthetics, and analgesics including alcohol, nitrous oxide, dextromethorphan, phencyclidine, and ketamine. This report investigates the role of NMDA receptor inhibition in ketamine-induced anesthesia by comparing the effects of systemic injections of ketamine and the highly selective NMDA receptor antagonist CGS 19755 on intracortical electrophysiological activity and behavior in rhesus macaques. Changes in cortical electrophysiology following sub-anesthetic doses of CGS 19755 resemble the "gamma-burst" activity caused by anesthetic doses of ketamine, while the behavioral effects of the two drugs differ considerably. This shows that while NMDA antagonism is sufficient to cause a key neural correlate of ketamine anesthesia, it is not sufficient on its own to cause anesthesia. These findings shed light on a previously unappreciated effect of systemic NMDA antagonism, and clarify the relationship between electrophysiological changes caused by ketamine and ketamine's anesthetic mechanisms.
RESUMEN
Resting-state functional MRI (rsfMRI) provides a view of human brain organization based on correlation patterns of blood oxygen level dependent (BOLD) signals recorded across the whole brain. The neural basis of resting-state BOLD fluctuations and their correlation remains poorly understood. We simultaneously recorded oxygen level, spikes, and local field potential (LFP) at multiple sites in awake, resting monkeys. Following a spike, the average local oxygen and LFP voltage responses each resemble a task-driven BOLD response, with LFP preceding oxygen by 0.5 s. Between sites, features of the long-range correlation patterns of oxygen, LFP, and spikes are similar to features seen in rsfMRI. Most of the variance shared between sites lies in the infraslow frequency band (0.01-0.1 Hz) and in the infraslow envelope of higher-frequency bands (e.g. gamma LFP). While gamma LFP and infraslow LFP are both strong correlates of local oxygen, infraslow LFP explains significantly more of the variance shared between correlated oxygen signals than any other electrophysiological signal. Together these findings are consistent with a causal relationship between infraslow LFP and long-range oxygen correlations in the resting state.