Abstracts

We studied the effect of 1 Hz vs. 200 Hz stimulation on interictal spiking, intracranial EEG (icEEG) power spectra and extracellular glutamate release using intracranial stimulation and microdialysis in epilepsy patients., Subjects were patients (n = 9) with intractable complex partial seizures admitted for icEEG monitoring. Microdialysis probes were inserted inside depth electrodes and implanted in suspected seizure onset sites. The study was performed during the interictal period after antiepileptic drug taper. The suspected seizure focus (n = 2 hippocampus, n = 7 neocortex) was stimulated with 1 Hz for 15 min and 1.5 hr later with 200 Hz, every 5 sec, 10 pulses in randomized counterbalanced order. The stimulation pulse was 0.2 msec bipolar square wave, at stimulation strength that did not induce afterdisharges (2 mA to 12 mA). icEEG data was collected for 30 min prior to and 1 hr after each stimulation. Microdialysis samples were collected every 2 min, at flow rate 2 [micro]l/min. icEEG data was analyzed for spike count and changes in the power spectrum and compared to 10 min baseline prior to the stimulation. Microdialysate was analyzed with HPLC for changes in glutamate levels., None of the patients experienced clinical seizures during stimulation. One Hz stimulation resulted in 51% decrease in interictal spiking (49% [plusmn] 21) during the first 5 min following stimulation (p[lt]0.05, paired t-test comparing data averaged over 5 min pre- and post-stimulus). 200 Hz stimulation resulted in 72% (172% [plusmn] 70 spikes/min) increase in spiking rate during the first 5 min following stimulation, which was not significantly different from baseline. The 1 Hz stimulation resulted in significant decrease in theta power lasting for 5 min, while the 200 Hz stimulation resulted in significant increase in both delta and theta power that also lasted [sim]5 min (p[lt]0.05, n=9, paired t-tests). The extracellular glutamate levels at the stimulation site increased by 50% (2 min post-stimulation) with 200 Hz stimulus, and were unchanged during and following the 1 Hz stimulus (n=3 each). The glutamate levels remained unchanged in all non-stimulated probes (n=7)., One Hz 15 min stimulation in the human brain resulted in enduring suppression of spike activity, decrease in specific EEG power spectra, and no glutamate efflux at the stimulated site. In contrast, 200 Hz stimulation caused transient increase in spiking activity and specific EEG power spectra, and glutamate efflux. Although neither of the stimulations induced seizures, this work suggests that 1 Hz stimulation may be more effective in suppressing excitability., (Supported by NIH R01-NS044102, H. P. Zaveri; NIH P01-NS-39092, D.D. Spencer; Epilepsy Project-Epilepsy Foundation and BIRWCH 1K12DA14038-01, I. Cavus.)