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Non-invasive temporal interference electrical stimulation of the human hippocampus

Ines R. Violante, Ketevan Alania, Antonino M. Cassarà, Esra Neufeld, Emma Acerbo, Romain Carron, Adam Williamson, Danielle L. Kurtin, Edward Rhodes, Adam Hampshire, Niels Kuster, Edward S. Boyden, Alvaro Pascual-Leone, Nir Grossman
doi: https://doi.org/10.1101/2022.09.14.507625
Ines R. Violante
1School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
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  • For correspondence: ines.violante@surrey.ac.uk nirg@imperial.ac.uk
Ketevan Alania
2Department of Brain Sciences, Imperial College London, London W12 0HS, UK
3UK Dementia Research Institute (UK DRI) at Imperial College London, London, W12 0NN, UK
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Antonino M. Cassarà
4Foundation for Research on Information Technologies in Society (IT’IS), 8004 Zurich, Switzerland
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Esra Neufeld
4Foundation for Research on Information Technologies in Society (IT’IS), 8004 Zurich, Switzerland
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Emma Acerbo
5Aix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France
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Romain Carron
5Aix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France
6Department of Functional and Stereotactic Neurosurgery, Timone University Hospital, Marseille, France
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Adam Williamson
5Aix-Marseille Université, Inserm, Institut de Neurosciences des Systèmes (INS) UMR_S 1106, Marseille, France
7Center for Bioelectronic Medicine, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden
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Danielle L. Kurtin
1School of Psychology, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
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Edward Rhodes
2Department of Brain Sciences, Imperial College London, London W12 0HS, UK
3UK Dementia Research Institute (UK DRI) at Imperial College London, London, W12 0NN, UK
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Adam Hampshire
8The Computational, Cognitive and Clinical Neuroimaging Laboratory, Imperial College London SW7 2BU, UK
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Niels Kuster
4Foundation for Research on Information Technologies in Society (IT’IS), 8004 Zurich, Switzerland
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Edward S. Boyden
9Departments of Brain and Cognitive Sciences, Media Arts and Sciences, and Biological Engineering, McGovern and Koch Institutes, MIT, Cambridge, MA 02139, USA
10Howard Hughes Medical Institute, Cambridge, MA 02138, USA
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Alvaro Pascual-Leone
11Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA 02131, USA
12Department of Neurology, Harvard Medical School, Boston, MA 02115, USA
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Nir Grossman
2Department of Brain Sciences, Imperial College London, London W12 0HS, UK
3UK Dementia Research Institute (UK DRI) at Imperial College London, London, W12 0NN, UK
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  • For correspondence: ines.violante@surrey.ac.uk nirg@imperial.ac.uk
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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 modelling 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 (fMRI) and behaviour 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.

Competing Interest Statement

N.G. and E.S.B are inventors of a patent on the technology, assigned to MIT. E.S.B., N.G., N.K., A.P-L. and E.N. are co-founders of TI Solutions AG, a company committed to producing hardware and software solutions to support TI research.

Footnotes

  • The manuscript has been revised. Updated text, figures and supplemental material.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 02, 2022.
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Non-invasive temporal interference electrical stimulation of the human hippocampus
Ines R. Violante, Ketevan Alania, Antonino M. Cassarà, Esra Neufeld, Emma Acerbo, Romain Carron, Adam Williamson, Danielle L. Kurtin, Edward Rhodes, Adam Hampshire, Niels Kuster, Edward S. Boyden, Alvaro Pascual-Leone, Nir Grossman
bioRxiv 2022.09.14.507625; doi: https://doi.org/10.1101/2022.09.14.507625
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Non-invasive temporal interference electrical stimulation of the human hippocampus
Ines R. Violante, Ketevan Alania, Antonino M. Cassarà, Esra Neufeld, Emma Acerbo, Romain Carron, Adam Williamson, Danielle L. Kurtin, Edward Rhodes, Adam Hampshire, Niels Kuster, Edward S. Boyden, Alvaro Pascual-Leone, Nir Grossman
bioRxiv 2022.09.14.507625; doi: https://doi.org/10.1101/2022.09.14.507625

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