title: Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness.
abstract: The neurophysiological mechanisms by which anesthetic drugs cause loss of consciousness are poorly understood. Anesthetic actions at the molecular, cellular, and systems levels have been studied in detail at steady states of deep general anesthesia. However, little is known about how anesthetics alter neural activity during the transition into unconsciousness. We recorded simultaneous multiscale neural activity from human cortex, including ensembles of single neurons, local field potentials, and intracranial electrocorticograms, during induction of general anesthesia. We analyzed local and global neuronal network changes that occurred simultaneously with loss of consciousness. We show that propofol-induced unconsciousness occurs within seconds of the abrupt onset of a slow (<1 Hz) oscillation in the local field potential. This oscillation marks a state in which cortical neurons maintain local patterns of network activity, but this activity is fragmented across both time and space. Local (<4 mm) neuronal populations maintain the millisecond-scale connectivity patterns observed in the awake state, and spike rates fluctuate and can reach baseline levels. However, neuronal spiking occurs only within a limited slow oscillation-phase window and is silent otherwise, fragmenting the time course of neural activity. Unexpectedly, we found that these slow oscillations occur asynchronously across cortex, disrupting functional connectivity between cortical areas. We conclude that the onset of slow oscillations is a neural correlate of propofol-induced loss of consciousness, marking a shift to cortical dynamics in which local neuronal networks remain intact but become functionally isolated in time and space.
authors.affiliation: Department of Brain and Cognitive Sciences, Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, and Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Lewis
authors.forename: Veronica S
authors.initials: VS
authors.lastname: Weiner
authors.forename: Eran A
authors.initials: EA
authors.lastname: Mukamel
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Donoghue
authors.forename: Emad N
authors.initials: EN
authors.lastname: Eskandar
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Madsen
authors.forename: William S
authors.initials: WS
authors.lastname: Anderson
authors.forename: Leigh R
authors.initials: LR
authors.lastname: Hochberg
authors.forename: Sydney S
authors.initials: SS
authors.lastname: Cash
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Purdon
mesh_terms: D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology; D000768:Anesthesia, General; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D004827:Epilepsy / Q000503:physiopathology*; D006801:Humans; D016014:Linear Models; D009415:Nerve Net / Q000187:drug effects*; D015742:Propofol / Q000494:pharmacology*; D013997:Time Factors; D014474:Unconsciousness / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D018686:Anesthetics, Intravenous; D015742:Propofol