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Open Access Publications from the University of California

Scholarly Works (9 results)

  • Thesis
  • Peer Reviewed
UC Santa Barbara Electronic Theses and Dissertations (2023)

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.

    Cover page: Endocrine Modulation of large-scale brain networks — implications for women’s brain health
    • Article
    • Peer Reviewed
    UC Santa Barbara Previously Published Works (2021)
    Women constitute half of the world's population, yet neuroscience research does not serve the sexes equally. Fifty years of preclinical animal evidence documents the tightly-coupled relationship between our endocrine and nervous systems, yet human neuroimaging studies rarely consider how endocrine factors shape the structural and functional architecture of the human brain. Here, we quantify several blind spots in neuroimaging research, which overlooks aspects of the human condition that impact women's health (e.g. the menstrual cycle, hormonal contraceptives, pregnancy, menopause). Next, we illuminate potential consequences of this oversight: today over 100 million women use oral hormonal contraceptives, yet relatively few investigations have systematically examined whether disrupting endogenous hormone production impacts the brain. We close by presenting a roadmap for progress, highlighting the University of California Women's Brain Initiative which is addressing unmet needs in women's health research.
      Cover page: The scientific body of knowledge - Whose body does it serve? A spotlight on oral contraceptives and women's health factors in neuroimaging.
      • Article
      • Peer Reviewed
      UC Santa Barbara Previously Published Works (2024)
      Circadian, infradian, and seasonal changes in steroid hormone secretion have been tied to changes in brain volume in several mammalian species. However, the relationship between circadian changes in steroid hormone production and rhythmic changes in brain morphology in humans is largely unknown. Here, we examined the relationship between diurnal fluctuations in steroid hormones and multiscale brain morphology in a precision imaging study of a male who completed 40 MRI and serological assessments at 7 A.M. and 8 P.M. over the course of a month, targeting hormone concentrations at their peak and nadir. Diurnal fluctuations in steroid hormones were tied to pronounced changes in global and regional brain morphology. From morning to evening, total brain volume, gray matter volume, and cortical thickness decreased, coincident with decreases in steroid hormone concentrations (testosterone, estradiol, and cortisol). In parallel, cerebrospinal fluid and ventricle size increased from A.M. to P.M. Global changes were driven by decreases within the occipital and parietal cortices. These findings highlight natural rhythms in brain morphology that keep time with the diurnal ebb and flow of steroid hormones.
        Cover page: Circadian Rhythms Tied to Changes in Brain Morphology in a Densely Sampled Male.
        • Article
        • Peer Reviewed
        UC Santa Barbara Previously Published Works (2024)
        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 how the endocrine system dynamically regulates aspects of the human brain. Recently, we established estrogens ability to drive widespread patterns of connectivity and enhance the global efficiency of large-scale brain networks in a woman sampled every 24 h 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 and 7 A.M. and nadir between 7 and 8 P.M. To capture the brains 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 h across 30 consecutive days. Results confirmed robust diurnal fluctuations in testosterone, 17β-estradiol-the primary form of estrogen-and cortisol. Standardized regression analyses revealed widespread associations between testosterone, estradiol, and cortisol concentrations and whole-brain patterns of coherence. In particular, functional connectivity in the Dorsal Attention Network was coupled with diurnally fluctuating hormones. Further, comparing dense-sampling datasets between a man and a naturally cycling woman revealed that fluctuations in sex hormones are tied to patterns of whole-brain coherence in both sexes and to a heightened degree in the male. Together, these findings enhance our understanding of steroid hormones as rapid neuromodulators and provide evidence that diurnal changes in steroid hormones are associated with patterns of whole-brain functional connectivity.
          Cover page: Diurnal Fluctuations in Steroid Hormones Tied to Variation in Intrinsic Functional Connectivity in a Densely Sampled Male.
          • Article
          • Peer Reviewed
          UC Santa Barbara Previously Published Works (2020)
          The cerebellum contains the vast majority of neurons in the brain and houses distinct functional networks that constitute at least two homotopic maps of cerebral networks. It is also a major site of sex steroid hormone action. While the functional organization of the human cerebellum has been characterized, the influence of sex steroid hormones on intrinsic cerebellar network dynamics has yet to be established. Here we investigated the extent to which endogenous fluctuations in estradiol and progesterone alter functional cerebellar networks at rest in a woman densely sampled over a complete menstrual cycle (30 consecutive days). Edgewise regression analysis revealed robust negative associations between progesterone and cerebellar coherence. Graph theory metrics probed sex hormones' influence on topological brain states, revealing relationships between sex hormones and within-network integration in Ventral Attention, Dorsal Attention, and SomatoMotor Networks. Together these results suggest that the intrinsic dynamics of the cerebellum are intimately tied to day-by-day changes in sex hormones.
            Cover page: Cerebellar network organization across the human menstrual cycle
            • Article
            • Peer Reviewed
            UC Santa Barbara Previously Published Works (2020)
            The rhythmic production of sex steroid hormones is a central feature of the mammalian endocrine system. In rodents and nonhuman primates, sex hormones are powerful regulators of hippocampal subfield morphology. However, it remains unknown whether intrinsic fluctuations in sex hormones alter hippocampal morphology in the human brain. In a series of dense-sampling studies, we used high-resolution imaging of the medial temporal lobe (MTL) to determine whether endogenous fluctuations (Study 1) and exogenous manipulation (Study 2) of sex hormones alter MTL volume over time. Across the menstrual cycle, intrinsic fluctuations in progesterone were associated with volumetric changes in CA2/3, entorhinal, perirhinal, and parahippocampal cortex. Chronic progesterone suppression abolished these cycle-dependent effects and led to pronounced volumetric changes in entorhinal cortex and CA2/3 relative to freely cycling conditions. No associations with estradiol were observed. These results establish progesterone's ability to rapidly and dynamically shape MTL morphology across the human menstrual cycle.
              Cover page: Progesterone shapes medial temporal lobe volume across the human menstrual cycle
              • Article
              • Peer Reviewed
              UC Santa Barbara Previously Published Works (2020)
              The brain is an endocrine organ, sensitive to the rhythmic changes in sex hormone production that occurs in most mammalian species. 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 functional architecture of the human brain is largely unknown. In this dense-sampling, deep phenotyping study, we examine the extent to which endogenous fluctuations in sex hormones alter intrinsic brain networks at rest in a woman who underwent brain imaging and venipuncture for 30 consecutive days. Standardized regression analyses illustrate estrogen and progesterone's widespread associations with functional connectivity. Time-lagged analyses examined the temporal directionality of these relationships and suggest that cortical network dynamics (particularly in the Default Mode and Dorsal Attention Networks, whose hubs are densely populated with estrogen receptors) are preceded-and perhaps driven-by hormonal fluctuations. A similar pattern of associations was observed in a follow-up study one year later. Together, these results reveal the rhythmic nature in which brain networks reorganize across the human menstrual cycle. Neuroimaging studies that densely sample the individual connectome have begun to transform our understanding of the brain's functional organization. As these results indicate, taking endocrine factors into account is critical for fully understanding the intrinsic dynamics of the human brain.
                Cover page: Functional reorganization of brain networks across the human menstrual cycle
                • Article
                • Peer Reviewed
                UC Santa Barbara Previously Published Works (2024)
                Pregnancy is a period of profound hormonal and physiological changes experienced by millions of women annually, yet the neural changes unfolding in the maternal brain throughout gestation are not well studied in humans. Leveraging precision imaging, we mapped neuroanatomical changes in an individual from preconception through 2 years postpartum. Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, standing in contrast to increases in white matter microstructural integrity, ventricle volume and cerebrospinal fluid, with few regions untouched by the transition to motherhood. This dataset serves as a comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to further explore and understand the maternal brain.
                  Cover page: Neuroanatomical changes observed over the course of a human pregnancy
                  • Article
                  • Peer Reviewed
                  UC Irvine Previously Published Works (2024)
                  Pregnancy is a period of profound hormonal and physiological change experienced by millions of women annually, yet the neural changes unfolding in the maternal brain throughout gestation have not been studied in humans. Leveraging precision imaging, we mapped neuroanatomical changes in an individual from preconception through two years postpartum. Pronounced decreases in gray matter volume and cortical thickness were evident across the brain, which stand in contrast to increases in white matter microstructural integrity, ventricle volume, and cerebrospinal fluid, with few regions untouched by the transition to motherhood. This dataset serves as the first comprehensive map of the human brain across gestation, providing an open-access resource for the brain imaging community to stimulate further exploration and discovery.
                    Cover page: Neuroanatomical changes observed over the course of a human pregnancyCreative Commons 'BY' version 4.0 license
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