Oxytocin modulates fMRI responses to facial expression in macaques

Abstract

Increasing evidence has shown that oxytocin (OT), a mammalian hormone, modifies the way social stimuli are perceived and the way they affect behavior. Thus, OT may serve as a treatment for psychiatric disorders, many of which are characterized by dysfunctional social behavior. To explore the neural mechanisms mediating the effects of OT in macaque monkeys, we investigated whether OT would modulate functional magnetic resonance imaging (fMRI) responses in face-responsive regions (faces vs. blank screen) evoked by the perception of various facial expressions (neutral, fearful, aggressive, and appeasing). In the placebo condition, we found significantly increased activation for emotional (mainly fearful and appeasing) faces compared with neutral faces across the face-responsive regions. OT selectively, and differentially, altered fMRI responses to emotional expressions, significantly reducing responses to both fearful and aggressive faces in face-responsive regions while leaving responses to appeasing as well as neutral faces unchanged. We also found that OT administration selectively reduced functional coupling between the amygdala and areas in the occipital and inferior temporal cortex during the viewing of fearful and aggressive faces, but not during the viewing of neutral or appeasing faces. Taken together, our results indicate homologies between monkeys and humans in the neural circuits mediating the effects of OT. Thus, the monkey may be an ideal animal model to explore the development of OT-based pharmacological strategies for treating patients with dysfunctional social behavior.

Keywords: neuroimaging; nonhuman primate; oxytocin; social stimuli.

Fig. 1.

fMRI response to neutral faces compared with a blank screen in the localizer experiment and responses to emotional faces compared with neutral faces in the placebo condition. Face-responsive [neutral faces > blank screen, (A)] and valence effect [fearful/aggressive/appeasing faces > neutral faces (B)] activation maps are shown on lateral views of the right hemisphere of the inflated cortex (Top) and on coronal slices through the amygdala (Bottom) of monkey P. The locations of the coronal slices are marked by the black line on the lateral views. The color bars show the statistical values of the contrast between either neutral faces and a blank screen or between emotional and neutral faces. as, arcuate sulcus; ios, inferior occipital sulcus; ls, lateral sulcus; lus, lunate sulcus; pmts, posterior middle temporal sulcus; sts, superior temporal sulcus.

Fig. 2.

Averaged fMRI responses across all three subjects to various facial expressions within areas in the occipital and inferior temporal cortex in the placebo and OT conditions. Asterisks on histograms indicate a significant difference between emotional and neutral faces within treatment (*P < 0.05, **P < 0.01, ***P < 0.001) or a significant interaction between treatment and valence (^★P < 0.05, ^★★P < 0.01). FG, fear grin (fearful); N, neutral; LS, lip smack (appeasing); T, threat (aggressive).

Fig. 3.

Averaged fMRI responses across all three subjects to various facial expressions within subregions of the PFC (FEF, DLPFC, VLPFC and OFC), LIP, and the amygdala in the placebo and OT conditions. Asterisks on histograms indicate a significant difference between emotional and neutral faces within treatment (*P < 0.05, **P < 0.01, ***P < 0.001) or a significant interaction between treatment and valence (^★P < 0.05, ^★★P < 0.01).

Fig. 4.

FCMs averaged across all three subjects in the placebo condition. The FCMs evoked by neutral, fearful, aggressive, and appeasing faces are shown in A, B, C, and D, respectively. The color code indicates the level of partial pairwise correlation coefficients among the ROIs. IT, inferior temporal cortex; OC, occipital cortex.

Fig. 5.

Alteration in FCMs caused by OT administration. Differences between the placebo and OT conditions (FCMs in the placebo condition − FCMs in the OT condition) in partial pairwise correlation coefficients evoked by neutral, fearful, aggressive, and appeasing faces are shown in A, B, C, and D, respectively. The color code indicates the level of these differences. The dashed lines highlight functional coupling between the amygdala and areas in the occipital and inferior temporal cortex. Asterisks on matrices indicate a significant interaction between treatment and emotional faces versus neutral faces [(emotional vs. neutral in the placebo condition) vs. (emotional vs. neutral in the OT condition); *P < 0.05, **P < 0.01].