eprintid: 10111479
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/11/14/79
datestamp: 2020-10-07 14:12:18
lastmod: 2021-09-20 22:37:25
status_changed: 2020-10-07 14:12:18
type: article
metadata_visibility: show
creators_name: Cavanagh, SE
creators_name: Lam, NH
creators_name: Murray, JD
creators_name: Hunt, LT
creators_name: Kennerley, SW
title: A circuit mechanism for decision-making biases and NMDA receptor hypofunction
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F84
keywords: NMDA receptor, decision-making, ketamine, network model, neuroscience, rhesus macaque, schizophrenia
note: © 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.
abstract: 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.
date: 2020-09-29
date_type: published
official_url: http://dx.doi.org/10.7554/eLife.53664
oa_status: green
full_text_type: pub
pmcid: PMC7524553
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1816985
doi: 10.7554/eLife.53664
pii: 53664
lyricists_name: Kennerley, Steven
lyricists_id: SWKEN38
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: eLife
volume: 9
article_number: e53664
event_location: England
issn: 2050-084X
citation:        Cavanagh, SE;    Lam, NH;    Murray, JD;    Hunt, LT;    Kennerley, SW;      (2020)    A circuit mechanism for decision-making biases and NMDA receptor hypofunction.                   eLife , 9     , Article e53664.  10.7554/eLife.53664 <https://doi.org/10.7554/eLife.53664>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10111479/1/elife-53664-v2.pdf