Authors :
Presenting Author: Zachary Sanger, PhD, MS – University of Minnesota
Xinbing Zhang, BS – University of Minnesota
Thomas Lisko, BA – University of Minnesota
Thomas Henry, MD – University of Minnesota
Robert McGovern, MD – University of Minnesota
Theoden Netoff, PhD – University of Minnesota
Rationale:
Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) is an established therapy for drug-resistant epilepsy, yet its efficacy varies, and biomarkers of therapy efficacy and stimulation optimization are lacking. Through retrospective analysis of an ongoing prospective ANT DBS stimulation optimization study, modulation of a periodic slow gamma oscillation (20–50 Hz) was observed as a potential biomarker for identifying responders and to guide tuning for DBS therapy.
Methods:
In an IRB approved study at the University of Minnesota, 11 enrolled participants were implanted bilaterally with ANT DBS using Medtronic’s PERCEPT™ stimulator for treatment of drug resistant epilepsy. Neural activity in the ANT was measured in each participant during their routine neurological visits for at least one year with simultaneous seizure diary tracking. Within each visit, a Bayesian optimization approach was employed to identify stimulation parameters—frequency, pulse width, and amplitude—that minimized ANT broadband power. Results:
Of the 11 participants, 6 participants were responders by achieving greater than 50% seizure reduction. In 7 participants' a strong unilateral slow gamma band oscillation (SGO) was observed. Of the 11 subjects, 6 have SGO and are responders, 1 has SGO and is a non-responder, and 4 have no SGO and are non-responders (p< 0.05, Fisher-exact test). Multiple stimulation parameters, including the standard clinical setting (145 Hz, 90 μs), effectively reduced SGO in responders. In responders with SGO, chronic stimulation resulted in decreased SGO power over time, suggesting that it is a potential biomarker of therapeutic improvement. In 5 of 7 participants with SGO, a statistically significant correlation was found between seizure reduction and SGO power across visits.