Communications medicine · 2026
Enhancement of sleep slow wave activity using transcranial electrical stimulation with temporal interference: an interim analysis of the STRENGTHEN study.
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Schaeffer Erin L, Haber Ido, Fan Zhiwei, Bruno Simone, Mat Beril, Alauddin Tariq, Vigueras Giulietta, Neumann Lindsey, Smith Richard, Missey Florian, Williamson Adam, Achermann Peter, Beerli Stefan, Capstick Myles, Neufeld Esra, Kuster Niels, Goldman Robin I, Davidson Richard J, Marshall William, Albantakis Larissa, Jones Stephanie G, Cirelli Chiara, Boly Melanie, Tononi Giulio
Аннотация
BACKGROUND: Slow waves are oscillations that reflect rhythmic alternation of neuronal activity and mediate key restorative functions of non-rapid eye movement (NREM) sleep. Left ventromedial prefrontal cortex regions are a "hot spot" for slow wave generation. The enhancement of slow wave activity (SWA, 0.5-4 Hz) has been shown to be beneficial, as in improving memory performance. To overcome limitations of current techniques, we assessed the ability of a non-invasive neuromodulatory tool, Transcranial Electrical Stimulation with Temporal Interference (TES-TI), to enhance SWA during NREM sleep overnight in healthy humans.
METHODS: The current study is an interim analysis focused on the effects of TES-TI during NREM sleep in a laboratory setting. Two high frequency carriers with 1 Hz difference (TES15kHz-TI1Hz) produced amplitude-modulated temporal interference at 1Hz. Data were collected at the University of Wisconsin-Madison as part of the STRENGTHEN study (ClinicalTrials.gov, NCT06267521, 02/12/2024, single-blind, non-random allocation). Eligible participants were healthy adults (ages 18-50) assigned in parallel to one of four groups: (Group 1) TES15kHz (0 Hz difference frequency) 2 nights per week and meditation; (Group 2) TES15kHz-TI1Hz (1 Hz difference frequency) 2 nights per week and sham meditation; (Group 3) TES15kHz-TI1Hz 1 night per week and meditation; (Group 4) TES15kHz-TI1Hz 2 nights per week and meditation. Stimulation targeting left ventromedial prefrontal cortex occurred during NREM sleep over repeated nights ( ~ 10 stimulation periods, 3-min each, first half of night, 1-2 nights/week, 4-week protocol). Twenty-one participants (Groups 2, 3, 4) received TES15kHz-TI1Hz and seven participants received TES15kHz (Group 1). SWA was measured using simultaneous high-density electroencephalography with polysomnography.
RESULTS: We show that SWA is increased with TES15kHz-TI1Hz (N = 21 total; N = 5 Group 2, N = 10 Group 3, N = 6 Group 4), and the effect outlasts the stimulation period; higher frequencies (sigma and beta) decrease. During stimulation, SWA is greater in TES15kHz-TI1Hz than pure TES15kHz (N = 7 Group 1). The incremental effects of TES15kHz-TI1Hz on SWA between first and last intervention night are positively associated with subjective ratings of restorative sleep.
CONCLUSIONS: To our knowledge, this is the first study demonstrating that TES-TI enhances SWA and potentially its restorative function.
METHODS: The current study is an interim analysis focused on the effects of TES-TI during NREM sleep in a laboratory setting. Two high frequency carriers with 1 Hz difference (TES15kHz-TI1Hz) produced amplitude-modulated temporal interference at 1Hz. Data were collected at the University of Wisconsin-Madison as part of the STRENGTHEN study (ClinicalTrials.gov, NCT06267521, 02/12/2024, single-blind, non-random allocation). Eligible participants were healthy adults (ages 18-50) assigned in parallel to one of four groups: (Group 1) TES15kHz (0 Hz difference frequency) 2 nights per week and meditation; (Group 2) TES15kHz-TI1Hz (1 Hz difference frequency) 2 nights per week and sham meditation; (Group 3) TES15kHz-TI1Hz 1 night per week and meditation; (Group 4) TES15kHz-TI1Hz 2 nights per week and meditation. Stimulation targeting left ventromedial prefrontal cortex occurred during NREM sleep over repeated nights ( ~ 10 stimulation periods, 3-min each, first half of night, 1-2 nights/week, 4-week protocol). Twenty-one participants (Groups 2, 3, 4) received TES15kHz-TI1Hz and seven participants received TES15kHz (Group 1). SWA was measured using simultaneous high-density electroencephalography with polysomnography.
RESULTS: We show that SWA is increased with TES15kHz-TI1Hz (N = 21 total; N = 5 Group 2, N = 10 Group 3, N = 6 Group 4), and the effect outlasts the stimulation period; higher frequencies (sigma and beta) decrease. During stimulation, SWA is greater in TES15kHz-TI1Hz than pure TES15kHz (N = 7 Group 1). The incremental effects of TES15kHz-TI1Hz on SWA between first and last intervention night are positively associated with subjective ratings of restorative sleep.
CONCLUSIONS: To our knowledge, this is the first study demonstrating that TES-TI enhances SWA and potentially its restorative function.