Scientists find that neurochemicals play an unexpectedly important role in the...

With initial observations of their kind in the human brain, an international team of researchers found that two known neurochemicals – dopamine and serotonin – act at a rate of less than a second to affect people’s perception of the world and take action on their perception .

The discovery shows that researchers can continuously and simultaneously measure the activity of dopamine and serotonin in the human brain – their receptor and receiving sites are therapeutic targets for diseases ranging from depression to Parkinson’s disease.

In addition, the neurochemicals seem to incorporate people’s perception of the world into their actions, indicating that dopamine and serotonin play a far more expansive role in the human nervous system than previously known.

Dopamine and serotonin, known as neuromodulators, have traditionally been associated with reward processing – how well or how badly people perceive an outcome after an action.

The study online today in the journal Neuron opens the door to a deeper understanding of an expanded role of these systems and their role in human health.

“Enormous numbers of people around the world are ingesting pharmaceutical compounds to disrupt dopamine and serotonin transmitter systems and to alter their behavior and mental health,” said P. Read Montague, study lead author and professor and director the Center for Human Neuroscience Research and the Human Neuroimaging Laboratory at the Fralin Biomedical Research Institute of the Virginia Tech Carilion. “For the first time, moment-to-moment activity in these systems was measured and determined as part of perception and cognitive skills. These neurotransmitters work simultaneously and integrate activities on completely different time and space scales than expected. ”

A better understanding of the underlying effects of dopamine and serotonin during exercise and decision-making could provide important insights into psychiatric and neurological disorders, the researchers said.

“Every decision someone makes involves taking in information, interpreting that information, and making decisions about what they’re perceiving,” said Kenneth Kishida, a correspondent author on the study and assistant professor of physiology and pharmacology and neurosurgery at the Wake Forest School of Medicine. “There are a number of psychiatric and neurological disorders in which this process is altered in patients, and dopamine and serotonin are prime suspects.”

Montague, an honorary professor at the Wellcome Center for Human Neuroimaging at University College London and a professor of physics at Virginia Tech, said the lack of chemically specific methods for studying neuromodulation in humans in fast timescales has hampered understanding of these systems at the College of Science.

However, when making initial measurements, the scientists used an electrochemical method called “fast-scan cyclic voltammetry,” which uses a small carbon fiber microelectrode with low voltages to provide real-time detection of dopamine and serotonin activity.

In the study, researchers recorded variations in dopamine and serotonin using specially designed electrodes in five patients who had an electrode implanted for deep brain stimulation to treat essential tremor or Parkinson’s disease. The patients were awake during the operation and were playing a computer game designed to quantify aspects of thinking and behavior during the measurements.

Each round of the game, patients briefly saw a point cloud and were asked to assess the direction in which they were moving. The method, developed by related author Dan Bang, a postdoctoral fellow with Sir Henry Wellcome, and Steve Fleming, a Sir Henry Dale / Royal Society Fellow, both at the Wellcome Center for Human Neuroimaging at University College London, showed that The presence of dopamine and serotonin have been implicated in simple perceptual decisions outside the traditional context of rewards and losses.

“These neuromodulators play a much broader role in helping human behavior and thinking, and are specifically involved in how we process the outside world,” said Bang. “For example, if you move around a room and the lights are off, you move differently because you are not sure where objects are. Our work suggests that these neuromodulators – especially serotonin – play a role in signaling how insecure we are about the external environment. ”

Montague and Kishida, along with Terry Lohrenz, a research assistant professor, and Jason White, a senior research fellow who both now work at the Fralin Biomedical Research Institute, began working at the Baylor on a new statistical approach to identifying dopamine and serotonin signals Medical College in Houston, Texas.

“Ken rose to the challenge of doing rapid neurochemistry in humans while actively exercising,” Montague said. “Many other good groups of scientists have not been able to do this. Aside from computing enormous amounts of data, there are complex problems to be solved, including large basic algorithmic tasks. ”

Until recently, only slow methods like PET scanning could measure the impact of neurotransmitters, but they were nowhere near the frequency or volume of the fast-scan cyclic voltammetry seconds-to-second measurements.

Measurements in the new study were taken at Wake Forest Baptist Medical Center and included neurosurgical teams led by Adrian W. Laxton and Stephen B. Tatter.

“Neurosurgeons’ enthusiasm for this research stems from the same reasons that made them doctors. First and foremost, they want to do the best for their patients, and they have a real passion for understanding how the brain improves patient outcomes, “said Kishida, who oversaw data collection in the operating room during surgeries. “Both are collaborative scientists with Charles Branch, chairman of the Department of Neurosurgery at Wake Forest, who was a great advocate of the work.”

Likewise, Montague said, “You can’t do it without the surgeons being real partners, shoulder to shoulder, and certainly not without the people who let you take pictures of your brain while electrodes are being implanted to help you deal with the symptoms to alleviate. ”a neurological disorder. ”

Montague had read a study in the Procedure of the National Academy of Sciences This prompted him to turn to colleagues Bang and Fleming at University College London to tailor a task for patients during surgery that reveals real-time dopamine and serotonin signals to the outside world – separate from their frequently reported ones Roles in reward-related processes.

“I said I have this new way of measuring dopamine and serotonin, but you have to help me with the task,” Montague said. “You ended up in the study. The research really took a lot of hard work and involved a constellation of people to get these results. ”

The research was funded by grants to various researchers from the Wellcome Trust, the National Institutes of Health, including the National Institute on Drug Abuse, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke.

Scientists report on the roles of dopamine and serotonin in cognition and decision-making in humans

More information:
Neuron (2020). DOI: 10.1016 / j.neuron.2020.09.015

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