Unresponsiveness ≠ unconsciousness

Abstract

Consciousness is subjective experience. During both sleep and anesthesia, consciousness is common, evidenced by dreaming. A defining feature of dreaming is that, while conscious, we do not experience our environment; we are disconnected. Besides inducing behavioral unresponsiveness, a key goal of anesthesia is to prevent the experience of surgery (connected consciousness), by inducing either unconsciousness or disconnection of consciousness from the environment. Review of the isolated forearm technique demonstrates that consciousness, connectedness, and responsiveness uncouple during anesthesia; in clinical conditions, a median 37% of patients demonstrate connected consciousness. We describe potential neurobiological constructs that can explain this phenomenon: during light anesthesia the subcortical mechanisms subserving spontaneous behavioral responsiveness are disabled but information integration within the corticothalamic network continues to produce consciousness, and unperturbed norepinephrinergic signaling maintains connectedness. These concepts emphasize the need for developing anesthetic regimens and depth of anesthesia monitors that specifically target mechanisms of consciousness, connectedness, and responsiveness.

Figure 1

Electroencephalogram changes during non-rapid eye movement (NREM) to rapid eye movement-like (REM) transitions during sleep and general anesthesia. (A) During sleep, the change from NREM like activity to REM-like activity is accompanied by the loss of spindles and delta waves and a shift to higher frequency activity. (B) Midway through an operation REM-like activity was noted by loss of spindles and delta waves and a shift to higher frequency activity, in this snapshot, beta activity. (C) On emergence from anesthesia, the patient transitioned through both theta and gamma activity prior to waking, seemingly waking from a REM-like state (upper panel). This started at approximately 0.4 MAC of anesthesia, about 5 minutes from becoming responsive (lower panel). SWS = slow wave sleep. MAC = minimum alveolar concentration. SE = state entropy.

Figure 2

Schematic representing changes in responsiveness, neuromodulators and corticothalamic network connectivity with escalating propofol dose. Panel A: We define four particular states: awake, positive response on the isolate forearm technique (IFT +ve), dreaming and unconscious. With increasing doses of propofol (Panel B) patients transition through these states, first entering a state of environmentally connected consciousness (ECC = IFT +ve), then disconnected consciousness (DC = dreaming) before becoming unconscious. Panel B: depicts propofol dose. Panel C: Putative parallel changes in neuromodulators underlying behavioral changes with escalating doses of propofol. Ach = acetylcholine. Norepi = norepinephrine. ECC is hypothesized to require active norepinephrinergic and cholinergic signaling. Panel D: changes in corticothalamic network connectivity. Put-Amy = Putamen and Amygdala connectivity. CT-VATT = corticothalamic-ventral attention network connectivity. CT-Total = total corticothalamic connectivity. ECC requires adequate CT-Total and CT-VATT signaling.

Figure 3

Schematic showing the relationship of consciousness, external connectedness and responsiveness with mediators where known.