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bioRxiv · 10.1101/2022.10.31.514225

Evaluation of GABAAR-mediated inhibition in the human brain using TMS-evoked potentials

Sulcova, D.·Salatino, A.·Ivanoiu, A.·Mouraux, A.
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Abstract

GABAA receptor (GABAAR) - mediated inhibition participates in the control of cortical excitability, and its impairment likely contributes to the pathologic excitability changes that have been associated with multiple neurological disorders. Therefore, there is a need for its direct evaluation in the human brain, and the combination of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) might represent the optimal tool. TMS-evoked brain potentials (TEPs) capture the spread of activity across the stimulated brain network, and since this process at least partially depends on the GABAAR-mediated inhibition, TEPs may constitute relevant biomarkers of local GABAAergic function. Here, we aimed to assess the effect of GABAARs activation using TEPs, and to identify TEP components that are sensitive to the state of GABAAergic inhibition. In 20 healthy subjects, we recorded TEPs evoked by sub- and supra-threshold stimulation of the primary motor cortex (M1), motor-evoked potentials (MEPs) and resting-state EEG (RS-EEG). GABAARs were activated (1) pharmacologically by oral administration of alprazolam compared to placebo within each subject, and (2) physiologically using a sub-threshold conditioning stimulus to characterize the effect of short-latency intracortical inhibition (SICI). In supra-threshold TEPs, alprazolam suppressed the amplitude of components N17, N100 and P180, and increased component N45. The pharmacological modulation of N17 correlated with the change observed in MEPs and with the alprazolam-induced increase of lower {beta}-band RS-EEG. Only a reduction of N100 and P180 was found in sub-threshold TEPs. TEP SICI manifested as a reduction of N17, P60 and N100, and its effect on N17 correlated with the alprazolam-induced N17 suppression and {beta} increase. Our results indicate that N17 of supra-threshold TEPs could serve as a non-invasive biomarker of local cortical excitability reflecting the state of GABAAR-mediated inhibition in the sensorimotor network. Furthermore, the alprazolam-induced increase of {beta}-band oscillations possibly corresponds to the increased inhibitory neurotransmission within this network.

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Sulcova, D., Salatino, A., Ivanoiu, A., Mouraux, A.. 2022-11-01. Evaluation of GABAAR-mediated inhibition in the human brain using TMS-evoked potentials. https://doi.org/10.1101/2022.10.31.514225

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