Authors :
Presenting Author: Vaclav Kremen, MSc.Eng, EMBA, PhD – Mayo Clinic
Jindrich Adolf, MSc. – Czech Technical University in Prague; Irena Balzekas, N/A – Neurology – Mayo Clinic; Hal Blumenfeld, MD, Ph.D. – Yale University; Benjamin Brinkmann, Ph.D. – Neurology – Mayo Clinic; timothy Denison, Ph.D. – University of Oxford; Nichol Gregg, MD, Ph.D. – Neurology – Mayo Clinic; Barbara Jobst, MD, Ph.D. – Neurology – Dartmouth-Hitchcock Medical Center; Martina Krakorova, N/A – Neurology – Mayo Clinic; Brian Lundstrom, MD, Ph.D. – Neurology – Mayo Clinic; Kai Miller, MD, Ph.D. – Neurosurgery – Mayo Clinic; Filip Mivalt, MSc. – Mayo Clinic; Vladimir Sladky, MSc. – Neurology – Mayo Clinic; Erik St. Louis, MD, Ph.D. – Neurology – Mayo Clinic; Jamie Van Gompel, MD – Neurosurgery – Mayo Clinic; Gregory Worrell, MD, Ph.D. – Neurology – Mayo Clinic
Rationale:
Electrical brain stimulation of the anterior nucleus of the thalamus (EBS-ANT) using high frequency ( >100 Hz) duty cycle (one minute on and five minutes off) is an FDA approved therapy for drug resistant focal epilepsy. Clinical trials have demonstrated that EBS-ANT reduces seizures compared to baseline in blinded randomized trials and by 75% in long-term open-label studies. The use of high frequency stimulation aims to disrupt seizure propagation and the duty cycle stimulation, although its physiological effects are not well understood, helps conserve battery life. However, the impact of EBS-ANT on sleep, cognition, and memory remains unclear.Methods:
To address this gap, we developed an ecosystem consisting of the investigational Medtronic Summit RC+STM neural sense and stimulation device, smartphone, smartwatch, and cloud infrastructure. This enabled automated collection and analysis of heterogeneous data including long-term EEG. We implanted this system in 10 human subjects with temporal lobe epilepsy across three hospitals as part of two investigational device exemption (IDE) protocols. In a group of five patients, we specifically examined the effects of EBS-ANT on sleep. Continuous EEG sensing allowed accurate sleep classification and seizure monitoring.Results:
We compared seizure and sleep outcomes during low frequency (2 and 7 Hz) and high frequency duty cycle stimulation. In four patients, we found no significant difference in seizure rate reduction between low frequency and high frequency stimulation. In one patient, high frequency stimulation had a noticeably worse impact on seizure rate compared to low frequency. Our analysis of sleep patterns revealed that EBS-ANT influences sleep, with high frequency EBS-ANT disrupting sleep by increasing wakefulness after sleep onset and decreasing both NREM and REM sleep duration (on average 6.47 ± 0.9 hours). In contrast, low frequency EBS-ANT preserved overall sleep duration and sleep architecture, including NREM and REM sleep (on average 8.2 ± 0.5 hours). Conclusions:
These results suggest possible sleep-related benefits for low frequency compared to high frequency stimulation. Low frequency EBS-ANT may be a viable alternative to conventional high frequency stimulation.Funding:
NIH Brain Initiative UH2&3 NS095495 Neurophysiologically-Based Brain State Tracking & Modulation in Focal Epilepsy, R01-NS92882 Reliable Seizure Prediction Using Physiological Signals and Machine Learning, UG3/UH3 112826 Thalamic stimulation to prevent impaired consciousness in epilepsy, DARPA HR0011-20-2-0028 Manipulating and Optimizing Brain Rhythms for Enhancement of Sleep (Morpheus), Mayo Clinic, and Medtronic Inc. Medtronic provided the investigational Medtronic Summit RC+S
TM devices.