TY - JOUR TI - A circuit mechanism for decision-making biases and NMDA receptor hypofunction AU - Cavanagh, Sean Edward AU - Lam, Norman H AU - Murray, John D AU - Hunt, Laurence Tudor AU - Kennerley, Steven Wayne A2 - Donner, Tobias H A2 - Frank, Michael J A2 - Tsetsos, Konstantinos A2 - Wyart, Valentin VL - 9 PY - 2020 DA - 2020/09/29 SP - e53664 C1 - eLife 2020;9:e53664 DO - 10.7554/eLife.53664 UR - https://doi.org/10.7554/eLife.53664 AB - Decision-making biases can be features of normal behaviour, or deficits underlying neuropsychiatric symptoms. We used behavioural psychophysics, spiking-circuit modelling and pharmacological manipulations to explore decision-making biases during evidence integration. Monkeys showed a pro-variance bias (PVB): a preference to choose options with more variable evidence. The PVB was also present in a spiking circuit model, revealing a potential neural mechanism for this behaviour. To model possible effects of NMDA receptor (NMDA-R) antagonism on this behaviour, we simulated the effects of NMDA-R hypofunction onto either excitatory or inhibitory neurons in the model. These were then tested experimentally using the NMDA-R antagonist ketamine, a pharmacological model of schizophrenia. Ketamine yielded an increase in subjects’ PVB, consistent with lowered cortical excitation/inhibition balance from NMDA-R hypofunction predominantly onto excitatory neurons. These results provide a circuit-level mechanism that bridges across explanatory scales, from the synaptic to the behavioural, in neuropsychiatric disorders where decision-making biases are prominent. KW - decision-making KW - network model KW - NMDA receptor KW - schizophrenia KW - ketamine JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -