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.

Department of Brain Sciences Imperial College London London UK

Department of Functional and Stereotactic Neurosurgery Timone University Hospital Marseille France

Department of Information Technology and Electrical Engineering Swiss Federal Institute of Technology Zurich Switzerland

Department of Neurology and Neurosurgery Emory University Hospital Atlanta GA USA

Department of Neurology Harvard Medical School Boston MA USA

Departments of Brain and Cognitive Sciences Media Arts and Sciences and Biological Engineering McGovern and Koch Institutes Massachusetts Institute of Technology Cambridge MA USA

Foundation for Research on Information Technologies in Society Zurich Switzerland

Hinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health Hebrew SeniorLife Boston MA USA

Howard Hughes Medical Institute Cambridge MA USA

Institut de Neurosciences des Systèmes Aix Marseille University INSERM Marseille France

International Clinical Research Center St Anne's University Hospital and Faculty of Medicine Masaryk University Brno Czech Republic

School of Psychology Faculty of Health and Medical Sciences University of Surrey Guildford UK

UK Dementia Research Institute Imperial College London London UK

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Nat Neurosci. 2023 Dec;26(12):2252. doi: 10.1038/s41593-023-01517-y. PubMed

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Non-invasive temporal interference electrical stimulation of the human hippocampus