使用人类颅内神经生理学描述氯胺酮诱导的分离期间和随后与异丙酚相互作用时的大脑动力学。

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

机构信息

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Department of Biomedical Engineering, Boston University, Boston, MA, USA.

出版信息

Nat Commun. 2023 Mar 29;14(1):1748. doi: 10.1038/s41467-023-37463-3.

DOI:10.1038/s41467-023-37463-3

PMID:36991011

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10060225/

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.

摘要

氯胺酮可产生抗抑郁作用，治疗抵抗性抑郁症患者，但它的有用性是有限的，由其精神副作用。氯胺酮被认为通过 NMDA 受体和 HCN1 通道发挥作用，产生与这些作用相关的脑振荡。使用人类颅内记录，我们发现氯胺酮在前额皮质和海马中产生伽马振荡，这些结构以前被认为与氯胺酮的抗抑郁作用有关，在后内侧皮质中产生 3Hz 振荡，以前被提议作为其分离作用的机制。我们分析了随后给予异丙酚后的振荡变化，异丙酚的 GABA 能活性拮抗氯胺酮的 NMDA 介导的去抑制作用，以及共同的 HCN1 抑制作用，以确定归因于 NMDA 介导的去抑制作用与 HCN1 抑制作用的动力学。我们的结果表明，氯胺酮以不同的神经回路以不同的频率相关的活动模式来产生其抗抑郁和分离感觉作用。这些见解可能有助于指导大脑动态生物标志物和新型抑郁症治疗方法的发展。