‘The goal is to understand who you are.’

For someone who studies the brain’s ability to predict future experiences, there is little about Nghia Nguyen’s life that could be described as predictable.

Nguyen, a graduating student in neuroscience, was born in the very south of Vietnam, where his mother chopped banana leaves for work and his backyard was a rice paddy. “We grew up very poor,” he said. “Every day was a struggle to survive.” Their lives changed due to the American Homecoming Act, which allowed relatives of former American soldiers to immigrate to the U.S. with green cards. Nguyen’s grandfather, whom he’d never met, was an African American soldier in the Vietnam War. The law allowed applicants to prove their racial identity without a birth certificate. “When they saw my dad with an afro,” he said, “they were like, ‘This guy is clearly not full Vietnamese.’”

Nguyen and his family ended up in Burlington, Vermont. His mother packaged candy and his father took on a variety of jobs, like pumping gas and painting houses. They lived on North Street, along with seemingly all the other low-income and immigrant families in the area, about a mile north of downtown.

Though he and his sister attended schools that weren’t especially well-resourced, he said the teachers were kind and helped them learn English. His parents never made him work, and Nguyen and his sister focused their energy on getting perfect grades. “It wasn’t really even my parents’ expectations of me,” he said. “It’s just me observing the world around me and thinking, ‘How can I change that?’”

Nguyen secured full financial aid at Stanford, where he immediately felt himself playing catch-up. “Kids came in saying, ‘I’m going to skip three courses because I already know how to code,’” Nguyen recalled. “I was like, ‘What is coding?’” He picked his major, biomechanical engineering, because it seemed like the most practical and hardest option.

A year or two in, he felt like he’d caught up with his peers, which made him realize that his deficit had been because of an opportunity disparity rather than an innate skill difference. He also got encouragement from his sister to start doing research. “I know you don’t like to do stuff,” she said, “but just try it.”

He applied to several summer research positions for on-campus labs and received one offer. When he arrived, he remembers the professor telling him that he had not been the lab’s first choice. Nguyen didn’t care: “I was just glad they took me.”

The job was to train mice on olfactory tasks. He would present an odor to a mouse, which he would direct toward a certain place to earn a reward. He learned to use a miniscope to get live images of mice brains as they performed different activities.

Conducting research felt like the first time his schoolwork actually applied to real life, and he loved it. “Neuroscience is a very self-fulfilling endeavor because the goal is to understand who you are,” he said. “And so doing these experiments gave me a very technical, tangible reason for the things I do every day. Why do I go seek food when I’m hungry? Why do I feel stressed in these moments? It gave me a very mechanistic reason for exactly why these things are happening.”

After graduating from college, Nguyen wondered if he should just try to make as much money as possible to help his mother retire. “But I really love neuroscience,” he said. “It was the only thing I ever really was passionate about.” Once he realized that he was paid for doing Ph.D. research and that he wouldn’t be burdening his family, the decision was easier.

At Harvard, Nguyen joined the lab of Mark Andermann, professor of medicine at Harvard Medical School, who studies how the body determines which sensory cues are attended to, learned, and remembered. For his dissertation, Nguyen studied what the brain is doing when daydreaming or not doing anything in particular. “We know which neurons are responsible for vision, for hunger, for thirst, for learning,” he said, “but we don’t really know what the neurons are doing when we’re really doing nothing — like sleeping and zoning out.”

Even when they’re not seemingly completing a discrete task, neurons still fire. The field has historically called this behavior “spontaneous activity,” but Nguyen doesn’t think the term is accurate. “It seems pretty taxing to fire all the time and just have it be random,” he said. “This activity is not spontaneous.”

To answer what the brain was doing during wakeful rest, Nguyen showed mice one of two videos of black and white blobs moving across a screen, recording the activity of 7,000 neurons in the process. Between the movies, Nugyen peered into their neuronal activity as they sat in a dark room.

Nguyen expected that the mice, after watching the videos, would play back the movies in their head during breaks as they experienced it the previous time. The hypothesis was consistent with the field’s traditional concept of replay or reactivation — that after experiencing something, you replay that experience in your head. Over time, through repeated exposures, it becomes easier to distinguish between different stimuli. Your experience looking at a painting for the 60th time is different than your first experience looking at it.

But Nguyen found that the mice’s brains didn’t repeat the experience of watching the movies; their brains actually predicted how they would experience the movies in the future. “It was the opposite of what we expected,” Nguyen said. “We never expected to have in our mind the representation of an experience that we have not experienced yet.”

The results shocked Nguyen and were novel enough to land in the scientific journal Nature. “Contrary to prevailing theories,” the paper states, “reactivations systemically differed from previous patterns evoked by the stimulus. Instead, they were more similar to future patterns evoked by the stimulus, thereby predicting representational drift.”

Nguyen recognizes that there is more to be done to confirm his findings, and he hopes to continue working on similar problems in future research. He also wants to explore other observations from his project — like how the same neurons that processed the movie fired together even before mice watched it for the very first time.

The potential implications of that line of thinking are astounding. “Everything you will ever see ever, has already been played in your mind,” Nguyen said, smiling. “It’s like before you saw me, I’ve already existed.”

After an unpredictable upbringing, Nguyen is grateful to have wound up at Harvard. “Some people have bad experiences with their Ph.D., but every day, I thought, ‘I’m so privileged to do this stuff,’” he said. “There’s no way my parents would ever get this opportunity. I’m living such a surreal life.”