Lesions to the mediodorsal thalamus but not orbitofrontal cortex enhance volatility beliefs linked to paranoia

Beliefs – attitudes toward some state of the environment – guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans yet the brain regions responsible for volatility beliefs remain unknown. Orbitofrontal cortex (OFC) is central to adaptive behavior whereas magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal-learning task following excitotoxic lesions of MDmc (n=3) or OFC (n=3) and compared performance with that of unoperated rhesus macaques (n=14). Computational analyses indicated that lesions of the MDmc, but not OFC, were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans). In contrast, OFC lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models these results have implications for understanding paranoia.