Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK.
School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
Neuroimage. 2020 Nov 1;221:117189. doi: 10.1016/j.neuroimage.2020.117189. Epub 2020 Jul 23.
Cortical recordings of task-induced oscillations following subanaesthetic ketamine administration demonstrate alterations in amplitude, including increases at high-frequencies (gamma) and reductions at low frequencies (theta, alpha). To investigate the population-level interactions underlying these changes, we implemented a thalamo-cortical model (TCM) capable of recapitulating broadband spectral responses. Compared with an existing cortex-only 4-population model, Bayesian Model Selection preferred the TCM. The model was able to accurately and significantly recapitulate ketamine-induced reductions in alpha amplitude and increases in gamma amplitude. Parameter analysis revealed no change in receptor time-constants but significant increases in select synaptic connectivity with ketamine. Significantly increased connections included both AMPA and NMDA mediated connections from layer 2/3 superficial pyramidal cells to inhibitory interneurons and both GABA and NMDA mediated within-population gain control of layer 5 pyramidal cells. These results support the use of extended generative models for explaining oscillatory data and provide in silico support for ketamine's ability to alter local coupling mediated by NMDA, AMPA and GABA-A.
在亚麻醉剂量氯胺酮给药后，对皮层记录到的任务诱发振荡进行分析，结果显示其幅度发生了改变，包括高频（γ）的增加和低频（θ、α）的减少。为了研究这些变化背后的群体水平相互作用，我们实现了一个能够再现宽带频谱响应的丘脑-皮层模型（TCM）。与现有的仅包含皮层的 4 种群模型相比，贝叶斯模型选择更倾向于 TCM。该模型能够准确且显著地再现氯胺酮诱导的α波幅度降低和γ波幅度增加。参数分析显示，氯胺酮并未改变受体时间常数，但选择性地增加了突触连接。与氯胺酮相关的连接显著增加，包括来自 2/3 层浅层锥体神经元的 AMPA 和 NMDA 介导的连接，以及 GABA 和 NMDA 介导的 5 层锥体神经元的群体内增益控制的连接。这些结果支持使用扩展生成模型来解释振荡数据，并为氯胺酮改变 NMDA、AMPA 和 GABA-A 介导的局部耦合的能力提供了计算机模拟支持。
