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1000
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Abstract/Summary
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Interacting with dynamic and ever-changing environments requires frequent updating of our beliefs about the world. By learning the relationships that link events in the current environmental context, it is possible to prepare and execute fast, accurate responses to those events that are predictable. However, the world’s complex dynamics give rise to uncertainty about the relationships that exist between events and uncertainty about how these relationships might change over time. Several neuromodulators have been proposed to signal these different forms of uncertainty, but their relative contributions to updating beliefs and modulating responses have remained elusive. Here we combine a probabilistic reaction time task, pharmacological interventions, and a hierarchical Bayesian learning model to identify the roles of noradrenaline, acetylcholine, and dopamine in individual computations of uncertainty. We propose that noradrenaline modulates learning about the instability of the relationships that link environmental events. Acetylcholine balances the attribution of uncertainty to unexpected events occurring within an environmental context or to gross violations of our expectations following a context change. In contrast, dopamine sensitises our actions to our beliefs about uncertainty.
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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.
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