‘The aim is to comprehend who you are.’

For an individual investigating the brain’s capacity to forecast future experiences, little in Nghia Nguyen’s life can be labeled as predictable.

Nguyen, a graduating scholar in neuroscience, originated from the southernmost part of Vietnam, where his mother worked with banana leaves and his backyard was a rice field. “We lived in significant poverty,” he remarked. “Each day posed a challenge for survival.” Their circumstances transformed when the American Homecoming Act was implemented, allowing relatives of former American soldiers to move to the U.S. with green cards. Nguyen’s grandfather, whom he had never met, was an African American serviceman during the Vietnam War. The legislation allowed applicants to establish their racial background without a birth certificate. “When they saw my father with an afro,” he noted, “they thought, ‘This individual is clearly not entirely Vietnamese.’”

Nguyen and his family settled in Burlington, Vermont. His mother packaged sweets while his father undertook various jobs, including fueling cars and painting houses. They resided on North Street, alongside what seemed to be all other low-income and immigrant families in the vicinity, about a mile north of the downtown area.

Even though he and his sister attended schools that were not particularly well-funded, he expressed that the educators were supportive and assisted them in acquiring English skills. His parents never compelled him to work, and Nguyen and his sister directed their efforts towards achieving outstanding grades. “It wasn’t truly my parents’ expectations,” he stated. “It was merely me observing the environment around me and wondering, ‘How can I bring about change?’”

Nguyen obtained complete financial assistance at Stanford, where he quickly felt as if he was striving to catch up. “Students came in saying, ‘I’m going to opt for three courses because I already understand coding,’” Nguyen recalled. “I was like, ‘What is coding?’” He selected his major, biomechanical engineering, because it appeared to be the most practical and challenging option available.

After a year or so, he felt he had caught up with his classmates, which led him to realize that his previous disadvantage was due to a lack of opportunities rather than a difference in inherent abilities. He also received encouragement from his sister to embark on research. “I know you don’t enjoy doing things,” she urged, “but just give it a shot.”

He submitted applications for several summer research posts at on-campus laboratories and received a single offer. Upon his arrival, he recalls the professor informing him that he had not been the lab’s first preference. Nguyen didn’t mind: “I was just thrilled to be chosen.”

The task involved training mice on olfactory activities. He would present a scent to a mouse, directing it towards a specific area to earn a reward. He learned to employ a miniscope to capture live images of mouse brains as they engaged in various tasks.

Engaging in research felt like the first instance wherein his academic work genuinely related to real life, and he relished it. “Neuroscience is a profoundly rewarding pursuit because the aim is to understand yourself,” he stated. “Thus, conducting these experiments provided me with a tangible, technical justification for my daily actions. Why do I seek food when feeling hungry? Why do I experience stress during certain situations? It gave me a mechanistic explanation for why these events occur.”

After completing his undergraduate studies, Nguyen contemplated whether he should attempt to accumulate as much wealth as possible to aid his mother in retiring. “But I genuinely love neuroscience,” he confessed. “It was the sole field I was ever truly enthusiastic about.” Once he discovered that he would be compensated for pursuing Ph.D. research and that he wouldn’t be imposing a burden on his family, the choice became easier.

At Harvard, Nguyen joined the laboratory of Mark Andermann, a professor of medicine at Harvard Medical School, who investigates how the body determines which sensory cues are attended to, learned, and remembered. For his dissertation, Nguyen examined what the brain does during daydreaming or periods of inaction. “We understand which neurons are responsible for vision, hunger, thirst, and learning,” he mentioned, “but we don’t fully understand what the neurons do when we’re effectively inactive — such as sleeping or zoning out.”

Even when they appear to be not engaging in a specific task, neurons continue to activate. The field has traditionally labeled this phenomenon as “spontaneous activity,” but Nguyen believes the term is misleading. “It seems quite demanding to be firing all the time without any purpose,” he argued. “This activity is not spontaneous.”

To investigate what the brain is doing during wakeful rest, Nguyen presented mice with one of two videos displaying black and white shapes moving across a screen, tracking the activity of 7,000 neurons in the process. Between the films, Nguyen monitored their neuronal activity while they were in a dim room.

Nguyen anticipated that the mice, after viewing the videos, would mentally replay the films during breaks, recalling their previous experience. The hypothesis aligned with the field’s established notion of replay or reactivation — that following an experience, you recall it in your mind. Over time, after repeated exposure, differentiating between distinct stimuli becomes simpler. Your experience observing a painting for the 60th time is not the same as your first viewing.

However, Nguyen discovered that the mice’s brains did not revisit the experience of watching the films; instead, their brains effectively predicted how they would perceive the videos in the future. “It was the opposite of our expectations,” Nguyen remarked. “We never anticipated having in our minds a representation of an experience we had not yet encountered.”

The findings astonished Nguyen and were significant enough to be featured in the scientific journal Nature. “Contrary to prevailing theories,” the paper states, “reactivations systematically diverged from earlier patterns evoked by the stimulus. Instead, they were more akin to forthcoming patterns prompted by the stimulus, thereby predicting representational drift.”

Nguyen acknowledges that further research is needed to validate his conclusions, and he is eager to continue investigating similar questions in upcoming studies. He also wishes to delve into other findings from his project — such as how the identical neurons that processed the film fired together even before the mice observed it for the very first time.

The potential ramifications of that line of reasoning are remarkable. “Everything you will ever experience has already played out in your mind,” Nguyen said, beaming. “It’s as if before you saw me, I had already existed.”

After an unpredictable upbringing, Nguyen feels fortunate to have ended up at Harvard. “Some individuals have negative experiences during their Ph.D., but each day, I thought, ‘I’m so fortunate to engage in this work,’” he expressed. “There’s no way my parents would ever have this chance. I am living an incredibly surreal life.”