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

B.I. Silbert, Alexandra Heaton, Robin Cash, I.R. James, John Dunne, N.D. Lawn, Peter Silbert, Francis Mastaglia, Gary Thickbroom

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

© 2015 British Epilepsy Association. 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.
Original languageEnglish
Pages (from-to)36-42
JournalSeizure
Volume26
DOIs
Publication statusPublished - 2015

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Motor Cortex
gamma-Aminobutyric Acid
Epilepsy
Transcranial Magnetic Stimulation
Idiopathic Generalized Epilepsy
Theoretical Models
Brain

Cite this

Silbert, B.I. ; Heaton, Alexandra ; Cash, Robin ; James, I.R. ; Dunne, John ; Lawn, N.D. ; Silbert, Peter ; Mastaglia, Francis ; Thickbroom, Gary. / Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy. In: Seizure. 2015 ; Vol. 26. pp. 36-42.
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abstract = "{\circledC} 2015 British Epilepsy Association. 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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Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy. / Silbert, B.I.; Heaton, Alexandra; Cash, Robin; James, I.R.; Dunne, John; Lawn, N.D.; Silbert, Peter; Mastaglia, Francis; Thickbroom, Gary.

In: Seizure, Vol. 26, 2015, p. 36-42.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy

AU - Silbert, B.I.

AU - Heaton, Alexandra

AU - Cash, Robin

AU - James, I.R.

AU - Dunne, John

AU - Lawn, N.D.

AU - Silbert, Peter

AU - Mastaglia, Francis

AU - Thickbroom, Gary

PY - 2015

Y1 - 2015

N2 - © 2015 British Epilepsy Association. 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.

AB - © 2015 British Epilepsy Association. 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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DO - 10.1016/j.seizure.2015.01.014

M3 - Article

VL - 26

SP - 36

EP - 42

JO - Seizure

JF - Seizure

SN - 1059-1311

ER -