Sleep promotes generalization of extinction of conditioned fear

Abstract

Study objective: To examine the effects of sleep on fear conditioning, extinction, extinction recall, and generalization of extinction recall in healthy humans.

Design: During the Conditioning phase, a mild, 0.5-sec shock followed conditioned stimuli (CS+s), which consisted of 2 differently colored lamps. A third lamp color was interspersed but never reinforced (CS-). Immediately after Conditioning, one CS+ was extinguished (CS+E) by presentation without shocks (Extinction phase). The other CS+ went unextinguished (CS+U). Twelve hours later, following continuous normal daytime waking (Wake group, N=27) or an equal interval containing a normal night's sleep (Sleep group, N=26), conditioned responses (CRs) to all CSs were measured (Extinction Recall phase). It was hypothesized that the Sleep versus Wake group would show greater extinction recall and/or generalization of extinction recall from the CS+E to the CS+U.

Setting: Academic medical center.

Subjects: Paid normal volunteers.

Measurements and results: Square-root transformed skin conductance response (SCR) measured conditioned responding. During Extinction Recall, the Group (Wake or Sleep) x CS+ Type (CS+E or CS+U) interaction was significant (P = 0.04). SCRs to the CS+E did not differ between groups, whereas SCRs to the CS+U were significantly smaller in the Sleep group. Additionally, SCRs were significantly larger to the CS+U than CS+E in the Wake but not the Sleep group.

Conclusions: After sleep, extinction memory generalized from an extinguished conditioned stimulus to a similarly conditioned but unextinguished stimulus. Clinically, adequate sleep may promote generalization of extinction memory from specific stimuli treated during exposure therapy to similar stimuli later encountered in vivo.

Figure 1

The experimental protocol involved a sequential fear conditioning, extinction and extinction recall protocol completed in 2 sessions separated by 12 hours. Habituation, Conditioning and Extinction phases took place at the first session occurring in the morning for the Wake group and the evening for the Sleep group. Following 12 hours that contained a normal night's sleep in the Sleep group and continuous waking in the Wake group, subjects completed the Extinction Recall phase. During the Conditioning phase, fear conditioning was established to 2 separate CS+ stimuli by following their presentation with a mild electric-shock US. Conditioning to one CS+ (the CS+E) was subsequently extinguished during the Extinction phase while the other remained unextinguished (the CS+U). CS+ stimuli were presented within photographic images of two different rooms (contexts) displayed on a computer screen. One room was the Conditioning phase context and the other the Extinction phase context. At the Extinction Recall phase that followed the 12-hour delay, both types of CS+ stimuli were presented within the Extinction phase's context.

Figure 2

Average square-root transformed SCRs during each trial of the Extinction Recall phase illustrating the significant Group × CS+ Type interaction in a 3-factor, repeated-measures ANOVA. Upper 2 graphs: interaction decomposed by CS+ Type. Lower 2 graphs: interaction decomposed by Group. Error bars represent standard error. μS: microSiemens; n.s. P > 0.1; *P < 0.05; **P < 0.01.