Anesthesia & Analgesia, Journal Year: 2022, Volume and Issue: 134(6), P. 1114 - 1117

Published: May 10, 2022

See Article, pages 1118, 1126 and 1140 For its 125th anniversary issue, the editors of Science highlighted 125 big questions that continue to perplex humankind. The question at heart neuroscience core anesthesiology about biological basis consciousness is listed just after “What Universe Made of?” Anesthetics annually ablate in under 4% humanity. As if estimate was not astounding enough, time again, human brain journeys back from abyss general anesthesia with a renewed ability sense world. Henry Beecher’s challenge, issued 75 years ago,1 utilize second power probe neural substrates enabling mental processes explore variety ways which distinct anesthetics transiently alter or ultimately extinguish perception. Placed more modern context, have disconnect salience incoming sensory stimuli. Even deep anesthesia, primary cortex remains appropriately responsive; nevertheless, fracture higher-order perceptual representations consistent cognitive unbinding.2 Remarkably, on discontinuing anesthetic drug exposure, spontaneously hops among metastable intermediate states as emergence proceeds.3 Neurophysiologic behavioral functions recover,4 coherent experiences rebind, itself rebounds. magic afforded by thus continues captivate philosophers, physicians, neuroscientists, naturalists. In this centennial year issue Anesthesia & Analgesia, readers are treated submissions address modulation content and/or level consciousness.5–7 an updated roadmap for specialty, Dr George Mashour, who founded University Michigan Center Consciousness Science, issues impassioned call provide fundamental neuroscientific insights,5 echoing updating challenge. Mashour highlights leading, times competing, theoretical frameworks explaining consciousness. focuses prefrontal crucial node (Figure).Figure.: Schematic reactivation cortex.The encompasses broad array anatomically heterogeneous subregions. Each has own widespread, yet pattern cortical subcortical connectivity. sends reciprocal projections arousal-promoting targets brainstem diencephalon, supporting notion it can modulate Moreover, least one subregion requisite member all 6 large-scale networks: default-mode, dorsal attention, ventral frontoparietal, cingulo-opercular, networks.8 From rodents up through humans, multiple lines evidence identify central role cognition. circuits enable complex executive functions, such problem solving decision-making, require planning goal-directed behaviors, creative thinking, mind wandering, even ruminating.9 Hence, surprising anesthetic-induced function been hypothesized essential mechanism sedative hypnotics erode However, important point out because each reciprocally connected corresponding parietal cortex, some importance prefrontal, opposed posterior parietal, hot spots work Ihalainen et al10 example. By considering mechanistic overlap physiologic, pharmacologic, pathologic compromised, emphasizes immense opportunity affords. Leveraging chemically mechanistically reversibly perturb, indefinitely impair, yet, remarkably permit reassembly, investigators incredible set tools objectively interrogate circuit activity patterns prohibit Study forward state transition into, reverse of, unresponsiveness, along careful inclusion subhypnotic dosing schemes, offers added rigor quest critical correlates capacity study recovery during differentiates comatose ones proceeds unpredictably, incompletely, all. Nevertheless, despite distinction, metabolic markers, neurophysiological imaging, electrophysiological complexity suggest common distinguish (un)consciousness arising neurologic disorders consciousness, natural nightly “disorders” found sleep, pharmacologic altered consciousness.11–15 Translational opportunities abound test these other full suite animal models. Work Pal al16 uses righting reflex gold standard surrogate return spectral analysis electroencephalogram (EEG) determine activation. They previously demonstrated cholinergic stimulation rouses rats stably anesthetized continuing inhale 1.9% 2.4% sevoflurane. Such impressive antagonism occur successful targeting prelimbic infralimbic regions but medial noradrenergic stimulation. attempt necessity activation transitions, Huels al17 targeted injections sodium channel blocker, tetrodotoxin, into barrel association cortices. While putative dysregulation action potential signaling areas facilitated induction sevoflurane only inactivation impaired sevoflurane,17 modulating consciousness.18 major source innervation originates basal forebrain, might rightly wonder whether enhancing input similarly sufficient arousal restore wakefulness sleep. Indeed, blue light-driven optogenetic forebrain neurons induces rapid transitions nonrapid eye movement (NREM) sleep waking (REM) enhanced activity, vivid dreams may occur.19 Using chemogenetic electrical Dean al6 further demonstrate they elevate acetylcholine levels, elicit EEG activation, concomitant increases respiratory rates. seemingly less efficacious than dialysis delivery carbachol itself,16 bilateral destabilize outright antagonize partially dependent cortex. Local administration tetrodotoxin markedly attenuated efficacy precipitate ongoing anesthesia.6 rodent model supports conclusion does indeed their ground-breaking publication neuroscience, Crick Koch20 suggested science first proxy itself. Their underlying logic specific experience must be encoded summated networks. Since proposition, postulated both humans animals. third submission 100th Brito al7 2 well-studied consciousness: Lempel-Ziv normalized symbolic transfer entropy. measures shown track consciousness.21,22 When applied spontaneous EEG, distinguishes nonresponsive patients fail display any overt signs awareness minimally conscious exhibit intermittent awareness. Furthermore, recently reviewed,23 decreases NREM individuals enter gamma-aminobutyric acid (GABA)ergic unconsciousness. Symbolic entropy provided landmark hypnotic doses anesthetics—propofol, sevoflurane, ketamine—produce disruption frontal feedback connectivity, while leaving feed-forward connectivity intact.24 Returning levels sought strengthen correlative associations. high-density intracranial exposed ketamine nitrous oxide, increased complexity. profile release differed between oxide. Ketamine consistently elevated oxide induction, followed decrease maintenance. Despite agent-specific differences, roughly linear correlation remained extracellular varied 4-fold. authors’ single chosen dose leave wanting fuller characterization additional psychedelic anesthetics. Inclusion doses, easily achieved ketamine, best cross-validate directional correlates24 models simultaneous invasive neurophysiologic sampling. we embark century research sciences, will imperative reliable also uncover molecular, neuronal, causes heeding Mashour’s charge specialty,5 field could finally realize see beyond pioneering vision Koch. DISCLOSURES Name: Max B. Kelz, MD, PhD. Contribution: sole author, M. Kelz reviewed interpreted literature wrote manuscript. Conflicts Interest: International Research Society Board Trustees, consulted Spark Therapeutics occasion within last 3 years. Neither activities were related work. This manuscript handled by: Thomas R. Vetter, MPH.

Language: Английский