{ "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.", "abstract_shown": true, "affiliations": [ "Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA", "Medical Scientist Training Program, University of Wisconsin-Madison, Madison, WI, USA", "Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, USA", "International Institute for Integrative Sleep Medicine (WPI-IIIS), Tsukuba Institute for Advanced Research (TIAR), University of Tsukuba, Tsukuba, Japan", "Institute de Neurosciences des Systèmes (INS), INSERM, Aix-Marseille Université, Marseille, France", "International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czechia", "Foundation for Research on Information Technologies in Society (IT'IS), Zurich, Switzerland", "Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland", "Department of Information Technology and Electrical Engineering, Swiss Federal Institute of Technology (ETH) Zurich, Zurich, Switzerland", "Center for Healthy Minds, University of Wisconsin-Madison, Madison, WI, USA", "Department of Psychology, University of Wisconsin-Madison, Madison, WI, USA", "Department of Mathematics and Statistics, Brock University, St. Catharines, ON, Canada", "Department of Neurology, University of Wisconsin-Madison, Madison, WI, USA. boly@neurology.wisc.edu", "Department of Psychiatry, University of Wisconsin-Madison, Madison, WI, USA. gtononi@wisc.edu" ], "article_type": null, "arxiv": null, "author_total": 24, "authors": [ { "affs": [ 0, 1 ], "name": "Erin L. Schaeffer", "orcid": "0000-0002-6855-9674" }, { "affs": [ 2, 0 ], "name": "Ido Haber", "orcid": "0000-0001-6850-4940" }, { "affs": [ 0, 3 ], "name": "Zhiwei Fan", "orcid": "0000-0003-0995-1702" }, { "affs": [ 0 ], "name": "Simone Bruno", "orcid": "0000-0003-2523-1924" }, { "affs": [ 0 ], "name": "Beril Mat", "orcid": "0000-0003-2959-5231" }, { "affs": [ 0 ], "name": "Tariq Alauddin" }, { "affs": [ 0 ], "name": "Giulietta Vigueras" }, { "affs": [ 0 ], "name": "Lindsey Neumann", "orcid": "0000-0002-2774-3360" }, { "affs": [ 0 ], "name": "Richard Smith" }, { "affs": [ 4, 5 ], "name": "Florian Missey", "orcid": "0000-0002-8386-0377" }, { "affs": [ 4, 5 ], "name": "Adam Williamson", "orcid": "0000-0002-5632-0084" }, { "affs": [ 6, 7 ], "name": "Peter Achermann", "orcid": "0000-0002-0208-3511" }, { "affs": [ 6 ], "name": "Stefan Beerli" }, { "affs": [ 6 ], "name": "Myles H. Capstick", "orcid": "0000-0002-5751-418X" }, { "affs": [ 6 ], "name": "Esra Neufeld", "orcid": "0000-0001-5528-6147" }, { "affs": [ 8, 6 ], "name": "Niels Kuster", "orcid": "0000-0002-5827-3728" }, { "affs": [ 9 ], "name": "Robin I. Goldman", "orcid": "0000-0002-4957-2486" }, { "affs": [ 9, 10 ], "name": "Richard J. Davidson", "orcid": "0000-0002-8506-4964" }, { "affs": [ 11, 0 ], "name": "William Marshall" }, { "affs": [ 0 ], "name": "Larissa Albantakis", "orcid": "0000-0003-1000-9917" }, { "affs": [ 0 ], "name": "Stephanie G. Jones", "orcid": "0000-0003-3034-3015" }, { "affs": [ 0 ], "name": "Chiara Cirelli", "orcid": "0000-0003-2563-677X" }, { "affs": [ 12 ], "name": "Mélanie Boly", "orcid": "0000-0001-9584-0907" }, { "affs": [ 13 ], "name": "Giulio Tononi", "orcid": "0000-0002-3892-4087" } ], "bibtex": "https://research.draconitic.com/paper/7jga1cjry7a0c.bib", "cited_by": 11, "doi": "10.1038/s43856-026-01744-x", "fulltext_url": "https://doi.org/10.1038/s43856-026-01744-x", "id": "7jga1cjry7a0c", "issns": [ "2730-664X" ], "landing_url": "https://doi.org/10.1038/s43856-026-01744-x", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "R" ], [ "openalex", "2808|Transcranial Magnetic Stimulation Studies" ] ], "openalex": "W7166827768", "pdf_url": "https://www.nature.com/articles/s43856-026-01744-x_reference.pdf", "pmcid": "PMC13687101", "pmid": "42386897", "published": "2026-07-01", "publisher": "Nature Portfolio", "ris": "https://research.draconitic.com/paper/7jga1cjry7a0c.ris", "sources": [ { "first_seen": "2026-10-30T13:46:19Z", "native_id": "198e6453cefa45e68d5498ed768522c4", "source": "doaj", "url": "https://doi.org/10.1038/s43856-026-01744-x" }, { "first_seen": "2026-11-03T13:20:34Z", "native_id": "W7166827768", "source": "openalex", "url": "https://doi.org/10.1038/s43856-026-01744-x" } ], "subjects": [ { "field": "medicine", "origin": "openalex:2808|Transcranial Magnetic Stimulation Studies", "subfield": "neurology" } ], "title": "Enhancement of sleep slow wave activity using transcranial electrical stimulation with temporal interference: an interim analysis of the STRENGTHEN study", "title_text": "Enhancement of sleep slow wave activity using transcranial electrical stimulation with temporal interference: an interim analysis of the STRENGTHEN study", "type": "peer-reviewed", "updated_at": "2026-11-08T13:20:48Z", "url": "https://research.draconitic.com/paper/7jga1cjry7a0c", "venue": "Communications Medicine", "versions": [] }