title: 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.
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, Massachusetts 02215, USA. svijayan9@gmail.com
authors.forename: Sujith
authors.initials: S
authors.lastname: Vijayan
authors.forename: Shinung
authors.initials: S
authors.lastname: Ching
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Purdon
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Kopell
mesh_terms: D000513:Alpha Rhythm / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007262:Infusions, Intravenous; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D015742:Propofol / Q000008:administration & dosage*; D013788:Thalamus / Q000187:drug effects / Q000502:physiology*; D014474:Unconsciousness / Q000139:chemically induced / Q000503:physiopathology*
chemical_list: D015742:Propofol