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 Balanza, A. Paulk, R. Zelmann, N. Peled, Daniel J. Soper, Laura A. Santa Cruz Mercado, R. Peterfreund, L. Aglio, E. Eskandar, G. Cosgrove, Ziv M. Williams, R. Richardson, E. N. Brown, O. Akeju, S. Cash, P. Purdon
Nature Communications March 29, 2023 DOI: 10.1038/s41467-023-37463-3 via Semantic Scholar
Summary
Ketamine produces different brain oscillations in distinct regions: gamma oscillations in prefrontal cortex and hippocampus, linked to antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, linked to dissociative effects. By analyzing intracranial recordings from humans and comparing effects with propofol, the authors identified that these frequency-dependent patterns arise from distinct neural circuits, potentially guiding development of biomarkers and treatments for depression.
Study at a glance
| Characteristics | Observational study with intracranial recordings Peer reviewed |
|---|---|
| Population | Humans |
| Keywords | Medicine |
| Citations | 63 |
| Key finding | Ketamine produces gamma oscillations in prefrontal cortex and hippocampus and a 3 Hz oscillation in posteromedial cortex, suggesting distinct neural circuit engagement for antidepressant and dissociative effects. |
Abstract
The neural mechanisms underpinning ketamine’s dissociative and antidepressant effects remain poorly understood. Here, the authors analyzed ketamine-induced brain dynamics with intracranial recordings in humans and found that ketamine engages different brain areas in distinct frequency-dependent patterns that may relate to its dissociative and antidepressant effects. 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.