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The locus coeruleus–noradrenaline system in Parkinson’s disease – modulating impulsivity and reinforcement learning

The locus coeruleus–noradrenaline system plays an extensive role in cognition and behaviour. Understanding how this system is impacted by disease has important implications for treatment, and can offer insights into how the system functions in the healthy brain. My talk will focus on the locus coeruleus–noradrenaline system in Parkinson’s disease – in particular, the role it plays in impulsivity and reinforcement learning. Using a combined approach, we characterised the locus coeruleus using 7T MRI and probed the system in a pharmacological study with the noradrenergic reuptake inhibitor atomoxetine. Following on from extensive preclinical work linking stop-signal inhibition to the noradrenergic system, we show that stop-signal task performance is modulated by atomoxetine and dependent on locus coeruleus integrity. We also use this framework to further confirm a role for noradrenaline in navigating uncertainty during reinforcement learning, by showing improved learning behaviour under atomoxetine via computational modelling and pupillometry. Together, these findings advance ideas around noradrenergic therapy in Parkinson’s disease and hopefully provide some new insights into how the locus coeruleus–noradrenaline system orchestrates human behaviour.