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Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine

Shaw, Alexander D., Muthukumaraswamy, Suresh D., Saxena, Neeraj, Sumner, Rachael L., Adams, Natalie, Moran, Rosalyn J. and Singh, Krish D. 2020. Generative modelling of the thalamo-cortical circuit mechanisms underlying the neurophysiological effects of ketamine. NeuroImage 221 , 117189. 10.1016/j.neuroimage.2020.117189

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Abstract

Cortical recordings of task-induced oscillations following subanaesthetic ketamine administration demonstrate alterations in amplitude, including increases at high-frequencies (gamma) and reductions at low frequencies (theta, alpha). To investigate the population-level interactions underlying these changes, we implemented a thalamo-cortical model (TCM) capable of recapitulating broadband spectral responses. Compared with an existing cortex-only 4-population model, Bayesian Model Selection preferred the TCM. The model was able to accurately and significantly recapitulate ketamine-induced reductions in alpha amplitude and increases in gamma amplitude. Parameter analysis revealed no change in receptor time-constants but significant increases in select synaptic connectivity with ketamine. Significantly increased connections included both AMPA and NMDA mediated connections from layer 2/3 superficial pyramidal cells to inhibitory interneurons and both GABAA and NMDA mediated within-population gain control of layer 5 pyramidal cells. These results support the use of extended generative models for explaining oscillatory data and provide in silico support for ketamine's ability to alter local coupling mediated by NMDA, AMPA and GABA-A.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Elsevier
ISSN: 1053-8119
Funders: Wellcome Trust, MRC/EPSRC
Date of First Compliant Deposit: 29 July 2020
Date of Acceptance: 19 July 2020
Last Modified: 31 Aug 2020 16:57
URI: http://orca-mwe.cf.ac.uk/id/eprint/133859

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