Dr. Sarah Heilbronner
Associate Professor, Baylor College of Medicine
Postdoctoral Fellow, University of Rochester
PhD, Duke University
It was the scientific process rather than any one particular topic that first drew Dr. Sarah Heilbronner to a life in research. As an undergraduate, she was in the audience for a small open house designed to introduce students to research. One of the presentations piqued her interest, and she joined the lab on a bit of a whim. Once in the lab, though, she fell in love with the process of designing and implementing experiments and analyzing results. “It just engulfed me,” she remembers. Still enchanted with scientific discovery, today Sarah is an associate professor of neurosurgery at Baylor College of Medicine, where her lab is trying to uncover the wiring diagram of the human brain.
As an undergraduate at Harvard University, Sarah joined a lab that straddled the fields of neuroscience and evolutionary biology. Specifically, her project compared how risk influences food choices in chimpanzees and bonobos. In the wild, chimps’ food comes from riskier sources than that of bonobos, and Sarah wanted to understand whether this environmental factor had shaped decision making in the two species. In Sarah’s experiment, chimps and bonobos living at a zoo were presented with two options: one bowl that always contained four pieces of food, and another bowl that sometimes contained one piece of food and sometimes contained seven pieces. She found that chimps are more risk-tolerant—more willing to risk the disappointment of receiving only one piece of food for the chance to score seven. Sarah’s finding supports the concept that ecological pressures can help shape decision making. For a while, Sarah was torn between pursuing neuroscience or primatology, as she enjoyed both aspects of her work. Ultimately, she decided that she was happier pursuing the mechanisms underlying behavior rather than the behavior itself. With this in mind, she entered the neurobiology PhD program at Duke University.
At Duke, Sarah found a home in Dr. Michael Platt’s lab, where she continued studying decision making and reward in non-human primates (NHPs), but this time focusing on electrophysiological readouts. She zeroed in on the posterior cingulate cortex (CGp), a region thought to be an important decision-making hub. Despite demonstrated evolutionary and clinical importance, however, its exact roles in reward, learning, and decision making remained unclear. Sarah made two important discoveries that shed light on CGp function. First, recording from the CGp of monkeys performing various decision tasks, Sarah discovered that CGp neurons encode the salience, but not the subjective value, of a given option during decision making. Next, Sarah probed the role of the CGp during a learning task. She found that CGp neurons responded to errors, and their activity level was magnified in more exploratory contexts (i.e., in the presence of novel stimuli and low reward). These results suggest that the CGp might monitor performance and motivate exploration.
As Sarah considered postdocs, she was also dealing with a two-body problem. Her fiancé was starting a lab at the University of Rochester, so Sarah set up a series of meetings with PIs at Rochester whose work piqued her interest. The plan was to see if any of them were a good fit, and if not, to explore elsewhere and do a long-distance relationship. One of her meetings at Rochester was with Dr. Suzanne Haber, who focused on neuroanatomy. Sarah had not spent much time thinking about neuroanatomy, and likely would never have ventured into the subfield had it not been for her personally motivated focus on Rochester labs. During their chat, Suzanne took Sarah over to a microscope to show her the results of a tract tracing experiment in a monkey brain. That moment sitting at the microscope with Suzanne changed the course of Sarah’s career. Despite her successful graduate work, Sarah had started to feel that she did not have the right temperament for electrophysiology—she was constantly worried that there were too many unexplained variables that she couldn’t control for. Peering through Suzanne’s microscope at the tracing data, Sarah felt as if she were finally face-to-face with ground truth. She could see the neural connections with her own eyes. She left that meeting newly enthralled with neuroanatomy and with the idea of having Suzanne as a mentor. Ultimately, it was an easy decision to join the Haber lab for a postdoc.
In the Haber lab, Sarah first sought a better understanding of how the axons in the cingulum bundle, one of the brain’s major white matter tracts, link several different regions involved in executive function and emotion. Using anatomical tract tracing in several different species of monkeys, Sarah found that the cingulum bundle could be divided into four unique zones based on the specific regions sending fibers through that zone. This zonation could allow for more specific targeting of connections affected in brain disorders (e.g. targeting the subgenual cingulum bundle, which has been shown to have reduced strength in individuals vulnerable to major depressive disorder). During her postdoc, Sarah became increasingly interested in how connectomics—the mapping of neural connections in the brain—could further the understanding and treatment of psychiatric disorders. While much of our understanding of circuit dysfunction in psychiatric disorders comes from rodent disease models, their implications for larger brains are not straightforward. Thus, Sarah next set out to identify the homologies of the frontal-striatal networks between rodents and primates. Her segmented maps of the rat and monkey striata can serve as a translational scaffold, enabling insights from rodent models to be more faithfully applied to primate—and ultimately human—brains. This is a theme that has continued to motivate Sarah’s independent work.
In 2017, Sarah started her lab at the University of Minnesota and began tying her work to the Human Connectome Project, which is in part run out of Minnesota’s Center for Magnetic Resonance Research. Minnesota is also home to the Center for Mesoscale Connectomics, a project focused on solving the connectome of NHPs and/or humans at the mesoscale (microns to millimeters, or the resolution of a handful of axons). The focus on brain wiring, in addition to the supportive nature of her department, made the University of Minnesota a perfect place for Sarah to launch her career. Sarah’s lab has focused on improving our understanding of human brain connectivity. She strongly believes that aberrations in connectivity underlie psychiatric disorders, and that better treating these disorders requires a deeper understanding of which connections between different brain regions are altered and in which direction (whether two brain regions are more strongly or more weakly connected to each other than in neurotypical brains). To this end, Sarah’s lab compares tract tracing experiments from NHPs to diffusion tensor imaging (DTI) data from living humans. DTI takes advantage of the fact that water diffuses differently through various tissue types and is physically constrained, such as by bundles of axons moving in the same direction. This differential diffusion allows researchers to infer the size and location of axon bundles, but analyzing these images can be a challenge. One major issue is that there is no “ground truth” from tract tracing in human brains that can be used as a reference for analysis. By directly comparing DTI and direct anatomical tract tracing in the same NHPs, Sarah hopes to better understand the relationship between DTI and “ground-truth” anatomy, a relationship that can then be used to more accurately analyze DTI images from humans.
Sarah’s lab now has a new home at Baylor College of Medicine in Houston, Texas. Here, she works closely with clinicians to translate her understanding of brain wiring into treatment for neurological disease. One of the most promising translational techniques is DBS, which involves surgical implantation of a device into the human brain to stimulate surrounding fibers. It is most often used in the treatment of Parkinson’s disease and increasingly for obsessive compulsive disorder, and Sarah sees even broader potential. Because DBS devices stimulate a certain brain region over a period of years, there is almost certainly rewiring occurring, with the connections between some regions becoming stronger, and the connections between others becoming weaker. Original DBS devices were not compatible with MRI, but new technology will allow researchers like Sarah to visualize how DBS changes brain wiring, and how those changes correlate with patient outcomes—information that would lead to even better treatment strategies and more precise DBS device placement. Ultimately, to achieve more widespread applicability, there will need to be non-surgical approaches that can alter the strength of connections among different brain regions. When that technology is ready, Sarah’s work will be among the first to inform the best strategies for rewiring the brain to cure disease.
Find out more about Sarah and her lab’s research here.
Listen to Melissa’s full interview with Sarah on March 14, 2025 below!
