The administration of ketamine is associated with dose-dependent stabilization of cortical dynamics in humans.

Abstract

During wakefulness, external stimuli elicit conscious experiences. In contrast, dreams and drug-induced dissociated states, are characterized by vivid internally generated conscious experiences and reduced ability to perceive external stimuli. Understanding the physiological distinctions between normal wakefulness and dissociated states may therefore disambiguate signatures of responsiveness to external stimuli from those that underlie conscious experience. The hypothesis that conscious experiences are associated with brain criticality has received considerable theoretical and experimental support. Consistent with this hypothesis, statistical signatures of criticality are similar in normal wakefulness and dissociative states but are abolished in dreamless sleep and under anesthesia. Thus, while statistical measures of criticality are associated with the ability to have conscious experience, they do not readily distinguish between perception of the external world from internally generated percepts. Here, we investigate distinct, dynamical, signatures of criticality during escalating ketamine doses in high-density EEG in human male volunteers. We show that during normal wakefulness, EEG is found at a critical point between damped and exploding oscillations. With increasing doses of ketamine, as dissociative symptoms intensify, activity is progressively stabilized - most prominently at higher frequencies. We also show that stabilization is a more reliable marker of the effects of ketamine than conventional measures such as power spectra. These findings suggest that stabilization of cortical dynamics correlates with decreased ability to respond to and perceive external stimuli rather than the ability to have conscious experiences per se. Altogether, these results suggest that combining statistical and dynamical criticality measures may distinguish wakefulness, dissociation, and unconsciousness.Significance Statement During wakefulness, external stimuli elicit sensory perceptions while during unconsciousness, perception is absent. Dissociated states of consciousness, including those induced by ketamine, feature internally generated experiences and, concomitantly, reduced responsiveness to stimuli. Both normal wakefulness and dissociated states have been linked to statistical criticality, a regime in which the brain operates at the transition between order and disorder. Here, we study a distinct notion of criticality - transition between stable and unstable oscillations and show that ketamine induces dose-dependent stabilization of normally critical brain dynamics. Thus, departure from dynamical criticality is associated with states of reduced responsiveness rather than unconsciousness. Combining statistical and dynamical criticality measures may better distinguish connected and dissociated states of consciousness.