Sex differences in the functional connectivity of the amygdalae in association with cortisol

Abstract

Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal-occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required.

Keywords: Cortisol; Frontal cortex; Hippocampus; Resting-state; Striatum; Task-independent.

Figure 1

(1 column). Women had a stronger functional connectivity of the left amygdala (AMY, green) to the left hippocampus (HIP), the left inferior frontal gyrus (IFG), the left postcentral gyrus (PCG) and the left middle temporal gyrus (MTG), all in red, than men.

Figure 2

In men (blue) higher cortisol levels were associated with stronger resting-state functional connectivity (rsFC) of the left amygdala (AMY, green) with bilateral caudate nucleus (CN), left putamen (PUT), right mid-orbital frontal gyrus (OFG), left middle frontal gyrus (MFG), right superior frontal gyrus (SFG). A) depicts the regions; B) shows the association between cortisol level and rsFC of the left amygdala and SFG, MFG as well as OFG in men (blue, positive) and women (red). (log-transf.=log-transformed). Significant correlations of the whole-brain analysis (p<0.05) are marked with an asterisk.

Figure 3

(2 columns). In women (red) higher cortisol levels were associated with decreased resting-state functional connectivity (rsFC) of the left amygdala (AMY, green) with bilateral caudate nucleus (CN), left putamen (PUT), left anterior cingulate gyrus (ACC), right mid-orbital frontal gyrus (OFG), right middle frontal gyrus (MFG), right superior frontal gyrus (SFG) and left parietal-occipital sulcus (POS) with adjacent cortical regions precuneus and cuneus. A) depicts the regions; B) shows the association between cortisol level and rsFC of the left amygdala and CN, ACC, MFG, and POS in women (red, negative) and men (blue). (log-transf.=log-transformed). Significant correlations of the whole-brain analysis (p<0.05) are marked with an asterisk.

Figure 4

(2 columns). In women (red) higher cortisol levels were associated with decreased resting-state functional connectivity (rsFC) of the right amygdala (AMY, green) with left supplementary motor area (SMA) and right superior frontal gyrus (SFG). A) depicts the regions; B) shows the association between cortisol level and rsFC of the right amygdala and SFG as well as SMA in women (red, negative) and men (blue). (log-transf.=log-transformed). Significant correlations of the whole-brain analysis (p<0.05) are marked with an asterisk.

Figure 5

(1 column). Higher cortisol levels are associated with higher gray matter volume of the right amygdala (AMY, yellow) in both, women and men (log-transf.=log transformed).