Functional reorganization of brain networks across the human menstrual cycle

Abstract

The brain is an endocrine organ, sensitive to the rhythmic changes in sex hormone production that occurs in most mammalian species. In rodents and nonhuman primates, estrogen and progesterones impact on the brain is evident across a range of spatiotemporal scales. Yet, the influence of sex hormones on the functional architecture of the human brain is largely unknown. In this dense-sampling, deep phenotyping study, we examine the extent to which endogenous fluctuations in sex hormones alter intrinsic brain networks at rest in a woman who underwent brain imaging and venipuncture for 30 consecutive days. Standardized regression analyses illustrate estrogen and progesterones widespread associations with functional connectivity. Time-lagged analyses examined the temporal directionality of these relationships and suggest that cortical network dynamics (particularly in the Default Mode and Dorsal Attention Networks, whose hubs are densely populated with estrogen receptors) are preceded--and perhaps driven--by hormonal fluctuations. A similar pattern of associations was observed in a follow-up study one year later. Together, these results reveal the rhythmic nature in which brain networks reorganize across the human menstrual cycle. Neuroimaging studies that densely sample the individual connectome have begun to transform our understanding of the brains functional organization. As these results indicate, taking endocrine factors into account is critical for fully understanding the intrinsic dynamics of the human brain. HighlightsO_LIIntrinsic fluctuations in sex hormones shape the brains functional architecture. C_LIO_LIEstradiol facilitates tighter coherence within whole-brain functional networks. C_LIO_LIProgesterone has the opposite, reductive effect. C_LIO_LIOvulation (via estradiol) modulates variation in topological network states. C_LIO_LIEffects are pronounced in network hubs densely populated with estrogen receptors. C_LI