Non-invasive temporal interference electrical stimulation of the human hippocampus

• Type of Material: Article
• Authors: Ines R. Violante, University of Surrey; Ketevan Alania, Imperial College London; Antonino M. Cassarà, Foundation for Research on Information Technologies in Society; Esra Neufeld, Foundation for Research on Information Technologies in Society; Emma Acerbo, Emory University; Romain Carron, Timone University; Adam Williamson, St. Anne's University; Danielle L. Kurtin, University of Surrey; Edward Rhodes, Imperial College London; Adam Hampshire, Imperial College London; Niels Kuster, Swiss Federal Institute of Technology; Edward S. Boyden, Massachusetts Institute of Technology; Alvaro Pascual-Leone, Harvard University; Nir Grossman, Imperial College London
• Language: English
• Date: 2023-10-19
• Publisher: Springer Nature
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023, corrected publication 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): https://doi.org/10.1038/s41593-023-01456-8
• Title of Journal or Parent Work: Nature Neuroscience
• Volume: 26
• Issue: 11
• Start Page: 1994
• End Page: 2004
• Grant/Funding Information: I.R.V. was supported by the Biotechnology and Biological Sciences Research Council (BB/S008314/1). A.H. was supported by the UK Dementia Research Institute Care Research and Technology Centre and Biomedical Research Centre at Imperial College London. E.S.B. was supported by L. Yang, J. Doerr, HHMI, NIH R01MH117063, and E. and K. Poitras. N.G. is supported by the UK Dementia Research Institute (UK DRI)—an initiative funded by the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK, National Institute for Health and Care Research (NIHR) Imperial Biomedical Research Centre, and the American Alzheimer’s Association. A.W. was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (716867). D.L.K. was supported by the University of Surrey’s Vice-Chancellor Scholarship Award. A.P.-L. was partly supported by the National Institutes of Health (R01AG076708, R01AG059089 and R03AG072233) and the Bright Focus Foundation.
• Keywords: Neuroscience; Medical research; Biological techniques
• Research Categories: Biology, Neuroscience

Abstract

Deep brain stimulation (DBS) via implanted electrodes is used worldwide to treat patients with severe neurological and psychiatric disorders. However, its invasiveness precludes widespread clinical use and deployment in research. Temporal interference (TI) is a strategy for non-invasive steerable DBS using multiple kHz-range electric fields with a difference frequency within the range of neural activity. Here we report the validation of the non-invasive DBS concept in humans. We used electric field modeling and measurements in a human cadaver to verify that the locus of the transcranial TI stimulation can be steerably focused in the hippocampus with minimal exposure to the overlying cortex. We then used functional magnetic resonance imaging and behavioral experiments to show that TI stimulation can focally modulate hippocampal activity and enhance the accuracy of episodic memories in healthy humans. Our results demonstrate targeted, non-invasive electrical stimulation of deep structures in the human brain.