The influence of anaesthetic agents on spiking and subthreshold activity in visual cortex revealed by electrophysiology and high-resolution functional MRI

The state of unconsciousness during anaesthesia is not characterized by a global disruption of CNS activity. Instead consciousness is mediated by a specific subset of brain states or processes selectively affected by anaesthetics. Our aim is to study the action sites of different types of anaesthetics in the monkey brain (M. mulatta). Here we report on the neural effects of Ketamine, a dissociative anaesthetic acting primarily on the NMDA receptor, and Midazolam, a benzodiazepine affecting GABA(A)-receptors. Ketamine exhibits both inhibitory and excitatory effects at different brain sites. Midazolam, however, is known to increase the GABA(A)-receptor function, and therefore to inhibit cortical activity. To study the primary sites-of-action of these agents in the monkey brain, high-resolution functional magnetic resonance imaging (fMRI) was used to measure stimulus induced activity changes in the alert and anaesthetized monkey. The activity of neurons in visual cortex was recorded during scanning, as well as in separate experiments outside the scanner. Following the acquisition of base-line data, a bolus of the test-substance was applied intravenously via a computerized infusion pump. Brain activity was monitored continuously before, during and after the infusion. The data presented here focus on the effects of anaesthetics on subthreshold and spiking activity and the BOLD-signal. A comparison of the influences on these different neural signals allows studying the site and type of action of anaesthetics in more detail. In addition it has the potential to afford further insights into the neural processes underlying the BOLD-signal