Abstracts

Rationale: Deep brain electrical stimulation (DBS) is a treatment modality being explored for many neurological diseases and is a potentially potent means for disrupting the aberrant rhythms that arise during the epileptic seizures that afflict over 1% of the population. However, current DBS protocols typically employed are formulated a priori and do not reflect the electrophysiological dynamics within the brain as seizures arise which may underlie their limited efficacy. Furthermore, most stimulation paradigms in therapeutic devices seek to reduce the frequency of seizure onset but are not specifically tailored to terminate a seizure once ictal activity has initiated simply because past efforts at this goal have not yet shown strong efficacy. This study investigates how the efficacy of DBS to terminate seizures could be improved using endogenous dynamics to inform stimulation protocols. Methods: Multi-site brain dynamics within the circuit of Papez were calculated in a chronic rat limbic epilepsy model induced via LiCl/pilocaprine i.p. injections. Stimulation/recording electrodes were placed in the CA3 region of left and right hippocampi and the anteromedial nucleus of left thalamus. Deconvolution of local field potentials using empirical mode decomposition (EMD) and phase synchrony analysis revealed multisite coherence as seizures approached natural termination that could not be detected with Fourier analysis. Multisite stimulation used charge-neutral biphasic square waves at frequencies observed during naturally termination. Results: Synchronization of electrical activity across sites occurred as both spontaneous and evoked seizures naturally terminated in freely-moving rats. Further, the location and frequency (from 7 Hz to 300 Hz) of the synchrony varied between subjects but was stable in time within each animal. DBS efficacy was significantly more effective at rapidly stopping seizures when the frequency and location of multi-site stimulation reflected the endogenous synchrony dynamics observed in each subject as seizures naturally terminated. Conclusions: These results strongly support the approach of tailoring DBS protocols to individual endogenous rhythms that may represent how brains naturally resolve epileptic seizures. This methodology can significantly improve the overall efficacy of this potentially important therapy for seizure termination and may also show improved efficacy for seizure prevention. Funding: NIH R01 NS092760