Cerebellar network organization across the human menstrual cycle.

The cerebellum contains the vast majority of neurons in the brain and houses distinct functional networks that constitute at least two homotopic maps of cerebral networks. It is also a major site of sex steroid hormone action. While the functional organization of the human cerebellum has been characterized, the influence of sex steroid hormones on intrinsic cerebellar network dynamics has yet to be established. Here we investigated the extent to which endogenous fluctuations in estradiol and progesterone alter functional cerebellar networks at rest in a woman densely sampled over a complete menstrual cycle (30 consecutive days). Edgewise regression analysis revealed robust negative associations between progesterone and cerebellar coherence. Graph theory metrics probed sex hormones' influence on topological brain states, revealing relationships between sex hormones and within-network integration in Ventral Attention, Dorsal Attention, and SomatoMotor Networks. Together these results suggest that the intrinsic dynamics of the cerebellum are intimately tied to day-by-day changes in sex hormones.

Progesterone shapes medial temporal lobe volume across the human menstrual cycle.

The rhythmic production of sex steroid hormones is a central feature of the mammalian endocrine system. In rodents and nonhuman primates, sex hormones are powerful regulators of hippocampal subfield morphology. However, it remains unknown whether intrinsic fluctuations in sex hormones alter hippocampal morphology in the human brain. In a series of dense-sampling studies, we used high-resolution imaging of the medial temporal lobe (MTL) to determine whether endogenous fluctuations (Study 1) and exogenous manipulation (Study 2) of sex hormones alter MTL volume over time. Across the menstrual cycle, intrinsic fluctuations in progesterone were associated with volumetric changes in CA2/3, entorhinal, perirhinal, and parahippocampal cortex. Chronic progesterone suppression abolished these cycle-dependent effects and led to pronounced volumetric changes in entorhinal cortex and CA2/3 relative to freely cycling conditions. No associations with estradiol were observed. These results establish progesterone's ability to rapidly and dynamically shape MTL morphology across the human menstrual cycle.

Functional reorganization of brain networks across the human menstrual cycle.

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 progesterone's 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 progesterone's 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 brain's functional organization. As these results indicate, taking endocrine factors into account is critical for fully understanding the intrinsic dynamics of the human brain.