title: Extinction of conditioned fear is better learned and recalled in the morning than in the evening.
abstract: Sleep helps emotional memories consolidate and may promote generalization of fear extinction memory. We examined whether extinction learning and memory might differ in the morning and evening due, potentially, to circadian and/or sleep-homeostatic factors. Healthy men (N = 109) in 6 groups completed a 2-session protocol. In Session 1, fear conditioning was followed by extinction learning. Partial reinforcement with mild electric shock produced conditioned skin conductance responses (SCRs) to 2 differently colored lamps (CS+), but not a third color (CS-), within the computer image of a room (conditioning context). One CS+ (CS + E) but not the other (CS + U) was immediately extinguished by un-reinforced presentations in a different room (extinction context). Delay durations of 3 h (within AM or PM), 12 h (morning-to-evening or evening-to-morning) or 24 h (morning-to-morning or evening-to-evening) followed. In Session 2, extinction recall and contextual fear renewal were tested. We observed no significant effects of the delay interval on extinction memory but did observe an effect of time-of-day. Fear extinction was significantly better if learned in the morning (p = .002). Collapsing across CS + type, there was smaller morning differential SCR at both extinction recall (p = .003) and fear renewal (p = .005). Morning extinction recall showed better generalization from the CS + E to CS + U with the response to the CS + U significantly larger than to the CS + E only in the evening (p = .028). Thus, extinction is learned faster and its memory is better generalized in the morning. Cortisol and testosterone showed the expected greater salivary levels in the morning when higher testosterone/cortisol ratio also predicted better extinction learning. Circadian factors may promote morning extinction. Alternatively, evening homeostatic sleep pressure may impede extinction and favor recall of conditioned fear.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA. Electronic address: EPACE-SCHOTT@PARTNERS.ORG.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Pace-Schott
authors.forename: Rebecca M C
authors.initials: RM
authors.lastname: Spencer
authors.forename: Shilpa
authors.initials: S
authors.lastname: Vijayakumar
authors.forename: Nafis A K
authors.initials: NA
authors.lastname: Ahmed
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Verga
authors.forename: Scott P
authors.initials: SP
authors.lastname: Orr
authors.forename: Roger K
authors.initials: RK
authors.lastname: Pitman
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Milad
mesh_terms: D000293:Adolescent; D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005712:Galvanic Skin Response; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D011601:Psychophysics; D012189:Retrospective Studies; D012463:Saliva / Q000378:metabolism; D057566:Self Report; D013223:Statistics as Topic; D013739:Testosterone / Q000378:metabolism; D064232:Visual Analog Scale; D055815:Young Adult
chemical_list: D013739:Testosterone; D006854:Hydrocortisone
keywords: Circadian rhythm; Cortisol; Extinction; Fear conditioning; Sleep; Sleep homeostasis; Testosterone