title: Effect of conditioned stimulus exposure during slow wave sleep on fear memory extinction in humans.
abstract: OBJECTIVE
  Repeated exposure to a neutral conditioned stimulus (CS) in the absence of a noxious unconditioned stimulus (US) elicits fear memory extinction. The aim of the current study was to investigate the effects of mild tone exposure (CS) during slow wave sleep (SWS) on fear memory extinction in humans.
  
  
  METHODS
  The healthy volunteers underwent an auditory fear conditioning paradigm on the experimental night, during which tones served as the CS, and a mild shock served as the US. They were then randomly assigned to four groups. Three groups were exposed to the CS for 3 or 10 min or an irrelevant tone (control stimulus, CtrS) for 10 min during SWS. The fourth group served as controls and was not subjected to any interventions. All of the subjects completed a memory test 4 h after SWS-rich stage to evaluate the effect on fear extinction. Moreover, we conducted similar experiments using an independent group of subjects during the daytime to test whether the memory extinction effect was specific to the sleep condition.
  
  
  METHODS
  Ninety-six healthy volunteers (44 males) aged 18-28 y.
  
  
  RESULTS
  Participants exhibited undisturbed sleep during 2 consecutive nights, as assessed by sleep variables (all P > 0.05) from polysomnographic recordings and power spectral analysis. Participants who were re-exposed to the 10 min CS either during SWS and wakefulness exhibited attenuated fear responses (wake-10 min CS, P < 0.05; SWS-10 min CS, P < 0.01).
  
  
  CONCLUSIONS
  Conditioned stimulus re-exposure during SWS promoted fear memory extinction without altering sleep profiles.
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health and Key Laboratory of Mental Health, Peking University, Beijing, China.|National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Jia
authors.initials: J
authors.lastname: He
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health and Key Laboratory of Mental Health, Peking University, Beijing, China.
authors.forename: Hong-Qiang
authors.initials: HQ
authors.lastname: Sun
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Li
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health and Key Laboratory of Mental Health, Peking University, Beijing, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shi
authors.affiliation: National Institute on Drug Dependence, Peking University, Beijing, China.
authors.forename: Si-Zhi
authors.initials: SZ
authors.lastname: Ai
authors.affiliation: Sleep Medicine Center, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health and Key Laboratory of Mental Health, Peking University, Beijing, China.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Li
authors.affiliation: Sleep Medicine Center, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, China.
authors.forename: Xiang-Dong
authors.initials: XD
authors.lastname: Tang
authors.affiliation: Peking University Sixth Hospital/Institute of Mental Health and Key Laboratory of Mental Health, Peking University, Beijing, China.|National Institute on Drug Dependence, Peking University, Beijing, China.|Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
mesh_terms: D000161:Acoustic Stimulation; D000293:Adolescent; D000328:Adult; D003213:Conditioning, Psychological / Q000502:physiology*; D004569:Electroencephalography; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology*; D017286:Polysomnography; D012890:Sleep / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology; D055815:Young Adult
keywords: conditioned stimulus; extinction; fear memory; slow wave sleep