Abstracts

The effect of deep brain stimulation (DBS), also known as high frequency stimulation (HFS), on neural elements close to the stimulating electrode remains an important question. Although computational studies have suggested that HFS has a dual effect on neural elements (inhibiting cell bodies, while exciting axons), experimental evidence of these effects is conflicting and unclear. The current study investigates the hypothesis that [underline]HFS suppresses axonal conduction[/underline]. HFS application to the axon tracts themselves may provide novel, direct control for disrupting the propagation of seizure activity between brain regions., Experiments were carried out using in-vitro brain slices. Extracellular recording electrodes were positioned in the CA1 stratum pyramidale and/or alvear axon field to mointor evoked potentials. Electrical stimulation (0.5 Hz) was applied in the alveus producing compound action potentials (CAPs). Sinusoidal HFS (50Hz-10kHz) was applied to a third electrode located between the stimulating and recording electrodes. Filtering was used to remove the large stimulation artifact. Antidromic evoked field potential and compound action potential amplitude, width, and latency were analyzed prior, during, and post HFS. Extracellular potassium levels were monitored using single barreled ion-selective microelectrodes., Sinusoidal stimulation suppresses activity in cell bodies (evoked potentials) and axons (compound action potentials). Suppression was dependent on HFS amplitude and frequency, but independent of stimulus duration and synaptic input. The frequency range of this effect is nearly identical to that reported for DBS, with maximal suppression between 50 and 200Hz. At 2kHz, the suppression effect disappeared. The suppression effect was independent of synaptic transmission, and could not be attributed to desynchronization or damage. Suppression of axonal conduction was associated with an increase in extracellular peak potassium concentration ([italic]r[/italic] = 0.92), with complete suppression at a peak potassium threshold of 8.25mM. Bath application of elevated potassium produced significant suppression of axonal activity in 12 mM and 15mM KCl ACSF. However, 8.5 mM bath potassium levels failed to block axonal activity., Sinusoidal HFS suppresses axonal conduction. The frequency dependence of these suppression effects is identical to that observed for DBS in Parkinson[apos]s disease. Although the mechanism for HFS suppression is not known, damage to cells, increased inhibition, and desynchonization have been ruled out. An increase in extracellular potassium has been associated with the suppression effect; however, the potassium concentration decays significantly during stimulation while HFS suppression remains high. It is therefore likely, that, depolarization block is partially responsible for the effect. However, other mechanisms must play a role., (Supported by National Institutes of Health, the Epilepsy Foundation, and the Department of Education GAANN Fellowship program.)