SUB-SECOND DOPAMINE AND SEROTONIN DYNAMICS IN HUMAN THALAMUS DURING REINFORCEMENT LEARNING UNDER UNCERTAINTY

Striking the right balance between risky and safe choices is critical for adaptive behaviour. Indeed, risk preferences are emerging as a promising neuropsychiatric marker. For example, risk/aversion is elevated in anxiety and depression, whereas extreme risk-seeking is apparent in problem gambling. Animal research has long implicated the dopamine (DA) and serotonin (5-HT) systems in value processing, and medications that target these systems in neuropsychiatric disorders have been shown to affect risky behaviour. However, direct human evidence for the role of DA and 5-HT in shaping risk preferences is lacking. In an ongoing study, we address this gap by using fast scan cyclic voltammetry (FSCV) to record sub-second (10 Hz) DA and 5-HT fluctuations in human thalamus—a key hub through which these neuromodulators ascend to cortical regions in the primate brain—in essential tremor and Parkinson’s disease patients undergoing deep brain stimulation (DBS) surgery. The patients performed a reinforcement learning task where we used the tendency to choose options with higher outcome variance – pro-variance bias (PVB) – as a metric of their risk preference. Combining the FSCV recordings with computational modelling, our preliminary results show that both DA and 5-HT are positively modulated by trial-by-trial reward prediction errors (RPEs). Strikingly, however, they are differentially modulated by expected values (EVs). Furthermore, their respective responses to EVs differentially predict PVB. These findings provide direct human evidence for a functional dissociation between DA and 5-HT within a reinforcement learning framework and indicate distinct roles of DA and 5-HT in shaping human risk preferences.