title: Differential effects on fast and slow spindle activity, and the sleep slow oscillation in humans with carbamazepine and flunarizine to antagonize voltage-dependent Na+ and Ca2+ channel activity.
abstract: OBJECTIVE
  Sleep spindles play an important functional role in sleep-dependent memory consolidation. They are a hallmark of non-rapid eye movement (NREM) sleep and are grouped by the sleep slow oscillation. Spindles are not a unitary phenomenon but are differentiated by oscillatory frequency and topography. Yet, it is still a matter of debate whether these differences relate to different generating mechanisms. As corticothalamic networks are known to be involved in the generation of spindles and the slow oscillation, with Ca2+ and Na+ conductances playing crucial roles, we employed the actions of carbamazepine and flunarizine to reduce the efficacy of Na+ and Ca2+ channels, respectively, for probing in healthy human subjects mechanisms of corticothalamocortical excitability.
  
  
  METHODS
  For each pharmacologic substance a within-design study was conducted on 2 experimental nights in young, healthy adults.
  
  
  RESULTS
  Results indicate differential effects for slow frontocortical (approximately 10 Hz) and fast centroparietal (approximately 14 Hz) spindles. Carbamazepine enhanced slow frontal spindle activity conjointly with an increment in slow oscillation power (approximately 0.75 Hz) during deep NREM sleep. In contrast, fast centroparietal spindle activity (approximately 14 Hz) was decreased by carbamazepine. Flunarizine also decreased fast-spindle electroencephalogram power, but affected neither slow frontal spindle nor slow oscillation frequency bands.
  
  
  CONCLUSIONS
  Our findings indicate a differential pharmacologic response of the two types of sleep spindles and underscore a close linkage of the generating mechanisms underlying the sleep slow oscillation and the slow frontal sleep spindles for the signal transmission processes manipulated in the current study.
authors.affiliation: Department of Neuroendocrinology, University of Lübeck, Lübeck, Germany.
authors.forename: Amr
authors.initials: A
authors.lastname: Ayoub
authors.forename: Dominic
authors.initials: D
authors.lastname: Aumann
authors.forename: Anne
authors.initials: A
authors.lastname: Hörschelmann
authors.forename: Atossa
authors.initials: A
authors.lastname: Kouchekmanesch
authors.forename: Pia
authors.initials: P
authors.lastname: Paul
authors.forename: Jan
authors.initials: J
authors.lastname: Born
authors.forename: Lisa
authors.initials: L
authors.lastname: Marshall
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography; D005260:Female; D005444:Flunarizine / Q000494:pharmacology*; D006801:Humans; D008297:Male; D012894:Sleep Stages / Q000187:drug effects* / Q000502:physiology; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D002220:Carbamazepine; D005444:Flunarizine
keywords: EEG; ion channels; sleep spindles; slow oscillations; theta