Dynamic community detection reveals transient reorganization of functional brain networks across a female menstrual cycle

Abstract

<jats:title>Abstract</jats:title><jats:p>Sex steroid hormones have been shown to alter regional brain activity, but the extent to which they modulate connectivity within and between large-scale functional brain networks over time has yet to be characterized. Here, we applied dynamic community detection techniques to data from a highly sampled female with 30 consecutive days of brain imaging and venipuncture measurements to characterize changes in resting-state community structure across the menstrual cycle. Four stable functional communities were identified consisting of nodes from visual, default mode, frontal control, and somatomotor networks. Limbic, subcortical, and attention networks exhibited higher than expected levels of nodal flexibility, a hallmark of between-network integration and transient functional reorganization. The most striking reorganization occurred in a default mode subnetwork localized to regions of the prefrontal cortex, coincident with peaks in serum levels of estradiol, luteinizing hormone, and follicle stimulating hormone. Nodes from these regions exhibited strong intra-network increases in functional connectivity, leading to a split in the stable default mode core community and the transient formation of a new functional community. Probing the spatiotemporal basis of human brain–hormone interactions with dynamic community detection suggests that ovulation results in a temporary, localized patterns of brain network reorganization.</jats:p><jats:sec><jats:title>Author Summary</jats:title><jats:p>Sex steroid hormones influence the central nervous system across multiple spatiotemporal scales. Estrogen and progesterone concentrations rise and fall throughout the menstrual cycle, but it remains poorly understood how day-to-day fluctuations in hormones shape human brain dynamics. Here, we assessed the structure and stability of resting-state brain network activity in concordance with serum hormone levels from a female who underwent fMRI and venipuncture for 30 consecutive days. Our results reveal that while network structure is largely stable over the menstrual cycle, there is temporary reorganization of several largescale functional brain networks during the ovulatory window. In particular, a default mode subnetwork exhibits increased connectivity with itself and with regions from temporoparietal and limbic networks, providing novel perspective into brain-hormone interactions.</jats:p></jats:sec>

Spectral dynamic causal modelling in healthy women reveals brain connectivity changes along the menstrual cycle

“…Remarkably, these findings suggest that the decomposition of DMN into anterior and posterior components, often described in ICA-analyses 24,55 at least in women, respond to hormonal factors. Relatedly, the PCC has been already identified not only as a highly interconnected node that may functionally switch between different brain networks 56 , but also as the most flexible node around the ovulatory window 13,14 . In Mueller et al study 13 , around ovulation, the PCC increased its functional connectivity to other nodes, including prefrontal areas related to the DMN, not included in our model.…”

“…Relatedly, the PCC has been already identified not only as a highly interconnected node that may functionally switch between different brain networks 56 , but also as the most flexible node around the ovulatory window 13,14 . In Mueller et al study 13 , around ovulation, the PCC increased its functional connectivity to other nodes, including prefrontal areas related to the DMN, not included in our model. The present results corroborate estradiol's suggested role as a facilitator for this function 13,14 , and extend previous work by adding the direction in which its levels affect the PCC connectivity, being mostly the efferent connections to the other networks the ones positively related to estradiol levels (Fig.…”

“…More importantly, as evidenced in hormonal replacement studies in rodents 9 and nonhuman primates [10][11][12] at least some of the reported neuroactive effects are dependent on a cyclic variation of hormone levels, as opposed to a continuous schedule of treatment. Although in humans such multilevel relationships between molecular mechanisms and neural functions are more difficult to determine, new results hint that neural reorganization attributed to the hormones also appears abolished when the endogenous fluctuation of ovarian hormones is disrupted [13][14][15] . This emphasizes the importance of studying menstrual cycle-related neural changes in healthy subjects, which still remains underinvestigated.…”

“…Further analyses in this dataset showed that during this time window several brain nodes increased their flexibility, defined as a measure of how often each node changes its affiliation among different networks or functional modules. Specifically, limbic and subcortical nodes were more flexible around ovulation and the mid-luteal phase, while the posterior DMN (PCC) was most flexible around ovulation, followed by an increased stability after the estradiol's peak 13 . Within the SN, higher activity and connectivity have been consistently reported during the luteal cycle phase and related to higher progesterone levels, both at rest and during tasks 35,36 .…”

Cerebellar network organization across the human menstrual cycle

“…The field of network neuroscience has begun to use dense-sampling methods to probe the properties of the human brain over unprecedented timescales to study the dynamic time-varying properties of the human brain over days, weeks, months, and years [34][35][36][37][38] . In a recent densesampling study from our group, a woman underwent 30 consecutive days of brain imaging and venipuncture across a complete menstrual cycle, revealing estradiol and progesterone's ability to modulate widespread patterns of connectivity across the cortex 37,39 . Given the sensitivity of the cerebral cortex to endogenous fluctuations in sex steroid hormones 33,37,[39][40][41] and accumulating evidence for sex hormone action in the cerebellum 42,43 , here we tested the hypothesis that sex hormones impact the intrinsic day-to-day dynamics of cerebellar circuits.…”