Bottom-up and top-down mechanisms of general anesthetics modulate different dimensions of consciousness
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There has been controversy regarding the precise mechanisms of anesthetic-induced unconsciousness, with two salient approaches that have emerged within systems neuroscience. One prominent approach is the "bottom up" paradigm, which argues that anesthetics suppress consciousness by modulating sleep-wake nuclei and neural circuits in the brainstem and diencephalon that have evolved to control arousal states. Another approach is the "top-down" paradigm, which argues that anesthetics suppress consciousness by modulating the cortical and thalamocortical circuits involved in the integration of neural information. In this article, we synthesize these approaches by mapping bottom-up and top-down mechanisms of general anesthetics to two distinct but inter-related dimensions of consciousness: level and content. We show how this explains certain empirical observations regarding the diversity of anesthetic drug effects. We conclude with a more nuanced discussion of how levels and contents of consciousness interact to generate subjective experience and what this implies for the mechanisms of anesthetic-induced unconsciousness.
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Anesthetic actions may map onto two dimensions: subcortical effects depress level of consciousness, while thalamocortical/corticocortical effects degrade content.
“it has been argued that anesthetic actions map on to these two dimensions, with effects in subcortical systems depressing level of consciousness and effects in thalamocortical and/or corticocortical systems degrading or disrupting the content of consciousness [125].”
From The Biology of General Anesthesia from Paramecium to Primate (2019) · cites this paper as [125]
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- Authors
- Mashour, G. A., & Hudetz, A. G.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Mashour, George A.
- Venue
- Frontiers in Neural Circuits
- Publisher
- Frontiers Media SA
- Published
- 2017-06-20
- Volume
- 11
- Pages
- 44-44
- ISSN
- 1662-5110 (ISSN-L)
- PMC
- PMC5476707
- OpenAlex
- W2702268872
- Cited by
- 133
- References
- 60
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 18 · 2023: 17 · 2022: 11 · 2021: 22 · 2020: 13 · 2019: 15 · 2018: 13 · 2017: 4 · 2012: 1
- FWCI
- 18.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neural Circuits (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Institutes of Health (GM098578, GM111293, GM056398, GM103894)
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Philosophy and Theoretical Science
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- general anesthetics, loss of consciousness, consciousness, sleep-wake regulation, arousal, thalamocortical circuits, cortical integration, level of consciousness, content of consciousness, subjective experience, anesthetic effects
- MeSH terms
- Anesthetics, Animals, Brain Mapping, Brain Stem, Cerebral Cortex, Consciousness, Diencephalon, Humans, Neural Pathways, Thalamus
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