Abstracts

Rationale:
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT-DBS) is an established therapy for drug-resistant epilepsy. However, the latency of DBS effects is long, stimulation parameter optimization can be a lengthy process, and seizure free outcomes are rare. Stereotactic intracranial EEG (sEEG) monitoring including a thalamic electrode presents an opportunity to trial different stimulation parameters and evaluate short latency effects of DBS on electrophysiological biomarkers, such as interictal epileptiform spikes (IES). Circadian and behavioral wake/sleep state dependencies have been observed for seizures and epileptiform spikes in focal epilepsy. Here, we investigate wake/sleep state dependent effects of high frequency thalamic stimulation on IES suppression and consider the implications for chronic neuromodulation.




Methods:
Nine patients underwent an overnight trial of 145-Hz thalamic stimulation during sEEG monitoring (8 subjects with anterior thalamus stimulation, 1 with pulvinar stimulation). Stimulation was delivered on a duty cycle (1-4 minute periods of active stimulation, 3-5 minutes off). Classification for awake and slow wave sleep (SWS) states were manually created by a human expert using sEEG delta/beta ratio and visual review. IES detection was performed using an established automated classifier on seizure onset zone channels. The sEEG segments impacted by noise (movement artifact, stimulation artifact, flat line, powerline noise) or containing seizures were removed. IES were evaluated in 1-minute windows. The IES rates (spikes/minute) were subsequently compared between active and inactive phase of stimulation during awake and SWS using the Mann-Whitney U rank test, with 0.05 significance threshold.




Results:
The average IES rate was suppressed on the group level during the active SANTE DBS phase (active: 7.0 ± 10.5, inactive: 13.7 ± 16.5, p < 0.05). Seven of the nine patients exhibited significantly reduced spike rates during the active phase (p < 0.05). Moreover, there was significantly greater suppression of IES during awake (active: 6.1 ± 9.9, inactive:15.0 ± 19.3, suppression: 59.3%) compared to SWS (active: 7.8 ± 10.9, inactive: 12.9 ± 15.4, suppression: 39.5% rate) (p < 0.05), with greater awake suppression seen in 6/9 individuals.