To examine whether oxytocin affected neural responses to infant laughter we contrasted the oxytocin group with the placebo group (oxytocinlaugh>control>placebolaugh>control and oxytocinlaugh>control<placebolaugh>control). There were no significant group differences in the whole brain analysis. ROI analysis showed that, compared with the placebo group, participants who received oxytocin showed reduced activation in the amygdala when they listened to infant laughter compared with control sounds. There was one significant cluster in the left amygdala and one significant cluster in the right amygdala (cluster 1: size=54, peak Z=2.79, MNI coordinates x, y, z (mm)=−22, −10, −16, cluster 2: size=22, peak Z=2.87, MNI coordinates x, y, z (mm)=24, −4, −24) (). There were no significant effects of oxytocin in the other regions of interest.
Figure 1 Oxytocin effect on bilateral amygdala (AMY) activation and mean Z-values and SEs of right amygdala activation during laugh, laugh-control, and laugh>control in the oxytocin and placebo group. ROI analysis, p<0.05, corrected by cluster (more ...)
In the whole brain analysis of functional activation the contrast of infant laughter vs
control sound revealed two large clusters of activation in the placebo group with peak voxels in the superior temporal gyri (Cluster 1: size=10
831 voxels, peak Z
=6.44, MNI coordinates x
(mm)=56, −14, −4, Cluster 2: size=7295 voxels, peak Z
=6.30, MNI coordinates x
(mm)=−58, −12, 0, see for an overview of statistics of the local maxima within these clusters). The pattern of activation included the bilateral temporal poles, the bilateral superior temporal gyrus, the bilateral OFC, the bilateral inferior and superior frontal gyrus, the bilateral amygdala, the brainstem, and the right putamen (see top panel for functional activation in the placebo group and lower panel for functional activation in the oxytocin group). ROI analyses indicated that there was no significant activation in the ventral striatum or in the insula during infant laughter compared with control sounds.
MNI Coordinates and Z-max Values for Local Maxima Within the Significantly Activated Clusters During Exposure to Infant Laughter Compared with Control Sound in the Placebo Group
Figure 2 Top panel: significant activation in bilateral temporal poles, the bilateral superior temporal gyrus (STG), the bilateral OFC, the bilateral inferior and superior frontal gyrus (IFG), the bilateral amygdala (AMY), the brainstem (BS), the ACC, and the (more ...)
In the next step we performed PPI analyses to examine whether oxytocin affected functional connectivity with the amygdala when participants listened to infant laughter compared with control sounds. The whole brain analysis revealed that oxytocin significantly enhanced connectivity between the right amygdala and the left OFC, the bilateral hippocampus, the left precuneus, the right angular gyrus, and the right middle temporal gyrus during infant laughter compared with the control sound (see and ). ROI analyses showed that functional connectivity between the bilateral amygdala and the caudal anterior cingulate was also enhanced by oxytocin during the exposure to infant laughter compared with control sounds (see and for an overview of functional connectivity in the oxytocin and placebo group). The average laugh>control connectivity change (or PPI) in the ACC in the oxytocin group was positive, but not significant (peak voxel oxytocin>placebo comparison x, y, z (mm)=−6, 10, 38, Z=2.30), whereas it is significantly increased as compared with the placebo PPI (peak voxel oxytocin>placebo comparison x, y, z (mm)=−6, 10, 38, Z=−2.56). Thus, there was a significant group difference although the PPI was not significant in the oxytocin group. We performed additional analyses examining whether left amygdala connectivity with the ACC was significantly different from right amygdala connectivity with the ACC. There was no significant difference (F (1,40)=0.19, p=0.89) and no significant hemisphere × treatment group (oxytocin vs placebo) interaction (F (1,40)=1.07, p=0.31). In sum, oxytocin decreased amygdala activation relative to the placebo condition during exposure to infant laughter and increased functional coupling between the amygdala and regions implicated in the perception and regulation of emotional cues.
Overview of Functional Connectivity During Infant Laughter Compared with Control Sound: MNI Coordinates, Cluster Size, and Z-max Values for Significant Clusters of Functional Connectivity
Figure 3 Left panel: oxytocin induced stronger functional connectivity between the right amygdala and the hippocampus (HIP), precuneus (PCC), OFC, and middle temporal gyrus (MTG) during the perception of infant laughter compared with control sound. Right panel: (more ...)
Independent-sample t-tests were used to examine the subjective rating of the laughing and control sounds. Participants who received oxytocin experienced more warm feelings (M=6.14, SD=1.11) when listening to the laughing sounds compared with participants in the placebo group (M=5.25, SD=1.62), t (39)=2.07, p<0.05 (not significant after Bonferroni correction for multiple comparisons). However, there was no significant group difference in reported affection, t (39)=1.14, p=0.26 and no significant group difference in how healthy the participants rated the laughing sound t (39)=0.49, p=0.63. Participants did not feel much irritation while listening to the control sounds (M=2.05, SD=1.32) and there was no significant group difference between the oxytocin and placebo group t (39)=0.94, p=0.35. To control for nonspecific effects of oxytocin on self-reported mood, we conducted repeated-measures analyses of variance with group (oxytocin and placebo) as between-subject factor and time (time 1: before drug administration, and time 2: after scanning) as within-subject factor. There were no significant time × group interaction effects on any of the mood items: anger F (1,40)=0.07, p=0.80, sadness F (1,40)=0.22, p=0.64, pleasantness F (1,40)=0.15, p=0.90, empathy F (1,40)=0.00, p=0.99, happiness F (1,40)=2.69, p=0.11, warm feeling F (1,40)=0.36, p=0.55, and calmness F (1,40)=0.01, p=0.91.