Abstracts

Rationale: Electrical brain stimulation (EBS) (i.e., deep brain stimulation and responsive neurostimulation) rarely results in seizure freedom. Neuromodulation is hampered by the lack of a suitable surrogate biomarker for seizures and the inefficient process to optimize stimulation parameters from an effectively infinite parameter space. Perturbational measures of brain excitability may serve as “on demand” biomarkers of epileptic networks to guide EBS optimization. Single pulse electrical stimulation (SPES) elicits cortico-cortical (or thalamo-cortical) evoked potentials (CCEPs/TCEPs), which reflect brain excitability and effective connectivity.

Methods: Six subjects with drug resistant focal or multifocal epilepsy underwent stereo EEG (sEEG) monitoring for seizure onset localization. Due to seizure onsets that were poorly localized, multifocal, or overlapped with eloquent cortex, subjects had 1–48 hours of therapeutic open-loop EBS using an external neurostimulator (Medtronic 37022) connected to sEEG electrodes. SPES (0.2 Hz frequency, 200 microsecond pulse width, 3–6 milliamps amplitude) was delivered to relevant brain regions prior to and after trials of therapeutic EBS. The CCEPs/TCEPs were evaluated at relevant seizure onset zone contacts and contacts with reliable CCEPs. Time-frequency analysis (continuous wavelet transform) was used to quantify evoked potential amplitude. Evoked potential amplitude in band (2–10 Hz) was measured 25–500 milliseconds after SPES (Fig. 1A–C). sEEG sampling rate was 512–2,048 Hz. Statistical significance was assessed with one-way ANOVA, with significance level P< 0.05. This study was approved by the Mayo Clinic Institutional Review Board.