Department of Psychology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
Department of Anesthesiology, Rambam Health Care Campus, Haifa, Israel; Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
PLoS Comput Biol. 2022 Jul 11;18(7):e1010294. doi: 10.1371/journal.pcbi.1010294. eCollection 2022 Jul.
Anesthetic manipulations provide much-needed causal evidence for neural correlates of consciousness, but non-specific drug effects complicate their interpretation. Evidence suggests that thalamic deep brain stimulation (DBS) can either increase or decrease consciousness, depending on the stimulation target and parameters. The putative role of the central lateral thalamus (CL) in consciousness makes it an ideal DBS target to manipulate circuit-level mechanisms in cortico-striato-thalamic (CST) systems, thereby influencing consciousness and related processes. We used multi-microelectrode DBS targeted to CL in macaques while recording from frontal, parietal, and striatal regions. DBS induced episodes of abnormally long, vacant staring with low-frequency oscillations here termed vacant, perturbed consciousness (VPC). DBS modulated VPC likelihood in a frequency-specific manner. VPC events corresponded to decreases in measures of neural complexity (entropy) and integration (Φ*), proposed indices of consciousness, and substantial changes to communication in CST circuits. During VPC, power spectral density and coherence at low frequencies increased across CST circuits, especially in thalamo-parietal and cortico-striatal pathways. Decreased consciousness and neural integration corresponded to shifts in cortico-striatal network configurations that dissociated parietal and subcortical structures. Overall, the features of VPC and implicated networks were similar to those of absence epilepsy. As this same multi-microelectrode DBS method-but at different stimulation frequencies-can also increase consciousness in anesthetized macaques, it can be used to flexibly address questions of consciousness with limited confounds, as well as inform clinical investigations of other consciousness disorders.
麻醉操作为意识的神经相关提供了急需的因果证据,但非特异性药物效应使它们的解释变得复杂。有证据表明,丘脑深部脑刺激(DBS)可以增加或降低意识,具体取决于刺激目标和参数。中央外侧丘脑(CL)在意识中的假定作用使其成为操纵皮质纹状体丘脑(CST)系统中回路水平机制的理想 DBS 靶点,从而影响意识和相关过程。我们在猕猴中使用多微电极 DBS 靶向 CL,同时记录来自额叶、顶叶和纹状体区域的信号。DBS 诱导出异常长而空洞的凝视发作,这里称为空洞、扰动意识(VPC)。DBS 以特定频率的方式调制 VPC 的可能性。VPC 事件与神经复杂性(熵)和整合(Φ*)的测量值降低相对应,这是意识的拟议指标,以及 CST 电路中的通信发生了实质性变化。在 VPC 期间,CST 电路中的低频功率谱密度和相干性增加,特别是在丘脑顶叶和皮质纹状体通路中。意识和神经整合的降低与皮质纹状体网络配置的变化相对应,这些变化使顶叶和皮质下结构分离。总体而言,VPC 的特征和涉及的网络与失神性癫痫相似。由于相同的多微电极 DBS 方法——但在不同的刺激频率下——也可以增加麻醉猕猴的意识,因此它可以用于灵活地解决意识问题,同时减少混淆,以及为其他意识障碍的临床研究提供信息。