Electroencephalogram signatures of loss and recovery of consciousness from propofol

Purdon, Patrick L.; Pierce, Eric T.; Mukamel, Eran A.; Prerau, Michael J.; Walsh, J.; Wong, Kin Foon Kevin; Salazar-Gomez, Andres F.; Harrell, P. Grace; Sampson, Aaron L.; Cimenser, Aylin; Ching, ShiNung; Kopell, Nancy; Tavares-Stoeckel, Casie; Habeeb, Kathleen; Merhar, Rebecca C.; Brown, Emery N.

doi:10.1073/pnas.1221180110

Cited by 663 publications

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“…Previous studies in humans have observed significant increases in slow oscillation power during loss of consciousness (7,12) and have established that these oscillations correspond to ON and OFF states where neurons are periodically silenced (11). Notably, unlike propofol-induced α waves, these slow oscillations are spatially incoherent (7,11), implying a state of "fragmentation" of cortical activity (11).…”

Section: Discussionmentioning

confidence: 92%

“…In humans, a well-defined pattern of oscillations has been observed during transition into propofol-induced unconsciousness. This pattern includes β oscillations that smoothly transition into α oscillations at the time of loss of consciousness (7,8). EEG source localization analyses in humans suggest that these β and α oscillations are generated approximately within dorsal medial prefrontal and anterior cingulate cortices (16).…”

Section: Resultsmentioning

confidence: 99%

“…Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7)(8)(9)(10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7,11,12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dynamics have shown that whereas α and β oscillations can be generated by propofol's actions in cortex alone (13), coherent α oscillations require the participation of both thalamus and cortex (14).…”

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Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Flores

Hartnack

Fath

et al. 2017

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

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144

131

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General anesthesia (GA) is a reversible drug-induced state of altered arousal required for more than 60,000 surgical procedures each day in the United States alone. Sedation and unconsciousness under GA are associated with stereotyped electrophysiological oscillations that are thought to reflect profound disruptions of activity in neuronal circuits that mediate awareness and cognition. Computational models make specific predictions about the role of the cortex and thalamus in these oscillations. In this paper, we provide in vivo evidence in rats that alpha oscillations (10-15 Hz) induced by the commonly used anesthetic drug propofol are synchronized between the thalamus and the medial prefrontal cortex. We also show that at deep levels of unconsciousness where movement ceases, coherent thalamocortical delta oscillations (1-5 Hz) develop, distinct from concurrent slow oscillations (0.1-1 Hz). The structure of these oscillations in both cortex and thalamus closely parallel those observed in the human electroencephalogram during propofol-induced unconsciousness. During emergence from GA, this synchronized activity dissipates in a sequence different from that observed during loss of consciousness. A possible explanation is that recovery from anesthesiainduced unconsciousness follows a "boot-up" sequence actively driven by ascending arousal centers. The involvement of medial prefrontal cortex suggests that when these oscillations (alpha, delta, slow) are observed in humans, self-awareness and internal consciousness would be impaired if not abolished. These studies advance our understanding of anesthesia-induced unconsciousness and altered arousal and further establish principled neurophysiological markers of these states.anesthesia | prefrontal cortex | thalamus | coherence | propofol G eneral anesthesia (GA) is a reversible drug-induced state consisting of unconsciousness, analgesia, amnesia, akinesia, and physiological stability (1). In the United States nearly 60,000 surgical procedures are conducted under GA every day, making GA one of the most common manipulations of the brain and central nervous system in medicine (1). The molecular mechanisms by which anesthetic drugs alter brain function have been well characterized (2, 3). Detailed analyses of neural circuitand systems-level mechanisms of GA are more recent (1, 4, 5). Understanding the system-wide effects of anesthetic drugs is necessary in order to understand how these drugs produce states of altered arousal and unconsciousness.One of the most commonly used anesthetic drugs is 2,6-diisopropylphenol (propofol), a GABA-A receptor agonist (6). Electroencephalogram (EEG) recordings in humans during gradual induction of unconsciousness with propofol show the appearance of frontal β oscillations (15-30 Hz) at the onset of sedation, followed by the appearance of coherent frontal α (8-12 Hz) oscillations (7-10) and widespread slow (0.1-1 Hz) and δ (1-4 Hz) oscillations (7, 11, 12) when subjects no longer respond to sensory stimuli. Biophysical models of neuronal dy...

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Section: Discussionmentioning

confidence: 92%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Flores

Hartnack

Fath

et al. 2017

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

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144

131

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“…13 Shifts in these phase-amplitude coupling patterns may have significant implications for anesthetic depth but do not necessarily influence the algorithm that generates BIS values. A further salient example is that a transition to a pre-burst suppression electroencephalographic pattern (e.g., from a delta spindle pattern) can represent an increase in anesthetic depth.…”

Section: Bispectral Index Is a Limited Index Of Brain Functionmentioning

confidence: 99%

“…13 Des décalages de ces aspects de couplage phase-amplitude peuvent avoir des implications significatives pour la profondeur de l'anesthésie, mais sans nécessairement influencer l'algorithme qui génère les valeurs BIS. Un autre exemple marquant est qu'une transition vers un aspect EEG de suppression pré-salve (par exemple à partir d'un aspect de pointe-onde delta) peut représenter une augmentation de la profondeur de l'anesthésie.…”

Section: L'indice Bispectral Est Un Indice Limité De La Fonction Céréunclassified

Dementia and sensitivity to anesthetics

Mashour

Avidan²

2014

Can J Anesth/J Can Anesth

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Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients

Claassen

Velázquez

Meyers

et al. 2016

Annals of Neurology

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Objective Accurate behavioral assessments of consciousness carry tremendous significance in guiding management, but are extremely challenging in acutely brain-injured patients. We evaluated whether EEG and multimodality monitoring parameters may facilitate assessment of consciousness in patients with subarachnoid hemorrhage. Methods A retrospective analysis was performed of 83 consecutively treated adults with subarachnoid hemorrhage. All patients were initially comatose and had invasive brain monitoring placed. Behavioral assessments were performed during daily interruption of sedation and categorized into three groups based on their best examination as (1) comatose, (2) arousable (eye opening or attending towards a stimulus), and (3) aware (command following). EEG features included spectral power and complexity measures. Comparisons were made using bootstrapping methods and partial least squares regression. Results We identified 389 artifact-free EEG clips following behavioral assessments. Increasing central gamma, posterior alpha, and diffuse theta-delta oscillations differentiated patients that were arousable from those in coma. Command following was characterized by a further increase in central gamma and posterior alpha, as well as an increase in alpha permutation entropy. These EEG features together with basic neurological examinations (e.g., pupillary light reflex) contributed heavily to a linear model predicting behavioral state while brain physiology measures (e.g., brain oxygenation), structural injury, and clinical course added less. Interpretation EEG measures of behavioral states provide distinctive signatures that complement behavioral assessments of patients with subarachnoid hemorrhage shortly after the injury. Our data support the hypothesis that impaired connectivity of cortex with both central thalamus and basal forebrain underlies decreasing levels of consciousness.

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Electroencephalogram signatures of loss and recovery of consciousness from propofol

Cited by 663 publications

References 77 publications

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Thalamocortical synchronization during induction and emergence from propofol-induced unconsciousness

Dementia and sensitivity to anesthetics

Bedside quantitative electroencephalography improves assessment of consciousness in comatose subarachnoid hemorrhage patients

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