In a study published today (Monday, February 26) Nature Human BehaviorScientists delve into the world of chemical neuromodulators in the human brain, specifically dopamine and serotonin, to reveal their role in social behavior.
The research, conducted on Parkinson's disease patients undergoing brain surgery while awake, focused on the brain's substantia nigra, a crucial area associated with motor control and reward processing.
Led by Virginia Tech computational neuroscientist Read Montague, the international team revealed a previously unknown neurochemical mechanism for a well-known human tendency to make decisions based on social context: People are more likely to accept computer offers while rejecting identical offers. of human players. .
Perspectives of an ultimatum game
In the study, four patients receiving deep brain stimulation surgery for Parkinson's disease were immersed in the ultimatum game of “take it or leave it,” a scenario in which they had to accept or reject different deals of $20 from players. human and computer. For example, a player may propose to keep $16, while the patient receives the remaining $4. If the patient rejects the division, neither of them receives anything.
“People can be taught what they should do in these types of games: They should accept even small rewards instead of no rewards,” said Montague, Virginia Tech Carilion Mountcastle Professor in the Fralin Biomedical Research Institute at VTC and the author. main of the study. “When people know they are playing with a computer, they play perfectly, like mathematical economists: they do what they should do. But when they play with a human being, they can't help it. They are often driven to punish the smallest offer by rejecting it. “.
Dopamine-serotonin dance
The idea that people make decisions based on social context is not new in neural economic games. But now, for the first time, researchers show that the impact of social context can arise from the dynamic interactions of dopamine and serotonin.
When people make decisions, dopamine seems to monitor and react to whether the current offer is better or worse than the previous one, as if it were a continuous monitoring system. Serotonin, meanwhile, appears to focus only on the current value of the specific offering in question, suggesting a more case-by-case evaluation.
This fast dance occurs in a slower context, where dopamine is generally higher when people perform other human beings; In other words, when justice comes into play. Together, these signals contribute to our brain's overall assessment of value during social interactions.
“We are highlighting several cognitive processes and finally receiving answers to questions in greater biological detail,” said the study's first author, Dan Bang, associate professor of clinical medicine and Lundbeck Foundation Fellow at Aarhus University in Denmark, and associate professor attach. at the Fralin Biomedical Research Institute.
“Dopamine levels are higher when people interact with another human being than with a computer,” Bang said. “And here it was important that we also measure serotonin to have confidence that the general response to social context is specific to dopamine.”
Seth Batten, a senior research associate in Montague's lab and co-first author of the study, built the carbon fiber electrodes that were implanted in patients receiving deep brain stimulation surgery and helped collect the data at the Mount Sinai Health System. In New York.
“The unique twist to our method is that it allows us to measure more than one neurotransmitter at a time; the impact of that should not be lost,” Batten said. “We've seen these signaling molecules before, but this is the first time we've seen them dance. No one has ever seen this dance of dopamine and serotonin in a social context before.”
Discovering the meaning of the electrochemical signals recorded from patients in surgery was a major challenge that took years to solve.
“The raw data we are collecting from patients is not specific to dopamine, serotonin or norepinephrine, but rather a mixture of them,” said Ken Kishida, co-author of the study and associate professor of translational neuroscience. and neurosurgery, at Wake Forest University School of Medicine. “Basically, we use machine learning-type tools to separate out what's in the raw data, understand the signature, and decode what's happening with dopamine and serotonin.”
In it Study of human behavior of nature.Researchers demonstrated how the rise and fall of dopamine and serotonin are intertwined with human cognition and behavior.
“In the world of model organisms, there is a candy store full of fantastic techniques for asking biological questions, but it's harder to ask questions about what makes you you,” said Montague, who is also director of the Research Center at Human Neuroscience. and the Human Neuroimaging Laboratory of the Fralin Biomedical Research Institute.
Address Parkinson's
“At some point, after we have tested enough people, we will be able to address the pathology of Parkinson's disease that has given us this opportunity,” said Montague, who is also a professor in the College of Science at Virginia Tech.
In Parkinson's disease, a significant loss of dopamine-producing neurons in the brainstem is a key feature that often coincides with the onset of symptoms.
This loss affects the striatum, a region of the brain strongly influenced by dopamine. As dopamine declines, serotonin terminals begin to sprout, revealing a complex interaction, as seen in rodent models.
“There's already preclinical evidence that wear and tear of the dopamine system is telling the serotonin system, 'Hey, we need to do something.' But we've never been able to observe the dynamics,” Montague said. “What we are doing now is the first step, but one would hope that once we have hundreds of patients, we can relate this to symptomatology and make some clinical statements about Parkinson's pathology.”
In that sense, researchers said a window is opening to learn about a wide range of brain disorders.
“The human brain is like a black box,” Kishida said. “We have developed another way to look inward and understand how these systems work and how they are affected by various clinical conditions.”
Michael Friedlander, executive director of the Fralin Biomedical Research Institute and a neuroscientist who was not involved in the study, said: “This work is changing the entire field of neuroscience and our ability to interrogate the human mind and brain, with technology that neither could not even be imagined not many years ago.”
Psychiatry is an example of a medical field that could benefit from this approach, he said.
“We have an enormous number of people in the world who suffer from a variety of psychiatric conditions, and in many cases, pharmacological solutions do not work very well,” said Friedlander, who is also vice president of health sciences and health sciences at Virginia Tech. technology. “Dopamine, serotonin, and other neurotransmitters are somehow closely related to those disorders. This effort adds real precision and quantification to understanding those problems. The one thing I think we can be sure of is that this work will be extremely important in the future.” future for the development of treatments.
More than a decade in the making
The effort to measure neurotransmitters in real time in the human brain began more than 12 years ago when Montague assembled a team of experts who “think a lot about thinking.”
In observations, the first of their kind in the human brain, which scientists published in Neuron in 2020, researchers revealed that dopamine and serotonin act at speeds of less than a second to shape how people perceive the brain. world and act based on their perception.
More recently, in a study published in October in the journal Current biologyThe researchers used their method of recording chemical changes in awake humans to gain insight into the brain's norepinephrine system, which has long been a target of medications to treat psychiatric disorders.
And, in December in the magazine Scientific advancesThe team revealed that rapid changes in dopamine levels reflect a specific calculation related to how humans learn from rewards and punishments.
“We have made active measurements of neurotransmitters several times in different regions of the brain, and now we have reached the point where we are touching crucial elements of what makes us human,” Montague said.