Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology

Fangyun Tian, Laura D. Lewis, David W. Zhou, Gustavo A. Balanza, Angelique C. Paulk, Rina Zelmann, Noam Peled, Daniel Soper, Laura A. Santa Cruz Mercado, Robert A. Peterfreund, Linda S. Aglio, Emad N. Eskandar, G. Rees Cosgrove, Ziv M. Williams, R. Mark Richardson, Emery N. Brown, Oluwaseun Akeju, Sydney S. Cash, Patrick L. Purdon

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Ketamine produces antidepressant effects in patients with treatment-resistant depression, but its usefulness is limited by its psychotropic side effects. Ketamine is thought to act via NMDA receptors and HCN1 channels to produce brain oscillations that are related to these effects. Using human intracranial recordings, we found that ketamine produces gamma oscillations in prefrontal cortex and hippocampus, structures previously implicated in ketamine’s antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, previously proposed as a mechanism for its dissociative effects. We analyzed oscillatory changes after subsequent propofol administration, whose GABAergic activity antagonizes ketamine’s NMDA-mediated disinhibition, alongside a shared HCN1 inhibitory effect, to identify dynamics attributable to NMDA-mediated disinhibition versus HCN1 inhibition. Our results suggest that ketamine engages different neural circuits in distinct frequency-dependent patterns of activity to produce its antidepressant and dissociative sensory effects. These insights may help guide the development of brain dynamic biomarkers and novel therapeutics for depression.

Original languageEnglish (US)
Article number1748
JournalNature communications
Volume14
Issue number1
DOIs
StatePublished - Dec 2023

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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