Three Brain Chemicals Affect How We Handle Uncertainty

New research has revealed how three important brain signaling chemicals affect the way that we handle uncertainty. It turns out that noradrenaline regulates our estimates of how unstable the environment is, acetylcholine helps us adapt to changing environments, and dopamine pushes us to act on our beliefs about uncertainty. The research, publishing 15 November in the open-access journal PLOS Biology, was led by Louise Marshall and Dr Sven Bestmann at the UCL (University College London) Institute of Neurology.

The study involved 128 healthy participants who took part in a reaction-time task designed to test how they handled uncertainty. Participants were all given either a placebo or a drug to block noradrenaline, acetylcholine or dopamine before starting the task. Participants responded to symbols that were presented one after the other by pressing a corresponding button. The probability of each symbol appearing was dependent on the symbol that appeared previously; for example, if a participant had just seen symbol A, there was an 85% chance that symbol B would appear next. Every 50 trials, these probability patterns changed without warning, so participants had to detect these new patterns and adjust their responses accordingly.

Brain chemicals and their role in how we deal with uncertainty. NeuroscienceNews.com image is credited to Edvard Munch and Roland Roberts.

Lead author Louise Marshall said: “Interacting with our dynamic and ever-changing environment requires us to frequently update our beliefs about the world. By learning the relationships that link events occurring in our environment, we can predict future events, and execute fast, accurate responses. However, the environment’s complex dynamics give rise to uncertainty about the relationships between events, and uncertainty about the stability of these relationships over time. Several brain chemicals have been proposed to modulate how we handle uncertainty. Here we combined pharmacological interventions and novel computational models to determine how noradrenaline, acetylcholine and dopamine enable our brains to learn the changing relationships in our environment. The results shed important light on how humans learn to behave under uncertainty.”

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Abstract
Pharmacological Fingerprints of Contextual Uncertainty
Successful interaction with the environment requires flexible updating of our beliefs about the world.

By estimating the likelihood of future events, it is possible to prepare appropriate actions in advance and execute fast, accurate motor responses. According to theoretical proposals, agents track the variability arising from changing environments by computing various forms of uncertainty. Several neuromodulators have been linked to uncertainty signalling, but comprehensive empirical characterisation of their relative contributions to perceptual belief updating, and to the selection of motor responses, is lacking. Here we assess the roles of noradrenaline, acetylcholine, and dopamine within a single, unified computational framework of uncertainty. Using pharmacological interventions in a sample of 128 healthy human volunteers and a hierarchical Bayesian learning model, we characterise the influences of noradrenergic, cholinergic, and dopaminergic receptor antagonism on individual computations of uncertainty during a probabilistic serial reaction time task. We propose that noradrenaline influences learning of uncertain events arising from unexpected changes in the environment. In contrast, acetylcholine balances attribution of uncertainty to chance fluctuations within an environmental context, defined by a stable set of probabilistic associations, or to gross environmental violations following a contextual switch. Dopamine supports the use of uncertainty representations to engender fast, adaptive responses.