We know dopamine and serotonin as neurotransmitters that play a role in our mood and in our aversive and appetite processes, but what else do they do? There are limited methodologies available to study the quick delivery of these neurotransmitters, within the human brain. Consequently, we have a narrow understanding of dopaminergic and serotonergic systems.
Fast scan cyclic voltammetry (FSCV), a technique which measures these neurotransmitters, has recently been adapted to manage conditions such as Parkinson’s disease (PD) and essential tremor (ET) and has therefore opened doors in studying serotonin and dopamine signalling, in the human brain. Using FSCV, scientists at Wake Forest School of Medicine conducted an observational study to monitor sub-second dopamine and serotonin signalling in PD and ET patients, as they completed a motion discrimination task (a dot motion task). This is the first of its kind.
The study participants were five patients from Wake Forest Baptist Medical Center (two with PD and three with ET), who were scheduled to undergo deep brain stimulation surgery. The presence of ET patients was crucial, as ET is not caused by changes in the function of dopamine or serotonin whereas PD is caused by a loss of dopamine-producing neurons. This allows the results to be applicable to other individuals. The Study was completed over the course of two days:
Day 1: A presurgical visit took place where, patients were trained on how to correctly complete the task which would result in ‘target levels of task performance’. A stimulus calibration was also carried out to normalise the experience amongst all patients and control effects of their individual conditions in their decision making.
Day 2: A carbon fiber microelectrode was inserted into deep structures within the brain, to measure levels of serotonin and dopamine signalling from their neurons, as the patients performed the dot motion task. Sub-second changes in the delivery of dopamine and serotonin to the striatum, using FSCV was also recorded. This was important as the striatum is known to contribute to our decision making, reward processes and movement.
The task. Patients had to decide on the direction of dot movement across their screens. These dots would move randomly in simple and disorderly patterns and then disappear. After the disappearance of the dots, the patients decided from a fixed point, the direction of dot migration (clockwise or counter-clockwise). This random movement was repeated 206-300 times per patient and in a third of the trials the patients were asked how confident they were in their choice, using a visual scale. The ability of the participants in tracking the dot movement and their confidence in choosing this movement allowed the behaviour of serotonin and dopamine to be established in decision making.
Overall, the scientists discovered within the striatum, sub-second dopamine and serotonin are involved in our decision making. The key finding of this study was: serotonin tracks uncertainty. The higher the levels of uncertainty the patient had about the dot movement the lower the levels of serotonin. Additionally, they discovered the levels of dopamine rose in anticipation of deciding the dot movement, whilst serotonin fell and when both transmitters reached a certain level, a decision was made. Dopamine and serotonin were found to have opposing functions in our decision making. A slight increase in dopamine resulted in a decision being made whilst a slight decrease in serotonin resulted in a decision not being made. However, this was only seen in one patient within the putamen nucleus and not the caudate nucleus (suggested to be a cognition-action axis). Therefore, more research is required in determining the function of each area of the striatum in decision making.
A limitation addressed by the scientists was the use of FSCV. This is because it is meant for in vitro use, not in vivo as was done here and this affects the reproducibility of this study. However, we have to remember two things. There are a small number of methodologies available in studying neuromodulation in the human brain this rapidly and this was the first study of its kind. More research is crucial in determining the role of dopamine and serotonin in our perceptual decision making. Knowing more about the behaviour of these transmitters may be of help in managing conditions such as PD or depression.
Original Source: Bang D, Kishida K, Lohrenz T, White J, Laxton A, Tatter S et al. Sub-second Dopamine and Serotonin Signaling in Human Striatum during Perceptual Decision-Making. Neuron. 2020.