Comprehensive profiling of brain dynamics during anesthesia across phylogeny

Abstract

The behavioral effects of anesthetics are highly conserved across species, hinting at shared and fundamental underlying mechanisms. Here we compile a dataset of multiscale neural activity during wakefulness and anesthesia, encompassing human, macaque, marmoset, mouse, zebrafish and nematode. Applying massive feature extraction, we characterize local neural dynamics across >6,000 time-series features. This reveals a conserved dynamical profile of anesthesia across species, characterized by shorter intrinsic timescales of neural activity and dampened inter-regional synchrony. Deep-brain stimulation of the macaque centromedian thalamus reverses this profile and restores behavioral responsiveness. This conserved dynamical phenotype covaries with conserved transcriptional profiles of excitatory and inhibitory neurotransmission. Biophysical modeling provides a potential mechanistic link between the macroscale dynamical phenotype of anesthesia and microscale effects of key molecular targets on the timescales of synaptic excitation and inhibition. These analyses reveal a shared neural endpoint of anesthesia: across species and scales, anesthetics induce spatiotemporal isolation of local neural activity.