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

NeuroImage

Suresh D Muthukumaraswamy¹  Natalie E Adams²  Rachael L Sumner³  Alexander D Shaw³  Krish D Singh⁴  Neeraj Saxena⁵  Rosalyn J Moran⁵ 

[1] Corresponding author.;Department of Anaesthetics, Intensive Care and Pain Medicine, Cwm Taf Morgannwg University Health Board, Llantrisant CF72 8XR, UK;Cardiff University Brain Research Imaging Centre (CUBRIC), Cardiff University, Maindy Road, Cardiff CF24 4HQ, UK;Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0SZ, UK;School of Pharmacy, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand;

关键词: ketamine;    Oscillations;    Neurophysiological modelling;    Neural mass;    MEG;    DCM;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown