Rapid fragmentation of neuronal networks at the onset of propofol-induced unconsciousness

Laura D. Lewis, Veronica S. Weiner, Eran A. Mukamel, Jacob A. Donoghue, Emad N. Eskandar, Joseph R. Madsen, William S. Anderson, Leigh R. Hochberg, Sydney S. Cash, Emery N. Brown, Patrick L. Purdon

Research output: Contribution to journalArticlepeer-review

275 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)E3377-E3386
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number49
StatePublished - Dec 4 2012
Externally publishedYes


  • Cortical networks
  • Electrophysiology
  • GABA
  • Single units

ASJC Scopus subject areas

  • General


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