@article{c8733b46fe964f69ad9222e71547636a,
title = "Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology",
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{\textquoteright}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{\textquoteright}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.",
author = "Fangyun Tian and Lewis, {Laura D.} and Zhou, {David W.} and Balanza, {Gustavo A.} and Paulk, {Angelique C.} and Rina Zelmann and Noam Peled and Daniel Soper and {Santa Cruz Mercado}, {Laura A.} and Peterfreund, {Robert A.} and Aglio, {Linda S.} and Eskandar, {Emad N.} and Cosgrove, {G. Rees} and Williams, {Ziv M.} and Richardson, {R. Mark} and Brown, {Emery N.} and Oluwaseun Akeju and Cash, {Sydney S.} and Purdon, {Patrick L.}",
note = "Funding Information: We would like to thank Dr. Timothy Houle, PhD, and Ariel Mueller, MS (Department of Anesthesia, Critical Care and Pain Medicine; Massachusetts General Hospital; Harvard Medical School) for insightful advice on statistical analysis. This work was supported by NIH grants 1R01AG056015 (PLP), P01GM118269 (ENB) and the Tiny Blue Dot Foundation (PLP, SSC, ACP, RZ, and DS). Funding Information: We would like to thank Dr. Timothy Houle, PhD, and Ariel Mueller, MS (Department of Anesthesia, Critical Care and Pain Medicine; Massachusetts General Hospital; Harvard Medical School) for insightful advice on statistical analysis. This work was supported by NIH grants 1R01AG056015 (PLP), P01GM118269 (ENB) and the Tiny Blue Dot Foundation (PLP, SSC, ACP, RZ, and DS). Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = dec,
doi = "10.1038/s41467-023-37463-3",
language = "English (US)",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}