Progesterone mediates brain functional connectivity changes during the menstrual cycle—a pilot resting state MRI study

Abstract

The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC) mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral dorsolateral prefrontal cortex (DLPFC) and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal Resting-state functional Magnetic Resonance Imaging (rs-fMRI) design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.

Using positron emission tomography to investigate hormone-mediated neurochemical changes across the female lifespan: implications for depression

“…Specifically, they observed a positive correlation between daily oestrogen level and microstructural integrity in the bilateral hippocampus with zero time lag, and the same oestrogen levels were negatively correlated with radial diffusivity. This paper extended previous papers that show menstrual cycle associated fluctuations in functional connectivity, particularly in the hippocampus (Ar elin et al, 2015;Lisofsky et al, 2015), by measuring on a daily basis. These in vivo findings from human neuroimaging studies further support the extensive evidence from animal research for an immediate subsequent effect of acute changes in oestrogen on brain plasticity across the menstrual cycle.…”

Functional Brain Networks Are Altered in Type 2 Diabetes and Prediabetes: Signs for Compensation of Cognitive Decrements? The Maastricht Study

“…Therefore, an investigation of the functional network properties of participants with diabetes and severe complications would be interesting. Third, numerous other factors of potential influence that deserve attention could not be investigated, for instance, the effects of sleep, fasting, estrogen/hormone medication, therapy compliance, and disease duration (45)(46)(47)(48). Finally, the effect of diabetes medication within the diabetes group (treated vs. untreated) should be investigated in future studies.…”

Hippocampal fractional amplitude of low‐frequency fluctuation and functional connectivity changes in premenstrual syndrome

“…Regarding function, Lisofsky et al found that the connectivity between the HIPP and the superior parietal lobe was significantly strengthened during the late luteal phase. In addition, Arelin et al reported that the menstrual cycle substantially impacted intrinsic function and the connectivity of the HIPP with brain areas associated with contextual memory‐regulation . Taken together, these structural and functional imaging findings indicate that hippocampal changes are involved in menstrual cycle‐related variations.…”

“…In addition, a functional connectivity (FC) method is used to describe the relationships between the neuronal activation patterns of anatomically distinct brain regions, revealing the level of functional communication between them . Two recent studies of resting state connectivity in females have demonstrated that the FC method shows sensitivity to investigate resting state connectivity data across the menstrual cycle . Thus, combining fALFF and FC may provide new insight into the complex role of the HIPP in the neural mechanisms of PMS.…”