New study reveals how dopamine and serotonin affect decision-making
Chemical messaging in the human brain: new study reveals how dopamine and serotonin affect decision-making
An important mode of communication in the brain involves neuromodulatory systems that widely broadcast chemical messages, known as neuromodulators. Like a conductor directing an orchestra, these systems regulate the activity of diverse populations of neurons, with each population interpreting the chemical instructions in a subtly different way. Examples include the dopaminergic and serotonergic systems that are believed to support a variety of physiological and psychological processes and whose disturbance has been implicated in a range of clinical conditions, including Parkinson’s disease, obsessive-compulsive disorder, and depression.
Neuromodulatory systems are, however, difficult to study in humans. We can examine the effects of drugs such as antidepressants that have neuromodulatory effects, but drugs are slow-acting and diffuse – they do not tell us how fast changes in neuromodulator levels in specific parts of the brain impact thought and behaviour. A new study published in Neuron and co-first-authored by Dr Dan Bang (Wellcome Centre for Human Neuroimaging at UCL) and Dr Kenneth T. Kishida (Wake Forest School of Medicine) addresses this issue, by leveraging recent technological innovations in human neuroscience.
The research was conducted at the Wake Forest Baptist Medical Center, in the United States, and involved close collaboration with the neurosurgical teams led by Dr Adrian W. Laxton and Dr Stephen B. Tatter. The opportunity to measure fast neuromodulation in humans occurs during neurosurgery where deep brain stimulating (DBS) electrodes are being implanted for the management of movement disorder symptoms (e.g., Parkinson’s disease and essential tremor). With minimal deviations from the standard of care, a research probe can be inserted into an area of the brain known as the striatum, an area central to the coordination of thought and behaviour, by following the same path as the DBS electrode. Using a method called “fast scan cyclic voltammetry”, adapted for use in humans by Dr Kenneth Kishida and senior author Professor Read Montague (Fralin Biomedical Research Institute at Virginia Tech Carilion and Wellcome Centre for Human Neuroimaging at UCL), the probe allows for the real-time measurement of neuromodulators such as dopamine and serotonin. Because patients have to be awake to ensure optimal placement of the DBS electrode, these measurements can be made while patients play a computer game that quantifies aspects of behaviour and thought. Patients consent to take part in the research and are free to stop at any time.
The computer game that patients played was developed by Dr Dan Bang and Dr Steve Fleming (Wellcome Centre for Human Neuroimaging and Department of Experimental Psychology at UCL) and asked players to make simple perceptual decisions. On each round of the game, patients briefly viewed a cloud of moving dots and were then required to judge which direction they were moving relative to a reference point. The advantage of using this task is that it allows for precise control of the different factors that affect people’s decisions. For example, uncertainty about which direction the dots were moving – the sensory information underlying their decision – can be manipulated by introducing randomly moving dots into the display. The researchers found, in one part of the striatum (caudate nucleus), that serotonin levels rapidly increased when uncertainty was high. In another part of the striatum (putamen), both dopamine and serotonin were found to trigger the action that indicated a patient’s decision. In a delicate balancing act, dopamine levels rapidly increased prior to an action (akin to “pressing the accelerator”), whereas serotonin levels rapidly decreased (akin to “releasing the brake”).
These first-of-their-kind findings advance our scientific understanding of the roles of dopamine and serotonin in human thought and behaviour. Precise mathematical models of these neuromodulators have been developed, but they have focused on their role in processing positive and negative outcomes (“reward prediction errors”) and not conscious experience. The findings also shed light on the effects of disturbances in, or pharmacological manipulations of, the dopaminergic and serotonergic systems. For example, disruption of the balance between dopamine and serotonin may affect an individual’s ability to time and execute their actions. Direct measurement of neuromodulation in humans promises to be an important tool for the field of neuroscience. Until recently, direct measurement has only been possible in animals such as rats, but animals are a limited model of the rich behaviours and thoughts carried by humans. This limitation has made it difficult to map out the role of neuromodulatory systems in complex mental health conditions such as depression. The researchers are now looking to study how neuromodulatory systems support emotion and other complex human experiences.
Dr Dan Bang said:
“We’ve thought that dopamine and serotonin at these fast time scales are mainly involved in reward processing – or how good or how bad an outcome is after taking an action. What we show here is that these neuromodulators play a much broader role in supporting human thought and behaviour, and in particular that they are involved in how we process the outside world. For example, if you move through a room and the lights are off, you move differently because you are uncertain about where objects are. Our work suggests that serotonin signals how uncertain we are about the outside environment.”
“While our study is the first to show that serotonin signals uncertainty in a perceptual task, Zach Mainen’s group in Lisbon has identified a similar role for serotonin in tasks where animals have to learn which actions to take from feedback. This broad role for serotonin in signalling uncertainty may help explain why SSRIs, a class of antidepressants that affect the serotonergic system, facilitate the breaking of negative thoughts and behaviour in some patients. From a computational point of view, uncertainty promotes learning and plasticity – uncertainty indicates that the system should find new solutions to old problems.”
Dr Steve Fleming added:
“In our previous work using this task together with brain imaging, we focused on how different parts of cortex supports computations of sensory uncertainty and decision confidence. But brain imaging is normally blind to neuromodulator levels. Here, by collaborating with the fantastic teams at Virginia Tech and Wake Forest, we have now got a unique insight into how these neurochemicals contribute to the decision process.”
The research was funded by Wellcome and the National Institutes of Health.
The full article is freely available at Neuron: Sub-second dopamine and serotonin signalling in human striatum during perceptual decision-making.