UC Santa Barbara

Since its inception, the field of neuroendocrinology has provided evidence for a tightly coupled relationship between the nervous and endocrine systems. In rodents and nonhuman primates, estrogen and progesterone’s impact on the brain is evident across a range of spatiotemporal scales. Yet, the influence of sex hormones on the structural and functional architecture of the human brain is largely unknown. The body of work presented in my dissertation aims to advance our understanding of the human brain through the lens of neuroendocrinology by examining how distinct hormonal transition periods shape brain morphology and function. In Study 1, I present findings from my keystone ‘28andMe’ precision imaging experiment, in which a participant underwent brain imaging and venipuncture every 24 hours over 30 consecutive days across a complete menstrual cycle and again, one year later, while on an oral hormonal contraceptive regimen. The results from this study reveal the rhythmic nature in which brain networks reorganize across the cycle, with transient increases in estradiol enhancing global efficiency of several large-scale networks. In Study 2, this approach was expanded by conducting the first precision imaging experiment on pregnancy, in which a primiparous woman underwent 26 MRI scans and venipuncture beginning 3 weeks pre-conception through two years postpartum. Pronounced decreases in gray matter volume and cortical thickness paired with increases in white matter microstructure were evident across the brain, with few regions untouched by the transition to motherhood. Finally, in Study 3, I present findings from our Midlife Hormones and Cognition Study, where a highly characterized sample of 85 midlife women (ages 43–60) in various states of ovarian decline underwent MRI scanning and venipuncture to establish how endocrine aging influences whole-brain intrinsic network organization. Results suggest that the frequency of menopause-related vasomotor and neurological symptoms exacerbate network connectivity decline in postmenopausal women, especially among higher-order cognitive networks. Together, these studies provide novel insight into the spatiotemporal extent of human brain–hormone relationships over the lifespan, a severely understudied area in cognitive neuroscience with significant implications for women’s health.