title: Phase-locked loop for precisely timed acoustic stimulation during sleep.
abstract: BACKGROUND
  A brain-computer interface could potentially enhance the various benefits of sleep.
  
  
  METHODS
  We describe a strategy for enhancing slow-wave sleep (SWS) by stimulating the sleeping brain with periodic acoustic stimuli that produce resonance in the form of enhanced slow-wave activity in the electroencephalogram (EEG). The system delivers each acoustic stimulus at a particular phase of an electrophysiological rhythm using a phase-locked loop (PLL).
  
  
  RESULTS
  The PLL is computationally economical and well suited to follow and predict the temporal behavior of the EEG during slow-wave sleep.
  
  
  METHODS
  Acoustic stimulation methods may be able to enhance SWS without the risks inherent in electrical stimulation or pharmacological methods. The PLL method differs from other acoustic stimulation methods that are based on detecting a single slow wave rather than modeling slow-wave activity over an extended period of time.
  
  
  CONCLUSIONS
  By providing real-time estimates of the phase of ongoing EEG oscillations, the PLL can rapidly adjust to physiological changes, thus opening up new possibilities to study brain dynamics during sleep. Future application of these methods hold promise for enhancing sleep quality and associated daytime behavior and improving physiologic function.
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, 710 N Lake Shore Drive, 5th floor, Chicago, IL 60611, USA. Electronic address: giovanni.santostasi@northwestern.edu.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Santostasi
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, 710 N Lake Shore Drive, 5th floor, Chicago, IL 60611, USA.
authors.forename: Roneil
authors.initials: R
authors.lastname: Malkani
authors.affiliation: Department of Psychiatry, School of Medicine, University of Wisconsin, 6001 Research Park Blvd, Madison, WI 53719, USA.
authors.forename: Brady
authors.initials: B
authors.lastname: Riedner
authors.affiliation: Department of Psychiatry, School of Medicine, University of Wisconsin, 6001 Research Park Blvd, Madison, WI 53719, USA.
authors.forename: Michele
authors.initials: M
authors.lastname: Bellesi
authors.affiliation: Department of Psychiatry, School of Medicine, University of Wisconsin, 6001 Research Park Blvd, Madison, WI 53719, USA.
authors.forename: Giulio
authors.initials: G
authors.lastname: Tononi
authors.affiliation: Department of Psychology, Northwestern University, 2029 Sheridan Rd, Evanston, IL 60208, USA.
authors.forename: Ken A
authors.initials: KA
authors.lastname: Paller
authors.affiliation: Department of Neurology, Feinberg School of Medicine, Northwestern University, 710 N Lake Shore Drive, 5th floor, Chicago, IL 60611, USA.
authors.forename: Phyllis C
authors.initials: PC
authors.lastname: Zee
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D058256:Brain Waves / Q000502:physiology*; D003700:Delta Rhythm / Q000502:physiology; D004569:Electroencephalography / Q000379:methods*; D058407:Electroencephalography Phase Synchronization / Q000502:physiology*; D006801:Humans; D012894:Sleep Stages / Q000502:physiology*
keywords: Brain–computer interface; Memory and learning; Phase-locked loop; Slow-wave sleep