2 chemicals may shape human perception more than previously thought — study

Scientists recently got an unprecedented glimpse into human brain activity.

By recording minute fluctuations in levels of chemicals that influence brain activity in real-time, researchers discovered that neurotransmitters dopamine and serotonin continuously operate at sub-second speeds to shape how our brains perceive the world.

For decades, scientists have known dopamine and serotonin are involved in regulating mood, learning, motivation, and decision-making. But the new findings, published Monday in the journal Neuron, suggest dopamine and serotonin are profoundly influential on human perception and behavior — far more than previously thought.

"Before this work, we have never had any data showing the fast operation of these transmitters during conscious human perception," study co-author, Read Montague, a computational neuroscientist at Virginia Tech Carilion, tells Inverse.

"The findings show that dopamine and serotonin carry perceptual information at timescales never before imagined and that this goes well beyond their putative role in reward learning, which has been the common view."

Risk and reward — Traditionally, dopamine and serotonin have been linked to reward processing — how the brain estimates potential rewards and losses in a particular scenario.

Based on these findings, these neurotransmitters and the neurons that produce and distribute them are "absolutely crucial for normal mental function" beyond reward processing, Montague says.

New technology called "fast scan cyclic voltammetry" enabled scientists to answer long-held questions about these neurotransmitter systems and their role in human health.

This electrochemical method uses a small carbon fiber microelectrode to detect real-time levels of dopamine and serotonin activity in the brain.

In this study, the researchers used the method to record the dopamine and serotonin levels of five people who were undergoing surgery to implant deep brain stimulation devices. Three of the participants were undergoing the surgery to treat essential tremor disease, while the other two were being treated for Parkinson's disease.

In this experiment, scientists focused on the brain's striatum — a part of the brain linked to perceptual decision-making.

"This work piggy-backed on neurosurgery to make direct recordings of dopamine and serotonin while subjects perceived visual motion and made action based on those perceptions," Montague explains.

The awake participants played a computer game during the procedure. In the game, participants briefly viewed a cloud of dots and were asked to judge the direction they were moving. The game was designed to quantify aspects of thought and behavior, while the scientists recorded their neurotransmitter activity.

Neuro-exploration — During the task and subsequent analysis, scientists observed that serotonin appeared to be involved in how the participants weigh sensory uncertainty. The team also found some evidence, albeit less robust, that dopamine plays a role in how participants perceived distance during the task.

"Dopamine and serotonin delivery to neural tissue carries fast information about perception and action extending well beyond the accepted view that they guide learning about reward and punishment," Montague says. "This work shows that these neurochemicals carry different kinds of neural information at the same time."

Looking closer at the putamen, an area in the brain's striatum, the team found evidence to suggest dopamine and serotonin have opposing mechanisms in driving these behaviors.

Specifically, the team saw that making a choice was preceded by a transient increase in dopamine, a result consistent with past studies showing dopamine promoting action or ‘‘pressing the accelerator." Meanwhile, they saw a concurrent transient decrease in serotonin in the putamen, consistent with inhibitory effects of serotonin.

"These neuromodulators play a much broader role in supporting human behavior and thought, and in particular they are involved in how we process the outside world," Dan Bang, study co-author and Sir Henry Wellcome Postdoctoral Fellow, said in a related statement.

"For example, if you move through a room and the lights are off, you move differently because you're uncertain about where objects are. Our work suggests these neuromodulators — serotonin in particular — are playing a role in signaling how uncertain we are about the outside environment."

What's next? — It is important to note how limited and preliminary this study is. The investigation included just five people who had either Parkinson's disease or essential tremor disease, so how these neurotransmitter systems work in the brains of a more general population is unclear.

Further studies involving larger, more diverse groups of people are needed to determine how serotonin and dopamine skew perception, and how those shifts influence action. In the future, understanding these dynamics could help clinicians better treat people with brain conditions that involve disruptions in neurotransmitter systems.

"Future work like this will provide a way to connect the direct delivery of dopamine and serotonin to mental states and perceptual processing in humans," Montague says. "This information will be crucial in trying to understand (in computational terms) how to characterize and treat depression, Parkinson's disease, and psychosis."

Abstract: Recent animal research indicates that dopamine and serotonin, neuromodulators traditionally linked to appetitive and aversive processes, are also involved in sensory inference and decisions based on such inference. We tested this hypothesis in humans by monitoring sub-second striatal dopamine and serotonin signaling during a visual motion discrimination task that separates sensory uncertainty from decision difficulty in a factorial design. Caudate nucleus recordings (n = 4) revealed multi-scale encoding: in three participants, serotonin tracked sensory uncertainty, and, in one participant, both dopamine and serotonin tracked deviations from expected trial transitions within our factorial design. Putamen recordings (n = 1) supported a cognition- action separation between caudate nucleus and putamen—a striatal sub-division unique to primates—with both dopamine and serotonin tracking decision times. These first-of-their-kind observations in the human brain reveal a role for sub-second dopamine and serotonin signaling in non-reward-based aspects of cognition and action.