Authors :
Presenting Author: Zheng Zhang, PhD – Yale University
Taruna Yadav, PhD – Yale School of Medicine
Vaclav Kremen, PhD – Mayo Clinic
Kristine Dacosta, Project Manager – Yale University
Maxime Oriol, Project Manager – Yale University
Devon Cormier, MA – Yale University
Christopher Benjamin, PhD – Yale University
Kate Christison-Lagay, PhD – Yale University
Eyiyemisi Damisah, MD – Yale University
Allyson Derry, BS – Yale University
Abhijeet Gummadavelli, MD PhD – Yale University
Tyler Hamilton, - – Yale University
Lawrence Hirsch, MD – Yale University School of Medicine
Patrice Lauture, - – Yale University
Bogdan Patedakis Litvinov, MD – Yale University
Dennis Spencer, MD – Yale University
Kim Bailey, - – Mayo Clinic
Karla Crockett, - – Mayo Clinic
Starr Guzman, - – Mayo Clinic
Vladimir Sladky, MSc – Mayo Clinic
Delana Weis, CCRP – Mayo Clinic
Jennifer Hong, MD – Dartmouth-Hitchcock Medical Center
Krzysztof Bujarski, MD – DHMC/Geisel School of Medicine
Charlotte Jeffreys, CCRC – Dartmouth-Hitchcock medical center
Anastasia Kanishcheva, MPH, CCRC – Dartmouth-Hitchcock Medical Centre
Grant Moncrief, NeuroPsy – Dartmouth-Hitchcock medical center
Robert Roth, NeuroPsy – Dartmouth-Hitchcock medical center
George Thomas, MD – Dartmouth-Hitchcock medical center
Jonathan Baker, PhD – Weill Cornel Medical School
Eun Young Choi, PhD – Stanford University
Jamie Hendorson, MD – Stanford University
Matthew Hook, - – University of Florida
Irina Korytov, - – University of Florida
Kyle O'Sullivan, MS – University of Utah
Brian Rutt, PhD – Stanford University
Joseph Giacino, PhD – Harvard Medical School
Benjamin Brinkmann, PhD – Mayo Clinic
George W Culler, MD – Dartmouth-Hitchcock medical center
Nicholas Gregg, MD – Mayo clinic, Rochester, Minnesota
Brian Lundstrom, MD PhD – Mayo clinic, Rochester, Minnesota
Imran Quraishi, MD, PhD – Yale School of Medicine
Joshua P Aronson, MD – Dartmouth-Hitchcock medical center
Jason Gerrard, MD – Yale University
Jamie J Van Gompel, MD – Mayo Clinic, Rochester MN, USA.
Christopher Butson, PhD – University of Florida
Nicholas Schiff, MD – Weill Cornel Medical School
Barbara Jobst, MD, Dr. MED, FAES, FAAN – Dartmouth Health
Gregory Worrel, MD,PhD – Mayo Clinics
Hal Blumenfeld, MD, PhD – Yale University
Rationale:
Thalamic intralaminar stimulation is being investigated to restore consciousness during temporal lobe seizures. To optimize thalamic stimulation during seizures, we used arousal from sleep as an indicator of stimulation arousal efficacy. This approach also provides a unique opportunity to study the effects of bilateral central lateral (CL) stimulation on conscious arousal during natural sleep in humans.Methods:
As part of the ongoing clinical trial, Stimulation of the Thalamus for Arousal Restoral in Temporal Lobe Epilepsy (START), we recruited five patients with medically refractory temporal lobe epilepsy, who were implanted with the investigational implantable neural sensing and stimulation device (INSS), targeting the CL nucleus and the bilateral hippocampi. An overnight sleep session was conducted during inpatient video-scalp EEG monitoring. Simultaneous intracranial recordings were acquired from the bilateral hippocampi and bilateral CL via the implanted device. Each patient’s maximum tolerated CL stimulation current—defined as the highest amplitude with no reported adverse effects—was determined during the awake state. Sleep stages were monitored in real time by clinical staff using scalp EEG. Electrical stimulation was remotely administered when patients entered non-rapid eye movement N2 or N3 sleep stages. Continuous CL stimulation was applied for 5-minute epochs, repeated across the night with systematic variation in stimulation parameters, including current amplitude, frequency (40 or 125 Hz), and pulse width (90 or 120 μs). Stimulation parameters and contact selection were guided by individualized computational modeling to optimize target engagement. Arousal responses were quantified by comparing EEG spectral power, respiratory rate, and body movements relative to a 5-minute pre-stimulation baseline.
Results:
All patients exhibited significant reductions in delta (1–3 Hz) and theta (4–7 Hz) band power during CL stimulation, based on the average power across the most effective stimulation for each patient, relative to baseline (mean reductions of 8 dB and 5.9 dB, respectively; p < 0.05, Wilcoxon rank-sum test), accompanied by concurrent increased respiratory rate and body movements during stimulation. In 2 of 5 patients, stimulation induced a transition from N2 sleep to wakefulness on EEG. The other 3 showed shifts from N3 to N2 or N2 to N1. All patients returned to sleep after stimulation, confirmed by EEG and behavior. These changes indicate transient arousal from sleep, suggesting the engagement of arousal-promoting neural mechanism during CL stimulation and further highlighting its role in modulating sleep–wake transitions in humans.