Virginia Tech Carilion Research Institute scientists have measured release of the key neurotransmitter with unprecedented temporal precision in the brains of people with Parkinson’s disease.
The measurements, collected during brain surgery as the conscious patients played an investment game, demonstrate how rapid dopamine release encodes information crucial for human choice.
The findings may have widespread implications not just for Parkinson’s disease, but for other neurological and psychiatric disorders as well, including depression and addiction.
The researchers detected changes in the levels of dopamine a thousand times faster than had previously been recorded in humans. These rapid measurements, combined with enhanced chemical specificity, enabled scientists to discover that dopamine has a far more complex role than formerly thought.
The study was published today in the Proceedings of the National Academy of Sciences.
“More than 20 years of research in nonhuman model organisms has painted a very specific picture of the suspected role of dopamine in guiding human behavior,” said Read Montague, director of the Human Neuroimaging Laboratory at the Virginia Tech Carilion Research Institute and senior author of the paper.
“And now, with these first-of-their-kind measurements, made directly in humans, we’ve discovered that this picture was woefully incomplete.”
Montague and his team worked with neurosurgeons at Wake Forest University Health Sciences – Stephen Tatter, Adrian Laxton, and the late Thomas Ellis – to measure dopamine signals in patients with Parkinson’s disease undergoing surgery to implant deep-brain stimulation electrodes. Deep-brain stimulation has been shown to alleviate Parkinson’s disease symptoms.
Seventeen patients volunteered to allow Montague’s team to record their dopamine signals during implantation surgery.
“We’re studying a system that’s falling apart in their brains,” said Dr. Ken Kishida, first author of the paper and a research scientist at the Virginia Tech Carilion Research Institute. “Parkinson’s disease is characterized by the death of dopamine-releasing neurons, and we’re trying to understand the underlying mechanisms of the disease process.”
Kishida and Montague both noted the generosity of the patients who volunteered for the study.
“This type of access to measure dopamine signals is invaluable,” Kishida said. “And we’ve made these measurements in 17 people – that’s 17 more than ever before.”
In order to capture the dopamine signals, especially in people with lower dopamine activity, the researchers had to develop extremely sensitive methods.
The researchers took readings of the ultra-quick dopamine pulses as conscious patients played an investment game. They expected to see dopamine responses in direct relation to expected rewards and actual outcomes. They didn’t.
“We analyzed the dataset of about a thousand pulses of dopamine, and it was flat,” said Montague, who is also a professor of physics in Virginia Tech’s College of Science and director of the Computational Psychiatry Unit of the Virginia Tech Carilion Research Institute. “The signals did not distinguish between a positive reaction and a negative one.”
Once the researchers had the measurements, they started to analyze what the dopamine was actually signaling.
“We found that dopamine tracks two factors – what happened and what could have happened,” Montague said. “Our dopamine neurons appear to track whether something could have been better or worse, and this information is encoded by the rapid changes in dopamine release. These findings may start to reveal, in computational terms, what’s missing in the dopamine system of Parkinson’s patients.”
The findings have been more than 20 years in the making, since Montague’s first computational studies examining the mechanisms of dopamine signaling.
The idea that “what could have been” is part of how people evaluate actual outcomes is not new. But no one expected that dopamine would be doing the job of combining this information in the human brain.
Now that researchers have measured multiple contributions to the individual dopamine signals, they have even more pathways to explore the human brain’s learning systems in health and disease.
Source: Virginia Tech