Differential Role of Prefrontal and Parietal Cortices in Controlling Level of Consciousness
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Abstract
Consciousness is determined both by level (e.g., being awake versus being anesthetized) and content (i.e., the qualitative aspects of experience). Subcortical areas are known to play a causal role in regulating the level of consciousness [1-9], but the role of the cortex is less well understood. Clinical and correlative data have been used both to support and refute a role for prefrontal and posterior cortices in the level of consciousness [10-22]. The prefrontal cortex has extensive reciprocal connections to wake-promoting centers in the brainstem and diencephalon [23, 24], and hence is in a unique position to modulate level of consciousness. Furthermore, a recent study suggested that the prefrontal cortex might be important in regulating level of consciousness [25] but causal evidence, and a comparison with more posterior cortical sites, is lacking. Therefore, to test the hypothesis that prefrontal cortex plays a role in regulating level of consciousness, we attempted to reverse sevoflurane anesthesia by cholinergic or noradrenergic stimulation of the prefrontal prelimbic cortex and two areas of parietal cortex in rat. General anesthesia was defined by loss of the righting reflex, a widely used surrogate measure in rodents. We demonstrate that cholinergic stimulation of prefrontal cortex, but not parietal cortex, restored wake-like behavior, despite continuous exposure to clinically relevant concentrations of sevoflurane anesthesia. Noradrenergic stimulation of the prefrontal and parietal areas resulted in electroencephalographic activation but failed to produce any signs of wake-like behavior. We conclude that cholinergic mechanisms in prefrontal cortex can regulate the level of consciousness.
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In rats anesthetized with sevoflurane, cholinergic manipulation of the medial prefrontal cortex, but not two posterior parietal cortex areas, restored wakefulness despite continuous anesthetic.
“In rats anesthetized with clinically relevant concentrations of sevoflurane anesthesia, cholinergic manipulation of the medial prefrontal cortex—but not two areas of the posterior parietal cortex—was sufficient to restore wakefulness despite continuous administration of the general anesthetic (Pal et al., 2018).”
From Conscious Processing and the Global Neuronal Workspace Hypothesis (2020) · cites this paper as Pal et al., 2018
The Results report that carbachol stimulation of prefrontal prelimbic cortex produced wake-like behavior during continuous, clinically relevant sevoflurane exposure, whereas stimulation of the two tested parietal regions did not. But the parietal Results section identifies those regions as the posterior parietal cortex and the medial parietal association cortex—not two areas of the posterior parietal cortex. (LLM, conf=0.86)
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Neural Network Mechanisms Underlying General Anesthesia: Cortical and Subcortical Nuclei
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- Authors
- Pal, D., Dean, J. G., Liu, T., Li, D., Watson, C. J., Hudetz, A. G., & Mashour, G. A.
- Affiliations
- University of Michigan (US)
- Corresponding author
- Mashour, George A.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 28
- Issue
- 13
- Pages
- 2145-2152.e5
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC6039257
- OpenAlex
- W2794797278
- Cited by
- 177
- References
- 49
- Citations by year
- 2026: 4 · 2025: 25 · 2024: 26 · 2023: 33 · 2022: 23 · 2021: 28 · 2020: 22 · 2019: 13 · 2018: 3
- FWCI
- 9.83
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion, cc-by-nc-nd)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01GM098578)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Keywords
- level of consciousness, prefrontal cortex, parietal cortex, sevoflurane anesthesia, cholinergic stimulation, noradrenergic stimulation, prelimbic cortex, righting reflex, wakefulness, anesthesia reversal
- MeSH terms
- Sevoflurane, Acetylcholine, Adrenergic alpha-Agonists, Anesthesia, Animals, Consciousness, Male, Norepinephrine, Parietal Lobe, Rats, Sprague-Dawley, Prefrontal Cortex, Cholinergic Agonists, Anesthetics, Inhalation, Rats
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