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Researchers at Wake Forest University School of Medicine (WFUSM) have used a new method to map dopamine regulation in real-time deep inside the brains of three humans. The study recently published in the journal Science Advances shows that dopamine plays a crucial role in not just recognizing rewards but also in learning from mistakes. This new information could help researchers better understand how dopamine signaling differs in psychiatric and neurological disorders. “Previously, research has shown that dopamine plays an important role in how animals learn from ‘rewarding’ (and possibly ‘punishing’) experiences,” said Dr Kenneth T. Kishida, associate professor of physiology and pharmacology and neurosurgery at WFUSM. “But little work has been done to directly assess what dopamine does on fast timescales in the human brain. This is the first study in humans to examine how dopamine encodes rewards and punishments and whether dopamine reflects an ‘optimal’ teaching signal that is used in today’s most advanced artificial intelligence research.” 

To conduct the study, the researchers used fast-scan cyclic voltammetry coupled with machine learning to measure dopamine levels in real time. Three patients scheduled to receive deep brain stimulation for essential tremors agreed to participate in the research. Each played a simple computer game with three stages. They had to learn through experience to make choices that maximized rewards while minimizing punishments. The players were rewarded with real monetary prizes for making the correct decisions and lost money as a penalty for wrong moves. Dopamine was measured once every 100 milliseconds in each player throughout the game.

What the researchers found was unexpected — dopamine plays a multifaceted and complex role, not just in processing wins but also in responding to losses. They also discovered that dopamine pathways operate on different timescales. 

“We found that dopamine not only plays a role in signaling both positive and negative experiences in the brain, but it seems to do so in a way that is optimal when trying to learn from those outcomes,” said Kishida. “What was also interesting is that it seems like there may be independent pathways in the brain that separately engage the dopamine system for rewarding versus punishing experiences. Our results reveal a surprising result that these two pathways may encode rewarding and punishing experiences on slightly shifted timescales separated by only 200 to 400 milliseconds in time.”

The study’s results highlight the importance of dopamine in decision-making mechanisms and how it can help us better understand psychiatric and neurological disorders. 

Kishida explains, “Traditionally, dopamine is often referred to as ‘the pleasure neurotransmitter. “However, our work provides evidence that this is not the way to think about dopamine. Instead, dopamine is a crucial part of a sophisticated system that teaches our brain and guides our behavior. That dopamine is also involved in teaching our brain about punishing experiences is an important discovery and may provide new directions in research to help us better understand the mechanisms underlying depression, addiction, and related psychiatric and neurological disorders.”