Top-down mechanisms of anesthetic-induced unconsciousness

Abstract

The question of how structurally and pharmacologically diverse general anesthetics disrupt consciousness has persisted since the nineteenth century. There has traditionally been a significant focus on "bottom-up" mechanisms of anesthetic action, in terms of sensory processing, arousal systems, and structural scales. However, recent evidence suggests that the neural mechanisms of anesthetic-induced unconsciousness may involve a "top-down" process, which parallels current perspectives on the neurobiology of conscious experience itself. This article considers various arguments for top-down mechanisms of anesthetic-induced unconsciousness, with a focus on sensory processing and sleep-wake networks. Furthermore, recent theoretical work is discussed to highlight the possibility that top-down explanations may be causally sufficient, even assuming critical bottom-up events.

Keywords: anesthesia; anesthetic mechanisms; consciousness; ketamine; propofol; sleep.

Figure 1

Consciousness is not correlated with activation of primary sensory cortex. This example of contrastive analysis demonstrates activation of primary auditory cortex even in the absence of conscious perception. By contrast, detection of the auditory stimulus is correlated with activation of a widespread network prominently involving frontal-parietal networks. Reproduced from Dehaene and Changeux (2011), Neuron, with permission.

Figure 2

Anesthetic-induced unconsciousness is not correlated with inactivation of primary sensory cortex. Transverse and sagittal sections of primary visual (A,C) and auditory (B,D) cortices during wakefulness (A,B) and propofol-induced unconsciousness (C,D); note the relative preservation across states. Reproduced from Boveroux et al. (2010), Anesthesiology, with permission.

Figure 3

Consciousness is not correlated with early event-related potentials. This electrophysiological study of visual processing concluded that early event-related potentials (reflecting more primary sensory processing) are not correlated with conscious perception. Top-down processing from prefrontal cortex was more closely associated with consciousness. Reproduced from Del Cul et al. (2007), PLoS Biology, with permission.

Figure 4

Anesthetic-induced unconsciousness is not correlated with effects on early evoked potentials. This study of visual evoked potentials in rats demonstrates a clear dose-dependent effect of the inhaled anesthetic desflurane on long-latency potentials, with sparing of early potentials reflecting processing in primary visual cortex. Reproduced from Hudetz et al. (2009), Anesthesiology, with permission.

Figure 5

Ventrolateral preoptic nucleus is not necessary for anesthetic-induced unconsciousness. Lesions of the ventrolateral preoptic nucleus reveal an acute effect of resistance but a chronic effect of hypersensitivity to the inhaled anesthetic isoflurane. Reproduced from Moore et al. (2012), Current Biology, with permission. ^*p < 0.05; ^***p < 0.001.

Figure 6

Inhibition of top-down connectivity is a common correlate of anesthetic-induced unconsciousness across three distinct classes of general anesthetics. This figure depicts frontal-to-parietal (feedback) and parietal-to-frontal (feedforward) connectivity before, during and after anesthetic-induced unconsciousness in surgical patients (A–C). Lower panels (D–F) show asymmetry of directional connectivity, with positive values representing feedback dominance and negative values representing feedforward dominance. Connectivity was measured using electroencephalography and symbolic transfer entropy, which is rooted in information theory. Blue shaded area represents induction of anesthesia; the period before induction is baseline consciousness and the period after is anesthetic-induced unconsciousness. Each state is separated into three substates of Baseline (B1–B3) and Anesthetized (A1–A3) conditions; the timescale is different because patients receiving ketamine were studied using a different protocol than patients receiving propofol and sevoflurane. FB, Feedback; FF, Feedforward. Reproduced from Lee et al. (2013), Anesthesiology, with permission.