Professor Demystifies Memory to Advance Dementia Care
New biomedical engineering professor studies the processes underpinning memory formation to create better therapies for cognitive disorders
Memories are crucial to shaping someone's identity: by remembering key moments and the people who have brought meaning to their life, one reaches toward the essence of who they are. Yet, the mechanisms the brain uses to structure those memories are poorly understood.
Jie Zheng, a new assistant professor in the Department of Biomedical Engineering at the University of California, Davis and the Department of Neurological Surgery at UC Davis Health, wants to demystify the mechanisms and principles that underpin cognitive functions, particularly episodic memory. This type of memory enables the recall of past experiences, such as the details of a 5th birthday party (say, feelings of happiness and the color of the balloons) or the first day of high school.
Through a deeper understanding of the systems that create and store memories, Zheng hopes to improve medical interventions for cognitive disorders like dementia. So far, in support of her outstanding research, she has received a K99/R00 award from the National Institute of Health's Brain Research Through Advancing Innovative Neurotechnologies, or BRAIN, Initiative and earned a Cermak-Corkin Postdoctoral award from the Memory Disorders Research Society in 2023.
Signaling a Different Approach
Not unlike an electrical communication system, the brain uses multiple frequency bands to share information. This similarity fascinates and drives Zheng, who took a circuitous route to cognitive neuroscience.
Within her first two years as a Ph.D. student at the University of California, Irvine, she was building off her bachelor's in electrical engineering through a program rooted in signal processing, or the analysis, modification and synthesis of data stored in electrical signals. A fortuitous meeting with the principal investigator of the lab next door made her reconsider her path.
"They were doing a lot of cool stuff with brain signals and how human cognitive functions work," Zheng said, describing the Human Intracranial Electrophysiology Lab led by Professor of Clinical Neurology Jack Lin. "I was chatting with [Professor Lin], and I realized, 'Oh, maybe I can utilize my signal processing skills to understand the biological and physiological functions in humans.'"
Zheng quickly switched to Lin's lab and learned to analyze brain signals recorded from intracranial electrophysiology — a clinical practice of monitoring the brain's electrical activity in patients by inserting electrodes within the skull.
While her research program pivoted to focus on emotional memory processing and investigating ways to improve therapies for memory disorders, her approach to these neurological questions remained rooted in the engineering field of signal processing.
"I think the engineering side of the question is critical," she said, "because we need to understand the brain. If we can know how memory works, maybe we can invent some closed-loop stimulation device to help patients with memory disorders or other cognitive function deficits."
Giving Shape to Memory
After receiving her doctorate in biomedical engineering from UC Irvine in 2018, Zheng accepted a postdoctoral research fellowship at Boston Children's Hospital, the primary pediatric teaching hospital of Harvard Medical School.
Through the fellowship, Zheng continued her training in intracranial electrophysiology. She also began focusing on single cell recording in humans, a highly specialized technique used in select laboratories worldwide. It requires neurosurgeons to place a specific electrode inside a skull to allow researchers to capture the activity of a single neuron, as well as brain waves.
With these tools, Zheng was able to make a groundbreaking discovery about how the brain is able to segment continuous experiences into events, the fundamental building blocks of memory.
The brain has two distinct types of neurons that activate when it encounters cognitive boundaries. Cognitive boundaries can be thought of as edits in a movie. A soft boundary would be a scene that shows someone walking down the street from various angles while a hard boundary would be a clip that cuts from a couple eating dinner at a restaurant to them driving home in a car.
From observing how neurons fired in patients as they watched film clips with different editing and storytelling techniques, Zheng found that there is one type of neuron that fires a lot at both soft and hard boundaries, helping pinpoint moments within a larger event, while another fires strongest at hard boundaries to establish when an event begins or ends. She calls the former boundary neurons and the latter event neurons.
The study is the first big step in Zheng's goal of understanding the mechanisms behind the brain's ability to break continuous experiences into specific memories and may prove important for treating people with memory disorders. It also serves as a signpost of the work Zheng will do in her lab at UC Davis.
"We want to extend this study to more real-life scenarios," she said. "In daily life, we don't really have those very sharp cuts seen in movies, so making more naturalistic moments, like going into a grocery store or walking through different places, and seeing how those neurons respond to a more continuous setup."
Zhang also wants to investigate how cognitive boundaries operate when someone is reading a book or listening to a podcast, among other research to explore the connections between emotions and the strength of memories.
Breaking Down Boundaries to Science
Throughout her career, Zheng has been very active in leadership and service roles.
She has started several services from the ground up, such as co-founding the Graduate Association of Biomedical Engineering Students at UC Irvine. Most recently, she served as co-chair of a mentoring committee and was a member of the Research Equity Diversity Inclusion steering committee at Boston Children's Hospital. She's currently an active member of Women in Neural Engineering, the Society for Neuroscience and the Memory Disorders Research Society.
She has collaborated with Frontiers for Young Minds, a journal that works with child scientists on accessible peer-reviewed articles, believing that translating science into accessible language inspires a lot of new ideas.
Since 2016, she has also mentored 16 students, from high schoolers to Ph.D. candidates at Harvard University. Mentorship is important to her, both academically and professionally.
"As a woman, I feel like there are still a lot of burdens for female scientists, especially after graduate school," Zheng said. "I saw a lot of people give up. I want to put myself [out there], and if there are any things my experiences can help with, I want to share that."