Hormone-Dependent Microstates and the Reconfiguration of Resting-State Dynamics across the Menstrual Cycle

Abstract

While behavioral fluctuations across the menstrual cycle (MC) are well-documented, the neural underpinnings of these changes remain elusive. This study investigated the hypothesis that cyclic variations in sex hormones modulate large-scale brain activation patterns. To test this, longitudinal magnetoencephalographic (MEG) recordings were acquired and source reconstructed from 24 naturally cycling women across three distinct MC phases: early follicular, peri-ovulatory, and mid-luteal. Microstate analysis was employed to characterize large-scale cortical dynamics as "visits" to specific global configurations (i.e., maps) of brain activity. Our results revealed significant variations in the occurrence of specific microstate maps, particularly between the early follicular and mid-luteal phases. Furthermore, the occurrence of these specific configurations was significantly associated with fluctuations in hormone levels. Critically, both the hormonal levels and microstate dynamics were predictive of individual longitudinal changes in psychological well-being. These findings propose a neurophysiological substrate for the behavioral effects of hormonal cycling, identifying specific topographic maps whose dynamics are sensitive to the hormonal profile and carry predictive power for psychological health. Collectively, these results underscore the necessity of accounting for the MC in neuroimaging research and introduce a novel framework for defining microstates (Hormone-Dependent Microstates - HDMs) with respect to slowly changing dynamical properties across a month-long timescale.