A circuit mechanism for irrationalities in decision-making and NMDA receptor hypofunction: behaviour, computational modelling, and pharmacology [article]

Sean E Cavanagh, Norman H Lam, John D Murray, Laurence T Hunt, Steven W Kennerley
2019 biorxiv/medrxiv   pre-print
Decision-making biases can be systematic features of normal behaviour, or deficits underlying neuropsychiatric symptoms. We used behavioural psychophysics, spiking-circuit modelling and pharmacological manipulations to explore decision-making biases in health and disease. Monkeys performed an evidence integration task in which they 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 neural
more » ... revealing a neural mechanism for this behaviour. Because NMDA receptor (NMDA-R) hypofunction is a leading hypothesis for neuropathology in schizophrenia, we simulated behavioural effects of NMDA-R hypofunction onto either excitatory or inhibitory neurons in the model. These were tested experimentally using the NMDA-R antagonist ketamine, yielding changes in decision-making consistent with lowered cortical excitation/inhibition balance from NMDA-R hypofunction 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.
doi:10.1101/826214 fatcat:yjbweq6zzrdc5j36dz2yfunvse