Human menstrual cycle variation in subcortical functional brain connectivity: a multimodal analysis approach

Area of Science:

• Neuroscience
• Neuroimaging
• Endocrinology

Background:

• Endogenous sex steroid fluctuations during the menstrual cycle (MC) are increasingly linked to changes in human brain functional connectivity.
• Resting-state fMRI (RS-fMRI) studies on MC-related connectivity are limited and show inconsistent findings, potentially due to methodological variations and small sample sizes.
• Hormonal shifts during the MC may induce subtle yet significant alterations in brain network dynamics, particularly in key functional areas.

Purpose of the Study:

• To investigate the impact of menstrual cycle phase on brain functional connectivity using a multimodal, region-of-interest (ROI)-based approach.
• To identify specific changes in intrinsic connectivity networks, global connectivity hierarchy, oscillatory activity, and seed-based functional connectivity across different MC phases.
• To provide a more robust understanding of hormonal modulation of brain networks by employing standardized analytical methods and a focused ROI strategy.

Main Methods:

• Sixty naturally cycling women underwent RS-fMRI scans during three distinct MC phases.
• Group-independent component analyses (G-ICA) were used to identify intrinsic connectivity networks.
• Eigenvector centrality (EC), amplitude of low-frequency fluctuations (ALFF), and seed-based analyses were applied to predefined ROIs (hippocampus, caudate, putamen) to assess global and local connectivity.

Main Results:

• During the luteal phase, decreased intrinsic connectivity was observed between the right angular gyrus and the default mode network.
• Heightened eigenvector centrality (EC) in the hippocampus and increased amplitude of low-frequency fluctuations (ALFF) in the caudate nucleus were noted during the luteal phase.
• Stronger putamen-thalamic connectivity was found in the luteal phase, while stronger fronto-striatal connectivity was observed in the pre-ovulatory phase.

Conclusions:

• Hormonal fluctuations across the menstrual cycle significantly modulate brain functional connectivity in specific networks and regions.
• Observed changes in brain connectivity during the luteal and pre-ovulatory phases may underlie associated behavioral, emotional, and sensorimotor variations.
• The proposed ROI-based multimodal approach offers a promising strategy for detecting subtle, phase-dependent alterations in brain network dynamics.