Thalamocortical mechanisms for the anteriorization of α rhythms during propofol-induced unconsciousness

Abstract

As humans are induced into a state of general anesthesia via propofol, the normal alpha rhythm (8-13 Hz) in the occipital cortex disappears and a frontal alpha rhythm emerges. This spatial shift in alpha activity is called anteriorization. We present a thalamocortical model that suggests mechanisms underlying anteriorization. Our model captures the neural dynamics of anteriorization when we adjust it to reflect two key actions of propofol: its potentiation of GABA and its reduction of the hyperpolarization-activated current Ih. The reduction in Ih abolishes the occipital alpha by silencing a specialized subset of thalamocortical cells, thought to generate occipital alpha at depolarized membrane potentials (>-60 mV). The increase in GABA inhibition imposes an alpha timescale on both the cortical and thalamic portions of the frontal component that are reinforced by reciprocal thalamocortical feedback. Anteriorization can thus be understood as a differential effect of anesthetic drugs on thalamic nuclei with disparate spatial projections, i.e.: (1) they disrupt the normal, depolarized alpha in posterior-projecting thalamic nuclei while (2) they engage a new, hyperpolarized alpha in frontothalamic nuclei. Our model generalizes to other anesthetics that include GABA as a target, since the molecular targets of many such anesthetics alter the model dynamics in a manner similar to that of propofol.

Figure 1.

Left, The frontal component consists of cortical PY cells and interneurons coupled to RE and TC. Right, The posterior component consists of TC cells, RE cells, and a specialized subset of TC cells (HTC) that are thought to generate awake alpha.

Figure 2.

EEG signature of anteriorization during the administration of propofol in a representative human subject. A, Power maps of 10.3 Hz activity. Baseline indicates the subject is at rest and Levels 1–5 indicate increasing effect site concentration levels of propofol. B, Spectograms from a posterior electrode. C, Spectograms from a frontal electrode.

Figure 3.

Activity pattern and power spectrum of the LFP of the frontal and occipital circuits during the resting state. A, Spiking activity of PY neurons, (B) TC neurons, (C) RE neurons, (D) and LFP of frontal component. E, Spiking activity of HTC neurons, (F) TC neurons, (G) RE neurons, (H) and LFP of occipital component.

Figure 4.

Activity pattern and power spectrum of the LFP of the frontal and occipital circuits during propofol-induced anesthesia. A–H, Same as in Fig. 3.