Propofol Anesthesia and Sleep: A High-Density EEG Study

Murphy, Michael; Bruno, Marie-Aurélie; Riedner, Brady A.; Boveroux, Pierre; Noirhomme, Quentin; Landsness, Eric C.; Brichant, Jean-François; Phillips, Christophe; Massimini, Marcello; Laureys, Steven; Tononi, Giulio; Boly, Mélanie

doi:10.1093/sleep/34.3.283

Cited by 350 publications

(346 citation statements)

References 58 publications

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“…The trough-max pattern could be an instantiation of the slow cortical potential, a category of lowfrequency activity in which surface-negative deflections are associated with high-frequency activity (51). Anesthesia-induced phase-amplitude modulation has been studied previously (51)(52)(53)(54). However, our results establish the existence of two distinct patterns of low-frequency phase modulation of the alpha/beta oscillation amplitudes and show that each pattern is linked to a different state of unconsciousness.…”

Section: Discussionsupporting

confidence: 53%

Electroencephalogram signatures of loss and recovery of consciousness from propofol

Purdon

Pierce

Mukamel

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

677

849

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Significance Anesthesiologists reversibly manipulate the brain function of nearly 60,000 patients each day, but brain-state monitoring is not an accepted practice in anesthesia care because markers that reliably track changes in level of consciousness under general anesthesia have yet to be identified. We found specific behavioral and electrophysiological changes that mark the transition between consciousness and unconsciousness induced by propofol, one of the most commonly used anesthetic drugs. Our results provide insights into the mechanisms of propofol-induced unconsciousness and establish EEG signatures of this brain state that could be used to monitor the brain activity of patients receiving general anesthesia.

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Section: Discussionsupporting

confidence: 53%

Electroencephalogram signatures of loss and recovery of consciousness from propofol

Purdon

Pierce

Mukamel

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

677

849

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“…7,9,10 This proposal received empirical support from studies (mentioned in the first section of the article) that showed a disruption of gamma synchrony between different brain areas under the influence of a wide variety of anesthetics. 22,23 More recent work, however, has shown that gamma synchrony can persist, or even increase, under general anesthesia, 106 and the significance of gamma coherence for consciousness has been questioned in general. 107 According to a recent framework from cognitive psychology, binding would depend on top-down signals that selectively reinforce and sustain those representations in the early sensory cortices that encode aspects of sensory information that belong together.…”

Section: Integrating the Present Hypothesis With Existing Frameworkmentioning

confidence: 99%

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

Meyer

2015

Anesthesiology

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Despite considerable progress in the identification of the molecular targets of general anesthetics, it remains unclear how these drugs affect the brain at the systems level to suppress consciousness. According to recent proposals, anesthetics may achieve this feat by interfering with corticocortical topdown processes, that is, by interrupting information flow from association to early sensory cortices. Such a view entails two immediate questions. First, at which anatomical site, and by virtue of which physiological mechanism, do anesthetics interfere with top-down signals? Second, why does a breakdown of top-down signaling cause unconsciousness? While an answer to the first question can be gleaned from emerging neurophysiological evidence on dendritic signaling in cortical pyramidal neurons, a response to the second is offered by increasingly popular theoretical frameworks that place the element of prediction at the heart of conscious perception. Science magazine posed this question in a special section titled "What don't we know?," dedicated to the greatest challenges of contemporary science. 1 "Scientists are chipping away at the drugs' effects on individual neurons," the article reads, "but understanding how they render us unconscious will be a tougher nut to crack." This prediction proved correct: a decade later, we have expanded considerably our knowledge of the molecular targets of general anesthetics, but it remains enigmatic how these drugs affect the brain at the systems level. Why does the potentiation of γ-aminobutyric acid (GABA) receptors caused by propofol or desflurane cause unconsciousness? How are the brain's computational processes affected by this and other molecular mechanisms of anesthetics, so that patients undergoing surgery cease to experience their surrounds in terms of sight, sound, and touch? Anesthesiologists and cognitive neuroscientists alike have been captivated by these questions and have proposed a number of models in an attempt to answer them, such as Flohr's "information processing theory of anesthesia," 2 Alkire's "thalamic consciousness switch hypothesis," 3-6 Mashour's "cognitive unbinding paradigm," 7,8 John and Prichep's "anesthetic cascade," 9 or Hudetz's "forgotten present." 10,11 We shall return to some of these frameworks in a later section of the article.One recent development is particularly intriguing. Given that the most striking feature of general anesthesia is an interruption of the patient's ability to perceive the environment, it would appear intuitive for anesthetics to interfere primarily with bottom-up information flow along the sensory pathways, that is, with the signals that carry perceptual information from the thalamus to the primary sensory cortices and on to unimodal and multimodal association cortices. However, the very opposite appears to be the case. Several recent studies-carried out in both humans and animals, and using a variety of different anesthetic agents-have investigated differences in directional corticocortical connectivity bet...

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“…Induction of general anesthesia with propofol is associated with a marked increase in EEG power in the alpha (8 -13 Hz) band in the frontal cortices (Feshchenko et al, 2004;Cimenser et al, 2011;Supp et al, 2011). Simultaneously, normal "eyes-closed" alpha power in posterior and specifically, in occipital electrodes is severely attenuated (Cimenser et al, 2011;Murphy et al, 2011;Purdon et al, 2013). Although many studies have examined and characterized anteriorization over the last 35 years, the mechanisms underlying anteriorization remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Thalamocortical Mechanisms for the Anteriorization of Alpha Rhythms during Propofol-Induced Unconsciousness

Vijayan

Ching

Purdon

et al. 2013

Journal of Neuroscience

167

188

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As humans are induced into a state of general anesthesia via propofol, the normal alpha rhythm (8 -13 Hz) in the occipital cortex disappears and a frontal alpha rhythm emerges. This spatial shift in alpha activity is called anteriorization. We present a thalamocortical model that suggests mechanisms underlying anteriorization. Our model captures the neural dynamics of anteriorization when we adjust it to reflect two key actions of propofol: its potentiation of GABA and its reduction of the hyperpolarization-activated current I h . The reduction in I h abolishes the occipital alpha by silencing a specialized subset of thalamocortical cells, thought to generate occipital alpha at depolarized membrane potentials (ϾϪ60 mV). The increase in GABA inhibition imposes an alpha timescale on both the cortical and thalamic portions of the frontal component that are reinforced by reciprocal thalamocortical feedback. Anteriorization can thus be understood as a differential effect of anesthetic drugs on thalamic nuclei with disparate spatial projections, i.e.: (1) they disrupt the normal, depolarized alpha in posterior-projecting thalamic nuclei while (2) they engage a new, hyperpolarized alpha in frontothalamic nuclei. Our model generalizes to other anesthetics that include GABA as a target, since the molecular targets of many such anesthetics alter the model dynamics in a manner similar to that of propofol.

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Propofol Anesthesia and Sleep: A High-Density EEG Study

Abstract: Propofol anesthesia is a sleep-like state and slow waves are associated with diminished consciousness even in the presence of high gamma activity.

Cited by 350 publications

References 58 publications

Electroencephalogram signatures of loss and recovery of consciousness from propofol

Electroencephalogram signatures of loss and recovery of consciousness from propofol

The Role of Dendritic Signaling in the Anesthetic Suppression of Consciousness

Thalamocortical Mechanisms for the Anteriorization of Alpha Rhythms during Propofol-Induced Unconsciousness

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