title: Evidence for an excitatory GABAA response in human motor cortex in idiopathic generalised epilepsy.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors: Western Australian Neuroscience Research Institute, University of Western Australia, 4th Floor, A Block, QEII Medical Centre, Verdun Street, Nedlands, Perth, Western Australia 6009, Australia.
authors: Benjamin I
authors: BI
authors: Silbert
authors: Western Australian Neuroscience Research Institute, University of Western Australia, 4th Floor, A Block, QEII Medical Centre, Verdun Street, Nedlands, Perth, Western Australia 6009, Australia.
authors: Alexandra E
authors: AE
authors: Heaton
authors: Western Australian Neuroscience Research Institute, University of Western Australia, 4th Floor, A Block, QEII Medical Centre, Verdun Street, Nedlands, Perth, Western Australia 6009, Australia; Division of Brain, Imaging and Behaviour - Systems Neuroscience, Toronto Western Research Institute, University Health Network, 339 Bathurst Street, MP14-324, Toronto, Ontario M5T 2S8, Canada.
authors: Robin F H
authors: RF
authors: Cash
authors: Centre for Clinical Immunology and Biomedical Statistics, Institute for Immunology and Infectious Diseases, Murdoch University, Building 390, Discovery Way, Murdoch, Perth, Western Australia 6150, Australia.
authors: Ian
authors: I
authors: James
authors: Department of Neurology, Royal Perth Hospital, Level 8, A Block, GPO Box X2213, Perth, Western Australia 6001, Australia.
authors: John W
authors: JW
authors: Dunne
authors: Department of Neurology, Royal Perth Hospital, Level 8, A Block, GPO Box X2213, Perth, Western Australia 6001, Australia.
authors: Nicholas D
authors: ND
authors: Lawn
authors: Department of Neurology, Royal Perth Hospital, Level 8, A Block, GPO Box X2213, Perth, Western Australia 6001, Australia.
authors: Peter L
authors: PL
authors: Silbert
authors: Western Australian Neuroscience Research Institute, University of Western Australia, 4th Floor, A Block, QEII Medical Centre, Verdun Street, Nedlands, Perth, Western Australia 6009, Australia.
authors: Frank L
authors: FL
authors: Mastaglia
authors: Western Australian Neuroscience Research Institute, University of Western Australia, 4th Floor, A Block, QEII Medical Centre, Verdun Street, Nedlands, Perth, Western Australia 6009, Australia. Electronic address: gary.thickbroom@gmail.com.
authors: Gary W
authors: GW
authors: Thickbroom
mesh_terms: D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use; D001703:Biophysics; D004569:Electroencephalography; D004829:Epilepsy, Generalized / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism*; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D011963:Receptors, GABA-A
keywords: Cortical excitability; Disinhibition; Epilepsy; GABA; Transcranial magnetic stimulation