A united effort

When Abigail Greene and Daniel Barson were children growing up just north of New York City, they had no idea how intertwined their lives would become. Given their shared interests, their related futures are not surprising. Barson took a biology course in high school that asked him to write about whatever biological topic he was interested in, and he wrote about the brain. “It seems so mysterious,” he said. “It’s this ball of mush that sits in your head and defines who you are.”

Greene, who attended the same high school, was also drawn to neuroscience. “We don’t understand the brain in health well enough to understand disease,” said Greene. “If we can better understand how these processes work in the brain, we can understand how they differ in disease states.”

As teenagers, Greene and Barson participated in research that would set them on their respective paths. Barson worked in research at a nearby lab where he looked at spinal cord injuries on the cellular level to figure out why the neural cells did not regenerate. He found the work fascinating. “It seemed like the final frontier,” Barson said. Greene also joined a research lab in high school. There, she worked with Alzheimer’s patients and loved the experience.

The two young scientists started dating and then attended Princeton University together. There, Barson took a course that used math and computers to understand biological phenomena. Barson had never thought of cells as physical systems in that way before. “It was a totally new idea to me,” he said.

Greene took that same computer science course, titled “An Integrated, Quantitative Introduction to the Natural Sciences.” It opened her mind to neuroscientific possibilities. “It changed the way I think about science,” she said.

Greene and Barson were so drawn to using computers to understand neuroscience that they both applied to and enrolled in Yale School of Medicine. They also continued to be drawn to each other and got married in 2017.

Currently, Greene uses fMRI technology and machine learning to find patterns in brain imaging data at Yale. Her goal is to use neuroimaging data to predict phenotypic measures and learn more about the neural representation of the predicted phenotype. She has found that various complex phenotypes or processes do not reside in just one part of the brain but occur distributed across many areas. Particular characteristics of the brain that seem isolated or distinct often rely on a larger functional network.

“It’s the whole brain working in concert,” Greene said of her findings—work that she emphasizes is also being carried out in other laboratories. “By using machine learning approaches to identify phenotypically relevant patterns in the data, we can find these sprawling brain-phenotype relationships and better understand how they manifest themselves within the brain.”

In some ways, Barson’s neurological work at Yale could not be more different. He does not work with humans but with rodents; and he does not look at larger images of the whole brain. He looks at individual cells and whole-brain activity, seeking to bridge the knowledge gap between the two. To that end, he designs techniques to measure brain activity on both spatial scales simultaneously. “You can look at [the] whole brain and say, ‘This area relates to this task’,” said Barson. “You can also zoom in and look at interaction between neurons.”

These different angles are hugely beneficial to the two scientists. Barson’s deep knowledge of neurobiology is a sort of library Greene can consult. “Dan has an encyclopedic knowledge of the field,” she said. He often suggests she read certain papers, and the two enjoy bouncing ideas off each other.

“It’s incredibly useful to be able to come home to Abby,” said Barson. The two often work with similar types and sets of data, so they can help each other. But on an even deeper level, having two opposite perspectives on the brain—zoomed way out and zoomed way in—deepens both of their views. Scientists need both perspectives to understand the brain.

For instance, schizophrenia is correlated with problems at a cellular level: something goes wrong with connections between neurons. That is not the sort of thing you can study with an MRI; rather, it is cellular territory. But then, to understand how these cellular mutations affect the brain more broadly, physicians take a step back and look at neighborhoods of cells; long-distance connections between cells; and finally, the whole brain.

Greene helps Barson remember this bird’s-eye view. Barson, for his part, “can often lose the forest for the trees,” he said, and forgets that he is looking at brains. He sometimes overlooks the fact that his work has real-world implications for human cognition and disease. “I’ve been highly exposed to the tools of human neuroscience through Abby,” Barson said. “It has very much informed the work I do.”

Greene wants to both see patients and run a research lab, using her experiences with patients to inform her research. She is particularly interested in studying how trauma affects learning and memory. Greene hopes her work will change how doctors think about mental health. Her findings could help doctors better understand what broader processes go wrong in the brain rather than viewing mental disorders as a collection of symptoms. After all, two people can have the same neural problems and experience completely different symptoms, and vice versa. By finding the root of the problem, physicians could provide more effective treatment.

Barson also wants to both treat patients and study the effects of that treatment in a formal setting. He points out that neurological disorders are some of the costliest and most disabling of all diseases. “We’re spending the most money and feeling the most heartbreak over this,” he said. “There are very few solutions. Treatments are few and far between.”

He is especially interested in working with children because they have greater developmental plasticity than adults and therefore have so much potential. “You could change the course of their lives,” he said.