Oxytocin attenuates affective evaluations of conditioned faces and amygdala activity

Abstract

Social relations between humans critically depend on our affective experiences of others. Oxytocin enhances prosocial behavior, but its effect on humans' affective experience of others is not known. We tested whether oxytocin influences affective ratings, and underlying brain activity, of faces that have been aversively conditioned. Using a standard conditioning procedure, we induced differential negative affective ratings in faces exposed to an aversive conditioning compared with nonconditioning manipulation. This differential negative evaluative effect was abolished by treatment with oxytocin, an effect associated with an attenuation of activity in anterior medial temporal and anterior cingulate cortices. In amygdala and fusiform gyrus, this modulation was stronger for faces with direct gaze, relative to averted gaze, consistent with a relative specificity for socially relevant cues. The data suggest that oxytocin modulates the expression of evaluative conditioning for socially relevant faces via influences on amygdala and fusiform gyrus, an effect that may explain its prosocial effects.

Figures

Figure 1.

A, Stimuli. Four different face identities were used randomized over subjects across the four conditions defined by social relevance (direct vs averted gaze) and fear conditioning (CS+ vs CS−). B, Design. In a conditioning session, the CS+ faces were paired with shock with a 50% contingency. After conditioning, subjects were treated with either oxytocin or placebo. Treatment effects on affective associations to the faces were assessed in a testing session including likeability ratings and fMRI measurement of brain activity.

Figure 2.

A, Absolute likeability ratings in the oxytocin (left) and placebo (right) groups before and after conditioning (pretreatment 1 and 2) and before and after testing (posttreatment 1 and 2). B, Reduced likeability-based normalized evaluative conditioning index after oxytocin treatment. C, Reaction times to CS+ and CS− stimuli during testing in the two treatment groups. Slowing of CS+ reaction times characteristic of evaluative conditioning recall was abolished by oxytocin. Error bars indicate SE. *, Significant; (*), threshold significance; n.s., nonsignificant. For p values, see Results.

Figure 3.

Oxytocin modulates processing of socially relevant fear stimuli in the amygdala. A, Neural responses to CS+ relative to CS− face stimuli are stronger in the placebo than in the oxytocin group in anterior medial temporal lobe (aMTL) and ACC [(CS+ > CS−)placebo > (CS+ > CS−)oxytocin: (x, y, z) = (16, 8, −24); t = 3.70 and (x, y, z) = (10, 10, 44); t = 4.75, respectively]. B, Similar treatment effects were observed in the amygdala (Amy) when restricting the analysis to faces displaying direct gaze only [(CSdg+ > CSdg−)placebo > (CSdg+ > CSdg−)oxytocin: (x, y, z) = (18, 2, −20); t = 3.45]. C, In a three-way ANOVA, a comparison of direct- versus averted-gaze faces as a function of fear processing showed larger activation for direct gaze [(CSdg+ > CSdg−) > (CSag+ > CSag−) in the placebo group than the oxytocin group: (x, y, z) = (20, 0, −20); t = 3.55]. All activations are superimposed on a mean structural image and thresholded at p = 0.005. D, Parameter estimates characterizing the three-way interaction between fear conditioning, gaze, and treatment. Error bars indicate SE.

Figure 4.

Oxytocin modulates processing of socially relevant fear-conditioned stimuli in the fusiform gyrus. A–C, Processing of conditioned faces displaying direct gaze (CSdg+ > CSdg−) in the FFA in the placebo group [(x, y, z) = (36, −54, −12); t = 4.47] (A) and in the oxytocin group (same coordinate, no activation in FFA) (B) and the difference between the treatment groups [(x, y, z) = (38, −54, −12); t = 3.71] (C). D, Parameter estimates for the interaction in C. Error bars indicate SE. Activations are shown thresholded at p = 0.005.