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

Abstract

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.

Circadian rhythms tied to changes in brain morphology in a densely-sampled male

“…Functional coherence in posterior visual networks were particularly sensitive to TOD. Nodes belonging to central and peripheral visual networks demonstrated some of the strongest associations with diurnal variation in testosterone, estradiol, and cortisol (Grotzinger et al, 2023), paralleling the changes in GMV and CT we see here. Hormonal regulation of visual cortex has been demonstrated in rodent studies.…”

“…The methods for this study are reported in Grotzinger et al, 2023. Briefly, the participant underwent venipuncture and brain imaging every 12-24 hours for 30 consecutive days. At each session the participant completed a questionnaire to assess stress, sleep, and mood states, followed by endocrine sampling at 7 A.M. (morning sessions) and/or at 8 P.M. (evening sessions).…”

“…Resting-state functional MRI scans allowed for indirect assessments of head motion (Grotzinger et al, 2023).…”

Exploring sex-specific neuroendocrine influences on the sensorimotor-association axis in single individuals

“…Recently, a dense-sampling approach has been applied on a 23-year-old female (28&Me study; [46]) and a 26-year-old male (28&He study; [47]), who were respectively tested for 30 and 20 consecutive days in time-locked study sessions including brain imaging, venipuncture and salivary sampling, and self-report mood questionnaires. These studies -as well as subsequent studies using the female dataset (e.g., [48][49][50][51])-measured day-to-day changes in functional brain activity, reporting associations between hormonal fluctuations and the reorganization of functional networks.…”

“…In the current work, we capitalize on a dense sampling approach to investigate intraindividual variability along the S-A axis in two healthy young adults, one male and one female, from the aforementioned openly-available datasets [46,47]), probing the sexspecificity of neuroendocrine factors (i.e., steroid hormone levels), as well as perceived stress, associated with daily variability in functional brain organization. We first applied a dimensionality reduction algorithm to daily functional connectivity matrices in order to compute the S-A axis.…”