Short-term Anterior Thalamic Stimulation Renders Pattern-specific Effects on Limbic-network Evoked Cortical Responses in Drug-resistant Epilepsy Patients

Introduction: Anterior thalamic (ANT) stimulation can reduce seizure frequency by over 50% in patients with drug resistant epilepsy. Patient variance in seizure suppression may be explained by electrode engagement with the mammillothalamic tract. The current standard of care regularly spaced stimulation pulse pattern (145 Hz) may not be optimal for seizure suppression in all patients. Thus, we evaluated the effects of short-term stimulation utilizing a non-periodic pulse pattern delivered to the ANT.

Methods: Downstream measures of cortical excitability across the limbic network were assessed at discrete intervals before and after stimulation. Patients with drug-resistant limbic network onset epilepsy (n=7) were consented in an IRB approved ANT stimulation protocol during intracranial seizure monitoring. Periodic (PP) and non-periodic pulse (NPP) patterns were delivered to the ANT (five left, two right) via stereo-EEG electrodes at two current levels (3mA and 0.5mA) for short time intervals ( < 20 minutes). Stimulation blocks were flanked by no-stimulation periods and cortico-cortical evoked potential (CCEP) acquisition. CCEPs were evaluated for significant response using canonical response parameterization with significant modifications evaluated by latency (t-test comparison between pre and post stimulation distributions at discrete timepoints following pulse; Bonferroni corrected per-patient for number of channels C; p < 0.05/C).

Results: Significant responses were found primarily in frontal structures (73% of 346 contacts across all structures sampled) compared to parietal (34% of 62 contacts) or temporal structures (23% of 370 contacts). Stimulation pattern specific changes in evoked cortical potential waveforms were found specifically in the anterior cingulate region ipsilateral to stimulation. Further, regional cortical evoked responses had differential effects because of different patterns of stimulation with non-periodic stimulation significantly effecting early response components ( < 90ms) compared to the other stimulation conditions.

Conclusion : Measuring the effect of novel pattern ANT stimulation on anterograde limbic connectivity provides a candidate short time scale biomarker which in concept could drive stimulation adjustment.