Applying dense-sampling methods to reveal dynamic endocrine modulation of the nervous system

Laura Pritschet, Caitlin M Taylor, Tyler Santander, Emily G Jacobs, Laura Pritschet, Caitlin M Taylor, Tyler Santander, Emily G Jacobs

Abstract

The brain is an endocrine organ whose day-to-day function is tied to the rhythmic production of neuromodulatory hormones. Yet, traditional approaches to studying brain-hormone relationships in humans are often coarse in scope. By contrast, dense-sampling neuroimaging offers the unique ability to probe dynamic interactions between the nervous and endocrine systems. This review summarizes recent evidence of sex hormones' influence on structural and functional properties of the human brain. In particular, findings from the '28andMe' project suggest that estradiol modulates the topology of large-scale functional brain networks and progesterone rapidly shapes medial temporal lobe morphology across the menstrual cycle. This nascent body of work sets the stage for additional studies in larger cohorts. We end by discussing the potential of dense-sampling designs to further elucidate endocrine modulation of the brain, with implications for personalized medicine.

Keywords: MRI; deep imaging; personalized medicine; sex hormones.

Conflict of interest statement

COI The authors have no conflicts of interest to declare.

Figures

Figure 1.. Estradiol has a robust impact…
Figure 1.. Estradiol has a robust impact on intrinsic brain network properties in a densely sampled female.
A) Transient changes in estradiol across the menstrual cycle were associated with whole-brain coherence at rest (left) [9]. Warmer colors indicate increased coherence with higher concentrations of estradiol; cool colors indicate the reverse. Nodes without significant edges are omitted for clarity. Ovarian steroid hormones (estradiol, progesterone) and gonadotropin (LH, FSH) concentrations are plotted across the 30-day study (right).B) Time-lagged analyses suggest that estradiol drives Default Mode Network topology (left). Observed data (solid lines) vs. Vector Autoregressive model fits (dotted lines) are depicted for within-network efficiency (right). Note that the peak/trough of DMN network efficiency coincides with estradiol’s characteristic rise and fall across the ovulatory window (gray band) [9]. C) Network flexibility (calculated over a 5-day sliding window [27]) was also noticeably higher in many regions of the Temporal Parietal, Limbic, and Default Mode Networks during the ovulatory phase of the cycle. Peaks in flexibility were coincident with the ovulatory window (days 22–25) and the secondary peak in estradiol (days 5–10) (right). These findings are based on a densely-sampled female and should be examined in a larger cohort to assess generalizability. Abbreviations: DMN, Default Mode Network; DorsAttn, Dorsal Attention Network; FSH, Follicle Stimulating Hormone; LH, Luteinizing Hormone; SalVentAttn, Salience/Ventral Attention Network; SomMot, SomatoMotor Network; TempPar, Temporal Parietal Network.

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