Positive feedback is helpful for learning, but usually, our greatest lessons actually come from failure— and a new project at the University of Pittsburgh aims to uncover the neural mechanisms behind this phenomenon.

Helen Schwerdt, assistant professor of bioengineering at Pitt’s Swanson School of Engineering, received a five-year, $2.5 million R01 award from the National Institutes of Health (NIH) to study dopamine’s role in learning. Schwerdt’s team develops novel multimodal neural interfaces to understand how the brain and pathological mechanisms work and to improve treatment of debilitating neurological disorders.

“We’re interested in developing technologies to measure molecules in the brain, and figuring out how to optimally combine these types of molecular measurements with the conventional electrical measurements that we typically use to look at brain activity.” Schwerdt said. “Communication between neurons occurs both electrically and chemically, but the chemical aspect is less understood because we haven’t had the right tools to measure these signals together.”

Dopamine is a neurotransmitter found in the brain that plays a role in many body functions, including memory, movement, motivation, mood, attention and more. Schwerdt plans to investigate the lesser-known role of dopamine in learning, especially its connection to learning from punishment, which has received less attention compared to its role in reward systems.

“Reward is very important, and it’s an incentive for us to learn new things. But in real life, we commonly learn from negative incentives as well.” Schwerdt said. “The question is, how does the brain handle these two different types of incentives — is it the same circuits and the same neurons that handle both reward and punishment, or are they different?”

Schwerdt’s team has developed a method for sustained dopamine monitoring by implanting neural interfaces in Rhesus monkeys. Monitoring dopamine in the brain for years at a time will help the team measure dopamine’s impact over the course of learning, and dispersing the sensors in different areas of the brain will help the team assess how dopamine levels fluctuate differently in different brain areas.

“We fabricate the sensors in our lab, and when we implant them, we disperse the sensors all across the striatum, because the dopamine appears differently depending on where you record it in the brain.” Schwerdt said. “I believe that a lot of important past studies support the idea that the punishment-related dopamine signals are going to be in different areas of the brain than the reward-related signals.”

Once the neural interfaces are implanted, the team will test the monkeys with a set of trial and error learning tasks to examine how the dopamine behaves in real time. This will allow the team to learn if certain areas in the striatal brain region produce negative punishment related signals and assess how the signals evolve during the course of learning.

This project could eventually lead to a baseline standard that reveals how dopamine is behaving across the primate striatum during important cognitive behaviors. Studies of humans with Parkinson’s disease have shown impairments in learning from rewards and punishments, and Schwerdt hopes that these findings can also be translated into better understanding the disease, where dopamine dysregulation is a major factor.

“In the future, I would like to test these behaviors in a model of Parkinson’s disease so we can study how dopamine signals in the striatum change and how these changes contribute to behavioral symptoms.” Schwerdt said. “I’m particularly interested in exploring how these dopamine signals could be used as biomarkers to guide future treatments.”