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GABA-ergic dynamics in human frontotemporal networks confirmed by pharmaco- magnetoencephalography

Adams, Natalie E, Hughes, Laura E, Phillips, Holly N, Shaw, Alexander D, Murley, Alexander G, Nesbitt, David, Cope, Thomas E, Richard Bevan- Jones, W, Passamonti, Luca and Rowe, James B 2020. GABA-ergic dynamics in human frontotemporal networks confirmed by pharmaco- magnetoencephalography. Journal of Neuroscience 40 (8) , pp. 1640-1649. 10.1523/JNEUROSCI.1689-19.2019

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To bridge the gap between preclinical cellular models of disease and in vivo imaging of human cognitive network dynamics, there is a pressing need for informative biophysical models. Here we assess dynamic causal models (DCM) of cortical network responses, as generative models of magnetoencephalographic observations during an auditory oddball roving paradigm in healthy adults. This paradigm induces robust perturbations that permeate frontotemporal networks, including an evoked ‘mismatch negativity' response and transiently induced oscillations. Here, we probe GABAergic influences of the networks using double-blind placebo-controlled randomised-crossover administration of the GABA re-uptake inhibitor, tiagabine (oral, 10mg) in healthy older adults. We demonstrate the facility of conductance-based neural mass mean-field models, incorporating local synaptic connectivity, to investigate laminar-specific and GABAergic mechanisms of the auditory response. The neuronal model accurately recapitulated the observed magnetoencephalographic data. Using parametric empirical Bayes for optimal model inversion across both drug sessions, we identify the effect of tiagabine on GABAergic modulation of deep pyramidal and interneuronal cell populations. We found a transition of the main GABAergic drug effects from auditory cortex in standard trials to prefrontal cortex in deviant trials. The successful integration of pharmaco- magnetoencephalography with dynamic causal models of frontotemporal networks provides a potential platform on which to evaluate the effects of disease and pharmacological interventions.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher: Society for Neuroscience
ISSN: 1529-2401
Date of First Compliant Deposit: 21 January 2020
Date of Acceptance: 25 December 2019
Last Modified: 19 Jan 2021 01:33

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