Abstracts

Rationale: Previous studies have not found electrophysiological differences between neuronal excitability in focal and parafocal neocortical tissue excised from patients with intractable epilepsy. The purpose of this study is to determine whether differences in excitability can be found in focal versus parafocal tissue stratified by histology. Methods: Human neocortical tissue was removed from patients (n=19) with medically intractable epilepsy using a protocol approved by the IRB. EcoG, source localization and clinical relevance determined the sites selected for the slice studies. Slices for electrophysiological recordings were selected only when clear differences between the epileptic foci and surrounding areas (parafocal) were observed on intracranial EEG monitoring. Upon resection, the tissue was placed into artificial CSF (aCSF). Slices (500 μm) were sectioned perpendicular to the gyri such that the 6-layered cortex could be identified. The slices were immediately transferred to aCSF bubbled with carbogen at room temperature. Experiments were conducted in a recording chamber at 29 deg C. After 30 minutes the [K+]_o concentration of the aCSF was raised from 3 to 5 mM. Population recordings were obtained with suction electrodes positioned onto the surface of the cortical layers. Extra- and intracellular whole cell current-clamp recordings of cortical neurons were obtained using the blind patch technique. Results: Paroxysmal depolarization shift (PDS) bursting was found more frequently in the focal versus parafocal tissue, but only in patients with cryptogenic epilepsy. In patients with abnormal histology (AH), there were no significant differences in the likelihood of neurons to exhibit PDS bursting in focal versus parafocal areas suggesting that patients with AH have widely distributed rather than focal hyperexcitability. Bursting neurons are proposed to initiate neocortical rhythms underlying epilepsy. Here, we found NMDA-driven voltage-dependent bursting (NVB) neurons that are capable of generating repetitive rhythmic bursting activity. The human neocortical NVB neurons are classified based on their ability to generate repetitive rhythmic burst discharges of clustered action potentials upon depolarizing current injection. Interestingly, the surrounding parafocal tissue in patients with cryptogenic epilepsy have a significantly higher proportion of NVB neurons compared to focal tissue in this group (p<5%). In contrast, patients with AH demonstrate a dramatically different picture: the focus contains a higher proportion of NVB neurons compared to the surrounding parafocal region (p<1%). Conclusions: The present study demonstrates that electrophysiological differences between focal and parafocal areas can be observed. Furthermore, patients with AH have broader areas of hyperexcitability compared to patients with cryptogenic epilepsy. Funding supported by: Falk Foundation (WvD, JMR, CJM), Advancing Healthier Wisconsin (CJM), Emory T. Clark Foundation (CJM, AKT) and PACE (CJM)