Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

B.I. Silbert; A.E. Heaton; R.F.H. Cash; I. James; J.W. Dunne; N.D. Lawn; P.L. Silbert; F.L. Mastaglia; G.W. Thickbroom

doi:10.1016/j.seizure.2015.01.014

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Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

Journal article

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Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

B.I. Silbert, A.E. Heaton, R.F.H. Cash, I. James, J.W. Dunne, N.D. Lawn, P.L. Silbert, F.L. Mastaglia and G.W. Thickbroom

Seizure, Vol.26, pp.36-42

2015

DOI: https://doi.org/10.1016/j.seizure.2015.01.014

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Abstract

Purpose Impaired GABAergic inhibition has been implicated in the pathophysiology of epilepsy. The possibility of a paradoxical excitatory effect of GABA in epilepsy has been suggested, but has not been investigated in vivo. We investigated pre- and post-synaptic GABAergic mechanisms in patients with idiopathic generalised epilepsy (IGE). Method In 10 patients and 12 control subjects we explored short- and long-interval intracortical inhibition (SICI, LICI; post-synaptic GABAA and GABAB-mediated respectively) and long-interval intracortical facilitation (LICF; pre-synaptic disinhibition) using transcranial magnetic stimulation. Results While post-synaptic GABAB-mediated inhibition was unchanged in IGE (p = 0.09), LICF was reduced compared to controls (controls: 141 ± 17% of baseline; untreated patients: 107 ± 12%, p = 0.2; treated patients: 79 ± 10%, p = 0.003). GABAA-mediated inhibition was reduced in untreated patients (response amplitude 56 ± 4% of baseline vs. 26 ± 6% in controls, p = 0.004) and normalised with treatment (37 ± 12%, p = 0.5 vs. controls). When measured during LICI, GABAA-mediated inhibition became excitatory in untreated IGE (response amplitude 120 ± 10% of baseline, p = 0.017), but not in treated patients. Conclusion Pre- and post-synaptic GABA-mediated inhibitory mechanisms are altered in IGE. The findings lend in vivo support to evidence from experimental models and in vitro studies of human epileptic brain tissue that GABA may have a paradoxical excitatory role in ictogenesis.

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Title: Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy
Authors/Creators: B.I. Silbert (Author/Creator) - The University of Western Australia
A.E. Heaton (Author/Creator) - The University of Western Australia
R.F.H. Cash (Author/Creator) - The University of Western Australia
I. James (Author/Creator) - Murdoch University
J.W. Dunne (Author/Creator) - Royal Perth Hospital
N.D. Lawn (Author/Creator) - Royal Perth Hospital
P.L. Silbert (Author/Creator) - Royal Perth Hospital
F.L. Mastaglia (Author/Creator) - The University of Western Australia
G.W. Thickbroom (Author/Creator) - The University of Western Australia
Publication Details: Seizure, Vol.26, pp.36-42
Publisher: Elsevier Ltd.
Identifiers: 991005545558807891
Copyright: © 2015 British Epilepsy Association.
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.82 Gait & Posture; 1.82.811 Transcranial Magnetic Stimulation
Web Of Science research areas: Clinical Neurology; Neurosciences
ESI research areas: Neuroscience & Behavior