1297 Stimulation Pattern-Specific Modulation of Epileptiform Biomarkers During Short-Term Stimulation of the Anterior Nucleus of the Thalamus in Medication Refractory Epilepsy Patients

INTRODUCTION: Anterior thalamic (ANT) deep brain stimulation (DBS) can reduce seizure frequency by 75% in patients with medication-resistant focal epilepsy. However, a third of patients experience <50% seizure reduction and 10% no measurable reduction. Accurate mammillothalamic tract (MTT) targeting does not explain most observed seizure suppression variability. We suggest uniform application of high frequency (145 Hz) regularly spaced stimulation pulses may not be effective for all patients. A systematic investigation of alternative patterns, including irregularly spaced stimulation pulses (hypothesized to weaken hyperexcitability) is needed. METHODS: Patients were consented and underwent a research thalamic stimulation protocol after completion of seizure mapping and anti-epileptic medication resumption. Bipolar continuous ANT rhythmic (RS) or non-rhythmic stimulation (NRS) was delivered spanning the two contacts closest to the MTT during 18-minute blocks. Rates of high frequency oscillations (HFOs) and epileptic spikes were detected, quantified, and compared using the KS test (p-value <0.05). RESULTS: ANT stimulation was performed on three subjects (n=2 right ANT, n=1 left ANT). Rhythmic stimulation modulated HFO rates in 4.8%, 1.5%, and 1.5% of channels and epileptic spike rate in 68%, 49%, and 2% of channels across subjects, respectively. Non rhythmic stimulation modulated HFO rates in 2.4%, 2.6%, and 2.5% of channels, and modified epileptic spike rate in 45% and 6% of channels in subjects 2 and 3, respectively. In a seizure onset zone (SOZ) specific analysis, we found differential effects of RS and NRS on HFO and spiking rates. CONCLUSIONS: Epileptiform biomarkers are modulated in a significant fashion by short-term thalamic stimulation. Ongoing studies will explore an expanded library of non-rhythmic stimulation patterns to identify those with optimal epileptiform activity suppression. Future clinical trials of chronic thalamic stimulation directed by short-term trial stimulation are needed to validate this approach.