Diurnal fluctuations in steroid hormones tied to variation in intrinsic functional connectivity in a densely sampled male

Most of mammalian physiology is under the control of biological rhythms, including the endocrine system with time-varying hormone secretion. Precision neuroimaging studies provide unique insights into the means through which our endocrine system regulates dynamic properties of the human brain. Recently, we established estrogen’s ability to drive widespread patterns of connectivity and enhance the functional efficiency of large-scale brain networks in a woman sampled every 24h across 30 consecutive days, capturing a complete menstrual cycle. Steroid hormone production also follows a pronounced sinusoidal pattern, with a peak in testosterone between 6-7am and nadir between 7-8pm. To capture the brain’s response to diurnal changes in hormone production, we carried out a companion precision imaging study of a healthy adult man who completed MRI and venipuncture every 12-24 hours across 30 consecutive days. Results confirmed robust diurnal fluctuations in testosterone, cortisol, and estradiol. Standardized regression analyses revealed predominantly positive associations between testosterone, cortisol, and estradiol concentrations and whole-brain patterns of coherence. In particular, functional connectivity in Dorsal Attention and Salience/Ventral Attention Networks were coupled with diurnally fluctuating hormones. Further, comparing dense-sampling datasets between a man and naturally-cycling woman revealed that fluctuations in sex hormones are tied to patterns of whole-brain coherence to a comparable degree in both sexes. Together, these findings enhance our understanding of steroid hormones as rapid neuromodulators and provide evidence that diurnal changes in steroid hormones are tied to patterns of whole-brain functional connectivity. Significance Statement Diurnal variation is an essential biorhythm, yet the relationship between diurnal fluctuations in steroid hormones and the functional architecture of the human brain is virtually unknown. This precision neuroimaging study suggests that endogenous fluctuations in testosterone, estradiol, and cortisol concentrations are tied to rhythmic changes in coherence across the brain. Precision imaging studies that track individuals across major endocrine transitions (e.g. the diurnal cycle and menstrual cycle) demonstrate steroid hormones’ ability to modulate the functional architecture of the brain in both sexes, and provide a starting point for future studies to probe the functional significance of these rhythms for behavior.