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Peer-reviewedCC BYCommunications Medicine

Enhancement of sleep slow wave activity using transcranial electrical stimulation with temporal interference: an interim analysis of the STRENGTHEN study

  • Erin L. Schaeffer1,2
  • Ido Haber3,1
  • Zhiwei Fan1,4
  • Simone Bruno1
  • Beril Mat1
  • Tariq Alauddin1
  • Giulietta Vigueras1
  • Lindsey Neumann1
  • Richard Smith1
  • Florian Missey5,6
  • Adam Williamson5,6
  • Peter Achermann7,8
12 more authors
  • Stefan Beerli7
  • Myles H. Capstick7
  • Esra Neufeld7
  • Niels Kuster9,7
  • Robin I. Goldman10
  • Richard J. Davidson10,11
  • William Marshall12,1
  • Larissa Albantakis1
  • Stephanie G. Jones1
  • Chiara Cirelli1
  • Mélanie Boly13
  • Giulio Tononi14
14 affiliations
  1. 1Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA
  2. 2Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI, USA
  3. 3Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA
  4. 4International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba, Tsukuba, Japan
  5. 5Institute de Neurosciences des Systèmes (INS), INSERM, Aix-Marseille Université, Marseille, France
  6. 6International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czechia
  7. 7Foundation for Research on Information Technologies in Society (IT'IS), Zurich, Switzerland
  8. 8Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
  9. 9Department of Information Technology and Electrical Engineering, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland
  10. 10Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA
  11. 11Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA
  12. 12Department of Mathematics and Statistics, Brock University, St. Catharines, ON, Canada
  13. 13Department of Neurology, University of Wisconsin-Madison, Madison, WI, USA. [email protected]
  14. 14Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA. [email protected]
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{schaeffer2026enhancement,
  title = {{Enhancement of sleep slow wave activity using transcranial electrical stimulation with temporal interference: an interim analysis of the STRENGTHEN study}},
  author = {Erin L. Schaeffer and Ido Haber and Zhiwei Fan and Simone Bruno and Beril Mat and Tariq Alauddin and Giulietta Vigueras and Lindsey Neumann and Richard Smith and Florian Missey and Adam Williamson and Peter Achermann and Stefan Beerli and Myles H. Capstick and Esra Neufeld and Niels Kuster and Robin I. Goldman and Richard J. Davidson and William Marshall and Larissa Albantakis and Stephanie G. Jones and Chiara Cirelli and Mélanie Boly and Giulio Tononi},
  journal = {Communications Medicine},
  year = {2026},
  month = jul,
  doi = {10.1038/s43856-026-01744-x},
  url = {https://doi.org/10.1038/s43856-026-01744-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Enhancement of sleep slow wave activity using transcranial electrical stimulation with temporal interference: an interim analysis of the STRENGTHEN study
AU  - Erin L. Schaeffer
AU  - Ido Haber
AU  - Zhiwei Fan
AU  - Simone Bruno
AU  - Beril Mat
AU  - Tariq Alauddin
AU  - Giulietta Vigueras
AU  - Lindsey Neumann
AU  - Richard Smith
AU  - Florian Missey
AU  - Adam Williamson
AU  - Peter Achermann
AU  - Stefan Beerli
AU  - Myles H. Capstick
AU  - Esra Neufeld
AU  - Niels Kuster
AU  - Robin I. Goldman
AU  - Richard J. Davidson
AU  - William Marshall
AU  - Larissa Albantakis
AU  - Stephanie G. Jones
AU  - Chiara Cirelli
AU  - Mélanie Boly
AU  - Giulio Tononi
PY  - 2026
DA  - 2026/07/01
JO  - Communications Medicine
DO  - 10.1038/s43856-026-01744-x
UR  - https://doi.org/10.1038/s43856-026-01744-x
AB  - 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.
SN  - 2730-664X
ER  -