Oral contraceptive pill use and menstrual cycle phase are associated with altered resting state functional connectivity

Abstract

At rest, brain activity can be characterized not by an absence of organized activity but instead by spatially and temporally correlated patterns of activity. In this experiment, we investigated whether and to what extent resting state functional connectivity is modulated by sex hormones in women, both across the menstrual cycle and when altered by oral contraceptive pills. Sex hormones have been shown to have important effects on task-related activity, but few studies have investigated the extent to which they can influence the behavior of functional networks at rest. These hormones are dramatically altered by the use of hormonal contraception, which is used by approximately 100 million women worldwide. However, potential cognitive side effects of hormonal contraception have been given little attention. Here, we collected resting state data for naturally-cycling women (n=45) and women using combined oral contraceptive pills (n=46) and evaluated the differences in resting state activity between these two groups using Independent Components Analysis. We found that in the default mode network and in a network associated with executive control, resting state dynamics were altered both by the menstrual cycle and by oral contraceptive use. Specifically, the connectivity of the left angular gyrus, the left middle frontal gyrus, and the anterior cingulate cortex were different between groups. Because the anterior cingulate cortex and left middle frontal gyrus are important for higher-order cognitive and emotional processing, including conflict monitoring, changes in the relationship of these structures to the functional networks with which they interact may have important consequences for attention, affect, and/or emotion regulation.

Resting States Are Resting Traits – An fMRI Study of Sex Differences and Menstrual Cycle Effects in Resting State Cognitive Control Networks

“…Specifically, Petersen et al [94] found higher connectivity in the right anterior cingulate region for women tested in the menstrual phase (which they refer to as ‘early follicular’) as compared to the luteal phase, as well as higher connectivity in the left MFG in the menstrual phase as compared to women taking hormonal contraceptives. Despite of several methodological similarities between this and the current study, there were also some differences that might partly account for the conflicting findings.…”

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

“…Women using hormonal contraceptives have significantly larger prefrontal cortices, pre-and postcentral gyri, parahippocampal, and fusiform gyri and temporal regions, compared to women not using contraceptives (495). Resting state functional connectivity between the left angular gyrus, middle frontal gyrus, and anterior cingulated cortex are modulated by menstrual cycle phase and oral contraceptive use (489). In particular, oral contraceptive use and the luteal phase are associated with reduced connectivity between these regions, which are associated with cognitive and affective control (489).…”

“…Resting state functional connectivity between the left angular gyrus, middle frontal gyrus, and anterior cingulated cortex are modulated by menstrual cycle phase and oral contraceptive use (489). In particular, oral contraceptive use and the luteal phase are associated with reduced connectivity between these regions, which are associated with cognitive and affective control (489). Further, interhemispheric correlation between frontal regions is higher during ovulation and lower in the menses phase, whereas the opposite pattern in intrahemispheric connectivity is seen in occipital regions (583).…”

The transsexual brain – A review of findings on the neural basis of transsexualism

“…Chen, Wu, Lua, Mikyakoshi, & Nakai, 2013; Damoiseaux et al, 2008;Filippi et al, 2013; Hu et al, 2013;Petersen, Kilpatrick, Goharzad, & Cahill, 2014;Tian, Wang, Yan, & He, 2011). As transsexuals exhibit sex-atypical anatomy in several brain regions (see paragraph "Brain morphometry"), knowing whether resting-state patterns of transsexuals resemble those of subjects with the same biological sex or rather those with the same gender identity is potentially meaningful.…”