A circuit mechanism for decision-making biases and NMDA receptor hypofunction

• Published in: eLife
• Main Authors: Sean Edward Cavanagh, Norman H Lam, John D Murray, Laurence Tudor Hunt, Steven Wayne Kennerley
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2020-09-01
• Subjects: decision-making; network model; NMDA receptor; schizophrenia; ketamine
• Online Access: https://elifesciences.org/articles/53664

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.