Abstract 1 V. Kimiskidis, 1 D. Kazis, 1 S. Papagiannopoulos, 1 G. Vasiliadis, 1 F. Zara, 2 X. Fitsioris, 2 G. Georgiadis, and 1 A. Kazis ( 1 III Neurological Department, Aristotle University of Thessaloniki, Greece , 2 Neurological Department, “Papageorgiou” Hospital, Thessaloniki, Greece ) Purpose: Transcranial magnetic stimulation (TMS) studies reflecting cortical and spinal inhibitory mechanisms. Previous studies of SP in epilepsy have generally provided divergent results. The objective of the present study is to investigate SP in untreated patients with idiopathic generalised epilepsy (IGE) using a novel methodological approach. Method: Fourteen patients with IGE (9 females, median age 19 yrs, range: 16–22) entered the study. Seven patients suffered from juvenile myoclonic epilepsy (JME), 4 patients from idiopathic epilepsy with generalised tonic–clonic seizures on awakening and the rest from other idiopathic generalised epilepsy syndromes not better defined. All electrophysiological examinations were performed at least 48 hours after the occurrence of an epileptic seizure so as to account for the confounding factor of postictal changes. Results were compared with those of a control group comprising 13 healthy, age-matched subjects. SPs were investigated as recently described [Kimiskidis et al. Exp Brain Res 2005;163:21–31]. First, SPs were elicited using a wide range of stimulus intensities (SIs) (from 5 to 100% maximum SI at 5% increments). At each SI, 4 SPs were obtained and the average value of SP duration was used to construct a stimulus/response (S/R) curve of SI vs SP. The resulting S/R curves were then fitted to a Boltzman function, the best-fit values of which were statistically compared between the patient and the control group. Results: The SP S/R curve of the patients was significantly different compared to the controls (p > 0.0001, F-test and AIC). In particular, the Max value of the patient's curve was 257.5 ± 3.98 ms vs 221.4 ± 2.89 ms in the controls (p < 0.0001) and V50 was 46.95 ± 0.71 vs 51.03 ± 0.57 (p < 0.0001) whereas slope was not significantly different (9.94 ± 0.58 vs 10.09 ± 0.46, p > 0.05). Conclusion: SP, a GABAB receptor mediated event, is prolonged in IGE. Basic neurophysiology experiments prove that GABAB IPSPs are more efficiently activated in the presence of GABAA receptor antagonists. Therefore, it could be hypothesised that a hypofunction of GABAA receptors in patients with IGE results in increased GABAB IPSPs reflected in prolonged SPs.