Sex differences in effective fronto-limbic connectivity during negative emotion processing

Psychoneuroendocrinology. 2015 Dec;62:180-8. doi: 10.1016/j.psyneuen.2015.08.012. Epub 2015 Aug 17.


Background: In view of the greater prevalence of depression and anxiety disorders in women than in men, functional magnetic resonance imaging (fMRI) studies have examined sex-differences in brain activations during emotion processing. Comparatively, sex-differences in brain connectivity received little attention, despite evidence for important fronto-limbic connections during emotion processing across sexes. Here, we investigated sex-differences in fronto-limbic connectivity during negative emotion processing.

Methods: Forty-six healthy individuals (25 women, 21 men) viewed negative, positive and neutral images during an fMRI session. Effective connectivity between significantly activated regions was examined using Granger causality and psychophysical interaction analyses. Sex steroid hormones and feminine-masculine traits were also measured.

Results: Subjective ratings of negative emotional images were higher in women than in men. Across sexes, significant activations were observed in the dorso-medial prefrontal cortex (dmPFC) and the right amygdala. Granger connectivity from right amygdala was significantly greater than that from dmPFC during the 'high negative' condition, an effect driven by men. Magnitude of this effect correlated negatively with highly negative image ratings and feminine traits and positively with testosterone levels.

Discussion: These results highlight critical sex differences in brain connectivity during negative emotion processing and point to the fact that both biological (sex steroid hormones) and psychosocial (gender role and identity) variables contribute to them. As the dmPFC is involved in social cognition and action planning, and the amygdala-in threat detection, the connectivity results suggest that compared to women, men have a more evaluative, rather than purely affective, brain response during negative emotion processing.

Keywords: Effective connectivity; Emotion; Sex steroid hormones; Sex/gender differences; fMRI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention / physiology
  • Emotions / physiology*
  • Estradiol / blood
  • Female
  • Frontal Lobe / physiology*
  • Humans
  • Limbic System / physiology*
  • Magnetic Resonance Imaging
  • Male
  • Neural Pathways / physiology
  • Photic Stimulation
  • Progesterone / blood
  • Sex Characteristics*
  • Testosterone / blood
  • Young Adult


  • Testosterone
  • Progesterone
  • Estradiol