Abstracts

Rationale: We have previously demonstrated differences in excitability between focal versus parafocal neocortical tissue obtained from pediatric patients with intractable epilepsy stratified by histology. The purpose of the current study is to determine whether there are corresponding differences in inward voltage-activated currents between focal and parafocal tissue. Methods: Human neocortical tissue was removed from patients with medically intractable epilepsy and obtained for experimental use with an IRB-approved protocol. EcoG, source localization and clinical relevance determined the sites selected for subsequent in vitro electrophysiologic brain- slice studies. In this study, slices for electrophysiological recordings were selected only when clear differences between the epileptic foci (focal tissue) and surrounding area (parafocal tissue) were observed during intracranial EEG monitoring. Upon resection, the tissue was placed into artificial CSF (ACSF). Voltage-clamp recordings of layer V pyramidal neurons were conducted in a 25^?C recording chamber perfused with carbogen-saturated ACSF. The intracellular solution contained TEA and Cs, to block potassium currents. Voltage-activated sodium currents were blocked with either 1 M TTX or 20 M riluzole, while calcium currents were blocked with 200 M CdCl₂. Standard voltage step protocols were used. Results: A total of 36 neocortical neurons from 15 patients were analyzed with 18 neurons each coming from the parafocal versus focal regions. No significant differences in membrane properties between focal and parafocal areas were observed in terms of membrane capacitance, access resistance, or input resistance. However, persistent calcium (I Ca² P) current densities were significantly higher between -10.0 and 10mV in focal compared to parafocal regions (p=0.026, 0.050 and 0.014, respectively, n=21). No significant differences in transient Ca² or Na currents were observed between focal or parafocal neurons. Interestingly, persistent Na current (INaP) densities were also significantly enhanced between -40 and -10 mV in parafocal compared to focal regions, in this cohort (p<0.028, n=21). Conclusions: The present study suggests that there are significant voltage-dependent differences between focal and parafocal areas in neocortical tissue obtained from patients with intractable neocortical epilepsy. Funding supported by: Advancing Healthier Wisconsin (CJM) and Emory T. Clark Foundation (CJM, AKT).