Oral Contraceptives Modulate the Relationship Between Resting Brain Activity, Amygdala Connectivity and Emotion Recognition – A Resting State fMRI Study

Abstract

Recent research into the effects of hormonal contraceptives on emotion processing and brain function suggests that hormonal contraceptive users show (a) reduced accuracy in recognizing emotions compared to naturally cycling women, and (b) alterations in amygdala volume and connectivity at rest. To date, these observations have not been linked, although the amygdala has certainly been identified as core region activated during emotion recognition. To assess, whether volume, oscillatory activity and connectivity of emotion-related brain areas at rest are predictive of participant’s ability to recognize facial emotional expressions, 72 participants (20 men, 20 naturally cycling women, 16 users of androgenic contraceptives, 16 users of anti-androgenic contraceptives) completed a brain structural and resting state fMRI scan, as well as an emotion recognition task. Our results showed that resting brain characteristics did not mediate oral contraceptive effects on emotion recognition performance. However, sex and oral contraceptive use emerged as a moderator of brain-behavior associations. Sex differences did emerge in the prediction of emotion recognition performance by the left amygdala amplitude of low frequency oscillations (ALFF) for anger, as well as left and right amygdala connectivity for fear. Anti-androgenic oral contraceptive users (OC) users stood out in that they showed strong brain-behavior associations, usually in the opposite direction as naturally cycling women, while androgenic OC-users showed a pattern similar to, but weaker, than naturally cycling women. This result suggests that amygdala ALFF and connectivity have predictive values for facial emotion recognition. The importance of the different connections depends heavily on sex hormones and oral contraceptive use.

Evaluating the Cognitive Impacts of Drospirenone, a Spironolactone-Derived Progestin, Independently and in Combination With Ethinyl Estradiol in Ovariectomized Adult Rats

“…A growing body of research supports the tenet that oral contraceptives impact cognition and alter brain function in task- and composition- dependent manners (e.g., Gogos, 2013 ; Egan and Gleason, 2012 ; Beltz et al, 2015 , 2022 ; Porcu et al, 2019 ; Taylor et al, 2020 ; Ycaza Herrera et al, 2020 ; Gravelsins et al, 2021 ; Lewis et al, 2022 ; Menting-Henry et al, 2022 ). Overall, the current series of experiments found that the spironolactone-derived progestin drospirenone has beneficial effects for spatial working memory performance in a young adult Ovx rat model, and that the synthetic estrogen EE has variable effects on behavior that depend on dose and combination with drospirenone.…”

To start or to discontinue the pill – changes in progestogens reflected by resting-state connectivity and positive mood

“…Preliminary findings suggest that androgenicity of progestins affects brain structure [72], likelihood of mood-related side effects [73] and emotion recognition performance [74]. Furthermore, the relation between RSFC and emotion recognition seems to be differently modulated by OC androgenicity [36]. Therefore, controlling for progestin types, larger sample sizes for stratification or coding of the estrogenic, progestogenic and androgenic properties to reflect biological potencies using information from in vivo bioassays and/or receptor studies [75] is recommendable to account more systematically for OC-related side-effects on the brain as well as socio-affective functions.…”

“…Hence, altered hormone-related RSFC may indeed be part of the neural mechanisms underlying hormone-related mood changes. Similarly, OC intake appears to modulate the relationship between amygdala RSFC and emotion recognition performance differently than the menstrual cycle[36]. Therefore, hormonal influences on brain regions involved in emotion recognition may lead to hormone-related differences in emotion recognition performance.…”