Alteration of Consciousness by Anaesthetics: A Multiscale Modulation from the Molecular to the Systems Level

General anaesthesia has been used since the mid-nineteenth century, but its pharmacological mechanism remains unclear. Investigations probe smaller scales to understand how anaesthetics disrupt neural activity, causing loss of consciousness. Advances in neuroscience and molecular biology allow study from behavioral to molecular levels. This multiscale approach links molecular domain to general anaesthesia and consciousness, and how anaesthetics affect postoperative behavioral changes. This review discusses current knowledge on consciousness and general anaesthesia using pharmacokinetics, molecular biology, and advanced imaging (EEG, fMRI, PET, MEG). Understanding anaesthetic mechanisms may help solve the mystery of consciousness, and understanding consciousness could lead to new anaesthetic agents and technologies to controllably turn consciousness on and off, generating new concepts in neurocognitive pathophysiology disorders.

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Abstract

General anaesthesia has been used in medical practice since the mid-nineteenth century, but its pharmacological mechanism of action is still not entirely clear. In a top-down approach, investigations probe smaller and smaller scales to shed light on how anaesthetics disrupt or alter neural activity, ultimately resulting in loss of consciousness. In the past few decades, advances in neuroscience and molecular biology allowed for investigations on the brain structure and function from the behavioural level to the systems, cellular, and molecular level. This multiscale approach implicates the molecular domain as a fundamental link between general anaesthesia and consciousness, which also sheds light on how anaesthetic agents affect the pathogenesis of postoperative behavioural changes. This review discusses the current state of knowledge about the relationship between consciousness and general anaesthesia determined using pharmacokinetics, molecular biology, and advanced medical imaging, including EEG, fMRI, PET, MEG. It is hoped that the mechanisms of action of anaesthetic gases may help solve the mystery of consciousness. Conversely, understanding the cellular and molecular mechanisms of consciousness could lead to the design and development of new anaesthetic agents and technologies to controllably turn off and on consciousness. It could also generate new concepts in neurocognitive pathophysiology disorders.