Habenula-ventral tegmental area functional coupling and risk-aversion in humans

Abstract

Maladaptive responses to uncertainty, including excessive risk avoidance, are linked to a range of mental disorders. One expression of these is a pro-variance bias (PVB), wherein risk-seeking manifests in a preference for choosing options with higher variances/uncertainty. Here, using a magnitude learning task, we provide a behavioural and neural account of PVB in humans. We show that individual differences in PVB are captured by a computational model that includes asymmetric learning rates, allowing differential learning from positive prediction errors (PPEs) and negative prediction errors (NPEs). Using high-resolution 7T functional magnetic resonance imaging (fMRI), we identify distinct neural responses to PPEs and NPEs in value-sensitive regions including habenula (Hb), ventral tegmental area (VTA), nucleus accumbens (NAcc), and ventral medial prefrontal cortex (vmPFC). Prediction error signals in NAcc and vmPFC were boosted for high variance options. NPEs responses in NAcc were associated with a negative bias in learning rates linked to a stronger negative Hb-VTA functional coupling during NPE encoding. A mediation analysis revealed this coupling influenced NAcc responses to NPEs via an impact on learning rates. These findings implicate Hb-VTA coupling in the emergence of risk preferences during learning, with implications for psychopathology.