• Michael M Craig, Bratislav Misic, Ioannis Pappas, Ram M Adapa, David K Menon, and Emmanuel A Stamatakis.
• Division of Anaesthesia, Department of Medicine, School of Clinical Medicine, University of Cambridge, Cambridge, UK; Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge, UK. Electronic address: mmc57@cam.ac.uk.
• Br J Anaesth. 2021 Apr 1; 126 (4): 835-844.

BackgroundPropofol, a commonly used intravenous anaesthetic, binds to type A gamma aminobutyric acid (GABA) receptors in mammalian brain. Previous work on its anaesthetic action has characterised either the biochemistry underlying propofol binding or the associated changes in brain network dynamics during sedation. Despite these advances, no study has focused on understanding how propofol action at the cellular level results in changes in brain network connectivity.MethodsWe used human whole-brain microarray data to generate distribution maps for genes that mark the primary GABAergic cortical interneurone subtypes (somatostatin, parvalbumin [PV], and 5-hydroxytryptamine 3A. Next, 25 healthy participants underwent propofol-induced sedation during resting state functional MRI scanning. We used partial least squares analysis to identify the brain regions in which connectivity patterns were most impacted by propofol sedation. We then correlated these multimodal cortical patterns to determine if a specific interneurone subtype was disproportionately expressed in brain regions in which connectivity patterns were altered during sedation.ResultsBrain networks that were significantly altered by propofol sedation had a high density of PV-expressing GABAergic interneurones. Brain networks that anticorrelated during normal wakefulness, namely the default mode network and attentional and frontoparietal control networks, increased in correlation during sedation.ConclusionsPV-expressing interneurones are highly expressed in brain regions with altered connectivity profiles during propofol-induced sedation. This study also demonstrates the utility of leveraging multiple datasets to address multiscale neurobiological problems.Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

37 keywords...

hide…