Abstracts

Rationale: In generalized epileptic seizures, electrical discharges oscillate between cerebral cortex, thalamus and basal ganglia. In focal cortical seizure activity, specific cortical-subcortical circuits contribute to sustaining and propagating the seizure discharge. Experiments in animal models have identified specific brain regions such as the substantia nigra and the piriform cortex as critical for controlling the initiation or propagation of both generalized and focal seizure activity. We sought evidence for a brain area involved in seizure modulation common to human patients with a variety of focal epilepsy syndromes.Methods: Using electroencephalography combined with simultaneous functional MRI (EEG-fMRI) we studied 19 patients during rest with 1) focal epilepsies arising from any cortical location and 2) frequent (more than 1 per minute) interictal epileptiform discharges (IED) during data acquisition. By averaging across this group of subjects, we were able to detect, independently of the site of focal IEDs, IED time-locked hemodynamic responses occurring anywhere in the brain which were common to all 19 patients. In a separate group of 18 patients with focal neocortical epilepsies we carried out flumazenil positron emission tomography (FMZ PET), which marks the central benzodiazepine-GABA/A receptor complex. We used seizure frequency in the 6 months prior to the PET scan as a measure of severity of epilepsy.Results: We found a significant correlation (Z ~ 3) between IED and haemodynamic response common to all 19 patients most prominently in an area deep to frontal olfactory cortex, adjacent to putamen and claustrum on the same side as the presumed cortical epileptic focus (Figure A). FMZ binding reflecting GABA-A receptor density, correlated (Z ~ 4) negatively with seizure frequency in this same area deep to frontal olfactory cortex, adjacent to putamen and claustrum ipsilateral to the presumed cortical epileptic focus (Figure B).Conclusions: Conclusions: We provide in-vivo human evidence from haemodynamic studies of IED and neuroreceptor imaging studies related to seizures for an area located close to frontal olfactory cortex that appears to be part of the common network involved in the pathophysiology of ipsilateral IED and seizures and which may have a seizure-modulating role. Our findings suggest that this area may be a potential target for focal neurosurgical, stimulatory or pharmacological therapies.