Behavioral and neural signatures of transient arousal from sleep during bilateral central lateral thalamic stimulation in humans

Poster Session D - Monday, March 31, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Taruna Yadav¹ (taruna.yadav@yale.edu), Zheng Zhang¹, Vaclav Kremen², Kristine Dacosta¹, Maxime Oriol¹, Devon Cormier¹, Christopher Benjamin¹, Kate Christison-Lagay¹, Eyiyemisi Damisah¹, Allyson Derry¹, Abhijeet Gummadavelli¹, Tyler Hamilton¹, Lawrence Hirsch¹, Patrice Lauture¹, Bogdan Patedakis Litvinov¹, Dennis Spencer¹, Kim Bailey², Karla Crockett², Starr Guzman², Vladimir Sladky², Delana Weis², Jennifer Hong³, Krzystof Bujarski³, Charlotte Jeffreys³, Anastasia Kanishcheva³, Grant G. Moncrief³, Robert M. Roth³, George P. Thomas³, Jonathan Baker⁴, Eun Young Choi⁵, Jaimie Henderson⁵, Matthew Hook⁶, Irina Korytov⁶, Kyle O’Sullivan⁷, Brian Rutt⁵, Joseph Giacino⁸, Benjamin H. Brinkman², George Culler³, Nicholas Gregg², Brian Lundstrom², Xi Chen⁹, Jermaine Robertson⁹, Charles Mikell⁹, Sima Mofakham⁹, Imran H. Quraishi¹, Joshua P. Aronson³, Jason Gerrard¹, Jamie Van Gompel², Christopher R. Butson⁶, Nicholas Schiff⁴, Barbara Jobst³, Gregory Worrell², Hal Blumenfeld¹; ¹Yale School of Medicine, ²Mayo Clinic, ³Dartmouth-Hitchcock Medical Center, ⁴Weill Cornell Medical School, ⁵Stanford University Medical Center, ⁶University of Florida, ⁷University of Utah, ⁸Harvard Medical School, ⁹Stony Brook University

The role of the thalamic intralaminar region in arousal and sleep is well studied in animal models but little investigated in humans. Our aim is to examine the effects of bilateral stimulation of human central lateral thalamus (CL) during natural sleep. As part of an ongoing clinical trial, Stimulation of the Thalamus for Arousal Restoral in Temporal lobe epilepsy (START), an investigational neurostimulator (RC+STM) was implanted in five patients with medically refractory temporal lobe epilepsy. An overnight sleep study was conducted in patients admitted for video-scalp EEG recordings. Simultaneous neural recordings were obtained from the implanted device (bilateral hippocampi and bilateral CL). Patient’s maximum tolerated CL stimulation current with no reported side-effects was determined during the awake state. Clinicians tracked patient’s sleep state on scalp EEG and remotely delivered electrical stimulation once patient was in N2 or N3 sleep. The CL stimulation was delivered for 5 minutes and repeated over multiple epochs varying in stimulation current, frequency (40 or 125 Hz) and pulse width (90 or 120 μs). Arousal from sleep was quantified as changes in EEG band power, beta- to-delta ratio and behavior (movement and respiration) relative to 5-minute pre-stimulation baseline. All patients exhibited decreases in delta and theta power and increases in beta-delta ratio, respiration and body movement during stimulation, consistent with arousal from sleep. These findings demonstrate a key role of CL in human arousal and can serve as a potential target for therapeutic stimulation in seizures with impaired awareness and other disorders of arousal and attention.

Topic Area: METHODS: Neuroimaging