Mapping the Mind

Junior computer science and mathematics double major Brooke Guo analyzes neural connections to understand the causes of complex brain conditions like schizophrenia. 

When Brooke Guo arrived at the University of Maryland as a freshman in 2022, she knew she wanted to help people and work in a health-related field someday. Initially, she thought that meant she was destined to become a doctor. But she soon changed her mind during her first year at Maryland.

“I found out that going to medical school didn’t really appeal to me much,” said Guo, who is now a junior computer science and mathematics double major. “After starting my classes at UMD, I soon realized that there were a lot of other ways I could still help people and improve health outcomes for everyone.” 

While she was searching for a research opportunity that would fulfill requirements for the Integrated Life Sciences program in the Honors College, Guo was quickly drawn to Jonathan Simon, a professor with joint appointments in the Department of Electrical and Computer Engineering, Department of Biology and the Institute for Systems Research. 

“I saw that his work was a combination of neuroscience and computational analysis,” Guo explained. “It jumped out to me because it uniquely blended these disciplines that I’m interested in while also doing the fundamental work that doctors will rely on to treat patients. So, I applied, got in and I’ve been conducting research there ever since my freshman spring semester.” 

Numbers and neurons

For the past two years, Guo has dedicated herself to examining brain connectivity data in Simon’s lab. Her research focuses on two distinct types of neural connections: structural and functional.

“Structural connectivity is the physical connection between brain regions—so, the actual neurons going from one place to another,” Guo explained. “Functional connectivity, on the other hand, is about brain regions that work together. For example, when your ear hears something, one part of your brain registers the sound and another part interprets the meaning of that sound. They’re functionally connected, regardless if there’s a direct structural connection.”

This distinction is particularly important for understanding conditions like schizophrenia, where auditory hallucinations are a common symptom. Researchers have observed physical brain connection differences in people with schizophrenia, but the relationship between structural and functional connectivity remains unclear. Understanding the links could help doctors diagnose patients earlier, which can enhance quality of life and reduce potential long-term complications for people with the condition.

To investigate these relationships, Guo uses diffusion tensor imaging (DTI), a specialized MRI technique that tracks water movement through neural tissue. Working with DTI scans taken from subjects across D.C., Maryland and Virginia, Guo compares connectivity patterns between people with and without schizophrenia. 

“DTI scans kind of look like colorful, abstract art pieces, but it’s one of the only ways to track structural connectivity that we currently have,” Guo said. “Water diffuses along the direction of neural fibers and the scan shows this water movement. By analyzing these patterns, we can map the brain’s structural highways.”

The work is challenging. In a single brain region, thousands of neurons might intersect in different directions. Simon noted that Guo developed a strong scientific intuition, which helped guide the project.

“When faced with roadblocks, she’s shown great persistence in figuring out how to overcome them,” Simon said. “These qualities set her apart as an outstanding young researcher, especially at the intersection of neuroscience and computation.” 

Guo’s background in computer science and applied math played a key role in her work. Using the programming languages Python and R, she processes and statistically analyzes complex datasets, hoping to identify meaningful patterns that may signal the development of schizophrenia in a human brain and point to better ways to diagnose the condition. 

“If we can identify specific connectivity patterns and structures associated with schizophrenia, scientists and health care workers might eventually develop better diagnostic tools,” Guo said. “For a long time, diagnosis has heavily relied on observing behavioral symptoms, which could be similar to those linked with other unrelated conditions. Having a distinct neurological marker would be tremendously helpful for patients suffering from schizophrenia.” 

Breaking new ground in brain science

Guo’s research has already yielded some intriguing findings that could open new avenues of study for Simon’s lab. She recently began a parallel study with her graduate student mentor, electrical engineering Ph.D. student Vrishab Commuri, on how brain connectivity changes as humans grow older. 

“Brooke is working on a project in our lab that aims to quantify the changes in the ‘circuitry’ of brain connections that naturally occur with age,” Commuri said. “These circuits carry bioelectric signals between important brain areas, so even mild degradation might give rise to mild neurological impairment associated with healthy aging.”

Preliminary findings from their project suggest that older adults (aged 65-78 years) had stronger functional connections in their temporal lobes (parts of the brain near ears that handle hearing, memory and language), which corresponded with the shorter, more direct physical connections between those brain areas. Meanwhile, younger adults (aged 18-26 years) showed stronger communication between frontal lobe areas (brain regions responsible for thinking and decision-making. 

Guo believes that this work may one day help researchers better understand normal brain aging and neural conditions like schizophrenia that occur where connectivity changes over time. She hopes that her data analyses and development of computational tools might eventually go beyond research to improve patient care. 

“Even though I’m not directly prescribing medicine or providing therapy to patients, I can provide them with the basis for better strategies to treat their conditions,” Guo said. “I probably won’t become a medical doctor, but my goal is to continue helping people by completing this crucial and fundamental research.”