Many studies have shown that the human endocrine system modulates brain function, reporting associations between fluctuations in hormone concentrations and brain connectivity. However, how hormonal fluctuations impact fast changes in brain network organization over short timescales remains unknown. Here, we leverage a recently proposed framework for modeling co-fluctuations between the activity of pairs of brain regions at a framewise timescale. In previous studies we showed that timepoints corresponding to high-amplitude co-fluctuations disproportionately contributed to time-averaged functional connectivity pattern and that these co-fluctuation patterns could be clustered into a low-dimensional set of recurring “states”. Here, we assessed the relationship between these network states and quotidian variation in hormone concentrations. Specifically, we were interested in whether the frequency with which network states occurred was related to hormone concentration. We addressed this question using a dense-sampling dataset ( N = 1 brain). In this dataset, a single individual was sampled over the course of two endocrine states: a natural menstrual cycle and while the subject underwent selective progesterone suppression via oral hormonal contraceptives. During each cycle, the subject underwent 30 daily resting-state fMRI scans and blood draws. Our analysis of the imaging data revealed two repeating network states. We found that the frequency with which state 1 occurred in scan sessions was significantly correlated with follicle-stimulating and luteinizing hormone concentrations. We also constructed representative networks for each scan session using only “event frames” – those time points when an event was determined to have occurred. We found that the weights of specific subsets of functional connections were robustly correlated with fluctuations in the concentration of not only luteinizing and follicle-stimulating hormones, but also progesterone and estradiol. Author Summary We study a dense sampling dataset of one brain ( N = 1) imaged across two complete menstrual cycles (60 scan sessions). We identify network states – high-amplitude patterns of time-varying connectivity that reoccur across scan sessions – and show that the frequency with which states occur is linked to endogenous fluctuations in follicle-stimulating and luteinizing hormones. We further show that the weights of scan-specific and whole-brain co-fluctuation patterns are broadly associated with hormone fluctuations.

Network models describe the brain as sets of nodes and edges that represent its distributed organization. So far, most discoveries in network neuroscience have prioritized insights that highlight distinct groupings and specialized functional contributions of network nodes. Importantly, these functional contributions are determined and expressed by the web of their interrelationships, formed by network edges. Here, we underscore the important contributions made by brain network edges for understanding distributed brain organization. Different types of edges represent different types of relationships, including connectivity and similarity among nodes. Adopting a specific definition of edges can fundamentally alter how we analyze and interpret a brain network. Furthermore, edges can associate into collectives and higher order arrangements, describe time series, and form edge communities that provide insights into brain network topology complementary to the traditional node-centric perspective. Focusing on the edges, and the higher order or dynamic information they can provide, discloses previously underappreciated aspects of structural and functional network organization.

Functional connectivity (FC) describes the statistical dependence between neuronal populations or brain regions in resting-state fMRI studies and is commonly estimated as the Pearson correlation of time courses. Clustering or community detection reveals densely coupled sets of regions constituting resting-state networks or functional systems. These systems manifest most clearly when FC is sampled over longer epochs but appear to fluctuate on shorter timescales. Here, we propose a new approach to reveal temporal fluctuations in neuronal time series. Unwrapping FC signal correlations yields pairwise co-fluctuation time series, one for each node pair or edge, and allows tracking of fine-scale dynamics across the network. Co-fluctuations partition the network, at each time step, into exactly two communities. Sampled over time, the overlay of these bipartitions, a binary decomposition of the original time series, very closely approximates functional connectivity. Bipartitions exhibit characteristic spatiotemporal patterns that are reproducible across participants and imaging runs, capture individual differences, and disclose fine-scale temporal expression of functional systems. Our findings document that functional systems appear transiently and intermittently, and that FC results from the overlay of many variable instances of system expression. Potential applications of this decomposition of functional connectivity into a set of binary patterns are discussed. Author Summary Numerous studies of functional connectivity have revealed densely coupled sets of brain regions corresponding to resting-state networks or functional systems. Prior work suggests that functional connectivity fluctuates over time. Here, we extend those studies by suggesting that functional connectivity can be decomposed into a set of momentary network states, with each one partitioning the network into exactly two clusters or communities. We show that these bipartitions exhibit characteristic spatiotemporal patterns that are reproducible across participants and imaging runs, and can capture individual differences. Our decomposition approach discloses fine-scale dynamics of functional systems, and reveals that functional systems coalesce and dissolve at different times and on fast timescales. Numerous applications and extensions of the approach are discussed.