Top-down mechanisms of anesthetic-induced unconsciousness.

George A Mashour

doi:10.3389/fnsys.2014.00115

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.

Highlights

AND TERMINOLOGY The mechanism by which structurally and pharmacologically diverse general anesthetics can render an individual unconscious has remained incompletely understood since 1846
The goal of the present article is not to argue that anesthetics have no effects on molecular targets or subcortical structures such as sleep-wake nuclei, but rather to counterbalance the tendency to think of anesthetic mechanisms as a fundamentally or exclusively bottom-up process
Bottom-up explanations of anesthetic-induced unconsciousness have focused on subcortical nuclei that mediate the sleep-wake cycle or early cortical areas that mediate sensory processing

Summary

Introduction

AND TERMINOLOGY The mechanism by which structurally and pharmacologically diverse general anesthetics can render an individual unconscious has remained incompletely understood since 1846. From the pons to the midbrain to diencephalic structures such as the hypothalamus, a variety of subcortical nuclei project to and arouse the cortex through the actions of distinct neurotransmitters This represents a bottom-up pathway from subcortical wakepromoting nuclei to the cortex, sometimes with a synaptic relay in the thalamus. The third meaning of “bottom-up” relates to processes that occur from smaller to larger structural scales, e.g., from the molecular, to the cellular, to the neuroanatomical, to the network level of the brain. These three meanings of “bottom-up”—referring to sensory, arousal, and structural hierarchies—all have relevance to understanding the mechanism of anesthetic-induced unconsciousness

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Conclusion