Thalamocortical Mechanisms for the Anteriorization of Alpha 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 I h . The reduction in I h abolishes the occipital alpha by silencing a specialized subset of thalamocortical cells, thought to generate occipital alpha at depolarized membrane potentials (ϾϪ60 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.

EEG Source Reconstruction in Male Nonsmokers after Nicotine Administration during the Resting State

“…This pattern can be observed already a few minutes after closing the eyes. Second, Vijayan et al [51] evidenced that treatment with the anesthetic propofol during EC could artificially reproduce the above-mentioned anteriorization of α in healthy subjects. This pattern was correlated - together with an increase <1 Hz in oscillation - with the gradual loss of responsiveness to stimuli as the anesthetic dose was increased.…”

How the cortico-thalamic feedback affects the EEG power spectrum over frontal and occipital regions during propofol-induced sedation

“…Our results reveal that it is possible to replicate several observed EEG phenomena by modeling anaesthetic action only in the thalamo-cortical loops. Several previous studies describing EEG spectra by a cortico-thalamic model consider both thalamic and cortical anaesthetic action (Ching et al 2010;McCarthy et al 2008;Hindriks and van Putten 2012;Vijayan et al 2013) and point out the importance of cortical anaesthetic action. Even purely cortical models Wilson et al 2006) may explain several spectral features observed in EEG under anaesthesia.…”

“…This is in contrast to the theory of thalamic deactivation during general anaesthesia. A recent study (Vijayan et al 2013) suggests that reduction in hyperpolarization-activated current (I h ) silences bursting of a subset of thalamo-cortical cells leading to suppression of occipital α−activity. Their work indicated that increased GABAergic inhibition onto thalamo-cortical cells resulted in an α− resonance that is reinforced by reciprocal corticothalamic feedback, and hence leads to the emergence of frontal α−activity.…”

Simultaneous Recordings from the Primary Visual Cortex and Lateral Geniculate Nucleus Reveal Rhythmic Interactions and a Cortical Source for Gamma-Band Oscillations

“…Although gamma-band activity in precortical structures has been reported, the evidence in support of this in mammals comes from studies that made measurements in anesthetized cats (Neuenschwander and Singer, 1996;Castelo-Branco et al, 1998;Koepsell et al, 2009). Given the influence anesthesia can have on rhythmic brain activity (Xing et al, 2012a;Saxena et al, 2013;Vijayan et al, 2013), it is critical to investigate gamma-band activity and interareal interactions in the alert state.…”