When Emily Jacobs embarked on a career studying the brain in the early 2000s, a technique called functional magnetic resonance imaging, or fMRI, was having a moment. “Just like we have super powerful telescopes that can let us quantify the farthest reaches of the known universe, here we have this tool that could allow us to see the entire human brain and as a pulsing, living organ,” says Jacobs, a cognitive neuroscientist at the University of California, Santa Barbara.
By measuring changes in blood flow that serve as a proxy for brain activity, neuroscientists were getting new views of how different situations spur conversations between brain regions, and how the intensity of the conversations changes over time. “I was riding that wave of excitement,” Jacobs says.
But she soon realized there were big questions that weren’t being asked — questions important to half the world’s population. Do the natural hormonal changes that come with menstruation, pregnancy and menopause affect communication across the brain? What about hormonal contraceptives, such as the birth control pill, which are used by hundreds of millions of people globally? And what does it all mean for brain health and behavior?
The rise and fall of hormones is a big reason women have historically been excluded from biomedical research, even though hormones in men fluctuate too. The resulting gap in knowledge of female biology has led to inadequate mental, physical and reproductive health care. “Science, and especially neuroscience, has not served the sexes equally,” Jacobs says.
With a range of tools — fMRI, other types of MRI and brain imaging, blood testing, neuropsychological testing, virtual reality and more — Jacobs’ lab is trying to fill in gaps in our basic understanding of how hormones act in the human brain. And she is studying the hormones as a lens for bigger questions about brain changes.
“What’s really special about Emily’s work is that she does it at so many different levels. It’s so multifaceted,” says cognitive neuroscientist Caterina Gratton of Northwestern University in Evanston, Ill. “She has multiple different types of brain measures, from the molecular all the way up to brain systems.”
In a series of studies dubbed 28 and Me — for the 28 days of a typical menstrual cycle — Jacobs and colleagues closely monitored the brain of one woman for the duration of her natural menstrual cycle. Every 24 hours over 30 days, this 20-something woman’s brain was scanned, blood hormone levels checked and mood assessed.
As the woman’s estrogen levels peaked during ovulation, regions throughout the brain synced up. And regions in an important hub called the default mode network became tight conversationalists. What’s more, one part of this network rearranged itself to create a new and transient communication clique. After ovulation, when estrogen levels dropped and progesterone levels spiked, gray matter temporarily expanded in a brain structure tied to learning and memory.
When the same woman was examined a year later while on the pill, which quells progesterone, the changes weren’t observed.
The findings, described in 2021 in Current Opinion in Behavioral Sciences, provide strong evidence that the ebb and flow of sex hormones drives changes in the brain on a day-to-day basis, Jacobs and colleagues say. They also saw links between hormone fluctuations and brain changes in a male participant.
The observations led cognitive neuroscientist Caitlin Taylor, a postdoc in Jacobs’ lab, to wonder how the brain responds to chronic hormone suppression from oral contraceptive use. The team is launching a large-scale study to attempt to find out.
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Initially, Jacobs hesitated to green-light the research. She worried it could be twisted to erode access to contraception. Eventually, she relented, because women “deserve to have science that can serve us,” she says.
Another effort, which Jacobs and Taylor are building, will make data for such large-scale studies widely available. Called the University of California Women’s Brain Initiative, it aims to funnel records from the university system’s eight brain-imaging research centers into an open-access database. When a woman gets her brain scanned at one of the centers, her de-identified brain-imaging data, medical data and information about hormonal contraceptive use will be entered into the database. Once all eight centers are on board, there could be about 10,000 participants annually — way more than a single lab could recruit.
The expected mountain of data should be a boon to researchers asking big and small questions about brain health, Jacobs says. And she hopes it will improve women’s health care.
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