TY - JOUR KW - NMDA receptor KW - decision-making KW - ketamine KW - network model KW - neuroscience KW - rhesus macaque KW - schizophrenia N2 - 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. A1 - Cavanagh, SE A1 - Lam, NH A1 - Murray, JD A1 - Hunt, LT A1 - Kennerley, SW SN - 2050-084X AV - public Y1 - 2020/09/29/ UR - http://dx.doi.org/10.7554/eLife.53664 ID - discovery10111479 N1 - © 2020, Cavanagh et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. TI - A circuit mechanism for decision-making biases and NMDA receptor hypofunction VL - 9 JF - eLife ER -