Neural effects of propofol-induced unconsciousness and its reversal using thalamic stimulation.

André M Bastos,Mikael Lundqvist,Earl K Miller,Josefina Correa,Jacob A Donoghue,Jorge Yanar,Meredith Mahnke,Scott L Brincat,Ayan S Waite,Jefferson Roy,Emery N Brown

doi:10.7554/elife.60824

André M Bastos, Mikael Lundqvist + Show 9 more

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https://doi.org/10.7554/elife.60824

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Abstract

The specific circuit mechanisms through which anesthetics induce unconsciousness have not been completely characterized. We recorded neural activity from the frontal, parietal, and temporal cortices and thalamus while maintaining unconsciousness in non-human primates (NHPs) with the anesthetic propofol. Unconsciousness was marked by slow frequency (~1 Hz) oscillations in local field potentials, entrainment of local spiking to Up states alternating with Down states of little or no spiking activity, and decreased coherence in frequencies above 4 Hz. Thalamic stimulation 'awakened' anesthetized NHPs and reversed the electrophysiologic features of unconsciousness. Unconsciousness is linked to cortical and thalamic slow frequency synchrony coupled with decreased spiking, and loss of higher-frequency dynamics. This may disrupt cortical communication/integration.

Highlights

Propofol – the most widely used anesthetic – acts by enhancing GABAergic inhibition throughout the brain and central nervous system (Bai et al, 1999; Hapfelmeier et al, 2001; Hemmings et al, 2019; Hemmings et al, 2005)
We continuously recorded neural activity as the animals transitioned from the pre-propofol awake state, through loss of consciousness (LOC), to unconsciousness and recovery of consciousness (ROC) (Figure 1A)
We started by administering a high-infusion rate of propofol (280–580 mcg/kg/min, adjusted per individual animal) for 20 min to induce LOC

Summary

Introduction

Propofol – the most widely used anesthetic – acts by enhancing GABAergic inhibition throughout the brain and central nervous system (Bai et al, 1999; Hapfelmeier et al, 2001; Hemmings et al, 2019; Hemmings et al, 2005). One factor is that unconsciousness is caused by the phase-locking of neuronal spiking with the slow-delta oscillation This greatly reduces cortical spiking and limits cortical activity to brief Up-states of spiking followed by longer duration Down-states of little or no spiking (Lewis et al, 2012). The thalamus is highly interconnected with the cortex and receives important inputs from the brainstem arousal centers (Jones, 2007) Both thalamo-cortical and corticothalamic connectivity are highly layer specific, giving rise to specific hypotheses that propose either deep (layers 5/6) or superficial (layer 2/3) may be linked to loss of consciousness (Aru et al, 2019; Dehaene and Changeux, 2011). We continuously recorded neural activity as the animals transitioned from the pre-propofol awake state, through loss of consciousness (LOC), to unconsciousness and recovery of consciousness (ROC) (Figure 1A)

Results

Discussion

Materials and methods

Experimental procedures

Methods