title: Biophysical Modeling of Alpha Rhythms During Halothane-Induced Unconsciousness.
abstract: During the induction of general anesthesia there is a shift in power from the posterior regions of the brain to the frontal cortices; this shift in power is called anteriorization. For many anesthetics, a prominent feature of anteriorization is a shift specifically in the alpha band (8-13 Hz) from posterior to frontal cortices. Here we present a biophysical computational model that describes thalamocortical circuit-level dynamics underlying anteriorization of the alpha rhythm in the case of halothane. Halothane potentiates GABAAand increases potassium leak conductances. According to our model, an increase in potassium leak conductances hyperpolarizes and silences the high-threshold thalamocortical (HTC) cells, a specialized subset of thalamocortical cells that fire at the alpha frequency at relatively depolarized membrane potentials (>-60 mV) and are thought to be the generators of quiet awake occipital alpha. At the same time the potentiation of GABAAimposes an alpha time scale on both the cortical and the thalamic component of the frontal portion of our model. The alpha activity in the frontal component is further strengthened by reciprocal thalamocortical feedback. Thus, we argue that the dual molecular targets of halothane induce the anteriorization of the alpha rhythm by increasing potassium leak conductances, which abolishes occipital alpha, and by potentiating GABAA, which induces frontal alpha. These results provide a computational modeling formulation for studying highly detailed biophysical mechanisms of anesthetic action in silico.
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, MA 02215.
authors.forename: Sujith
authors.initials: S
authors.lastname: Vijayan
authors.affiliation: Department of Electrical and Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130.
authors.forename: ShiNung
authors.initials: S
authors.lastname: Ching
authors.affiliation: Harvard Medical School, Boston, MA 02115; Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114; Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Patrick L
authors.initials: PL
authors.lastname: Purdon
authors.affiliation: Harvard Medical School, Boston, MA 02115; Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA 02114; Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, MA 02215.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Kopell