title: Waking and sleep electroencephalogram variables as human sleep homeostatic process biomarkers after drug administration.
abstract: OBJECTIVE
  The correlation between theta activity during wakefulness and slow-wave activity (SWA) during sleep observed after sleep deprivation suggests such patterns can be used as electroencephalogram (EEG) biomarkers of the sleep homeostasis process. Since these EEG components would be very useful objective measures to assess CNS drug effects, we investigated whether the relationship between sleep homeostatic EEG biomarkers could be reproduced after an experimental pharmacological intervention.
  
  
  METHODS
  Seventeen healthy volunteers took part in a phase I randomized, double-blind, crossover design study. To increase sleep propensity, all participants received a single morning oral dose of olanzapine (5 mg) and placebo. Quantitative EEG analysis was done by power spectra calculations: theta activity (3.5-7.5 Hz) during wakefulness and SWA (0.5-4.0 Hz) during sleep. The relationship between the 2 EEG parameters was assessed by correlating the rise rate (percent/hour) of theta activity in wakefulness and the increase (percent) of SWA in the first non-REM sleep episode.
  
  
  RESULTS
  Following olanzapine administration we observed increases in theta activity during wakefulness, and increases in total sleep time, sleep efficiency and slow-wave sleep time during sleep. However, a weak and unreliable correlation was observed between the increases in theta activity and changes in sleep SWA.
  
  
  CONCLUSIONS
  From these results, we cannot affirm that these waking and sleep EEG variables behave as biomarkers of human sleep homeostasis after drug administration. It is possible that these EEG biomarkers reflect different physiological mechanisms if they are assessed during drug CNS effects.
authors.affiliation: Centre d'Investigació de Medicaments, Institut d'Investigacions Biomèdiques Sant Pau (IIB-Sant Pau), Barcelona, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Giménez
authors.forename: Sergio
authors.initials: S
authors.lastname: Romero
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Mañanas
authors.forename: Manuel-José
authors.initials: MJ
authors.lastname: Barbanoj
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000494:pharmacology*; D054316:Biomarkers, Pharmacological; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D004569:Electroencephalography / Q000379:methods*; D005260:Female; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D000077152:Olanzapine; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D013826:Theta Rhythm / Q000187:drug effects / Q000502:physiology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents; D054316:Biomarkers, Pharmacological; D001569:Benzodiazepines; D000077152:Olanzapine